Caffeine

Evidence-based effects and studies

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Effects
1273
Total evidences
1430

Effects and Evidences

Detailed analysis of research findings

Nightly sleep minutes

1 evidences

In a randomized 14-day crossover trial, caffeinated coffee increased ventricular ectopy and daily steps and reduced nightly sleep duration versus avoiding caffeine, with no significant change in atrial ectopy.

Trust comment: Randomized case-crossover trial with objective continuous monitoring in 100 adults and high adherence, giving high internal validity.

Study Details

PMID:36947466
Participants:100
Impact:-36 min (mean difference; significant)
Trust score:5/5

Mean and peak bar velocity (Vmean, Vpeak)

1 evidences

Acute caffeine (3 mg/kg) improved muscular velocity, power and endurance across sexes, with larger effects in lower-body (back squat) at moderate–high loads.

Trust comment: Well-powered, triple-blind randomized crossover trial (n=76) with detailed objective performance metrics and appropriate statistics.

Study Details

PMID:38892692
Participants:76
Impact:Increases across conditions; e.g., back squat Vmean +4.5–7.9% (depending on load and sex); bench press increases smaller/variable (several significant at 25–75% 1RM)
Trust score:5/5

Duration of oxygen therapy

1 evidences

In preterm infants (<32 weeks), early prophylactic caffeine reduced duration of oxygen therapy and other respiratory support needs compared with therapeutic (delayed) caffeine.

Trust comment: Randomized controlled trial with substantial sample size and clear primary endpoint showing statistically significant benefit; neonatal population and specific protocol increase applicability in that setting.

Study Details

PMID:33771081
Participants:181
Impact:Median 28 days (IQR 18–36) prophylactic vs 34 days (IQR 23–51) therapeutic (p=0.005)
Trust score:4/5

Frequency of post-dural puncture headache (PDPH)

1 evidences

Prophylactic acetaminophen + caffeine given before spinal anesthesia reduced frequency and severity of post-dural puncture headache and increased maternal satisfaction vs placebo.

Trust comment: Randomized double-blind trial with clear effects, but caffeine was co-administered with acetaminophen so caffeine-specific effects cannot be isolated; single-center and modest sample size.

Study Details

PMID:39371383
Participants:94
Impact:Intervention group 70% lower odds overall (OR 0.31); rates at 24 h 4.2% vs 19.6%, 48 h 14.6% vs 34.8%, 72 h 20.8% vs 45.7% (intervention vs placebo)
Trust score:3/5

Muscular endurance (repetitions)

1 evidences

Acute caffeine (3 mg/kg) alone improved muscular endurance, velocity and power (esp. back squat); co-ingestion with sodium bicarbonate did not produce additive benefit and attenuated caffeine's ergogenic effect.

Trust comment: Double-blind randomized crossover with objective measures; sample small (n=28) but design robust; lack of plasma measures limits mechanistic interpretation.

Study Details

PMID:39771003
Participants:28
Impact:Caffeine increased repetitions vs placebo: +7% at 65%1RM and +9.5–25% at 85%1RM depending on exercise; NaHCO3+CAF did not add benefit and often mitigated caffeine effect
Trust score:4/5

Time to first bowel movement (primary)

1 evidences

Oral caffeine (100 or 200 mg three times daily) after laparoscopic colectomy did not shorten time to first bowel movement or improve colonic transit compared with placebo.

Trust comment: Randomized double-blind placebo-controlled trial with balanced groups (n=60); moderate sample and negative primary outcome increases confidence in null result.

Study Details

PMID:35909263
Participants:60
Impact:No difference: mean ~67–68 hours across 200 mg, 100 mg, and placebo groups (P=0.887)
Trust score:4/5

blood caffeine concentration correlation

1 evidences

In healthy aeromedically fit pilots, a single 300 mg dose of caffeine at midnight reduced the nighttime decline in psychomotor performance after extended wakefulness.

Trust comment: Randomized double-blind crossover RCT in relevant population (n=30); well-controlled but moderate sample size.

Study Details

PMID:37726901
Participants:30
Impact:no significant correlation with performance
Trust score:4/5

caffeine blood level (peak ~60 min)

1 evidences

IV or enteral caffeine given in delivery room was feasible; most infants had measurable caffeine blood levels but respiratory outcomes matched historical controls.

Trust comment: Prospective randomized feasibility study with objective blood measures but small sample, some missing samples, and comparison to a historical control for clinical outcomes.

Study Details

PMID:36301511
Participants:38
Impact:measurable in 95% of cases; mean ~9.1 ± 5.2 µg/mL (IV) and ~8.3 ± 4.1 µg/mL (enteral)
Trust score:3/5

plasma lactate (post-sprint)

1 evidences

Acute 3 mg/kg caffeine improved peak and mean power in repeated Wingate sprints in both sexes with sex‑specific timing differences (males early sprints, females later sprints).

Trust comment: Well-powered (n=52), triple‑blind randomized crossover with appropriate controls and objective performance and metabolic measures.

Study Details

PMID:39662990
Participants:52
Impact:increased: immediately after Wt1 +13.9% and after Wt4 +8.0% (CAF vs placebo), more pronounced in males
Trust score:5/5

simple reaction time

4 evidences

In fasted young adults, combined caffeine (75 mg) + glucose (75 g) improved sustained attention and verbal memory consolidation beyond either substance alone; caffeine alone improved simple reaction time.

Trust comment: Double‑blind randomized design with moderate sample (n=72) and multiple cognitive measures; results need replication and dose/effort control.

Study Details

PMID:20521321
Participants:72
Impact:improved with caffeine alone (benefit observed)
Trust score:4/5

In a double-blind trial, 65 mg caffeine in coffee improved some working memory tasks (especially in extraverts) and sped simple reaction time and encoding.

Trust comment: Large randomized double-blind design with clear cognitive outcomes; moderate-high internal validity.

Study Details

PMID:23015541
Participants:128
Impact:+improved (faster) via caffeine
Trust score:4/5

A 2 mg/kg dose of caffeine made people react faster, detect more targets, and encode new information faster compared with placebo/withdrawal.

Trust comment: Controlled between-group design with adequate sample size (70) and objective performance measures, though specific effect magnitudes are not given.

Study Details

PMID:22992376
Participants:70
Impact:improved (faster) on caffeine
Trust score:4/5

Caffeine improved reaction time during administration and a conditioned context elicited similar improvement when placebo was given.

Trust comment: Controlled experimental design with small samples across two experiments; effects replicated within study but limited sample sizes.

Study Details

PMID:19931288
Participants:28
Impact:improved during caffeine (faster RT)
Trust score:3/5

working memory performance (serial recall, running memory)

1 evidences

In a double-blind trial, 65 mg caffeine in coffee improved some working memory tasks (especially in extraverts) and sped simple reaction time and encoding.

Trust comment: Large randomized double-blind design with clear cognitive outcomes; moderate-high internal validity.

Study Details

PMID:23015541
Participants:128
Impact:+improved in interaction with extraversion
Trust score:4/5

encoding speed of new information

2 evidences

In a double-blind trial, 65 mg caffeine in coffee improved some working memory tasks (especially in extraverts) and sped simple reaction time and encoding.

Trust comment: Large randomized double-blind design with clear cognitive outcomes; moderate-high internal validity.

Study Details

PMID:23015541
Participants:128
Impact:+increased (faster) via caffeine
Trust score:4/5

Forty mg caffeine delivered in chewing gum improved mood and sustained-attention task performance (faster encoding) compared with placebo or no gum in young adults.

Trust comment: Double-blind, placebo-controlled trial with adequate sample size (n=118) and clear behavioral outcomes.

Study Details

PMID:19330801
Participants:118
Impact:+ faster encoding with caffeine gum
Trust score:4/5

postural balance (firm and foam surface)

1 evidences

In middle-aged women, 12 weeks of Zumba improved postural balance and cognition; adding 100 mg/day caffeine with Zumba produced improvements in postural balance and cognitive tests in challenging conditions.

Trust comment: Randomized intervention with moderate sample size but unclear blinding and limited reporting of effect sizes for caffeine-specific additive effects.

Study Details

PMID:37279332
Participants:56
Impact:+improved with Zumba; CZG showed improvements in challenging conditions
Trust score:3/5

fat mass and fat-free mass

1 evidences

Over 6 weeks of resistance training, a caffeinated multi-ingredient pre-workout (≈406 mg caffeine) produced similar body composition, muscle thickness, and performance changes as an isocaloric carbohydrate comparator; waist circumference decreased in the PREW group.

Trust comment: Double-blind RCT with objective outcome measures and reasonable completion rate (41); habitual caffeine use may limit observed added benefits.

Study Details

PMID:40512050
Participants:41
Impact:both groups improved; no between-group differences
Trust score:4/5

alpha2 power (frontal/parietal)

1 evidences

In a randomized placebo-controlled crossover (200 mg caffeine), caffeine reduced several EEG band powers (alpha1/alpha2 and beta) with some differences between early-phase psychosis patients and healthy controls.

Trust comment: Within-subject randomized crossover design provides strong internal control, but overall sample is small and mixed medication status limits external validity.

Study Details

PMID:34806929
Participants:27
Impact:decreased with caffeine, effect larger in schizophrenia group
Trust score:3/5

1RM bench press

1 evidences

A multi-ingredient caffeine supplement did not change strength or cycling time-to-exhaustion in untrained men.

Trust comment: Double-blind placebo crossover but small sample and supplement contained other ingredients (not caffeine-only), limiting causal attribution to caffeine.

Study Details

PMID:19834348
Participants:21
Impact:no change
Trust score:3/5

anaerobic capacity / neuromuscular function

1 evidences

56 male sprinters randomized to control, caffeine, TMR, or both; caffeine and TMR reduced reaction times, TMR improved anaerobic/neuromuscular measures, and combined treatment slightly raised heart rate.

Trust comment: Larger randomized controlled trial with clear group allocation, but limited methodological detail in the summary provided.

Study Details

PMID:40221884
Participants:56
Impact:improved with TMR; caffeine had minimal impact
Trust score:4/5

sustained attention accuracy

2 evidences

In moderate caffeine consumers tested while deprived, caffeine improved sustained attention and alertness; these benefits were not seen when participants were not caffeine-deprived, consistent with withdrawal-reversal.

Trust comment: Controlled experimental design in humans (N=30) with clear behavioral outcomes, though some effect sizes/magnitudes not reported.

Study Details

PMID:12424547
Participants:30
Impact:increased with 1 mg/kg at breakfast (magnitude not reported)
Trust score:4/5

In a randomized single-blind crossover in healthy adults, caffeinated carbonated beverage produced faster and more frequent improvements in sustained attention and increased self-rated energy vs control; caffeine (carbonated or not) improved accuracy and reaction time vs control.

Trust comment: Randomized crossover with within-subject controls and per-protocol n=22; well-controlled but single-blind and modest sample size.

Study Details

PMID:35684105
Participants:22
Impact:OR=1.6 (CCB vs control); OR=1.42 (CB vs control); CCB produced earlier improvements (significant in 10/16 post-consumption blocks)
Trust score:4/5

post-OGTT insulin

1 evidences

In sleep-deprived healthy men, caffeinated (vs decaffeinated) coffee raised post-OGTT glucose and insulin and increased fasting insulin and insulin resistance (HOMA), indicating worse glucose homeostasis under these conditions.

Trust comment: Randomized crossover in humans (N=42) with metabolic assays and appropriate washouts; limited to sleep-deprived, moderate coffee consumers.

Study Details

PMID:27702715
Participants:42
Impact:increased (CC vs DC), p<0.001
Trust score:4/5

functional mobility (TUG test)

1 evidences

Over 12 weeks, Zumba training improved functional performance in middle-aged women; daily 100 mg caffeine alone also produced improvements and combining caffeine with Zumba led to the largest gains in mobility, lower-body endurance, and walking speed.

Trust comment: Randomized parallel-group single-blind trial with adequate group sizes for most arms (total n=69) and objective functional tests, though some groups smaller (n=12) and single-blind design.

Study Details

PMID:39463442
Participants:69
Impact:Ca+ZT: −1.11 s (7.62→6.51); ZT and Ca also improved (pre→post)
Trust score:4/5

perceived fatigue and perceptual/affective responses (RPE, effort, arousal, affect)

1 evidences

Across two crossover studies in habitual low–moderate consumers tested without enforced caffeine restriction (combined N≈56), oral caffeine (2.5 or 6 mg/kg) did not change time-to-exhaustion, perceived fatigue, perceptual or affective responses, or time perception.

Trust comment: Carefully controlled double-blind crossover studies in humans with thorough perceptual measures; good internal validity though ecological (no caffeine restriction) and subgroup sizes vary.

Study Details

PMID:40704635
Participants:56
Impact:no significant change with caffeine
Trust score:4/5

fine motor performance (9‑hole peg)

1 evidences

Post-hoc analysis of a randomized crossover trial (placebo vs ~98 mg caffeine) showing that individual trait mental/physical energy and fatigue modify caffeine's effects on mood, cognitive (serial subtraction) and fine-motor (9‑hole peg) performance—people with higher trait fatigue often gained more benefit.

Trust comment: Moderate-sized (n=30) randomized crossover parent trial but current analyses are post-hoc with multiple interactions and some effect estimates having wide CIs.

Study Details

PMID:33525438
Participants:30
Impact:improved (reduced completion time) with caffeine in high trait fatigue groups (dominant hand β=−9.40 s; nondominant hand β=−8.00 s)
Trust score:3/5

perceived task difficulty

1 evidences

Randomized double-blind crossover in recreational males showed dose-dependent benefits of caffeine mouth rinse on selective attention: faster completion time with 300 mg, fewer errors with 150 mg, and reduced perceived difficulty at 150 and 300 mg vs placebo.

Trust comment: Randomized double-blind crossover with objective cognitive tests and clear dose-response effects; sample limited to recreational males.

Study Details

PMID:39495309
Participants:30
Impact:decreased after 150 mg (p=0.006) and 300 mg (p<0.001) vs pre-rinse)
Trust score:4/5

tidal volume

2 evidences

Caffeine given immediately after birth to very preterm infants increased respiratory effort measures versus later administration.

Trust comment: Randomized controlled trial in 30 infants with direct physiological respiratory measurements; moderate sample size for neonatal RCT.

Study Details

PMID:28288150
Participants:30
Impact:5.2 (IQR 3.9–6.4) vs 4.4 (3.0–5.6) ml/kg; increase (p<0.05)
Trust score:4/5

Single 6 mg/kg caffeine increased blood pressure and tidal volume and raised plasma caffeine concentrations; epinephrine rose in able-bodied and paraplegic but not tetraplegic participants, with limited HRV changes.

Trust comment: Randomized, double‑blind, placebo‑controlled crossover with objective physiological measures, but subgroup sizes are small (n per subgroup limited).

Study Details

PMID:27776149
Participants:28
Impact:increased significantly in able‑bodied and paraplegic participants after caffeine
Trust score:4/5

vigilance (hits and reaction time)

1 evidences

Acute caffeine (50–450 mg) produced stimulant-like effects: increased blood pressure and arousal, improved vigilance, but worsened short-term memory in light nondependent users.

Trust comment: Well-powered within-subject double-blind design (n=102) showing consistent subjective and behavioral effects across doses.

Study Details

PMID:16541243
Participants:102
Impact:more hits and faster reaction times (improvement)
Trust score:4/5

Tmax (time to peak)

1 evidences

Single 200 mg caffeine given overtly or covertly to healthy adults; large within-person variability in PK measures but no average covert vs overt difference.

Trust comment: Randomized crossover in healthy humans with standard PK methods; small sample (n=28 analysed) limits precision but design and methods are sound.

Study Details

PMID:28561231
Participants:28
Impact:43% of individuals outside ±25% range (high intra-subject variability)
Trust score:4/5

subjective energy/fatigue

1 evidences

In a randomized single-blind crossover in healthy adults, caffeinated carbonated beverage produced faster and more frequent improvements in sustained attention and increased self-rated energy vs control; caffeine (carbonated or not) improved accuracy and reaction time vs control.

Trust comment: Randomized crossover with within-subject controls and per-protocol n=22; well-controlled but single-blind and modest sample size.

Study Details

PMID:35684105
Participants:22
Impact:↑ physical and mental energy; ↓ physical and mental fatigue (CCB and CB vs control; assessed at 60 min)
Trust score:4/5

subjective energy/concentration/mood

1 evidences

In 52 healthy female students, a single serving of standardized Turkish coffee (≈3 mg/kg caffeine) produced acute changes in subjective energy, concentration and sleep scores, reduced heart rate over time versus control, and was associated with reductions in fasting blood sugar at some post‑drink time points.

Trust comment: Randomized crossover with moderate sample size but potential expectancy/non-blinding and single-sex sample limit internal validity and generalizability.

Study Details

PMID:40077691
Participants:52
Impact:↑ increased self-reported energy, concentration and mood versus control (significant interactions)
Trust score:3/5

perceived strength and endurance

1 evidences

In elite jiu-jitsu athletes, 3 mg/kg caffeine increased throws in later SJFT sets, raised heart rate slightly, improved strength/endurance perception, and reduced fatigue perception, but did not change technical actions during real combat.

Trust comment: Randomized double-blind placebo-controlled trial in 22 elite athletes with objective performance and perceptual measures; moderate sample and some methodological limitations noted by authors.

Study Details

PMID:35277034
Participants:22
Impact:increase
Trust score:4/5

creative idea generation (divergent thinking)

1 evidences

Participants given 200 mg caffeine showed better convergent problem-solving but no change in creative idea generation or working memory.

Trust comment: Randomized double-blind placebo-controlled between-subject design with balanced groups (44 per arm) and clear outcomes; good internal validity.

Study Details

PMID:32086187
Participants:88
Impact:no significant change
Trust score:4/5

risk of cardiovascular malformations

1 evidences

Large case–control analysis found no clear evidence that maternal caffeine intake increases risk of cardiovascular birth defects.

Trust comment: Large, well-classified epidemiologic dataset (4,196 cases, 3,957 controls) with detailed exposure assessment, though observational design limits causal inference.

Study Details

PMID:17405163
Participants:8153
Impact:no significant association overall
Trust score:4/5

sustained attention / task performance

1 evidences

Forty mg caffeine delivered in chewing gum improved mood and sustained-attention task performance (faster encoding) compared with placebo or no gum in young adults.

Trust comment: Double-blind, placebo-controlled trial with adequate sample size (n=118) and clear behavioral outcomes.

Study Details

PMID:19330801
Participants:118
Impact:+ improved speed and performance on sustained-attention tasks with 40 mg caffeine gum
Trust score:4/5

ocular pulse amplitude (OPA)

1 evidences

In a crossover RCT including people with or at risk for glaucoma, one cup of caffeinated coffee (182 mg) produced small but statistically significant increases in intraocular pressure (IOP), ocular perfusion pressure and ocular pulse amplitude at 60–90 min vs decaffeinated coffee.

Trust comment: Prospective, double-masked crossover RCT with 106 participants and objective ophthalmic measures; small absolute changes likely of limited clinical relevance.

Study Details

PMID:22678051
Participants:106
Impact:+ ~0.18–0.23 mm at 60 and 90 min (statistically significant)
Trust score:4/5

incidence of dialysis headache

1 evidences

In hemodialysis patients, drinking regular versus decaffeinated coffee during sessions did not change the incidence of dialysis‑related headache or hypotension over 12 sessions.

Trust comment: Large randomized, double‑blind multicenter trial with high completion rate; results applicable to dialysis patients but specific population limits generalizability.

Study Details

PMID:33715955
Participants:139
Impact:no significant difference (regular 33.3% of sessions vs decaf 37.1%; P=0.522)
Trust score:4/5

body fat percentage

2 evidences

Drinking three cups/day of lightly roasted (higher polyphenols and caffeine) or regular coffee for 12 weeks reduced body fat percentage and increased muscle mass in overweight/obese adults; lightly roasted coffee produced a slightly greater fat percentage reduction.

Trust comment: Randomized, controlled crossover in humans with validated measures; small sample (n=38), high dropout and coffee contains multiple bioactives so caffeine-specific attribution is uncertain.

Study Details

PMID:39275165
Participants:38
Impact:LRC vs RC mean difference −0.8% (95% CI −1.4 to −0.2); p=0.029
Trust score:4/5

An 8-week randomized trial of an herbal mix (includes 240 mg/day caffeine) produced greater short-term weight and fat loss but more withdrawals and side effects.

Trust comment: Randomized, double-blind, placebo-controlled RCT but small, short-term and multi-ingredient so effects cannot be attributed solely to caffeine.

Study Details

PMID:11319627
Participants:48
Impact:-2.1% (active) vs +0.2% (placebo) over 8 weeks
Trust score:4/5

subjective drowsiness / tiredness

1 evidences

Across three small experiments, caffeine reduced subjective drowsiness but produced mixed effects on subjective effort and no consistent performance improvements.

Trust comment: Multiple small experiments with mixed and sometimes non-significant results; design described but limited power and complex interactions.

Study Details

PMID:7737103
Participants:52
Impact:caffeine reduced increases in drowsiness/tiredness vs placebo (experiment 1)
Trust score:3/5

self-rated alertness

2 evidences

Caffeine increased self-rated alertness, jitteriness, and blood pressure in healthy adults; theanine opposed caffeine's blood pressure rise.

Trust comment: Well-powered randomized double-blind placebo-controlled study with clear subjective and physiological endpoints.

Study Details

PMID:17891480
Participants:48
Impact:increased after caffeine
Trust score:4/5

In partially sleep-deprived healthy volunteers an acute energy shot improved multiple composite cognitive measures and self-rated alertness for up to 6 hours compared with placebo.

Trust comment: Randomized double-blind crossover with large N (94) and validated cognitive tests, but the active composition of the energy shot (explicit caffeine content) is not specified in the provided text, so attribution to caffeine is indirect.

Study Details

PMID:23587521
Participants:94
Impact:+improved (sustained up to 6h)
Trust score:3/5

body/skin temperature (tympanic and mean skin)

1 evidences

Caffeine plus heat exposure increased body and skin temperatures and amplified thermogenesis-related biomarkers (FGF‑21 and irisin).

Trust comment: Randomized trial with a fairly large male sample and quantified biomarker changes, though limited to healthy males and acute exposure.

Study Details

PMID:40635261
Participants:87
Impact:increased with caffeine plus thermotherapy
Trust score:4/5

sustained attention

1 evidences

A single 60 mg oral dose of caffeine improved sustained attention, reaction times, and subjective alertness in middle-aged healthy adults.

Trust comment: Randomized crossover with adequate sample (n=82) and objective+subjective measures, though blinding not specified in text provided.

Study Details

PMID:27649778
Participants:82
Impact:+ significant improvement vs placebo
Trust score:4/5

Birth weight

1 evidences

Reducing caffeine intake in pregnancy (moderate reduction) did not change babies' birth weight or length of gestation.

Trust comment: Large randomized double-blind controlled trial with >1100 completed outcomes; high methodological quality.

Study Details

PMID:17259189
Participants:1150
Impact:+16 g (adjusted difference; not statistically significant)
Trust score:5/5

time to exhaustion (T2EX)

1 evidences

In well-trained cyclists, caffeine in a performance bar improved time to exhaustion and complex cognitive task performance during and after prolonged exercise.

Trust comment: Controlled exercise trial in trained cyclists (n=24) with objective performance and cognitive measures; moderate sample size.

Study Details

PMID:18799996
Participants:24
Impact:increased (significant vs controls)
Trust score:4/5

odour identification

1 evidences

In healthy young adults, a 100 mg caffeine capsule had no overall effect on smell tests, but non-habitual caffeine users showed higher odour sensitivity and worse odour identification after caffeine; small mood trends were seen in habitual users.

Trust comment: Randomized double‑blind design and appropriate measures, but small non‑consumer subgroup and several effects are marginal/non‑significant.

Study Details

PMID:33123819
Participants:39
Impact:Non-consumers: mean −2.0 (caffeine) vs +0.75 (placebo) → −2.75 points (caffeine vs placebo)
Trust score:4/5

systolic and diastolic blood pressure

2 evidences

Across two small crossover experiments, caffeinated beverages acutely stimulated autonomic measures (blood pressure, skin conductance), altered heart rate and skin temperature, and increased energetic arousal, with some dose‑dependent physiological effects.

Trust comment: Randomized crossover design with physiological measures is robust, but sample sizes per experiment are small and some dose‑response patterns were inconsistent.

Study Details

PMID:10837840
Participants:32
Impact:Increased with caffeinated beverages (SBP showed dose-dependent effects)
Trust score:4/5

In healthy young men, 300 mg caffeine taken before moderate aerobic exercise delayed parasympathetic heart-rate recovery and slowed blood pressure return to baseline, without changing HR, respiratory rate or oxygen saturation.

Trust comment: Randomized crossover trial with objective measures and clear methods; moderate sample (32 completed) though limited to healthy young males and researcher was not blinded.

Study Details

PMID:29075019
Participants:32
Impact:delayed recovery to baseline (SBP recovery later by ~2 minutes vs placebo; DBP recovery delayed)
Trust score:4/5

concentric/eccentric force production

1 evidences

In 21 resistance‑trained participants, a caffeinated multi‑ingredient pre‑workout produced small, non‑significant increases in some concentric force measures (more evident in males) and modest subjective increases in energy/focus versus placebo, but overall supplements did not clearly outperform placebo.

Trust comment: Counterbalanced double‑blind design with objective force measures is strong, but small completed sample (n=21) and multi‑ingredient products limit isolateing caffeine effects.

Study Details

PMID:29209154
Participants:21
Impact:No statistically significant improvement overall; small increases in concentric force in males (~5–9% vs placebo) but not consistent
Trust score:4/5

Fatigue

1 evidences

In 21 active men, 5 mg/kg caffeine taken 1 h before repeated sprint running modestly improved fastest sprint time but increased fatigue and elevated heart rate and blood lactate.

Trust comment: Randomized double‑blind trial with physiological measures and clear reported effect sizes, though sample is modest (n=21).

Study Details

PMID:18799995
Participants:21
Impact:Increased by ~1.2% (reported increase in fatigue index)
Trust score:4/5

BIA impedance/resistance/reactance

1 evidences

In healthy adults, coffee (0, 200, 400 mg caffeine) transiently changed BIA-derived body composition measures after ~30–70 min, but changes were independent of caffeine dose and likely due to water intake.

Trust comment: Randomized double-blind crossover design with repeated measures but small sample; water intake confounds the observed BIA changes.

Study Details

PMID:33986493
Participants:25
Impact:Values increased after 30 min regardless of caffeine dose; no caffeine-dependent group differences (p>0.05)
Trust score:4/5

self-reported vigour / reward responsivity

1 evidences

Both actual caffeine and the expectation of having had caffeine improved attention and psychomotor speed; expectation alone improved self-reported vigor and reward responsivity.

Trust comment: Well-powered randomized expectancy/manipulation design showing both pharmacologic and placebo effects, though outcomes rely partly on self-report.

Study Details

PMID:21824504
Participants:88
Impact:Enhanced by expectancy of caffeine (yes/no questionnaire effects)
Trust score:4/5

COP complexity (sample entropy)

1 evidences

In healthy older adults, a caffeinated coffee dose (~3 mg/kg) produced limited effects on balance metrics and did not change functional physical performance measures.

Trust comment: Randomized crossover in older adults with objective balance measures; moderate sample size and limited to healthy volunteers.

Study Details

PMID:39321752
Participants:22
Impact:altered (study reports possible influence on balance complexity/strategy)
Trust score:4/5

executive updating

1 evidences

In rested young male habitual caffeine consumers, individualized morning caffeine doses reduced fatigue and improved simple and sustained attention and the executive updating domain, independent of meal ingestion.

Trust comment: Double-blind placebo-controlled trial with a relatively large sample (n=60) and thorough cognitive testing; males only which limits generalizability.

Study Details

PMID:26621326
Participants:60
Impact:improved (selective executive domain enhancement)
Trust score:4/5

vocal acoustic measures

1 evidences

In 58 adult females given 100 mg caffeine vs placebo after 24-h caffeine abstinence, no differences were found in acoustic or aerodynamic voice measures 30 minutes post-ingestion.

Trust comment: Moderate-sized randomized comparison with controlled abstinence; single conservative dose (100 mg) limits generalization to higher doses or habitual users.

Study Details

PMID:24408336
Participants:58
Impact:no change (100 mg caffeine vs placebo)
Trust score:3/5

10 km run time

1 evidences

In 29 healthy adults given sham low or high caffeine doses, belief/expectation did not change choice reaction time or 10 km running performance.

Trust comment: Within-subject sham-controlled design with adequate sample for the questions about expectancy; outcomes clearly null.

Study Details

PMID:33939237
Participants:29
Impact:no effect of sham dose (no change)
Trust score:4/5

sleep duration and stage 2 sleep amount

1 evidences

Evening 200 mg caffeine worsened objective sleep: longer time to fall asleep, lower sleep efficiency and shorter total sleep time in both age groups.

Trust comment: Double-blind crossover with polysomnography and EEG in 24 participants; objective high-quality sleep measures.

Study Details

PMID:16704567
Participants:24
Impact:decreased after 200 mg caffeine
Trust score:5/5

subjective fatigue over session

1 evidences

Caffeinated coffee improved encoding of new information and reduced fatigue over the morning, but raised blood pressure and pulse; breakfast improved mood and some memory measures.

Trust comment: Large sample (n=144) and controlled conditions; between-group design but with valid behavioral and cardiovascular measures.

Study Details

PMID:10463623
Participants:144
Impact:reduced/ counteracted by caffeine
Trust score:4/5

anxiety

1 evidences

Realistic multi-dose caffeine intake (4×65 mg) and a single 200 mg dose both increased alertness and anxiety and improved several task-performance measures.

Trust comment: Double-blind, within-subjects design mimicking real-world intake; modest sample (n=24) but well-controlled.

Study Details

PMID:12404081
Participants:24
Impact:increased with both dosing regimens
Trust score:4/5

vertical jump height (VJH) and recovery

1 evidences

Repeated coffee mouth-rinses (dose-related) increased futsal-specific endurance distance and improved/accelerated recovery of vertical jump performance versus control.

Trust comment: Randomized, double-blind crossover in 24 elite players with objective performance tests though placebo effects noted and plasma caffeine not measured.

Study Details

PMID:37190757
Participants:24
Impact:increased after baseline CMR and faster recovery post-FIET with LDC/HDC (HDC > PLA and CON at several timepoints)
Trust score:4/5

multitasking performance

1 evidences

In a crossover pilot trial with a caffeine active control, caffeine improved post-lunch rapid visual information processing and some multitasking measures versus placebo.

Trust comment: Randomized crossover pilot with active caffeine control, moderate sample but multiple interventions and pilot design limit strength.

Study Details

PMID:38367243
Participants:30
Impact:improved (significant in some dose/time comparisons)
Trust score:3/5

caffeine plasma AUC / terminal half-life

1 evidences

In a large balanced placebo crossover, both caffeine (300 mg) and expectancy produced similar subjective effects (energy, reduced sleepiness); placebo altered caffeine pharmacokinetics.

Trust comment: Large, well-controlled randomized balanced placebo crossover with objective and subjective outcomes and solid statistical analysis.

Study Details

PMID:21092089
Participants:168
Impact:AUC and t1/2 higher when caffeine described as caffeine vs described as placebo (AUC difference significant)
Trust score:5/5

1-RM squat

1 evidences

High-dose caffeine (8 mg/kg) increased maximal strength in bench press, deadlift, and squat and raised plasma Ca2+ compared with placebo or lower dose.

Trust comment: Randomized double-blind crossover with mechanistic measures but limited to 21 recreational young men, restricting broader applicability.

Study Details

PMID:36432607
Participants:21
Impact:PLA 119.4 kg → CF8 130.1 kg (+10.7 kg)
Trust score:4/5

headache

1 evidences

Ingesting 6 mg/kg caffeine increased reported neutral, positive and negative effects versus placebo; obese women reported more adverse effects (e.g., urine output, increased vigor, headaches) 1 hour after ingestion.

Trust comment: Randomized placebo-controlled groups with a large sample (n=160); clear self-reported outcome measures though effect sizes are based on questionnaire reports.

Study Details

PMID:39800623
Participants:160
Impact:+24% (increase vs placebo; 1 h post-ingestion)
Trust score:4/5

cognitive flexibility (task-switching)

1 evidences

In healthy young women, caffeine alone improved working memory accuracy at ~T2 and combined tDCS+caffeine improved working memory accuracy (T1 and T2) and Stroop accuracy (T1) versus sham; caffeine alone did not improve inhibitory control and neither intervention affected cognitive flexibility.

Trust comment: Randomized, sham-controlled parallel design with adequate N (80) and task-based outcomes; single-blind and female-only sample limit generalizability.

Study Details

PMID:40888092
Participants:80
Impact:no change (no significant effects for caffeine, tDCS, or combined)
Trust score:4/5

beta power (12–20 Hz)

1 evidences

200 mg caffeine reduced lower-alpha (alpha1, 8–10 Hz) power primarily in participants with higher habitual caffeine consumption; overall caffeine effects did not differ reliably across menstrual phases.

Trust comment: Well-controlled randomized crossover design with EEG and hormone assays; moderate analyzed sample (n=56) after dropouts and effects moderated by habitual caffeine consumption.

Study Details

PMID:35904580
Participants:56
Impact:initial global reduction (p = 0.027) that was not significant after controlling for habitual consumption
Trust score:4/5

Urgency episodes

1 evidences

In women with urinary incontinence, reducing fluid intake improved some symptoms, but switching from caffeinated to decaffeinated drinks did not improve urinary symptoms.

Trust comment: Randomized crossover trial with objective diary measures and 69 completers, though effects of caffeine restriction were negative while fluid changes showed benefit.

Study Details

PMID:15947624
Participants:69
Impact:no change with caffeine restriction
Trust score:4/5

Liking/pleasantness for flavored drink (latent learning)

1 evidences

Repeated exposure to a novel caffeinated-flavoured drink while not caffeine-deprived did not produce later increased liking when subjects were caffeine-deprived; liking increased only when drinks were consumed while deprived and contained caffeine.

Trust comment: Well-controlled double-blind placebo study with reasonable sample (4 groups of 13) addressing conditioned liking, though specific effect sizes are small/more behavioral.

Study Details

PMID:11594442
Participants:52
Impact:no change in test (undeprived) group; increased in deprived+caffeine group; decreased in deprived+placebo group
Trust score:4/5

performance when caffeine correctly identified

1 evidences

In 42 trained cyclists, 6 mg/kg caffeine improved ~30‑min time‑trial performance versus placebo and control; correct identification of caffeine further increased the observed benefit.

Trust comment: Adequately powered randomized study with control and placebo arms and clear effects, though subjective identification influenced outcomes.

Study Details

PMID:27882605
Participants:42
Impact:+4.8–6.5% (vs control)
Trust score:4/5

diastolic blood pressure (DBP)

3 evidences

A single cup of coffee (80 mg caffeine) produced a small rise in systolic BP but overall no statistically significant effect on BP at one hour in healthy young adults.

Trust comment: Randomized controlled trial with adequate sample size and objective BP measures; effect sizes small and not clearly clinically significant.

Study Details

PMID:27051992
Participants:104
Impact:+2.11 mmHg (P = 0.64) — not statistically significant
Trust score:4/5

In tactical males, 300 mg caffeine and a 150 mg caffeine + methylliberine + theacrine combo similarly improved vigilance reaction time; caffeine raised DBP vs placebo while the combo raised SBP but not DBP.

Trust comment: Randomized, placebo-controlled trial with moderate sample (n=48 completed) and appropriate measures; between-group design limits within-subject sensitivity but overall reliable.

Study Details

PMID:36016763
Participants:48
Impact:increase in CAF vs PLA (P=0.025); no increase in CMT vs PLA
Trust score:4/5

In 165 healthy men and women across age/hormonal-status groups, acute caffeine increased systolic and diastolic blood pressure by a few mmHg.

Trust comment: Well-powered randomized crossover with clear, consistent BP increases, though single-dose challenge design limits long-term inference.

Study Details

PMID:20500126
Participants:165
Impact:+3.0 mmHg (±0.4) (not significant in older men subgroup)
Trust score:4/5

Daily step count

1 evidences

In a randomized 14-day crossover trial, caffeinated coffee increased ventricular ectopy and daily steps and reduced nightly sleep duration versus avoiding caffeine, with no significant change in atrial ectopy.

Trust comment: Randomized case-crossover trial with objective continuous monitoring in 100 adults and high adherence, giving high internal validity.

Study Details

PMID:36947466
Participants:100
Impact:+1058 steps (mean difference; significant)
Trust score:5/5

CYP1A2 genotype effect (modifier)

1 evidences

In a randomized, double-blind, placebo-controlled trial, caffeine (2–4 mg/kg) improved 10-km cycling time overall but effects were strongly modified by CYP1A2 genotype (benefit in AA, harm in CC).

Trust comment: Well-powered randomized, double-blind, placebo-controlled crossover with objective performance measures and genotype stratification.

Study Details

PMID:29509641
Participants:101
Impact:AA: ergogenic; AC: no effect; CC: impaired at higher dose
Trust score:5/5

Sprint peak power attenuation

1 evidences

Acute coffee and anhydrous caffeine before testing produced small improvements: coffee improved leg-press 1RM versus anhydrous caffeine, and caffeine attenuated reductions in sprint power/total work versus placebo.

Trust comment: Randomized acute trial with objective performance tests and moderate sample size (male-only), but some outcomes lacked reported effect sizes.

Study Details

PMID:26394649
Participants:54
Impact:CAF and COF attenuated sprint power reductions vs placebo (no numeric effect size reported)
Trust score:4/5

Weight gain (short-term)

1 evidences

Large randomized trial in very low birth-weight infants: caffeine reduced bronchopulmonary dysplasia (oxygen use at 36 weeks) and shortened positive airway pressure duration, with transiently reduced early weight gain and no increase in death or brain injury.

Trust comment: Large, multicenter randomized controlled trial with clinically important neonatal outcomes and robust statistical analysis.

Study Details

PMID:16707748
Participants:2006
Impact:Temporary reduction in weight gain (mean difference -23 g at 2 weeks; significant)
Trust score:5/5

subjective sleepiness

6 evidences

In healthy aeromedically fit pilots, a single 300 mg dose of caffeine at midnight reduced the nighttime decline in psychomotor performance after extended wakefulness.

Trust comment: Randomized double-blind crossover RCT in relevant population (n=30); well-controlled but moderate sample size.

Study Details

PMID:37726901
Participants:30
Impact:improved (less sleepiness vs placebo)
Trust score:4/5

Repeated nighttime caffeine gum improved objective performance during 50 h wakefulness but did not change overall self-reported sleepiness or fatigue.

Trust comment: Controlled laboratory, randomized administration with repeated measures; moderate sample size and objective outcomes support credibility.

Study Details

PMID:27061779
Participants:24
Impact:no change (overall)
Trust score:4/5

Bright light combined with 100 mg caffeine gum improved driving performance and subjective sleepiness more than caffeine alone in sleep-restricted young drivers.

Trust comment: Randomized simulator study with objective and subjective measures but limited to a simulator setting and moderate sample size.

Study Details

PMID:35398627
Participants:30
Impact:improved only with Light+Caffeine (P<0.0001)
Trust score:3/5

In 40 young adults, 36 h sleep deprivation impaired temporal (recency) memory; a single 350 mg caffeine dose reduced subjective sleepiness but did not restore temporal memory performance.

Trust comment: Randomized placebo-controlled groups with neuropsychological endpoints; caffeine given acutely and effects on sleepiness measured, but cognitive remediation was not observed.

Study Details

PMID:10718074
Participants:40
Impact:reduced by 350 mg caffeine in sleep-deprived subjects
Trust score:4/5

In sleep-deprived adults, stimulants had different effects: caffeine improved alertness measures but did not enhance cartoon humor appreciation.

Trust comment: Randomized, double-blind sleep-deprivation study with specified sample size and clear outcome reporting, moderate-to-high quality.

Study Details

PMID:16796223
Participants:54
Impact:- decreased sleepiness (improved ratings) with caffeine
Trust score:4/5

Caffeine, naps, and especially their combination improved alertness and vigilance in laboratory and field night-shift settings.

Trust comment: Large multi-part study (68 laboratory participants, 53 field participants; total n=121) with lab and real-world data showing consistent alertness/performance benefits, though shift-worker populations vary.

Study Details

PMID:16453980
Participants:121
Impact:decreased (napping plus caffeine vs placebo in field study)
Trust score:4/5

adverse effects

1 evidences

In PD outpatients, 100 mg/day caffeine adjuvant (2×50 mg/day) for 3 weeks was associated with substantial motor improvement (UPDRS III) compared to placebo, though some patients reported transient side effects.

Trust comment: Double-blind RCT with clear clinical outcome (UPDRS III) but small sample (n=27) limits generalizability.

Study Details

PMID:39280310
Participants:27
Impact:increased (26.6% in caffeine group vs 0% placebo)
Trust score:4/5

resting metabolic rate

1 evidences

A bioactive combination including caffeine increased resting metabolic rate (thermogenesis) in men, and propranolol (beta-blocker) reduced about half of that thermogenic response.

Trust comment: Randomized double-blind crossover study with objective metabolic measures, but caffeine was part of a multi-ingredient mix so attribution to caffeine alone is indirect.

Study Details

PMID:19497591
Participants:22
Impact:+5% increase in RMR (≈73 kJ/5 h) with the bioactive combination vs placebo.
Trust score:3/5

mean power output (Wmean)

2 evidences

Acute 3 mg/kg caffeine improved peak and mean power in repeated Wingate sprints in both sexes with sex‑specific timing differences (males early sprints, females later sprints).

Trust comment: Well-powered (n=52), triple‑blind randomized crossover with appropriate controls and objective performance and metabolic measures.

Study Details

PMID:39662990
Participants:52
Impact:increased: Wt3 +3.5%, Wt4 +3.9% (CAF vs placebo)
Trust score:5/5

NaHCO3 and caffeine each improved some aspects of repeated-sprint performance, but their coingestion did not produce a synergistic benefit.

Trust comment: Randomized double-blind placebo-controlled crossover with objective performance measures but modest sample size.

Study Details

PMID:38335952
Participants:25
Impact:increase (NaHCO3 vs placebo: +4.2% in Wt3; p=0.001)
Trust score:4/5

plasma lactate

1 evidences

In healthy elderly adults, 6 mg/kg caffeine increased plasma epinephrine, free fatty acids, and lactate (percent increases consistent at rest, 5 min, and exhaustion), and increased insulin-resistance measures.

Trust comment: Randomized double-blind crossover in 30 elderly subjects with clear metabolic measures; moderate sample size but robust findings.

Study Details

PMID:16886964
Participants:30
Impact:+~46% (rest), +36% (5 min), +48% (exhaustion)
Trust score:4/5

verbal memory (learning and consolidation)

1 evidences

In fasted young adults, combined caffeine (75 mg) + glucose (75 g) improved sustained attention and verbal memory consolidation beyond either substance alone; caffeine alone improved simple reaction time.

Trust comment: Double‑blind randomized design with moderate sample (n=72) and multiple cognitive measures; results need replication and dose/effort control.

Study Details

PMID:20521321
Participants:72
Impact:improved with combined caffeine + glucose (not seen with either alone)
Trust score:4/5

P100 amplitude (PR‑VEP)

1 evidences

In 40 adults randomized to ~216 mg caffeine vs placebo, pattern‑reversal VEP P100 latency and amplitude measured at baseline and 1 h post‑dose were unchanged after caffeine.

Trust comment: Randomized controlled design with adequate sample for electrophysiology endpoints; single acute dose and single post‑test timepoint limit scope.

Study Details

PMID:30793994
Participants:40
Impact:no significant change 1 h after ~216 mg caffeine (no difference from baseline)
Trust score:4/5

waist circumference

3 evidences

Over 6 weeks of resistance training, a caffeinated multi-ingredient pre-workout (≈406 mg caffeine) produced similar body composition, muscle thickness, and performance changes as an isocaloric carbohydrate comparator; waist circumference decreased in the PREW group.

Trust comment: Double-blind RCT with objective outcome measures and reasonable completion rate (41); habitual caffeine use may limit observed added benefits.

Study Details

PMID:40512050
Participants:41
Impact:decreased (−1.8 cm within PREW group)
Trust score:4/5

In obese adults after weight loss, rye bread enriched with green tea extract (providing ~123–158 mg caffeine/day) did not improve weight-loss maintenance but was associated with slightly better blood pressure control and a marginally smaller waist circumference.

Trust comment: Randomized single-blind pilot with moderate sample size; results suggest modest BP effects but limited clinical impact and pilot design.

Study Details

PMID:25494205
Participants:55
Impact:-1.22 cm (mean difference; statistically significant but not clinically meaningful)
Trust score:3/5

A multi-ingredient product (including caffeine and ephedrine) produced modest additional weight loss (~1.5 kg) and greater reductions in BMI and waist circumference versus placebo over 12 weeks; no BP or pulse increases were observed.

Trust comment: Large randomized placebo-controlled trial but attribution to caffeine is limited because the active product contained ephedrine and other ingredients and actual caffeine dose was lower than intended.

Study Details

PMID:15356670
Participants:102
Impact:decreased (greater reduction vs placebo)
Trust score:3/5

frontal alpha1 power (eyes-open)

1 evidences

In a randomized placebo-controlled crossover (200 mg caffeine), caffeine reduced several EEG band powers (alpha1/alpha2 and beta) with some differences between early-phase psychosis patients and healthy controls.

Trust comment: Within-subject randomized crossover design provides strong internal control, but overall sample is small and mixed medication status limits external validity.

Study Details

PMID:34806929
Participants:27
Impact:decreased with caffeine
Trust score:3/5

risk of sudden cardiac death (SCD)

1 evidences

In this large prospective cohort of postmenopausal women, total caffeine intake (and coffee/tea consumption) was not associated with risk of sudden cardiac death.

Trust comment: Very large prospective cohort with repeated dietary assessment, though observational design means residual confounding is possible.

Study Details

PMID:23615825
Participants:93676
Impact:no association with total caffeine intake or coffee/tea consumption
Trust score:4/5

reaction time (Flanker/Stroop)

1 evidences

56 male sprinters randomized to control, caffeine, TMR, or both; caffeine and TMR reduced reaction times, TMR improved anaerobic/neuromuscular measures, and combined treatment slightly raised heart rate.

Trust comment: Larger randomized controlled trial with clear group allocation, but limited methodological detail in the summary provided.

Study Details

PMID:40221884
Participants:56
Impact:decrease (improved) with caffeine, TMR, or combination (significant)
Trust score:4/5

memory recall

1 evidences

In a crossover trial comparing guarana, caffeine (5 mg/kg) and placebo, caffeine showed no clear improvement in reaction time or memory versus placebo but did prevent post-exercise increases in simple reaction time variability.

Trust comment: Randomized double-blind crossover with 25 participants and objective cognitive measures; primary focus on guarana but included matched caffeine arm.

Study Details

PMID:36146946
Participants:25
Impact:no change vs placebo
Trust score:4/5

subjective alertness/mood

2 evidences

A single 60 mg oral dose of caffeine improved sustained attention, reaction times, and subjective alertness in middle-aged healthy adults.

Trust comment: Randomized crossover with adequate sample (n=82) and objective+subjective measures, though blinding not specified in text provided.

Study Details

PMID:27649778
Participants:82
Impact:+ increased alertness and contentment (significant)
Trust score:4/5

In regular caffeine consumers tested when fatigued, repeated low doses of caffeine improved subjective mood/alertness and enhanced several performance measures, with dose‑dependent effects.

Trust comment: Well-controlled double‑blind study with objective assays and balanced conditions, though some details of effect sizes are not reported in the summary.

Study Details

PMID:16272184
Participants:60
Impact:Improved with caffeine (dose-dependent)
Trust score:4/5

arousal/motivation (RTE, FAS)

1 evidences

Resistance-trained men completed multiple caffeine and placebo trials; caffeine often increased arousal and dynamic muscle-power measures but effects varied across repeated trials.

Trust comment: Within-subject, double-blind randomized design with repeated measures and objective performance tests, but small completed sample (n=22) and variable repeatability.

Study Details

PMID:36297102
Participants:22
Impact:increased post-ingestion
Trust score:4/5

perceived exertion (steady-state)

1 evidences

Active adults performed cycling in normoxia and simulated altitude after 6 mg/kg caffeine; caffeine did not improve exercise capacity but changed some physiological and perceptual responses during steady-state.

Trust comment: Randomized controlled crossover with 29 participants and clear physiological outcomes; null effect on capacity reduces risk of overclaim.

Study Details

PMID:40675560
Participants:29
Impact:reduced
Trust score:4/5

leg cycling time-trial performance

1 evidences

Two experiments showed 5 mg/kg caffeine increased knee-extensor strength and motor-unit recruitment and improved leg-cycling time-trial performance while reducing pain and perceived effort in some conditions.

Trust comment: Controlled experimental studies with objective neuromuscular and performance outcomes; modest sample sizes but clear percent effect estimates reported.

Study Details

PMID:25211364
Participants:26
Impact:improved (+4.9% mean)
Trust score:4/5

sustained attention (RVIP) reaction time

1 evidences

In moderate caffeine consumers tested while deprived, caffeine improved sustained attention and alertness; these benefits were not seen when participants were not caffeine-deprived, consistent with withdrawal-reversal.

Trust comment: Controlled experimental design in humans (N=30) with clear behavioral outcomes, though some effect sizes/magnitudes not reported.

Study Details

PMID:12424547
Participants:30
Impact:decreased (improved) in deprived subjects (magnitude not reported)
Trust score:4/5

post-OGTT glucose

1 evidences

In sleep-deprived healthy men, caffeinated (vs decaffeinated) coffee raised post-OGTT glucose and insulin and increased fasting insulin and insulin resistance (HOMA), indicating worse glucose homeostasis under these conditions.

Trust comment: Randomized crossover in humans (N=42) with metabolic assays and appropriate washouts; limited to sleep-deprived, moderate coffee consumers.

Study Details

PMID:27702715
Participants:42
Impact:increased (CC vs DC), p<0.001
Trust score:4/5

lower body endurance strength (30s chair stand CS-30)

1 evidences

Over 12 weeks, Zumba training improved functional performance in middle-aged women; daily 100 mg caffeine alone also produced improvements and combining caffeine with Zumba led to the largest gains in mobility, lower-body endurance, and walking speed.

Trust comment: Randomized parallel-group single-blind trial with adequate group sizes for most arms (total n=69) and objective functional tests, though some groups smaller (n=12) and single-blind design.

Study Details

PMID:39463442
Participants:69
Impact:Ca+ZT: +4.07 reps (19.27→23.34); ZT: +2.45; Ca: +2.30 (pre→post)
Trust score:4/5

time to exhaustion (TTE)

1 evidences

Across two crossover studies in habitual low–moderate consumers tested without enforced caffeine restriction (combined N≈56), oral caffeine (2.5 or 6 mg/kg) did not change time-to-exhaustion, perceived fatigue, perceptual or affective responses, or time perception.

Trust comment: Carefully controlled double-blind crossover studies in humans with thorough perceptual measures; good internal validity though ecological (no caffeine restriction) and subgroup sizes vary.

Study Details

PMID:40704635
Participants:56
Impact:no significant change with caffeine (2.5 or 6 mg/kg) vs placebo
Trust score:4/5

cognitive task performance (serial subtraction attempts)

1 evidences

Post-hoc analysis of a randomized crossover trial (placebo vs ~98 mg caffeine) showing that individual trait mental/physical energy and fatigue modify caffeine's effects on mood, cognitive (serial subtraction) and fine-motor (9‑hole peg) performance—people with higher trait fatigue often gained more benefit.

Trust comment: Moderate-sized (n=30) randomized crossover parent trial but current analyses are post-hoc with multiple interactions and some effect estimates having wide CIs.

Study Details

PMID:33525438
Participants:30
Impact:caffeine benefits moderated by trait: interaction examples include trait physical fatigue × caffeine β=+4.40 (serial 3) and caffeine × high trait mental fatigue β=+5.70 (serial tasks)
Trust score:3/5

selective attention errors

1 evidences

Randomized double-blind crossover in recreational males showed dose-dependent benefits of caffeine mouth rinse on selective attention: faster completion time with 300 mg, fewer errors with 150 mg, and reduced perceived difficulty at 150 and 300 mg vs placebo.

Trust comment: Randomized double-blind crossover with objective cognitive tests and clear dose-response effects; sample limited to recreational males.

Study Details

PMID:39495309
Participants:30
Impact:reduced errors with 150 mg (Part D 7.00→5.63, p=0.04; Part C 8.77→7.10, p=0.02)
Trust score:4/5

subgroup (≥8 h abstinence or >100 prior laparoscopies)

1 evidences

Randomized double-blind placebo-controlled parallel trial in surgeons/attendees (n=107) found no significant effect of caffeinated coffee (≈230 mg from 340 mL) vs decaffeinated coffee on laparoscopic simulator performance (fine motor dexterity).

Trust comment: Large sample for this question, randomized double-blind design with validated simulator outcomes; pragmatic sample from a surgical congress may limit generalizability to clinical operations.

Study Details

PMID:34459976
Participants:107
Impact:no significant differences in effect score in exploratory subgroups (p>0.05)
Trust score:4/5

minute volume

1 evidences

Caffeine given immediately after birth to very preterm infants increased respiratory effort measures versus later administration.

Trust comment: Randomized controlled trial in 30 infants with direct physiological respiratory measurements; moderate sample size for neonatal RCT.

Study Details

PMID:28288150
Participants:30
Impact:189±74 vs 162±70 ml/kg/min; increase (p<0.05)
Trust score:4/5

subjective arousal/positive mood

1 evidences

Acute caffeine (50–450 mg) produced stimulant-like effects: increased blood pressure and arousal, improved vigilance, but worsened short-term memory in light nondependent users.

Trust comment: Well-powered within-subject double-blind design (n=102) showing consistent subjective and behavioral effects across doses.

Study Details

PMID:16541243
Participants:102
Impact:increase (reported)
Trust score:4/5

Cmax (peak concentration)

1 evidences

Single 200 mg caffeine given overtly or covertly to healthy adults; large within-person variability in PK measures but no average covert vs overt difference.

Trust comment: Randomized crossover in healthy humans with standard PK methods; small sample (n=28 analysed) limits precision but design and methods are sound.

Study Details

PMID:28561231
Participants:28
Impact:30% of individuals outside ±25% range; mean absolute deviation ~1.43%; 90% CI within 80–125% (no significant covert-vs-overt difference)
Trust score:4/5

reaction time (mean)

1 evidences

In a randomized single-blind crossover in healthy adults, caffeinated carbonated beverage produced faster and more frequent improvements in sustained attention and increased self-rated energy vs control; caffeine (carbonated or not) improved accuracy and reaction time vs control.

Trust comment: Randomized crossover with within-subject controls and per-protocol n=22; well-controlled but single-blind and modest sample size.

Study Details

PMID:35684105
Participants:22
Impact:CCB vs control: −12.06 (mean difference; CI −16.64 to −7.49, p<0.0001)
Trust score:4/5

calculation speed

1 evidences

In 201 healthy volunteers, acute caffeine (200 mg added to decaf coffee) increased blood pressure and calculation speed overall; CYP1A2 genotype (rs762551 CC) showed larger systolic BP rise in low habitual consumers (≤90 mg/day).

Trust comment: Prospective double-blind randomized trial with substantial sample (n=201) and genotype stratification; effects clinically measured.

Study Details

PMID:30773300
Participants:201
Impact:↑ improved (significant increase in speed after caffeine; p<0.05)
Trust score:4/5

fasting blood sugar

1 evidences

In 52 healthy female students, a single serving of standardized Turkish coffee (≈3 mg/kg caffeine) produced acute changes in subjective energy, concentration and sleep scores, reduced heart rate over time versus control, and was associated with reductions in fasting blood sugar at some post‑drink time points.

Trust comment: Randomized crossover with moderate sample size but potential expectancy/non-blinding and single-sex sample limit internal validity and generalizability.

Study Details

PMID:40077691
Participants:52
Impact:↓ significant reductions at 60 and 120 min post-ingestion in the coffee group (p<0.05–0.01)
Trust score:3/5

Smoking cessation success

1 evidences

Among 162 caffeine-using smokers in cessation programs, continuing caffeine use after quitting raised plasma caffeine to ~203% of baseline by 3 weeks; abstainers reported transient increased fatigue and decreased stimulation but cessation rates were similar.

Trust comment: Randomized assignment within cessation programs and large sample, but older study and secondary measures limit modern generalizability.

Study Details

PMID:9022872
Participants:162
Impact:No difference at 16 days, 6 months, or 12 months
Trust score:3/5

heart rate during SJFT

1 evidences

In elite jiu-jitsu athletes, 3 mg/kg caffeine increased throws in later SJFT sets, raised heart rate slightly, improved strength/endurance perception, and reduced fatigue perception, but did not change technical actions during real combat.

Trust comment: Randomized double-blind placebo-controlled trial in 22 elite athletes with objective performance and perceptual measures; moderate sample and some methodological limitations noted by authors.

Study Details

PMID:35277034
Participants:22
Impact:≈+3% vs placebo
Trust score:4/5

problem-solving (convergent thinking)

1 evidences

Participants given 200 mg caffeine showed better convergent problem-solving but no change in creative idea generation or working memory.

Trust comment: Randomized double-blind placebo-controlled between-subject design with balanced groups (44 per arm) and clear outcomes; good internal validity.

Study Details

PMID:32086187
Participants:88
Impact:improved (significant vs placebo)
Trust score:4/5

rating of perceived exertion (RPE)

2 evidences

In trained male CrossFit athletes, caffeine combined with active tDCS reduced execution time in a Clean & Jerk time-trial; caffeine or tDCS alone did not produce significant effects on average.

Trust comment: Randomized, double-blind, placebo-controlled crossover in trained athletes but modest sample size (n=30) limits precision.

Study Details

PMID:40219021
Participants:30
Impact:no change
Trust score:4/5

High-dose caffeine (8 mg/kg) increased maximal strength in bench press, deadlift, and squat and raised plasma Ca2+ compared with placebo or lower dose.

Trust comment: Randomized double-blind crossover with mechanistic measures but limited to 21 recreational young men, restricting broader applicability.

Study Details

PMID:36432607
Participants:21
Impact:PLA 4.87 → CF8 7.37 (+2.5 points)
Trust score:4/5

ocular perfusion pressure (OPP)

1 evidences

In a crossover RCT including people with or at risk for glaucoma, one cup of caffeinated coffee (182 mg) produced small but statistically significant increases in intraocular pressure (IOP), ocular perfusion pressure and ocular pulse amplitude at 60–90 min vs decaffeinated coffee.

Trust comment: Prospective, double-masked crossover RCT with 106 participants and objective ophthalmic measures; small absolute changes likely of limited clinical relevance.

Study Details

PMID:22678051
Participants:106
Impact:+ ~1.3–1.6 mm Hg at 60 and 90 min (statistically significant)
Trust score:4/5

serum irisin

1 evidences

Caffeine plus heat exposure increased body and skin temperatures and amplified thermogenesis-related biomarkers (FGF‑21 and irisin).

Trust comment: Randomized trial with a fairly large male sample and quantified biomarker changes, though limited to healthy males and acute exposure.

Study Details

PMID:40635261
Participants:87
Impact:+28.70% vs control after thermotherapy (P < 0.001)
Trust score:4/5

WOD GRACE execution time

1 evidences

In trained male CrossFit athletes, caffeine combined with active tDCS reduced execution time in a Clean & Jerk time-trial; caffeine or tDCS alone did not produce significant effects on average.

Trust comment: Randomized, double-blind, placebo-controlled crossover in trained athletes but modest sample size (n=30) limits precision.

Study Details

PMID:40219021
Participants:30
Impact:reduced (combined CAF + a-tDCS vs other conditions; p=0.013)
Trust score:4/5

proportion of responders to caffeine

1 evidences

In trained male CrossFit athletes, caffeine combined with active tDCS reduced execution time in a Clean & Jerk time-trial; caffeine or tDCS alone did not produce significant effects on average.

Trust comment: Randomized, double-blind, placebo-controlled crossover in trained athletes but modest sample size (n=30) limits precision.

Study Details

PMID:40219021
Participants:30
Impact:60% showed performance improvement after 400 mg CAF
Trust score:4/5

Session rating of perceived exertion (s-RPE)

1 evidences

Double-blind randomized placebo-controlled crossover in 52 taekwondo athletes (elite and sub-elite) showed that 3 mg/kg caffeine acutely improved agility and kicking performance and reduced session RPE, with effects varying by sex and competitive level.

Trust comment: Well-powered (a priori), double-blind randomized placebo-controlled crossover with sport-specific tests and objective measures; good internal validity.

Study Details

PMID:37612360
Participants:52
Impact:Elite CAF 7.7 vs CON 9.6 → −1.9 points (~−20%)
Trust score:5/5

odour sensitivity (threshold)

1 evidences

In healthy young adults, a 100 mg caffeine capsule had no overall effect on smell tests, but non-habitual caffeine users showed higher odour sensitivity and worse odour identification after caffeine; small mood trends were seen in habitual users.

Trust comment: Randomized double‑blind design and appropriate measures, but small non‑consumer subgroup and several effects are marginal/non‑significant.

Study Details

PMID:33123819
Participants:39
Impact:Non-consumers: mean +3.06 (caffeine) vs +1.25 (placebo) → +1.81 points (caffeine vs placebo)
Trust score:4/5

fastest sprint time

1 evidences

In 21 active men, 5 mg/kg caffeine taken 1 h before repeated sprint running modestly improved fastest sprint time but increased fatigue and elevated heart rate and blood lactate.

Trust comment: Randomized double‑blind trial with physiological measures and clear reported effect sizes, though sample is modest (n=21).

Study Details

PMID:18799995
Participants:21
Impact:Reduced by 0.06 s (≈1.4% improvement)
Trust score:4/5

time to exhaustion (users)

1 evidences

A 5 mg/kg dose of caffeine increased cycling time-to-exhaustion in both users and nonusers, with larger and longer-lasting effects in nonusers.

Trust comment: Randomized crossover with clear outcome but small sample and subgroup sizes (13 users, 8 nonusers) limit generalizability.

Study Details

PMID:12235019
Participants:21
Impact:+4.1 min at 1 h; +4.9 min at 3 h; +1.0 min at 6 h vs placebo (1 & 3 h significant)
Trust score:3/5

attention and psychomotor speed

1 evidences

Both actual caffeine and the expectation of having had caffeine improved attention and psychomotor speed; expectation alone improved self-reported vigor and reward responsivity.

Trust comment: Well-powered randomized expectancy/manipulation design showing both pharmacologic and placebo effects, though outcomes rely partly on self-report.

Study Details

PMID:21824504
Participants:88
Impact:Improved with actual caffeine and with expectation of caffeine (behavioral measures)
Trust score:4/5

physical function (Senior Fitness Test)

1 evidences

In healthy older adults, a caffeinated coffee dose (~3 mg/kg) produced limited effects on balance metrics and did not change functional physical performance measures.

Trust comment: Randomized crossover in older adults with objective balance measures; moderate sample size and limited to healthy volunteers.

Study Details

PMID:39321752
Participants:22
Impact:no significant change vs placebo or control
Trust score:4/5

simple and sustained attention

1 evidences

In rested young male habitual caffeine consumers, individualized morning caffeine doses reduced fatigue and improved simple and sustained attention and the executive updating domain, independent of meal ingestion.

Trust comment: Double-blind placebo-controlled trial with a relatively large sample (n=60) and thorough cognitive testing; males only which limits generalizability.

Study Details

PMID:26621326
Participants:60
Impact:improved (acute benefit irrespective of meal)
Trust score:4/5

perceived exertion (RPE)

2 evidences

In 48 male volleyball players, 4-week supplementation plus resistance training showed that combined Rhodiola + caffeine improved jump power and reduced perceived exertion more than either supplement or placebo.

Trust comment: Randomized double-blind placebo-controlled trial with adequate sample (n=48) and validated performance measures, though limited to male volleyball players and lacking some biochemical mechanistic data.

Study Details

PMID:40005009
Participants:48
Impact:decrease (RHO and CAF+RHO vs control; significant, p<0.01)
Trust score:4/5

5 mg/kg caffeine improved ~30-min cycling time-trial performance and modestly altered physiological responses in trained male cyclists.

Trust comment: Randomized double-blind placebo-controlled crossover in trained cyclists (n=40) with clear physiological and performance measures.

Study Details

PMID:33170731
Participants:40
Impact:−0.5 (units)
Trust score:4/5

perceived intoxication / stimulation

1 evidences

In 28 light caffeine consumers, caffeine altered some alcohol-related cognitive performance measures and increased subjective stimulation without reducing absolute perceived intoxication.

Trust comment: Randomized within-subject crossover with controlled dosing (alcohol/caffeine) and objective cognitive tasks, but modest sample size (n=28).

Study Details

PMID:22173851
Participants:28
Impact:no change in absolute perceived intoxication; increased subjective stimulation
Trust score:4/5

Rate of perceived exertion (RPE)

1 evidences

Caffeine (6.5 mg/kg) improved total repetitions in resistance training compared with placebo in active women; no additional benefit from combining with carbohydrate rinse.

Trust comment: Double-blind, randomized, placebo-controlled crossover with objective performance outcomes though modest sample size.

Study Details

PMID:32851636
Participants:29
Impact:no significant difference; Bayesian trend toward lower RPE with caffeine
Trust score:4/5

sleep efficiency

2 evidences

Evening 200 mg caffeine worsened objective sleep: longer time to fall asleep, lower sleep efficiency and shorter total sleep time in both age groups.

Trust comment: Double-blind crossover with polysomnography and EEG in 24 participants; objective high-quality sleep measures.

Study Details

PMID:16704567
Participants:24
Impact:decreased after 200 mg caffeine
Trust score:5/5

After 26 h wakefulness, caffeine did not worsen recovery or next-night sleep compared with placebo.

Trust comment: Randomized placebo-controlled trial in 32 subjects; clear methods but modest sample size limits generalizability.

Study Details

PMID:38790126
Participants:32
Impact:no significant change with caffeine vs placebo
Trust score:4/5

encoding of new information (attention/learning)

1 evidences

Caffeinated coffee improved encoding of new information and reduced fatigue over the morning, but raised blood pressure and pulse; breakfast improved mood and some memory measures.

Trust comment: Large sample (n=144) and controlled conditions; between-group design but with valid behavioral and cardiovascular measures.

Study Details

PMID:10463623
Participants:144
Impact:improved after caffeinated coffee (vs decaffeinated)
Trust score:4/5

alertness

9 evidences

Realistic multi-dose caffeine intake (4×65 mg) and a single 200 mg dose both increased alertness and anxiety and improved several task-performance measures.

Trust comment: Double-blind, within-subjects design mimicking real-world intake; modest sample (n=24) but well-controlled.

Study Details

PMID:12404081
Participants:24
Impact:increased with both dosing regimens
Trust score:4/5

Caffeinated coffee increased alertness and psychomotor performance in people with colds (restoring them to healthy levels); decaffeinated coffee also produced improvements.

Trust comment: Relatively old study with partial reporting (only subset returned with colds) and placebo-like effects from decaf reduce specificity of caffeine effect.

Study Details

PMID:9443519
Participants:46
Impact:increased (restored to healthy levels)
Trust score:3/5

In a randomized crossover trial, a 75 mg caffeine positive-control produced consistent alerting and performance-enhancing effects versus placebo in healthy adults (n=72).

Trust comment: Well-powered, pre-registered, randomized double-blind crossover with clear positive-control effects (n=72), supporting internal validity.

Study Details

PMID:37299382
Participants:72
Impact:increased (consistent alerting effect of 75 mg caffeine vs placebo)
Trust score:5/5

In children who habitually consume caffeine, a 50 mg dose after overnight abstinence restored cognitive accuracy, prevented withdrawal headache, and increased alertness; non/low-consumers showed no clear benefit.

Trust comment: Randomized double-blind placebo-controlled trial in children (n=26); small sample but appropriate design.

Study Details

PMID:16423144
Participants:26
Impact:increased relative to placebo (in habitual consumers)
Trust score:4/5

Single 600 mg slow-release caffeine decreased calmness and prolonged sleep onset but did not change alertness the next day.

Trust comment: Randomized double-blind parallel trial with a large sample (120) but limited to young males and single-dose testing.

Study Details

PMID:9025802
Participants:120
Impact:no change (N2 vs N1)
Trust score:4/5

In 379 participants, caffeine (100 mg then 150 mg) increased anxiety in genetically susceptible individuals (ADORA2A rs5751876 TT) especially among low habitual consumers; habitual consumption reduced anxiogenic response (tolerance) and no net alerting benefit was seen in some groups.

Trust comment: Large randomized double-blind design with genetic stratification and habitual-consumption groups (n=379); strong design for behavioral/genetic effects.

Study Details

PMID:20520601
Participants:379
Impact:no clear net alerting benefit in low consumers; habitual consumers showed tolerance (reduced anxiety response)
Trust score:4/5

In 80 healthy volunteers, a 200 mg caffeine active control increased subjective alertness and affected cardiovascular measures.

Trust comment: Within-subjects placebo-controlled design with a large sample (n=80) gives moderate-high reliability though caffeine was an active control rather than the primary focus.

Study Details

PMID:23420115
Participants:80
Impact:increased (subjective)
Trust score:4/5

In 24 adults, an 80 mg‑caffeine energy drink increased self-rated alertness and reduced depression scores; combining it with alcohol did not alter blood alcohol or subjective intoxication versus alcohol alone.

Trust comment: Double‑blind, placebo‑controlled crossover is strong methodology, though sample size is modest (n=24).

Study Details

PMID:25163441
Participants:24
Impact:increased (energy drink alone, 80 mg caffeine)
Trust score:4/5

In a 54.5 h total sleep deprivation trial with 50 adults, a single 600 mg caffeine dose maintained performance and alertness relative to placebo, comparable to effective modafinil doses.

Trust comment: Well‑controlled sleep‑deprivation trial with placebo and active comparators; caffeine arm small (n≈10) but design is robust.

Study Details

PMID:11862356
Participants:50
Impact:maintained/improved versus placebo (caffeine 600 mg)
Trust score:4/5

FIET distance (futsal intermittent endurance)

1 evidences

Repeated coffee mouth-rinses (dose-related) increased futsal-specific endurance distance and improved/accelerated recovery of vertical jump performance versus control.

Trust comment: Randomized, double-blind crossover in 24 elite players with objective performance tests though placebo effects noted and plasma caffeine not measured.

Study Details

PMID:37190757
Participants:24
Impact:HDC vs CON: +350.2 m (1677.7 vs 1327.5), p<0.001; LDC also > CON
Trust score:4/5

rapid visual information processing (attention)

1 evidences

In a crossover pilot trial with a caffeine active control, caffeine improved post-lunch rapid visual information processing and some multitasking measures versus placebo.

Trust comment: Randomized crossover pilot with active caffeine control, moderate sample but multiple interventions and pilot design limit strength.

Study Details

PMID:38367243
Participants:30
Impact:improved (significant vs placebo at 120 min)
Trust score:3/5

5 km cycling time

2 evidences

Ingesting coffee providing 3 mg/kg caffeine improved 5 km cycling time (~9 s faster, ≈1.9% vs placebo) in both men and women.

Trust comment: Well-powered, double-blind crossover with objective performance and biochemical measures; modest sample but rigorous design.

Study Details

PMID:31731467
Participants:38
Impact:-9 s (~-1.9% vs placebo; COF: 482 ± 51 s vs PLA: 491 ± 53 s)
Trust score:4/5

Caffeinated coffee (3 mg/kg) improved 5-km cycling time (~8 seconds) and habitual caffeine intake level did not modify this ergogenic effect.

Trust comment: Moderate-sized double-blind randomized crossover with clear outcome and appropriate analysis; results generalize to recreationally active adults.

Study Details

PMID:33260141
Participants:46
Impact:-8 ± 12 seconds (mean improvement vs placebo)
Trust score:4/5

blood lactate at completion

1 evidences

Ingesting coffee providing 3 mg/kg caffeine improved 5 km cycling time (~9 s faster, ≈1.9% vs placebo) in both men and women.

Trust comment: Well-powered, double-blind crossover with objective performance and biochemical measures; modest sample but rigorous design.

Study Details

PMID:31731467
Participants:38
Impact:increased (higher after coffee vs placebo/control)
Trust score:4/5

systolic blood pressure (AUC4 total effect)

1 evidences

In a large balanced placebo crossover, both caffeine (300 mg) and expectancy produced similar subjective effects (energy, reduced sleepiness); placebo altered caffeine pharmacokinetics.

Trust comment: Large, well-controlled randomized balanced placebo crossover with objective and subjective outcomes and solid statistical analysis.

Study Details

PMID:21092089
Participants:168
Impact:+29.9 mm Hg*hr
Trust score:5/5

1-RM deadlift

1 evidences

High-dose caffeine (8 mg/kg) increased maximal strength in bench press, deadlift, and squat and raised plasma Ca2+ compared with placebo or lower dose.

Trust comment: Randomized double-blind crossover with mechanistic measures but limited to 21 recreational young men, restricting broader applicability.

Study Details

PMID:36432607
Participants:21
Impact:PLA 120.7 kg → CF8 132.8 kg (+12.1 kg)
Trust score:4/5

vigor / activeness

1 evidences

Ingesting 6 mg/kg caffeine increased reported neutral, positive and negative effects versus placebo; obese women reported more adverse effects (e.g., urine output, increased vigor, headaches) 1 hour after ingestion.

Trust comment: Randomized placebo-controlled groups with a large sample (n=160); clear self-reported outcome measures though effect sizes are based on questionnaire reports.

Study Details

PMID:39800623
Participants:160
Impact:+29% (increase vs placebo; 1 h post-ingestion)
Trust score:4/5

inhibitory control accuracy (Stroop incongruent ACC)

1 evidences

In healthy young women, caffeine alone improved working memory accuracy at ~T2 and combined tDCS+caffeine improved working memory accuracy (T1 and T2) and Stroop accuracy (T1) versus sham; caffeine alone did not improve inhibitory control and neither intervention affected cognitive flexibility.

Trust comment: Randomized, sham-controlled parallel design with adequate N (80) and task-based outcomes; single-blind and female-only sample limit generalizability.

Study Details

PMID:40888092
Participants:80
Impact:increase (tDCS+caffeine significant at T1 vs caffeine alone and sham; caffeine alone not significant)
Trust score:4/5

theta power (4–8 Hz)

1 evidences

200 mg caffeine reduced lower-alpha (alpha1, 8–10 Hz) power primarily in participants with higher habitual caffeine consumption; overall caffeine effects did not differ reliably across menstrual phases.

Trust comment: Well-controlled randomized crossover design with EEG and hormone assays; moderate analyzed sample (n=56) after dropouts and effects moderated by habitual caffeine consumption.

Study Details

PMID:35904580
Participants:56
Impact:parietal decrease observed without covariate (p < 0.001) but not significant after controlling for habitual consumption
Trust score:4/5

Mean and peak power (Wmean, Wpeak)

1 evidences

Acute caffeine (3 mg/kg) improved muscular velocity, power and endurance across sexes, with larger effects in lower-body (back squat) at moderate–high loads.

Trust comment: Well-powered, triple-blind randomized crossover trial (n=76) with detailed objective performance metrics and appropriate statistics.

Study Details

PMID:38892692
Participants:76
Impact:Increases at moderate–high loads, especially back squat (Wmean +4–8.5% depending on load/sex)
Trust score:5/5

Duration of respiratory support / mechanical ventilation requirement

1 evidences

In preterm infants (<32 weeks), early prophylactic caffeine reduced duration of oxygen therapy and other respiratory support needs compared with therapeutic (delayed) caffeine.

Trust comment: Randomized controlled trial with substantial sample size and clear primary endpoint showing statistically significant benefit; neonatal population and specific protocol increase applicability in that setting.

Study Details

PMID:33771081
Participants:181
Impact:Prophylactic caffeine reduced durations of respiratory support and fewer infants required mechanical ventilation / late mechanical ventilation (significant)
Trust score:4/5

PDPH severity (VAS)

1 evidences

Prophylactic acetaminophen + caffeine given before spinal anesthesia reduced frequency and severity of post-dural puncture headache and increased maternal satisfaction vs placebo.

Trust comment: Randomized double-blind trial with clear effects, but caffeine was co-administered with acetaminophen so caffeine-specific effects cannot be isolated; single-center and modest sample size.

Study Details

PMID:39371383
Participants:94
Impact:Significantly milder pain from 18–72 h post-op in intervention group (several timepoints p≤0.04)
Trust score:3/5

Mean velocity and mean power (Vmean, Wmean)

1 evidences

Acute caffeine (3 mg/kg) alone improved muscular endurance, velocity and power (esp. back squat); co-ingestion with sodium bicarbonate did not produce additive benefit and attenuated caffeine's ergogenic effect.

Trust comment: Double-blind randomized crossover with objective measures; sample small (n=28) but design robust; lack of plasma measures limits mechanistic interpretation.

Study Details

PMID:39771003
Participants:28
Impact:Caffeine increased Vmean (~3.7–5.4%) and Wmean (~5.2–5.5%) in back squat at 65–85%1RM (p≤0.05)
Trust score:4/5

Colonic transit time / time to tolerance of solid food / hospital stay

1 evidences

Oral caffeine (100 or 200 mg three times daily) after laparoscopic colectomy did not shorten time to first bowel movement or improve colonic transit compared with placebo.

Trust comment: Randomized double-blind placebo-controlled trial with balanced groups (n=60); moderate sample and negative primary outcome increases confidence in null result.

Study Details

PMID:35909263
Participants:60
Impact:No measurable differences between caffeine doses and placebo in per-protocol and secondary analyses
Trust score:4/5

subjective anxiety

1 evidences

In 29 patients with panic disorder and 53 healthy controls (n=82), 150 mg caffeine did not increase subjective anxiety but did raise physiological arousal (SCR), increase costly avoidance behavior, and impair exteroceptive attention.

Trust comment: Well-powered randomized, double-blind, placebo-controlled crossover with clear pre-registered outcomes and robust mixed-model analyses.

Study Details

PMID:40577029
Participants:82
Impact:no significant change with 150 mg caffeine (primary outcome not supported)
Trust score:5/5

apnoea frequency and days with apnoea

1 evidences

In preterm infants (n=78) comparing high-dose versus lower-dose caffeine citrate, there was no difference in frequency or days with apnoea; side-effect rates showed non-significant trends toward being higher with the higher dose.

Trust comment: Parallel randomized, blinded RCT with appropriate methods and completed sample size for planned power, though some outcomes may be under-reported and long-term effects were not assessed.

Study Details

PMID:33922783
Participants:78
Impact:no significant difference between high- and low-dose caffeine (p≈0.84–0.93)
Trust score:4/5

proportion needing mechanical ventilation ≤72 h

1 evidences

IV or enteral caffeine given in delivery room was feasible; most infants had measurable caffeine blood levels but respiratory outcomes matched historical controls.

Trust comment: Prospective randomized feasibility study with objective blood measures but small sample, some missing samples, and comparison to a historical control for clinical outcomes.

Study Details

PMID:36301511
Participants:38
Impact:7/38 (18%); similar to historical control (18%) — no difference
Trust score:3/5

choice reaction time accuracy

1 evidences

In older adults (42) and Parkinson's patients (24) who abstained from caffeine for a week, a single 100 mg caffeine dose improved response selection (accuracy) on choice reaction and Stroop tasks, sped Stroop RTs, improved dual-task (RSVP) performance via better T1 identification but impaired single-task RSVP performance; effects did not differ by disease.

Trust comment: Randomized single‑blind crossover with full 7‑day withdrawal, adequate sample for older/Parkinson groups and appropriate statistics, though modest dose and multiple comparisons limit certainty.

Study Details

PMID:35006304
Participants:66
Impact:reduced errors on caffeine (statistically significant, p=0.049)
Trust score:4/5

caloric intake on days with caffeine

1 evidences

In a cohort of infants of Latina mothers followed to 18–36 months (106 children with follow-up), days when children consumed caffeine were associated with higher calorie intake and lower intake of key nutrients; the educational intervention did not prevent overweight.

Trust comment: Longitudinal dietary recall data with modest sample and secondary analyses; associations plausible but observational and subject to dietary recall and confounding.

Study Details

PMID:32081767
Participants:106
Impact:+121 kcal per day on days when caffeine was consumed (compared with days without caffeine)
Trust score:3/5

acute caffeine effect on PVT reaction time

1 evidences

In 37 healthy adults undergoing total sleep deprivation with crossover acute caffeine/placebo, acute caffeine improved PVT reaction time, but higher habitual caffeine intake (>50 mg/day) was associated with worse vigilant attention (longer RT) and lower individual alpha frequency (IAF).

Trust comment: Controlled crossover sleep‑deprivation protocol with EEG and mixed‑model analyses; modest sample but well‑described methods and clear effects.

Study Details

PMID:36981883
Participants:37
Impact:acute caffeine reduced reaction time during TSD (main treatment effect, p=0.001)
Trust score:4/5

Systolic blood pressure

11 evidences

In 201 healthy volunteers, acute caffeine (200 mg added to decaf coffee) increased blood pressure and calculation speed overall; CYP1A2 genotype (rs762551 CC) showed larger systolic BP rise in low habitual consumers (≤90 mg/day).

Trust comment: Prospective double-blind randomized trial with substantial sample (n=201) and genotype stratification; effects clinically measured.

Study Details

PMID:30773300
Participants:201
Impact:↑ increased overall after caffeine; in CYP1A2 rs762551 CC (≤90 mg/day) mean Δ = +11.8 ± 5.9 mmHg vs AA/CA Δ = +4.1 ± 5.5 mmHg
Trust score:4/5

A single caffeinated energy shot acutely raised systolic and diastolic blood pressure, but these elevations were not sustained after repeated daily use; ECG intervals were unchanged.

Trust comment: Randomized double-blind crossover with objective cardiovascular measures but small sample and limited chronic-phase effects.

Study Details

PMID:26708636
Participants:26
Impact:acute increase (significant at 3 and 5 h after single dose)
Trust score:4/5

In 100 male undergraduates, both actual caffeine and the expectation of caffeine affected mood and performance; caffeine increased BP, pulse, and reduced fatigue.

Trust comment: Well-powered balanced-placebo design (n=100) separating pharmacological and expectancy effects; clear internal validity.

Study Details

PMID:8991966
Participants:100
Impact:increase (significant; main effect of caffeine vs no caffeine)
Trust score:4/5

Higher doses of caffeine (500 mg vs 100 mg) increased ambulatory systolic and diastolic blood pressure and heart rate during the workday.

Trust comment: Double-blind, randomized crossover ambulatory study in habitual drinkers showing dose-related BP and HR increases; small sample (n=21) but clear objective measures.

Study Details

PMID:9625220
Participants:21
Impact:+4 mmHg (higher vs lower caffeine dose)
Trust score:4/5

Managers deprived of their usual caffeine showed withdrawal discomfort and decreased performance on several complex task measures.

Trust comment: Double-blind crossover in habitual high-caffeine consumers; decent design but specific population and high baseline intake limit broad applicability.

Study Details

PMID:7568623
Participants:25
Impact:+higher during normal caffeine consumption (fell during deprivation)
Trust score:3/5

Over 14 days, an ephedra‑caffeine weight‑loss product produced no significant changes in measured cardiovascular parameters versus placebo in healthy overweight adults.

Trust comment: Randomized double‑blind trial in humans but product contained ephedra plus caffeine and duration was short (14 days); modest sample size (n=27).

Study Details

PMID:12355332
Participants:27
Impact:no change
Trust score:3/5

In patients undergoing EPS, oral caffeine (5 mg/kg) increased systolic and diastolic blood pressure but did not affect cardiac conduction parameters or SVT inducibility.

Trust comment: Prospective randomized placebo-controlled study in a clinical population with adequate sample (n=80).

Study Details

PMID:25081280
Participants:80
Impact:significant increase vs placebo
Trust score:4/5

In patients with familial LQTS, an energy drink containing caffeine acutely raised blood pressure and in some individuals caused large QTc prolongation.

Trust comment: Randomized double-blind crossover in a clinical LQTS cohort (n=24) with clinically relevant hemodynamic and safety findings.

Study Details

PMID:28189188
Participants:24
Impact:+7 ±16 mmHg (peak) vs +1 ±16 mmHg with control (≈+6% vs +0.8%, p=0.046)
Trust score:4/5

Single 6 mg/kg caffeine increased blood pressure and tidal volume and raised plasma caffeine concentrations; epinephrine rose in able-bodied and paraplegic but not tetraplegic participants, with limited HRV changes.

Trust comment: Randomized, double‑blind, placebo‑controlled crossover with objective physiological measures, but subgroup sizes are small (n per subgroup limited).

Study Details

PMID:27776149
Participants:28
Impact:increased (able‑bodied ≈ +9 mmHg; tetraplegic ≈ +19 mmHg; paraplegic median +11 mmHg, not always significant)
Trust score:4/5

In 110 men, acute caffeine raised systolic and diastolic blood pressure modestly (~+4 mmHg and +3 mmHg) and increased plasma adrenaline.

Trust comment: Well-controlled double-blind crossover with objective BP and genetic analyses; sample size moderate and measures robust.

Study Details

PMID:22170367
Participants:110
Impact:+4 mm Hg (mean)
Trust score:4/5

In overweight patients, a 6-week ephedrine (20 mg) plus caffeine (200 mg) treatment produced modest blood pressure reductions in some groups, heart-rate increase in normotensives, weight loss across groups, and frequent side-effects.

Trust comment: Randomized, double-blind, parallel groups with a substantial completed sample (n=112) but findings confounded by combined ephedrine+caffeine product and multiple treatment groups.

Study Details

PMID:15481766
Participants:112
Impact:decrease in some groups (e.g., -5.5 mmHg in hypertensive patients on non-beta-blockers; -4.4 mmHg in normotensives on E+C)
Trust score:3/5

Heart rate

13 evidences

56 male sprinters randomized to control, caffeine, TMR, or both; caffeine and TMR reduced reaction times, TMR improved anaerobic/neuromuscular measures, and combined treatment slightly raised heart rate.

Trust comment: Larger randomized controlled trial with clear group allocation, but limited methodological detail in the summary provided.

Study Details

PMID:40221884
Participants:56
Impact:slight increase with combined caffeine + TMR (p<0.05)
Trust score:4/5

In 52 healthy female students, a single serving of standardized Turkish coffee (≈3 mg/kg caffeine) produced acute changes in subjective energy, concentration and sleep scores, reduced heart rate over time versus control, and was associated with reductions in fasting blood sugar at some post‑drink time points.

Trust comment: Randomized crossover with moderate sample size but potential expectancy/non-blinding and single-sex sample limit internal validity and generalizability.

Study Details

PMID:40077691
Participants:52
Impact:↓ decreased over time after Turkish coffee (significant time × group effects reported)
Trust score:3/5

Caffeine in hot drinks produced dose-dependent autonomic/cardio responses (e.g., changes in heart rate, blood pressure and baroreflex measures) during ingestion.

Trust comment: Controlled experimental design with multiple doses and repeated measures in healthy women (n=21), but subgroup dosing and small groups limit power.

Study Details

PMID:22614720
Participants:21
Impact:+ increased HR with 134 mg added caffeine and with regular coffee (phases 1–2)
Trust score:4/5

In 7- to 9-year-old children, moderate caffeine lowered heart rate and raised blood pressure during rest and low-moderate exercise but did not change VO2 or RER.

Trust comment: Randomized double-blind crossover in a defined pediatric sample (n=52) with clear physiological measures.

Study Details

PMID:16540840
Participants:52
Impact:decrease (significantly lower at rest and during 25 and 50 W)
Trust score:4/5

In healthy children, low–moderate caffeine doses raised preexercise blood pressure and lowered heart rate by ~5–6 bpm; metabolic measures were largely unchanged.

Trust comment: Randomized, double-blind, counterbalanced study with 40 participants and clear physiologic measures; applicable to children but limited to acute responses.

Study Details

PMID:18408611
Participants:40
Impact:≈5 bpm lower (CAF-3) and ≈6 bpm lower (CAF-5) vs placebo at rest and during exercise
Trust score:4/5

Higher doses of caffeine (500 mg vs 100 mg) increased ambulatory systolic and diastolic blood pressure and heart rate during the workday.

Trust comment: Double-blind, randomized crossover ambulatory study in habitual drinkers showing dose-related BP and HR increases; small sample (n=21) but clear objective measures.

Study Details

PMID:9625220
Participants:21
Impact:+3 bpm (higher vs lower caffeine dose)
Trust score:4/5

Over 14 days, an ephedra‑caffeine weight‑loss product produced no significant changes in measured cardiovascular parameters versus placebo in healthy overweight adults.

Trust comment: Randomized double‑blind trial in humans but product contained ephedra plus caffeine and duration was short (14 days); modest sample size (n=27).

Study Details

PMID:12355332
Participants:27
Impact:no change
Trust score:3/5

One cup of caffeinated espresso acutely raised blood pressure and heart rate but did not change QTc in healthy adults.

Trust comment: Randomized, double-blind crossover with objective ECG/BP measures and N=40, though limited to healthy adults and short-term effects.

Study Details

PMID:21288364
Participants:40
Impact:+~2 bpm at 30 min
Trust score:4/5

In a double-blind crossover study of 23 mildly overweight adults, an acute multi-ingredient supplement containing high caffeine did not change heart rate or blood pressure but reduced RER in low-caffeine users.

Trust comment: Double-blind, placebo-controlled crossover with complete follow-up (n=23) but small sample and multi-ingredient product limits attribution to caffeine alone.

Study Details

PMID:21448304
Participants:23
Impact:no change
Trust score:4/5

Over 8 weeks, the caffeine arm showed no statistically significant changes in vital signs or routine lab safety measures compared with other groups.

Trust comment: Controlled supplementation study including a caffeine arm, but modest sample size and short duration limit detection of uncommon/long-term effects.

Study Details

PMID:25591969
Participants:48
Impact:no significant change (8-week supplementation)
Trust score:3/5

In healthy young men, 300 mg caffeine taken before moderate aerobic exercise delayed parasympathetic heart-rate recovery and slowed blood pressure return to baseline, without changing HR, respiratory rate or oxygen saturation.

Trust comment: Randomized crossover trial with objective measures and clear methods; moderate sample (32 completed) though limited to healthy young males and researcher was not blinded.

Study Details

PMID:29075019
Participants:32
Impact:no significant effect
Trust score:4/5

A single 500 mg caffeine dose in habitual coffee drinkers raised ambulatory blood pressure by ~4/3 mmHg, lowered heart rate by ~2 bpm, and increased urinary free epinephrine by ~32%, amplifying stress-related cardiovascular responses.

Trust comment: Within-subject double-blind design with ambulatory measures and moderate sample size; findings plausible though single high dose may limit real-world generalizability.

Study Details

PMID:12140349
Participants:47
Impact:decrease (≈−2 bpm)
Trust score:4/5

In overweight patients, a 6-week ephedrine (20 mg) plus caffeine (200 mg) treatment produced modest blood pressure reductions in some groups, heart-rate increase in normotensives, weight loss across groups, and frequent side-effects.

Trust comment: Randomized, double-blind, parallel groups with a substantial completed sample (n=112) but findings confounded by combined ephedrine+caffeine product and multiple treatment groups.

Study Details

PMID:15481766
Participants:112
Impact:+4.9 beats/min (increase in normotensive E+C group)
Trust score:3/5

cognitive performance (simple reaction time, visuospatial memory)

1 evidences

In middle-aged women, 12 weeks of Zumba improved postural balance and cognition; adding 100 mg/day caffeine with Zumba produced improvements in postural balance and cognitive tests in challenging conditions.

Trust comment: Randomized intervention with moderate sample size but unclear blinding and limited reporting of effect sizes for caffeine-specific additive effects.

Study Details

PMID:37279332
Participants:56
Impact:+improved in Zumba plus caffeine group (CZG) in challenging conditions
Trust score:3/5

muscle thickness and performance outcomes

1 evidences

Over 6 weeks of resistance training, a caffeinated multi-ingredient pre-workout (≈406 mg caffeine) produced similar body composition, muscle thickness, and performance changes as an isocaloric carbohydrate comparator; waist circumference decreased in the PREW group.

Trust comment: Double-blind RCT with objective outcome measures and reasonable completion rate (41); habitual caffeine use may limit observed added benefits.

Study Details

PMID:40512050
Participants:41
Impact:increased/improved in both groups with no additional PREW benefit
Trust score:4/5

beta power (frontal)

1 evidences

In a randomized placebo-controlled crossover (200 mg caffeine), caffeine reduced several EEG band powers (alpha1/alpha2 and beta) with some differences between early-phase psychosis patients and healthy controls.

Trust comment: Within-subject randomized crossover design provides strong internal control, but overall sample is small and mixed medication status limits external validity.

Study Details

PMID:34806929
Participants:27
Impact:decreased with caffeine (notably in healthy controls)
Trust score:3/5

reaction time

4 evidences

Crossover trial in active young adults: 6 mg/kg caffeine acutely improved reaction time but did not change attention or memory and increased some side effects.

Trust comment: Randomized crossover with objective cognitive tests in healthy adults; modest sample size but clear within-subject comparisons and reported CIs/P values.

Study Details

PMID:39231871
Participants:29
Impact:Physical RT −0.04 s and Motor RT −0.04 s with 6 mg/kg vs placebo (statistically significant)
Trust score:4/5

Caffeine increased blood pressure; expectancy/placebo effects influenced subjective alertness in one experiment, while reaction time showed no consistent change.

Trust comment: Two randomized experiments (N=45 each) with controls for expectancy; robust design shows pharmacologic and expectancy effects though some outcomes were null.

Study Details

PMID:17228991
Participants:90
Impact:no significant change
Trust score:4/5

In 48 habitual caffeine consumers deprived 24 h, caffeine (200 mg) improved aspects of cognition and reduced fatigue; taurine and glucose had different or no effects.

Trust comment: Randomized, double-blind mixed-design with 48 participants and multiple objective cognitive endpoints; reasonably reliable.

Study Details

PMID:22819803
Participants:48
Impact:reduced (faster) simple and choice reaction times with caffeine
Trust score:4/5

In a randomized double-blind placebo-controlled trial (n=60) a citicoline-caffeine beverage improved sustained attention, reaction time, and working memory measures and increased P300 amplitudes on EEG vs placebo.

Trust comment: Randomized double-blind placebo-controlled trial with EEG and neurocognitive outcomes and a moderate sample (n=60).

Study Details

PMID:25046515
Participants:60
Impact:faster reaction times on continuous performance test (significant)
Trust score:4/5

simple reaction time (SRT)

2 evidences

In a crossover trial comparing guarana, caffeine (5 mg/kg) and placebo, caffeine showed no clear improvement in reaction time or memory versus placebo but did prevent post-exercise increases in simple reaction time variability.

Trust comment: Randomized double-blind crossover with 25 participants and objective cognitive measures; primary focus on guarana but included matched caffeine arm.

Study Details

PMID:36146946
Participants:25
Impact:no significant change vs placebo (post-exercise caffeine 315 ms vs placebo 323 ms)
Trust score:4/5

A multivitamin–mineral product with guarana improved decision-making speed for about 30–90 min and maintained parasympathetic HRV measures during the first hour compared with caffeine alone or placebo.

Trust comment: Randomized, double-blind within-subject design with moderate sample (n=56); caffeine dose equivalent was included for direct comparison.

Study Details

PMID:25558905
Participants:56
Impact:No effect observed for caffeine or guarana at the doses used
Trust score:4/5

subjective drug effects

1 evidences

Healthy young adults who regularly use caffeine got 200 mg caffeine plus varied CBD doses; self-reported drug effects and anxiety did not change.

Trust comment: Randomized single-session human study with moderate sample size but relied on subjective Zoom self-reports and is preliminary.

Study Details

PMID:37917507
Participants:54
Impact:no change
Trust score:3/5

rated mental alertness

1 evidences

In moderate caffeine consumers tested while deprived, caffeine improved sustained attention and alertness; these benefits were not seen when participants were not caffeine-deprived, consistent with withdrawal-reversal.

Trust comment: Controlled experimental design in humans (N=30) with clear behavioral outcomes, though some effect sizes/magnitudes not reported.

Study Details

PMID:12424547
Participants:30
Impact:increased after caffeine (magnitude not reported)
Trust score:4/5

fasting insulin / insulin resistance (HOMA)

1 evidences

In sleep-deprived healthy men, caffeinated (vs decaffeinated) coffee raised post-OGTT glucose and insulin and increased fasting insulin and insulin resistance (HOMA), indicating worse glucose homeostasis under these conditions.

Trust comment: Randomized crossover in humans (N=42) with metabolic assays and appropriate washouts; limited to sleep-deprived, moderate coffee consumers.

Study Details

PMID:27702715
Participants:42
Impact:fasting insulin increased (p=0.001); insulin resistance increased (p=0.039)
Trust score:4/5

walking speed (10MWT)

1 evidences

Over 12 weeks, Zumba training improved functional performance in middle-aged women; daily 100 mg caffeine alone also produced improvements and combining caffeine with Zumba led to the largest gains in mobility, lower-body endurance, and walking speed.

Trust comment: Randomized parallel-group single-blind trial with adequate group sizes for most arms (total n=69) and objective functional tests, though some groups smaller (n=12) and single-blind design.

Study Details

PMID:39463442
Participants:69
Impact:Ca+ZT: improvement from 8.72→7.62 (pre→post); also improved in ZT and Ca groups
Trust score:4/5

time perception

1 evidences

Across two crossover studies in habitual low–moderate consumers tested without enforced caffeine restriction (combined N≈56), oral caffeine (2.5 or 6 mg/kg) did not change time-to-exhaustion, perceived fatigue, perceptual or affective responses, or time perception.

Trust comment: Carefully controlled double-blind crossover studies in humans with thorough perceptual measures; good internal validity though ecological (no caffeine restriction) and subgroup sizes vary.

Study Details

PMID:40704635
Participants:56
Impact:no significant change with caffeine
Trust score:4/5

short-interval intracortical inhibition (A-SICI, T-SICIp)

1 evidences

200 mg caffeine (chewing gum) did not significantly alter paired-pulse TMS measures of short-interval intracortical inhibition in healthy adults.

Trust comment: Randomized double-blind crossover in 24 healthy subjects; negative findings consistent across tested SICI measures.

Study Details

PMID:38124685
Participants:24
Impact:no change (p>0.10–0.50)
Trust score:4/5

rate of rise to maximum tidal volume (RoR)

1 evidences

Caffeine given immediately after birth to very preterm infants increased respiratory effort measures versus later administration.

Trust comment: Randomized controlled trial in 30 infants with direct physiological respiratory measurements; moderate sample size for neonatal RCT.

Study Details

PMID:28288150
Participants:30
Impact:median 14.3 vs 11.2 ml/kg/s; increase (significant)
Trust score:4/5

short-term memory

1 evidences

Acute caffeine (50–450 mg) produced stimulant-like effects: increased blood pressure and arousal, improved vigilance, but worsened short-term memory in light nondependent users.

Trust comment: Well-powered within-subject double-blind design (n=102) showing consistent subjective and behavioral effects across doses.

Study Details

PMID:16541243
Participants:102
Impact:impaired performance
Trust score:4/5

Physical activity energy expenditure (PAEE)

1 evidences

Double-blind crossover in active males given ~5 mg/kg/day caffeine for 4 days: caffeine did not change resting, total, or physical-activity energy expenditure or accelerometer-measured activity patterns.

Trust comment: Well-controlled double-blind crossover using doubly labelled water and accelerometry (gold standards); small sample (n=21) limits generalisability.

Study Details

PMID:23869233
Participants:21
Impact:No significant difference (mean change −13.7 ± 248.0 kcal/day; p=0.803)
Trust score:4/5

resting energy expenditure (REE)

1 evidences

In healthy active adults, single doses of thermogenic drinks with 100–140 mg caffeine increased resting metabolic rate; the 140 mg formula also increased resting fat oxidation, with no clear effects on exercise fat oxidation or VO2max.

Trust comment: Randomized double‑blind crossover with objective metabolic measures in 32 participants; well‑controlled but acute and modest sample size limits external generalizability.

Study Details

PMID:32054486
Participants:32
Impact:140 mg > placebo (+~4% total REE AUC; 140 mg=101.0 kcal vs placebo=97.3 kcal); 140 mg > 100 mg (+~2%)
Trust score:4/5

3-km running performance

1 evidences

Randomized, placebo-controlled trial in 80 men: acute pre-exercise 3 mg/kg caffeine improved 3-km running time and Wingate mean power output across groups; habitual caffeine use attenuated ergogenicity.

Trust comment: Large randomized controlled design with repeated testing and counterbalancing; effects reported across groups though exact effect sizes not provided in excerpt.

Study Details

PMID:39905628
Participants:80
Impact:Improved with pre-exercise 3 mg/kg caffeine (statistically significant, p<0.05)
Trust score:4/5

Pain relief (SPRID0–8 h)

1 evidences

Phase III double-blind randomized trial in dental pain: ibuprofen 400 mg + caffeine 100 mg provided superior and faster analgesia versus ibuprofen alone, caffeine alone, and placebo over 8 h with acceptable tolerability.

Trust comment: Large, phase III randomized double-blind trial (n=562) with validated dental pain model and robust statistical analyses; high internal validity.

Study Details

PMID:28805281
Participants:562
Impact:Ibuprofen/caffeine adjusted mean 52.3 vs ibuprofen 40.2 (adjusted mean difference ~12.1; p<0.0001), ~30% greater pain reduction over 8 h
Trust score:5/5

Special Judo Fitness Test (TOT throws)

1 evidences

Randomized double-blind crossover in trained judoists: acute 6 and 9 mg/kg caffeine improved judo-specific performance (throws) and increased heart rate; habitual caffeine consumers were less responsive.

Trust comment: Well-controlled randomized double-blind crossover in trained athletes with discipline-specific tests; small sample (n=22) limits precision and generalisability.

Study Details

PMID:31488190
Participants:22
Impact:6 and 9 mg/kg increased total throws versus 3 mg/kg, placebo, and baseline (statistically significant; p<0.001); 9 mg/kg > 6 mg/kg in some comparisons
Trust score:4/5

multi-tasking performance

1 evidences

In 150 healthy adults, a drink with 40 mg caffeine + 60 g glucose improved overall multi-tasking performance and speed on some tasks versus placebo or glucose alone, without changing mood.

Trust comment: Large randomized, double-blind, placebo-controlled trial with objective cognitive endpoints, though some authors had industry ties.

Study Details

PMID:25196040
Participants:150
Impact:↑ improved overall MTF score (caffeine–glucose Δ +1469 vs placebo Δ +632; p=0.005)
Trust score:4/5

Vertical jump performance (CMJ and SJ)

1 evidences

In 32 well-trained collegiate sprinters/jumpers, very low (1 mg/kg) to moderate (3–6 mg/kg) caffeine doses improved vertical jump performance, with 6 mg/kg producing significant enhancement.

Trust comment: Randomized, double-blind, crossover with athletic participants and sufficient sample for performance outcomes, though generalizability to non-athletes is limited.

Study Details

PMID:37414404
Participants:32
Impact:Improved at 1, 3, and 6 mg/kg; 6 mg/kg significantly better than placebo (dose-independent improvement noted)
Trust score:4/5

perceived fatigue

1 evidences

In elite jiu-jitsu athletes, 3 mg/kg caffeine increased throws in later SJFT sets, raised heart rate slightly, improved strength/endurance perception, and reduced fatigue perception, but did not change technical actions during real combat.

Trust comment: Randomized double-blind placebo-controlled trial in 22 elite athletes with objective performance and perceptual measures; moderate sample and some methodological limitations noted by authors.

Study Details

PMID:35277034
Participants:22
Impact:decrease
Trust score:4/5

working memory

1 evidences

Participants given 200 mg caffeine showed better convergent problem-solving but no change in creative idea generation or working memory.

Trust comment: Randomized double-blind placebo-controlled between-subject design with balanced groups (44 per arm) and clear outcomes; good internal validity.

Study Details

PMID:32086187
Participants:88
Impact:no significant change
Trust score:4/5

tetralogy of Fallot (subset)

1 evidences

Large case–control analysis found no clear evidence that maternal caffeine intake increases risk of cardiovascular birth defects.

Trust comment: Large, well-classified epidemiologic dataset (4,196 cases, 3,957 controls) with detailed exposure assessment, though observational design limits causal inference.

Study Details

PMID:17405163
Participants:8153
Impact:nonsignificant modest elevations for moderate intake (OR ~1.3–1.5) but not consistent
Trust score:4/5

mood (positive affect)

1 evidences

Forty mg caffeine delivered in chewing gum improved mood and sustained-attention task performance (faster encoding) compared with placebo or no gum in young adults.

Trust comment: Double-blind, placebo-controlled trial with adequate sample size (n=118) and clear behavioral outcomes.

Study Details

PMID:19330801
Participants:118
Impact:+ more positive mood after caffeinated gum (and placebo gum had some mood effect)
Trust score:4/5

resting fat oxidation (RFO)

1 evidences

In healthy active adults, single doses of thermogenic drinks with 100–140 mg caffeine increased resting metabolic rate; the 140 mg formula also increased resting fat oxidation, with no clear effects on exercise fat oxidation or VO2max.

Trust comment: Randomized double‑blind crossover with objective metabolic measures in 32 participants; well‑controlled but acute and modest sample size limits external generalizability.

Study Details

PMID:32054486
Participants:32
Impact:140 mg increased RFO at 60 and 90 min vs placebo (significant); 100 mg showed smaller/temporal changes (decrease at 30 min, no sustained increase)
Trust score:4/5

intradialytic hypotension

1 evidences

In hemodialysis patients, drinking regular versus decaffeinated coffee during sessions did not change the incidence of dialysis‑related headache or hypotension over 12 sessions.

Trust comment: Large randomized, double‑blind multicenter trial with high completion rate; results applicable to dialysis patients but specific population limits generalizability.

Study Details

PMID:33715955
Participants:139
Impact:no significant difference (regular 27% vs decaf 26%; P=0.539)
Trust score:4/5

cognitive performance (auditory attention, visual coding, Raven's)

1 evidences

Across three small experiments, caffeine reduced subjective drowsiness but produced mixed effects on subjective effort and no consistent performance improvements.

Trust comment: Multiple small experiments with mixed and sometimes non-significant results; design described but limited power and complex interactions.

Study Details

PMID:7737103
Participants:52
Impact:effects on task performance were generally non-significant across experiments
Trust score:3/5

jitteriness/anxiety ratings

1 evidences

Caffeine increased self-rated alertness, jitteriness, and blood pressure in healthy adults; theanine opposed caffeine's blood pressure rise.

Trust comment: Well-powered randomized double-blind placebo-controlled study with clear subjective and physiological endpoints.

Study Details

PMID:17891480
Participants:48
Impact:increased after caffeine
Trust score:4/5

reaction time / saccadic peak velocity

1 evidences

A single 60 mg oral dose of caffeine improved sustained attention, reaction times, and subjective alertness in middle-aged healthy adults.

Trust comment: Randomized crossover with adequate sample (n=82) and objective+subjective measures, though blinding not specified in text provided.

Study Details

PMID:27649778
Participants:82
Impact:+ faster reaction time and increased peak saccadic velocity (significant)
Trust score:4/5

proportion spontaneously voiding

1 evidences

In this pilot RCT, warm caffeinated coffee increased initial void volumes after catheter removal but did not change the proportion who spontaneously voided.

Trust comment: Small randomized pilot study (n=30) with clinically relevant outcomes but limited power and short follow-up.

Study Details

PMID:24022423
Participants:30
Impact:no significant difference between caffeine and water groups
Trust score:3/5

length of gestation

1 evidences

Reducing caffeine intake in pregnancy (moderate reduction) did not change babies' birth weight or length of gestation.

Trust comment: Large randomized double-blind controlled trial with >1100 completed outcomes; high methodological quality.

Study Details

PMID:17259189
Participants:1150
Impact:-1.31 days (adjusted difference; not statistically significant)
Trust score:5/5

systolic/diastolic blood pressure

1 evidences

Acute caffeine raises blood pressure and five days of regular caffeine intake did not eliminate the BP response in about half of healthy adults.

Trust comment: Double-blind crossover trial with substantial sample (n≈97) and within-subject design; clinically relevant cardiovascular outcome.

Study Details

PMID:14967827
Participants:97
Impact:increased after 250 mg challenge (significant; P <0.001) even after 5 days regular intake
Trust score:4/5

complex cognitive processing speed

1 evidences

In well-trained cyclists, caffeine in a performance bar improved time to exhaustion and complex cognitive task performance during and after prolonged exercise.

Trust comment: Controlled exercise trial in trained cyclists (n=24) with objective performance and cognitive measures; moderate sample size.

Study Details

PMID:18799996
Participants:24
Impact:improved (faster performance on information-processing tests; significant)
Trust score:4/5

body mass

1 evidences

Controlled dosing over 11 days in healthy males showed no evidence that daily caffeine (up to 6 mg/kg/day) produced hypohydration or altered renal electrolyte measures compared with placebo.

Trust comment: Controlled dosing with multiple objective hydration and renal measures and reasonable sample size, but limited to young males.

Study Details

PMID:16131696
Participants:59
Impact:No significant change across caffeine doses (C0, C3, C6)
Trust score:4/5

mood — arousal/tense-anxiety

1 evidences

In healthy young adults, a 100 mg caffeine capsule had no overall effect on smell tests, but non-habitual caffeine users showed higher odour sensitivity and worse odour identification after caffeine; small mood trends were seen in habitual users.

Trust comment: Randomized double‑blind design and appropriate measures, but small non‑consumer subgroup and several effects are marginal/non‑significant.

Study Details

PMID:33123819
Participants:39
Impact:Consumers: arousal ~+4 points (caffeine vs placebo, trend); tense/anxiety showed smaller decline with caffeine (trend)
Trust score:4/5

vigilant attention (PVT)

1 evidences

In a large randomized study, 200 mg caffeine given after overnight sleep loss restored vigilant attention (PVT) deficits but generally did not improve higher‑order placekeeping performance for most participants.

Trust comment: Large sample, randomized placebo‑controlled design and clear task-specific effects give high confidence in the selective cognitive findings.

Study Details

PMID:34014758
Participants:276
Impact:Caffeine counteracted sleep‑deprivation impairment (performance restored)
Trust score:5/5

heart rate / skin temperature

1 evidences

Across two small crossover experiments, caffeinated beverages acutely stimulated autonomic measures (blood pressure, skin conductance), altered heart rate and skin temperature, and increased energetic arousal, with some dose‑dependent physiological effects.

Trust comment: Randomized crossover design with physiological measures is robust, but sample sizes per experiment are small and some dose‑response patterns were inconsistent.

Study Details

PMID:10837840
Participants:32
Impact:Heart rate decreased and skin temperature decreased compared to water; heart rate and skin temperature showed dose-response relationships
Trust score:4/5

subjective energy / focus

1 evidences

In 21 resistance‑trained participants, a caffeinated multi‑ingredient pre‑workout produced small, non‑significant increases in some concentric force measures (more evident in males) and modest subjective increases in energy/focus versus placebo, but overall supplements did not clearly outperform placebo.

Trust comment: Counterbalanced double‑blind design with objective force measures is strong, but small completed sample (n=21) and multi‑ingredient products limit isolateing caffeine effects.

Study Details

PMID:29209154
Participants:21
Impact:Increased after caffeinated supplement (example: energy +15% in males, +44% in females; effect sizes reported)
Trust score:4/5

physiological strain (HR and lactate)

1 evidences

In 21 active men, 5 mg/kg caffeine taken 1 h before repeated sprint running modestly improved fastest sprint time but increased fatigue and elevated heart rate and blood lactate.

Trust comment: Randomized double‑blind trial with physiological measures and clear reported effect sizes, though sample is modest (n=21).

Study Details

PMID:18799995
Participants:21
Impact:Mean HR +3.4 bpm; blood lactate pre +0.7 mmol/L and post +1.8 mmol/L
Trust score:4/5

BOLD activation (motor & visual areas)

1 evidences

Intravenous caffeine produced dose-dependent effects on brain imaging: intermediate dose (2.5 mg/kg) maximized BOLD activation increase; highest dose (5 mg/kg) maximized cerebral blood flow response.

Trust comment: Controlled experimental human study with simultaneous ASL/BOLD imaging but small sample and IV dosing limit direct relevance to typical oral caffeine use.

Study Details

PMID:19289172
Participants:27
Impact:Peak increase at 2.5 mg/kg: +32.2% (motor), +32.5% (visual) vs baseline
Trust score:3/5

urine output

2 evidences

In healthy adults, coffee (0, 200, 400 mg caffeine) transiently changed BIA-derived body composition measures after ~30–70 min, but changes were independent of caffeine dose and likely due to water intake.

Trust comment: Randomized double-blind crossover design with repeated measures but small sample; water intake confounds the observed BIA changes.

Study Details

PMID:33986493
Participants:25
Impact:No significant difference between decaf, 200 mg, and 400 mg groups (volumes similar; p>0.05)
Trust score:4/5

Ingesting 6 mg/kg caffeine increased reported neutral, positive and negative effects versus placebo; obese women reported more adverse effects (e.g., urine output, increased vigor, headaches) 1 hour after ingestion.

Trust comment: Randomized placebo-controlled groups with a large sample (n=160); clear self-reported outcome measures though effect sizes are based on questionnaire reports.

Study Details

PMID:39800623
Participants:160
Impact:+27% (increase vs placebo; 1 h post-ingestion)
Trust score:4/5

mood (self-reported depression)

1 evidences

Both actual caffeine and the expectation of having had caffeine improved attention and psychomotor speed; expectation alone improved self-reported vigor and reward responsivity.

Trust comment: Well-powered randomized expectancy/manipulation design showing both pharmacologic and placebo effects, though outcomes rely partly on self-report.

Study Details

PMID:21824504
Participants:88
Impact:Post-drink depression increased overall but less so in those receiving or expecting caffeine
Trust score:4/5

fatigue recovery (intermittent jump decline)

1 evidences

In 48 male volleyball players, 4-week supplementation plus resistance training showed that combined Rhodiola + caffeine improved jump power and reduced perceived exertion more than either supplement or placebo.

Trust comment: Randomized double-blind placebo-controlled trial with adequate sample (n=48) and validated performance measures, though limited to male volleyball players and lacking some biochemical mechanistic data.

Study Details

PMID:40005009
Participants:48
Impact:improvement (less decline across rounds with CAF+RHO; significant vs control, p<0.01)
Trust score:4/5

Stroop task accuracy (cognitive control/interference)

1 evidences

In 28 light caffeine consumers, caffeine altered some alcohol-related cognitive performance measures and increased subjective stimulation without reducing absolute perceived intoxication.

Trust comment: Randomized within-subject crossover with controlled dosing (alcohol/caffeine) and objective cognitive tasks, but modest sample size (n=28).

Study Details

PMID:22173851
Participants:28
Impact:worsened accuracy with caffeine (caffeine+alcohol condition)
Trust score:4/5

urinary leakage

1 evidences

In a randomized trial of 95 patients with urinary symptoms, an education intervention reduced caffeine intake and produced significant improvements in urinary urgency and frequency at one month.

Trust comment: Prospective randomized trial with a reasonable sample (n=95) showing significant symptom changes after caffeine reduction education.

Study Details

PMID:11979209
Participants:95
Impact:no clear/reported significant change
Trust score:4/5

specific symptoms (headache, tiredness)

1 evidences

In a population survey and a controlled blinded experiment (57 regular users enrolled), abrupt caffeine withdrawal produced symptomatic withdrawal in a subset (e.g., headaches/tiredness), whereas gradual withdrawal produced minimal symptoms.

Trust comment: Community survey plus randomized, double-blind controlled pilot with clear outcome reporting but modest sample for the controlled arm.

Study Details

PMID:10586387
Participants:57
Impact:observed among those reporting withdrawal
Trust score:4/5

Mean heart rate

1 evidences

In 240 preterm neonates with apnea, caffeine citrate was similarly effective to aminophylline overall, with caffeine showing a lower risk of tachycardia and lower mean heart rate.

Trust comment: Well-powered randomized controlled trial in the target population with clinically relevant endpoints.

Study Details

PMID:28474588
Participants:240
Impact:Mean HR higher in aminophylline group (P<0.001); caffeine lower
Trust score:5/5

sleep latency

2 evidences

Evening 200 mg caffeine worsened objective sleep: longer time to fall asleep, lower sleep efficiency and shorter total sleep time in both age groups.

Trust comment: Double-blind crossover with polysomnography and EEG in 24 participants; objective high-quality sleep measures.

Study Details

PMID:16704567
Participants:24
Impact:increased (longer sleep onset) after 200 mg caffeine
Trust score:5/5

Caffeine (200 mg) before sleep delayed sleep onset and reduced deep sleep, with stronger negative effects on daytime recovery sleep than nocturnal sleep.

Trust comment: Double-blind crossover study in 34 moderate caffeine consumers with polysomnography, providing objective sleep-stage data.

Study Details

PMID:16936703
Participants:34
Impact:increased (longer sleep latency)
Trust score:4/5

endurance performance time

1 evidences

A moderate caffeine dose (3 mg/kg) improved endurance cycling time similarly in women and men (~4–4.6% improvement).

Trust comment: Randomized, double-blind, placebo-controlled crossover with standardized controls and reported effect sizes.

Study Details

PMID:30629046
Participants:27
Impact:improved: women mean = 4.3% (95% CI 0.4–8.2%); men = 4.6% (2.3–6.8%)
Trust score:5/5

Leg press 1RM

1 evidences

Acute coffee and anhydrous caffeine before testing produced small improvements: coffee improved leg-press 1RM versus anhydrous caffeine, and caffeine attenuated reductions in sprint power/total work versus placebo.

Trust comment: Randomized acute trial with objective performance tests and moderate sample size (male-only), but some outcomes lacked reported effect sizes.

Study Details

PMID:26394649
Participants:54
Impact:COF > CAF (p=0.04)
Trust score:4/5

Bronchopulmonary dysplasia / supplemental oxygen at 36 weeks

1 evidences

Large randomized trial in very low birth-weight infants: caffeine reduced bronchopulmonary dysplasia (oxygen use at 36 weeks) and shortened positive airway pressure duration, with transiently reduced early weight gain and no increase in death or brain injury.

Trust comment: Large, multicenter randomized controlled trial with clinically important neonatal outcomes and robust statistical analysis.

Study Details

PMID:16707748
Participants:2006
Impact:Reduced: 36% (caffeine) vs 47% (placebo); adjusted OR 0.63 (95% CI 0.52–0.76; P<0.001)
Trust score:5/5

Muscular endurance (repetitions to failure at 65% 1RM)

1 evidences

Acute caffeine (3 mg/kg) improved muscular velocity, power and endurance across sexes, with larger effects in lower-body (back squat) at moderate–high loads.

Trust comment: Well-powered, triple-blind randomized crossover trial (n=76) with detailed objective performance metrics and appropriate statistics.

Study Details

PMID:38892692
Participants:76
Impact:Reps increased ~6–9% (bench press and back squat) vs placebo (p<0.01 to p<0.05)
Trust score:5/5

Bronchopulmonary dysplasia (BPD) incidence and length of stay (LOS)

1 evidences

In preterm infants (<32 weeks), early prophylactic caffeine reduced duration of oxygen therapy and other respiratory support needs compared with therapeutic (delayed) caffeine.

Trust comment: Randomized controlled trial with substantial sample size and clear primary endpoint showing statistically significant benefit; neonatal population and specific protocol increase applicability in that setting.

Study Details

PMID:33771081
Participants:181
Impact:Reduced incidence of mild–moderate BPD and shortened LOS with prophylactic caffeine (significant)
Trust score:4/5

Patient overall satisfaction

1 evidences

Prophylactic acetaminophen + caffeine given before spinal anesthesia reduced frequency and severity of post-dural puncture headache and increased maternal satisfaction vs placebo.

Trust comment: Randomized double-blind trial with clear effects, but caffeine was co-administered with acetaminophen so caffeine-specific effects cannot be isolated; single-center and modest sample size.

Study Details

PMID:39371383
Participants:94
Impact:Higher satisfaction in intervention group (e.g., 62.5% satisfied vs 28.3% in placebo; p=0.001)
Trust score:3/5

Gastrointestinal and muscular discomfort with NaHCO3-containing conditions

1 evidences

Acute caffeine (3 mg/kg) alone improved muscular endurance, velocity and power (esp. back squat); co-ingestion with sodium bicarbonate did not produce additive benefit and attenuated caffeine's ergogenic effect.

Trust comment: Double-blind randomized crossover with objective measures; sample small (n=28) but design robust; lack of plasma measures limits mechanistic interpretation.

Study Details

PMID:39771003
Participants:28
Impact:NaHCO3+CAF increased GI discomfort vs CAF alone (≈41–52% greater incidence) and increased perceived energy with CAF/NaHCO3+CAF vs placebo
Trust score:4/5

subjective stimulation/“feeling high”

1 evidences

Among undergraduates, 200 mg caffeine increased feelings of stimulation/high/anxiety and motivation; expecting a stronger stimulant (Adderall) amplified subjective stimulant effects and improved working memory, especially when combined with actual caffeine.

Trust comment: Randomized design with moderate sample (n=65) showing expectancy and pharmacological effects; relies mainly on self-report and lab cognitive tests.

Study Details

PMID:33734725
Participants:65
Impact:increased with caffeine (vs placebo); further increased when expecting Adderall
Trust score:3/5

physiological emotional reactivity (SCR)

1 evidences

In 29 patients with panic disorder and 53 healthy controls (n=82), 150 mg caffeine did not increase subjective anxiety but did raise physiological arousal (SCR), increase costly avoidance behavior, and impair exteroceptive attention.

Trust comment: Well-powered randomized, double-blind, placebo-controlled crossover with clear pre-registered outcomes and robust mixed-model analyses.

Study Details

PMID:40577029
Participants:82
Impact:increase (general SCR elevation with caffeine; p<0.001)
Trust score:5/5

tachycardia

1 evidences

In preterm infants (n=78) comparing high-dose versus lower-dose caffeine citrate, there was no difference in frequency or days with apnoea; side-effect rates showed non-significant trends toward being higher with the higher dose.

Trust comment: Parallel randomized, blinded RCT with appropriate methods and completed sample size for planned power, though some outcomes may be under-reported and long-term effects were not assessed.

Study Details

PMID:33922783
Participants:78
Impact:trend higher in high-dose group (20% vs 13%; not statistically significant)
Trust score:4/5

countermovement jump height

3 evidences

In 27 male rugby players, 3 mg/kg caffeine (capsule, gum, or mouth rinse) produced limited effects: a small increase in countermovement-jump height and one-set squat endurance, but most strength/power measures were unchanged.

Trust comment: Well-designed double-blind, mode-matched placebo crossover in athletes (n=27); effects were generally small and outcome-specific.

Study Details

PMID:39439175
Participants:27
Impact:small increase (e.g., capsule: 31.9 → 32.6 cm; overall main effect p = 0.035; ~+0.7 cm, small)
Trust score:4/5

In 26 recreationally trained men, acute caffeine (6 mg/kg) increased countermovement jump height versus control and versus placebo; maximal power output was unchanged.

Trust comment: Randomized double-blind crossover in recreational athletes with clear performance measures; moderate sample size.

Study Details

PMID:32707561
Participants:26
Impact:+6.6% (caffeine vs control); +4.0% (caffeine vs placebo)
Trust score:4/5

Acute caffeine (5 mg/kg) increased squat- and countermovement-jump heights and improved some force/velocity execution metrics in collegiate athletes.

Trust comment: Single-blind randomized crossover in 25 athletes with clear within-subject improvements and reported means/SDs for key outcomes.

Study Details

PMID:26626028
Participants:25
Impact:36.4 ± 6.9 cm (placebo) → 37.9 ± 7.4 cm (caffeine); p = 0.001 (≈+1.5 cm)
Trust score:4/5

proportion with subtherapeutic blood level (<5 µg/mL)

1 evidences

IV or enteral caffeine given in delivery room was feasible; most infants had measurable caffeine blood levels but respiratory outcomes matched historical controls.

Trust comment: Prospective randomized feasibility study with objective blood measures but small sample, some missing samples, and comparison to a historical control for clinical outcomes.

Study Details

PMID:36301511
Participants:38
Impact:25% of measured samples below 5 µg/mL at ~60 min after administration
Trust score:3/5

Stroop accuracy and reaction time

1 evidences

In older adults (42) and Parkinson's patients (24) who abstained from caffeine for a week, a single 100 mg caffeine dose improved response selection (accuracy) on choice reaction and Stroop tasks, sped Stroop RTs, improved dual-task (RSVP) performance via better T1 identification but impaired single-task RSVP performance; effects did not differ by disease.

Trust comment: Randomized single‑blind crossover with full 7‑day withdrawal, adequate sample for older/Parkinson groups and appropriate statistics, though modest dose and multiple comparisons limit certainty.

Study Details

PMID:35006304
Participants:66
Impact:accuracy improved (p=0.018); reaction time faster on caffeine (p=0.049)
Trust score:4/5

protein intake on days with caffeine

1 evidences

In a cohort of infants of Latina mothers followed to 18–36 months (106 children with follow-up), days when children consumed caffeine were associated with higher calorie intake and lower intake of key nutrients; the educational intervention did not prevent overweight.

Trust comment: Longitudinal dietary recall data with modest sample and secondary analyses; associations plausible but observational and subject to dietary recall and confounding.

Study Details

PMID:32081767
Participants:106
Impact:-3.8 g protein on days when caffeine was consumed (compared with days without caffeine)
Trust score:3/5

habitual caffeine consumption and vigilance

1 evidences

In 37 healthy adults undergoing total sleep deprivation with crossover acute caffeine/placebo, acute caffeine improved PVT reaction time, but higher habitual caffeine intake (>50 mg/day) was associated with worse vigilant attention (longer RT) and lower individual alpha frequency (IAF).

Trust comment: Controlled crossover sleep‑deprivation protocol with EEG and mixed‑model analyses; modest sample but well‑described methods and clear effects.

Study Details

PMID:36981883
Participants:37
Impact:higher habitual intake associated with longer PVT reaction times (worse vigilance) (habitual effect p=0.03)
Trust score:4/5

Diastolic blood pressure

11 evidences

In 201 healthy volunteers, acute caffeine (200 mg added to decaf coffee) increased blood pressure and calculation speed overall; CYP1A2 genotype (rs762551 CC) showed larger systolic BP rise in low habitual consumers (≤90 mg/day).

Trust comment: Prospective double-blind randomized trial with substantial sample (n=201) and genotype stratification; effects clinically measured.

Study Details

PMID:30773300
Participants:201
Impact:↑ increased overall after caffeine (p<0.05)
Trust score:4/5

A single caffeinated energy shot acutely raised systolic and diastolic blood pressure, but these elevations were not sustained after repeated daily use; ECG intervals were unchanged.

Trust comment: Randomized double-blind crossover with objective cardiovascular measures but small sample and limited chronic-phase effects.

Study Details

PMID:26708636
Participants:26
Impact:acute increase (significant at 1 and 5 h after single dose)
Trust score:4/5

In 100 male undergraduates, both actual caffeine and the expectation of caffeine affected mood and performance; caffeine increased BP, pulse, and reduced fatigue.

Trust comment: Well-powered balanced-placebo design (n=100) separating pharmacological and expectancy effects; clear internal validity.

Study Details

PMID:8991966
Participants:100
Impact:increase (significant; main effect of caffeine vs no caffeine)
Trust score:4/5

Higher doses of caffeine (500 mg vs 100 mg) increased ambulatory systolic and diastolic blood pressure and heart rate during the workday.

Trust comment: Double-blind, randomized crossover ambulatory study in habitual drinkers showing dose-related BP and HR increases; small sample (n=21) but clear objective measures.

Study Details

PMID:9625220
Participants:21
Impact:+3 mmHg (higher vs lower caffeine dose)
Trust score:4/5

Over 14 days, an ephedra‑caffeine weight‑loss product produced no significant changes in measured cardiovascular parameters versus placebo in healthy overweight adults.

Trust comment: Randomized double‑blind trial in humans but product contained ephedra plus caffeine and duration was short (14 days); modest sample size (n=27).

Study Details

PMID:12355332
Participants:27
Impact:no change
Trust score:3/5

In patients undergoing EPS, oral caffeine (5 mg/kg) increased systolic and diastolic blood pressure but did not affect cardiac conduction parameters or SVT inducibility.

Trust comment: Prospective randomized placebo-controlled study in a clinical population with adequate sample (n=80).

Study Details

PMID:25081280
Participants:80
Impact:significant increase vs placebo
Trust score:4/5

Knowing about a possible placebo had limited effect overall; uninformed participants showed some caffeine-induced increases in diastolic blood pressure and vigor and impaired hand steadiness at higher dose.

Trust comment: Relatively large randomized sample with dose comparisons and objective measures, though effects depended on instruction subgroups and some outcomes non-significant.

Study Details

PMID:12021824
Participants:52
Impact:increased with 125 mg caffeine in participants uninformed about placebo
Trust score:4/5

In patients with familial LQTS, an energy drink containing caffeine acutely raised blood pressure and in some individuals caused large QTc prolongation.

Trust comment: Randomized double-blind crossover in a clinical LQTS cohort (n=24) with clinically relevant hemodynamic and safety findings.

Study Details

PMID:28189188
Participants:24
Impact:+8 ±10 mmHg vs +2 ±9 mmHg (≈+11% vs +3%, p=0.01)
Trust score:4/5

Single 6 mg/kg caffeine increased blood pressure and tidal volume and raised plasma caffeine concentrations; epinephrine rose in able-bodied and paraplegic but not tetraplegic participants, with limited HRV changes.

Trust comment: Randomized, double‑blind, placebo‑controlled crossover with objective physiological measures, but subgroup sizes are small (n per subgroup limited).

Study Details

PMID:27776149
Participants:28
Impact:increased (able‑bodied ≈ +8 mmHg; tetraplegic ≈ +27 mmHg)
Trust score:4/5

In 110 men, acute caffeine raised systolic and diastolic blood pressure modestly (~+4 mmHg and +3 mmHg) and increased plasma adrenaline.

Trust comment: Well-controlled double-blind crossover with objective BP and genetic analyses; sample size moderate and measures robust.

Study Details

PMID:22170367
Participants:110
Impact:+3 mm Hg (mean)
Trust score:4/5

In overweight patients, a 6-week ephedrine (20 mg) plus caffeine (200 mg) treatment produced modest blood pressure reductions in some groups, heart-rate increase in normotensives, weight loss across groups, and frequent side-effects.

Trust comment: Randomized, double-blind, parallel groups with a substantial completed sample (n=112) but findings confounded by combined ephedrine+caffeine product and multiple treatment groups.

Study Details

PMID:15481766
Participants:112
Impact:decrease (-3.9 mmHg in normotensives on E+C); overall 24-h diastolic effect variable
Trust score:3/5

countermovement jump height (CMJ)

1 evidences

In 90 male adolescent athletes, acute caffeine (6 mg/kg) improved several performance measures (strength, jump height, sit-ups, and Yo-Yo endurance) versus placebo; these ergogenic effects were independent of ADORA2A and CYP1A2 genotypes.

Trust comment: Large (n=90) double-blind, randomized crossover in athletes; robust design supports findings though limited to adolescent male athletes.

Study Details

PMID:36385314
Participants:90
Impact:+1.3 cm (49.6 vs 48.3 cm)
Trust score:4/5

blood lactate

3 evidences

Acute caffeine (6 mg/kg) increased repetitions to failure across sets, raised post-exercise blood lactate, and reduced perceived pain during low-load knee-extension with blood-flow restriction.

Trust comment: Double-blind crossover in trained men (n=22) with clear statistically significant performance and physiological differences; moderate sample size.

Study Details

PMID:30039986
Participants:22
Impact:increased by +1.8 mmol/L (7.8 vs 6.0 mmol/L)
Trust score:4/5

Caffeine increased time to exhaustion and oxygen deficit in a supramaximal anaerobic test and raised metabolic markers.

Trust comment: Randomized double-blind trial with physiological measures but small sample (24) and mixed drug comparisons.

Study Details

PMID:11474345
Participants:24
Impact:increased
Trust score:4/5

In 30 resistance-trained men, acute caffeine (6 mg/kg) increased blood lactate during resistance exercise, with greater lactate elevations in carriers of the MCT1 A allele (TA+AA) versus TT genotype; potassium responses varied by genotype and intervention.

Trust comment: Controlled crossover genetic study with objective measures but small, specific athletic sample limiting broad applicability.

Study Details

PMID:39771017
Participants:30
Impact:increased with caffeine; higher in A-allele carriers vs TT (significant intervention × genotype)
Trust score:3/5

choice reaction time (CRT)

3 evidences

In a crossover trial comparing guarana, caffeine (5 mg/kg) and placebo, caffeine showed no clear improvement in reaction time or memory versus placebo but did prevent post-exercise increases in simple reaction time variability.

Trust comment: Randomized double-blind crossover with 25 participants and objective cognitive measures; primary focus on guarana but included matched caffeine arm.

Study Details

PMID:36146946
Participants:25
Impact:no significant change vs placebo
Trust score:4/5

In 29 healthy adults given sham low or high caffeine doses, belief/expectation did not change choice reaction time or 10 km running performance.

Trust comment: Within-subject sham-controlled design with adequate sample for the questions about expectancy; outcomes clearly null.

Study Details

PMID:33939237
Participants:29
Impact:no effect of sham dose (no change in μ, σ, τ)
Trust score:4/5

In healthy young adults, 75 mg caffeine reduced prefrontal oxygenated haemoglobin and increased deoxygenated haemoglobin and improved some reaction-time and mood measures; co‑administration with L‑theanine abolished the oxy‑Hb reduction and removed the behavioural benefits.

Trust comment: Well-controlled double-blind, within-subjects study with NIRS and behavioral measures but modest sample size (n=24).

Study Details

PMID:25761837
Participants:24
Impact:faster (~54 ms faster vs placebo; ~11% improvement)
Trust score:4/5

flavour pleasantness

1 evidences

Among moderate habitual consumers, drinks containing caffeine became more pleasant over repeated exposures when caffeine intake was maintained, whereas pleasantness decreased in withdrawn participants.

Trust comment: Double-blind behavioral study with a relatively large sample (n=48) supporting reinforcement via withdrawal alleviation.

Study Details

PMID:12589525
Participants:48
Impact:increased over 4 days in maintained (caffeinated) group; decreased in withdrawn group
Trust score:4/5

anxiety (self-report)

1 evidences

Healthy young adults who regularly use caffeine got 200 mg caffeine plus varied CBD doses; self-reported drug effects and anxiety did not change.

Trust comment: Randomized single-session human study with moderate sample size but relied on subjective Zoom self-reports and is preliminary.

Study Details

PMID:37917507
Participants:54
Impact:no change
Trust score:3/5

muscular power (CMJ JH, PP, PF)

1 evidences

Resistance-trained men completed multiple caffeine and placebo trials; caffeine often increased arousal and dynamic muscle-power measures but effects varied across repeated trials.

Trust comment: Within-subject, double-blind randomized design with repeated measures and objective performance tests, but small completed sample (n=22) and variable repeatability.

Study Details

PMID:36297102
Participants:22
Impact:increased (statistically significant overall)
Trust score:4/5

exercise capacity (time to exhaustion/incremental)

1 evidences

Active adults performed cycling in normoxia and simulated altitude after 6 mg/kg caffeine; caffeine did not improve exercise capacity but changed some physiological and perceptual responses during steady-state.

Trust comment: Randomized controlled crossover with 29 participants and clear physiological outcomes; null effect on capacity reduces risk of overclaim.

Study Details

PMID:40675560
Participants:29
Impact:no change
Trust score:4/5

maximal voluntary contraction (knee extensors, MVC)

1 evidences

Two experiments showed 5 mg/kg caffeine increased knee-extensor strength and motor-unit recruitment and improved leg-cycling time-trial performance while reducing pain and perceived effort in some conditions.

Trust comment: Controlled experimental studies with objective neuromuscular and performance outcomes; modest sample sizes but clear percent effect estimates reported.

Study Details

PMID:25211364
Participants:26
Impact:increased (+6.3%)
Trust score:4/5

recruitment breaths

1 evidences

Caffeine given immediately after birth to very preterm infants increased respiratory effort measures versus later administration.

Trust comment: Randomized controlled trial in 30 infants with direct physiological respiratory measurements; moderate sample size for neonatal RCT.

Study Details

PMID:28288150
Participants:30
Impact:13% vs 9%; increase
Trust score:4/5

respiratory exchange ratio (RER)

1 evidences

In a double-blind crossover study of 23 mildly overweight adults, an acute multi-ingredient supplement containing high caffeine did not change heart rate or blood pressure but reduced RER in low-caffeine users.

Trust comment: Double-blind, placebo-controlled crossover with complete follow-up (n=23) but small sample and multi-ingredient product limits attribution to caffeine alone.

Study Details

PMID:21448304
Participants:23
Impact:−0.03 units (from 0.84 to 0.81) ≈ −3.6% in low-caffeine users
Trust score:4/5

Attention and memory

1 evidences

Crossover trial in active young adults: 6 mg/kg caffeine acutely improved reaction time but did not change attention or memory and increased some side effects.

Trust comment: Randomized crossover with objective cognitive tests in healthy adults; modest sample size but clear within-subject comparisons and reported CIs/P values.

Study Details

PMID:39231871
Participants:29
Impact:No change with 3 or 6 mg/kg (no statistically significant effects)
Trust score:4/5

Total and resting energy expenditure (TEE, REE)

1 evidences

Double-blind crossover in active males given ~5 mg/kg/day caffeine for 4 days: caffeine did not change resting, total, or physical-activity energy expenditure or accelerometer-measured activity patterns.

Trust comment: Well-controlled double-blind crossover using doubly labelled water and accelerometry (gold standards); small sample (n=21) limits generalisability.

Study Details

PMID:23869233
Participants:21
Impact:No significant differences between caffeine and placebo (TEE Δ ≈ 60.8 ± 417.4 kcal/day, p=0.512; REE Δ ≈ 13.6 ±153.1 kcal/day, p=0.689)
Trust score:4/5

Wingate mean power output (MPO)

1 evidences

Randomized, placebo-controlled trial in 80 men: acute pre-exercise 3 mg/kg caffeine improved 3-km running time and Wingate mean power output across groups; habitual caffeine use attenuated ergogenicity.

Trust comment: Large randomized controlled design with repeated testing and counterbalancing; effects reported across groups though exact effect sizes not provided in excerpt.

Study Details

PMID:39905628
Participants:80
Impact:Improved with pre-exercise 3 mg/kg caffeine (statistically significant, p<0.05)
Trust score:4/5

Time to meaningful pain relief

3 evidences

Phase III double-blind randomized trial in dental pain: ibuprofen 400 mg + caffeine 100 mg provided superior and faster analgesia versus ibuprofen alone, caffeine alone, and placebo over 8 h with acceptable tolerability.

Trust comment: Large, phase III randomized double-blind trial (n=562) with validated dental pain model and robust statistical analyses; high internal validity.

Study Details

PMID:28805281
Participants:562
Impact:Median 1.13 h for ibuprofen/caffeine vs 1.78 h for ibuprofen (≈0.65 h faster onset)
Trust score:5/5

In a large multicenter RCT, the acetaminophen+aspirin+caffeine combination provided faster and greater pain relief than ibuprofen and placebo in patients with severe migraine.

Trust comment: Large, well-conducted RCT, but caffeine was given as part of a fixed combination so individual effect of caffeine cannot be isolated.

Study Details

PMID:24733408
Participants:1555
Impact:faster by 16 min vs ibuprofen (132 vs 148 min, p=0.026)
Trust score:4/5

A single dose of a two-tablet analgesic containing acetaminophen, aspirin, and caffeine relieved migraine pain faster and more effectively than ibuprofen or placebo.

Trust comment: Large multicenter double-blind randomized placebo-controlled trial with clear endpoints and large sample size.

Study Details

PMID:16618262
Participants:1555
Impact:AAC median time to meaningful PAR ~20 minutes earlier than ibuprofen (P < .036)
Trust score:5/5

Heart rate (post-exercise)

1 evidences

Randomized double-blind crossover in trained judoists: acute 6 and 9 mg/kg caffeine improved judo-specific performance (throws) and increased heart rate; habitual caffeine consumers were less responsive.

Trust comment: Well-controlled randomized double-blind crossover in trained athletes with discipline-specific tests; small sample (n=22) limits precision and generalisability.

Study Details

PMID:31488190
Participants:22
Impact:HR right after and 1 min after SJFT increased after 6 and 9 mg/kg versus 3 mg/kg/placebo (p≈0.01–0.02)
Trust score:4/5

subjective alertness

6 evidences

In young adults consuming combinations of beer and caffeine (various doses), alcohol decreased alertness and increased hedonic tone; high caffeine doses counteracted alcohol-related decreases in subjective alertness but did not reverse alcohol-induced performance impairments.

Trust comment: Large randomized double-blind design (n=146) with multiple doses and repeated measures; robust sample and methods support moderate–high trust.

Study Details

PMID:23377024
Participants:146
Impact:Alcohol ↓ alertness (p<0.005); highest caffeine dose removed alcohol-induced drop in alertness (p<0.05)
Trust score:4/5

Caffeine increased blood pressure; expectancy/placebo effects influenced subjective alertness in one experiment, while reaction time showed no consistent change.

Trust comment: Two randomized experiments (N=45 each) with controls for expectancy; robust design shows pharmacologic and expectancy effects though some outcomes were null.

Study Details

PMID:17228991
Participants:90
Impact:increase via expectancy/placebo in one experiment
Trust score:4/5

Placebo-caffeine study (participants believed they drank caffeinated water): social influence moderated responses—confirming confederate increased subjective alertness, reduced cognitive interference and raised product endorsement; disconfirming confederate produced larger SBP decreases.

Trust comment: Well-powered randomized experiment with objective physiological and cognitive measures, though it tested placebo expectancy (female-only sample).

Study Details

PMID:27875567
Participants:99
Impact:higher in confirming vs disconfirming confederate (adj means 3.82 vs 3.51; difference +0.31 units; P=0.003)
Trust score:4/5

In 27 healthy volunteers, 50 mg caffeine improved alertness and attention-switching accuracy; combined L-theanine (100 mg) plus caffeine improved speed and accuracy on attention-switching and reduced distraction in memory tasks.

Trust comment: Placebo-controlled crossover with adequate sample for cognitive testing (n=27); results are consistent and specific to combined treatment effects.

Study Details

PMID:18681988
Participants:27
Impact:improved at 60 minutes with 50 mg caffeine
Trust score:4/5

A nutrient-enriched breakfast bar (containing a low caffeine dose of 21.5 mg among many other ingredients) produced acute improvements in alertness, attention and several cognitive tasks versus placebo on Day 1 and Day 56.

Trust comment: Well-designed randomized double-blind placebo-controlled trial with adequate sample (N=95) though many active ingredients and multiple outcomes limit attribution to caffeine alone.

Study Details

PMID:29215606
Participants:95
Impact:Increased (Bond-Lader alertness main effect F(1,93)=8.919, p=0.004)
Trust score:4/5

In young adults, a single dose of 97 mg L-theanine combined with 40 mg caffeine improved task-switching accuracy and increased self-reported alertness while reducing tiredness.

Trust comment: Randomized placebo-controlled study with moderate sample, but intervention combined L-theanine and caffeine so caffeine-specific effects are confounded.

Study Details

PMID:21040626
Participants:44
Impact:+ significant increase (p < 0.01)
Trust score:3/5

mathematical reasoning speed

1 evidences

In 150 healthy adults, a drink with 40 mg caffeine + 60 g glucose improved overall multi-tasking performance and speed on some tasks versus placebo or glucose alone, without changing mood.

Trust comment: Large randomized, double-blind, placebo-controlled trial with objective cognitive endpoints, though some authors had industry ties.

Study Details

PMID:25196040
Participants:150
Impact:↑ faster performance with caffeine–glucose vs glucose-only (significant; p≤0.034)
Trust score:4/5

Plasma caffeine concentration after smoking cessation

1 evidences

Among 162 caffeine-using smokers in cessation programs, continuing caffeine use after quitting raised plasma caffeine to ~203% of baseline by 3 weeks; abstainers reported transient increased fatigue and decreased stimulation but cessation rates were similar.

Trust comment: Randomized assignment within cessation programs and large sample, but older study and secondary measures limit modern generalizability.

Study Details

PMID:9022872
Participants:162
Impact:+103% at 3 weeks (203% of baseline) in continued caffeine users
Trust score:3/5

SJFT throws (sets 2 and 3)

1 evidences

In elite jiu-jitsu athletes, 3 mg/kg caffeine increased throws in later SJFT sets, raised heart rate slightly, improved strength/endurance perception, and reduced fatigue perception, but did not change technical actions during real combat.

Trust comment: Randomized double-blind placebo-controlled trial in 22 elite athletes with objective performance and perceptual measures; moderate sample and some methodological limitations noted by authors.

Study Details

PMID:35277034
Participants:22
Impact:+8.1% (set 2) and +5.6% (set 3) vs placebo
Trust score:4/5

time to exhaustion

3 evidences

Caffeine increased time to exhaustion and oxygen deficit in a supramaximal anaerobic test and raised metabolic markers.

Trust comment: Randomized double-blind trial with physiological measures but small sample (24) and mixed drug comparisons.

Study Details

PMID:11474345
Participants:24
Impact:increased (C increased time to exhaustion in MAOD test)
Trust score:4/5

In elite male endurance athletes, 4.5 mg·kg-1 caffeine increased endurance performance and several physiological markers during incremental running to exhaustion.

Trust comment: Randomized double-blind placebo-controlled crossover in elite athletes with objective physiological measures; small, all-male elite sample limits generalizability.

Study Details

PMID:34033621
Participants:23
Impact:+19.4 s (355 ± 41 → 375 ± 41 s)
Trust score:4/5

A pre-workout drink containing BHB salts, ~100 mg caffeine and amino acids increased blood ketones and improved time-to-exhaustion by ~8–10% versus water.

Trust comment: Randomized crossover but small sample (n=24) and caffeine was co-administered with ketone salts and amino acids, so caffeine-specific effects are unclear.

Study Details

PMID:32330107
Participants:24
Impact:+8.3% (Keto-Naïve) and +9.8% (Keto-Adapted) vs water
Trust score:3/5

atrial septal defect

1 evidences

Large case–control analysis found no clear evidence that maternal caffeine intake increases risk of cardiovascular birth defects.

Trust comment: Large, well-classified epidemiologic dataset (4,196 cases, 3,957 controls) with detailed exposure assessment, though observational design limits causal inference.

Study Details

PMID:17405163
Participants:8153
Impact:inverse trend with coffee (single significant pattern, possibly chance)
Trust score:4/5

exercise maximal fat oxidation and EE (MFO, EE)

1 evidences

In healthy active adults, single doses of thermogenic drinks with 100–140 mg caffeine increased resting metabolic rate; the 140 mg formula also increased resting fat oxidation, with no clear effects on exercise fat oxidation or VO2max.

Trust comment: Randomized double‑blind crossover with objective metabolic measures in 32 participants; well‑controlled but acute and modest sample size limits external generalizability.

Study Details

PMID:32054486
Participants:32
Impact:no significant difference across drinks (no clear effect)
Trust score:4/5

subjective effort

1 evidences

Across three small experiments, caffeine reduced subjective drowsiness but produced mixed effects on subjective effort and no consistent performance improvements.

Trust comment: Multiple small experiments with mixed and sometimes non-significant results; design described but limited power and complex interactions.

Study Details

PMID:7737103
Participants:52
Impact:placebo increased subjective effort; caffeine effects on effort were sex- and task-dependent (e.g., decreased effort in men but increased in women in one experiment)
Trust score:3/5

pain perception

1 evidences

Acute caffeine (6 mg/kg) increased repetitions to failure across sets, raised post-exercise blood lactate, and reduced perceived pain during low-load knee-extension with blood-flow restriction.

Trust comment: Double-blind crossover in trained men (n=22) with clear statistically significant performance and physiological differences; moderate sample size.

Study Details

PMID:30039986
Participants:22
Impact:decreased (second set −1.5 points; third set −0.8 points vs placebo)
Trust score:4/5

void volume

1 evidences

In this pilot RCT, warm caffeinated coffee increased initial void volumes after catheter removal but did not change the proportion who spontaneously voided.

Trust comment: Small randomized pilot study (n=30) with clinically relevant outcomes but limited power and short follow-up.

Study Details

PMID:24022423
Participants:30
Impact:+ increased void volume with caffeinated coffee (significant)
Trust score:3/5

dp/dt (cardiac contractility index)

1 evidences

Caffeine in hot drinks produced dose-dependent autonomic/cardio responses (e.g., changes in heart rate, blood pressure and baroreflex measures) during ingestion.

Trust comment: Controlled experimental design with multiple doses and repeated measures in healthy women (n=21), but subgroup dosing and small groups limit power.

Study Details

PMID:22614720
Participants:21
Impact:- decreased dp/dt (67 mg phase1; decreased with regular coffee all phases)
Trust score:4/5

flavour liking (conditioned preference)

1 evidences

Moderate caffeine users developed increased liking for a novel caffeinated flavour when tested in a caffeine-deprived state; liking extinguished if caffeine was removed or deprivation changed.

Trust comment: Controlled human experimental study with moderate sample size; psychological conditioning outcomes are internally valid but specialized.

Study Details

PMID:10986106
Participants:36
Impact:increased during caffeine-deprived training with caffeinated drink
Trust score:3/5

persistence of BP response

1 evidences

Acute caffeine raises blood pressure and five days of regular caffeine intake did not eliminate the BP response in about half of healthy adults.

Trust comment: Double-blind crossover trial with substantial sample (n≈97) and within-subject design; clinically relevant cardiovascular outcome.

Study Details

PMID:14967827
Participants:97
Impact:present in ~50% of participants after repeated daily dosing
Trust score:4/5

Taekwondo-specific agility (TSAT) time

1 evidences

Double-blind randomized placebo-controlled crossover in 52 taekwondo athletes (elite and sub-elite) showed that 3 mg/kg caffeine acutely improved agility and kicking performance and reduced session RPE, with effects varying by sex and competitive level.

Trust comment: Well-powered (a priori), double-blind randomized placebo-controlled crossover with sport-specific tests and objective measures; good internal validity.

Study Details

PMID:37612360
Participants:52
Impact:Elite overall: −0.5 s (~−8.5%) with CAF vs CON (5.4 s vs 5.9 s)
Trust score:5/5

Foveal choroidal thickness

1 evidences

In healthy young adults, a single 200 mg oral caffeine dose caused a significant decrease in choroidal thickness measured by OCT at 1 and 3 hours post-ingestion compared with placebo.

Trust comment: Objective OCT measurements and placebo control strengthen validity, but modest sample size (n=36) limits precision.

Study Details

PMID:24861902
Participants:36
Impact:Median decrease from 337 μm to 311 μm at 1 h and 3 h (−26 μm, ~−7.7%)
Trust score:4/5

24-h urine volume and electrolytes (Na+, K+)

1 evidences

Controlled dosing over 11 days in healthy males showed no evidence that daily caffeine (up to 6 mg/kg/day) produced hypohydration or altered renal electrolyte measures compared with placebo.

Trust comment: Controlled dosing with multiple objective hydration and renal measures and reasonable sample size, but limited to young males.

Study Details

PMID:16131696
Participants:59
Impact:No significant change across doses
Trust score:4/5

placekeeping (procedural cognitive control)

1 evidences

In a large randomized study, 200 mg caffeine given after overnight sleep loss restored vigilant attention (PVT) deficits but generally did not improve higher‑order placekeeping performance for most participants.

Trust comment: Large sample, randomized placebo‑controlled design and clear task-specific effects give high confidence in the selective cognitive findings.

Study Details

PMID:34014758
Participants:276
Impact:No significant improvement for most participants (caffeine did reduce number failing criterion)
Trust score:5/5

energetic arousal (mood)

2 evidences

Across two small crossover experiments, caffeinated beverages acutely stimulated autonomic measures (blood pressure, skin conductance), altered heart rate and skin temperature, and increased energetic arousal, with some dose‑dependent physiological effects.

Trust comment: Randomized crossover design with physiological measures is robust, but sample sizes per experiment are small and some dose‑response patterns were inconsistent.

Study Details

PMID:10837840
Participants:32
Impact:Increased after caffeinated beverages (acute effect)
Trust score:4/5

Amounts of caffeine plus theobromine present in normal portions of chocolate improved energetic arousal and cognitive function versus placebo/white chocolate.

Trust comment: Two double-blind placebo-controlled experiments (n=20 and n=22) showing consistent mood and cognitive effects at chocolate-equivalent methylxanthine doses.

Study Details

PMID:15549276
Participants:42
Impact:improved with cocoa/methylxanthine doses
Trust score:4/5

global cognitive decline rate

1 evidences

In older women with vascular disease/risks, higher usual caffeine intake (mainly caffeinated coffee) was associated with slower cognitive decline over ~5 years.

Trust comment: Large prospective cohort with repeated cognitive testing and covariate adjustment, but observational design cannot prove causation and residual confounding is possible.

Study Details

PMID:23422357
Participants:2475
Impact:Slower decline in highest vs lowest quintile (>371 vs <30 mg/day); effect equivalent to ~7 years younger over 5 years
Trust score:3/5

cerebral blood flow (CBF) response

1 evidences

Intravenous caffeine produced dose-dependent effects on brain imaging: intermediate dose (2.5 mg/kg) maximized BOLD activation increase; highest dose (5 mg/kg) maximized cerebral blood flow response.

Trust comment: Controlled experimental human study with simultaneous ASL/BOLD imaging but small sample and IV dosing limit direct relevance to typical oral caffeine use.

Study Details

PMID:19289172
Participants:27
Impact:Maximal increase at 5 mg/kg (highest dose) vs lower doses
Trust score:3/5

lower limb explosive power (jump height / CMJ / 5-Jump / 20J)

1 evidences

In 48 male volleyball players, 4-week supplementation plus resistance training showed that combined Rhodiola + caffeine improved jump power and reduced perceived exertion more than either supplement or placebo.

Trust comment: Randomized double-blind placebo-controlled trial with adequate sample (n=48) and validated performance measures, though limited to male volleyball players and lacking some biochemical mechanistic data.

Study Details

PMID:40005009
Participants:48
Impact:increase (CAF+RHO vs control; statistically significant, p<0.05 to p<0.01)
Trust score:4/5

stop-signal accuracy (inhibitory control)

1 evidences

In 28 light caffeine consumers, caffeine altered some alcohol-related cognitive performance measures and increased subjective stimulation without reducing absolute perceived intoxication.

Trust comment: Randomized within-subject crossover with controlled dosing (alcohol/caffeine) and objective cognitive tasks, but modest sample size (n=28).

Study Details

PMID:22173851
Participants:28
Impact:attenuation of alcohol-related deficit (improved accuracy with caffeine + alcohol vs alcohol alone)
Trust score:4/5

blood pressure (systolic and diastolic)

1 evidences

One cup of caffeinated espresso acutely raised blood pressure and heart rate but did not change QTc in healthy adults.

Trust comment: Randomized, double-blind crossover with objective ECG/BP measures and N=40, though limited to healthy adults and short-term effects.

Study Details

PMID:21288364
Participants:40
Impact:+~4–5 mmHg SBP, +~3–4 mmHg DBP within 60 min
Trust score:4/5

urinary frequency

2 evidences

In a randomized trial of 95 patients with urinary symptoms, an education intervention reduced caffeine intake and produced significant improvements in urinary urgency and frequency at one month.

Trust comment: Prospective randomized trial with a reasonable sample (n=95) showing significant symptom changes after caffeine reduction education.

Study Details

PMID:11979209
Participants:95
Impact:improved (significant; p=0.037)
Trust score:4/5

Regular coffee (450 mg/day) increased urinary urgency and frequency in young healthy volunteers, especially in prior low coffee users.

Trust comment: Double-blinded parallel human trial with standardized exposure and validated symptom indices; modest sample (n=49).

Study Details

PMID:26703981
Participants:49
Impact:significant increase with regular coffee (450 mg/day) vs decaf/abstinence (P < 0.05)
Trust score:4/5

withdrawal symptoms (gradual)

1 evidences

In a population survey and a controlled blinded experiment (57 regular users enrolled), abrupt caffeine withdrawal produced symptomatic withdrawal in a subset (e.g., headaches/tiredness), whereas gradual withdrawal produced minimal symptoms.

Trust comment: Community survey plus randomized, double-blind controlled pilot with clear outcome reporting but modest sample for the controlled arm.

Study Details

PMID:10586387
Participants:57
Impact:minimal or none (in gradual group)
Trust score:4/5

mind-wandering frequency

1 evidences

Participants given 200 mg caffeinated gum showed better sustained attention, reported being more on-task and had less mind-wandering versus placebo.

Trust comment: Large sample with placebo comparison and behavioral measures, though effect sizes not fully quantified in abstract.

Study Details

PMID:39098270
Participants:127
Impact:decreased (fewer spontaneous instances)
Trust score:4/5

plasma caffeine concentration

2 evidences

In 100 healthy drivers, a single 200 mg caffeine dose improved some executive/cognitive test performance and shortened brake reaction time versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with objective cognitive and driving outcomes in 100 healthy adults; some limitations noted by authors (washout/habit effects).

Study Details

PMID:30379815
Participants:100
Impact:+~9.87 μg/ml (0.23 → 10.10 μg/ml; p<0.001)
Trust score:4/5

Plasma caffeine concentrations showed a small overall rise after CPAP treatment but did not differ between therapeutic and subtherapeutic CPAP groups.

Trust comment: Analysis used stored samples from a randomized CPAP trial with adequate group sizes, though caffeine changes were small and clinically marginal.

Study Details

PMID:12947143
Participants:101
Impact:small overall increase when groups combined (p=0.02); no difference between therapeutic and subtherapeutic CPAP groups
Trust score:4/5

energy level (AUC4 total effect)

1 evidences

In a large balanced placebo crossover, both caffeine (300 mg) and expectancy produced similar subjective effects (energy, reduced sleepiness); placebo altered caffeine pharmacokinetics.

Trust comment: Large, well-controlled randomized balanced placebo crossover with objective and subjective outcomes and solid statistical analysis.

Study Details

PMID:21092089
Participants:168
Impact:+29.5 mm*hr
Trust score:5/5

Premature ventricular contractions (PVC)

1 evidences

In a randomized 14-day crossover trial, caffeinated coffee increased ventricular ectopy and daily steps and reduced nightly sleep duration versus avoiding caffeine, with no significant change in atrial ectopy.

Trust comment: Randomized case-crossover trial with objective continuous monitoring in 100 adults and high adherence, giving high internal validity.

Study Details

PMID:36947466
Participants:100
Impact:+51% (rate ratio 1.51; significant)
Trust score:5/5

10-km cycling time (performance)

1 evidences

In a randomized, double-blind, placebo-controlled trial, caffeine (2–4 mg/kg) improved 10-km cycling time overall but effects were strongly modified by CYP1A2 genotype (benefit in AA, harm in CC).

Trust comment: Well-powered randomized, double-blind, placebo-controlled crossover with objective performance measures and genotype stratification.

Study Details

PMID:29509641
Participants:101
Impact:Overall -3% (4 mg/kg); AA genotype: -4.8% at 2 mg/kg and -6.8% at 4 mg/kg (significant); CC genotype: +13.7% at 4 mg/kg (worse)
Trust score:5/5

Sprint total work (TW)

1 evidences

Acute coffee and anhydrous caffeine before testing produced small improvements: coffee improved leg-press 1RM versus anhydrous caffeine, and caffeine attenuated reductions in sprint power/total work versus placebo.

Trust comment: Randomized acute trial with objective performance tests and moderate sample size (male-only), but some outcomes lacked reported effect sizes.

Study Details

PMID:26394649
Participants:54
Impact:CAF showed significant improvement in sprint 1 TW (CI-significant)
Trust score:4/5

Duration of positive airway pressure

1 evidences

Large randomized trial in very low birth-weight infants: caffeine reduced bronchopulmonary dysplasia (oxygen use at 36 weeks) and shortened positive airway pressure duration, with transiently reduced early weight gain and no increase in death or brain injury.

Trust comment: Large, multicenter randomized controlled trial with clinically important neonatal outcomes and robust statistical analysis.

Study Details

PMID:16707748
Participants:2006
Impact:Positive airway pressure discontinued ~1 week earlier with caffeine (median 31.0 vs 32.0 weeks; P<0.001)
Trust score:5/5

psychomotor performance

3 evidences

In healthy aeromedically fit pilots, a single 300 mg dose of caffeine at midnight reduced the nighttime decline in psychomotor performance after extended wakefulness.

Trust comment: Randomized double-blind crossover RCT in relevant population (n=30); well-controlled but moderate sample size.

Study Details

PMID:37726901
Participants:30
Impact:reduced decline during night vs placebo
Trust score:4/5

In young adults consuming combinations of beer and caffeine (various doses), alcohol decreased alertness and increased hedonic tone; high caffeine doses counteracted alcohol-related decreases in subjective alertness but did not reverse alcohol-induced performance impairments.

Trust comment: Large randomized double-blind design (n=146) with multiple doses and repeated measures; robust sample and methods support moderate–high trust.

Study Details

PMID:23377024
Participants:146
Impact:Effects of alcohol and caffeine on performance were independent; caffeine did not remove alcohol-induced performance impairment (p<0.05 for effects)
Trust score:4/5

Caffeinated coffee increased alertness and psychomotor performance in people with colds (restoring them to healthy levels); decaffeinated coffee also produced improvements.

Trust comment: Relatively old study with partial reporting (only subset returned with colds) and placebo-like effects from decaf reduce specificity of caffeine effect.

Study Details

PMID:9443519
Participants:46
Impact:increased (restored to healthy levels)
Trust score:3/5

motor improvement (UPDRS III)

1 evidences

In PD outpatients, 100 mg/day caffeine adjuvant (2×50 mg/day) for 3 weeks was associated with substantial motor improvement (UPDRS III) compared to placebo, though some patients reported transient side effects.

Trust comment: Double-blind RCT with clear clinical outcome (UPDRS III) but small sample (n=27) limits generalizability.

Study Details

PMID:39280310
Participants:27
Impact:improved in 80.0% of caffeine vs 16.7% placebo (ARR 63.3%, NNT 2; OR ~20; p<0.01)
Trust score:4/5

working memory performance

1 evidences

Among undergraduates, 200 mg caffeine increased feelings of stimulation/high/anxiety and motivation; expecting a stronger stimulant (Adderall) amplified subjective stimulant effects and improved working memory, especially when combined with actual caffeine.

Trust comment: Randomized design with moderate sample (n=65) showing expectancy and pharmacological effects; relies mainly on self-report and lab cognitive tests.

Study Details

PMID:33734725
Participants:65
Impact:improved when participants expected Adderall (strongest when receiving caffeine + expecting Adderall)
Trust score:3/5

peak power output (Wpeak)

2 evidences

Acute 3 mg/kg caffeine improved peak and mean power in repeated Wingate sprints in both sexes with sex‑specific timing differences (males early sprints, females later sprints).

Trust comment: Well-powered (n=52), triple‑blind randomized crossover with appropriate controls and objective performance and metabolic measures.

Study Details

PMID:39662990
Participants:52
Impact:improved: Wt1 +3.0%, Wt3 +4.1%, Wt4 +4.8% (CAF vs placebo); sex-specific patterns (males ↑ early sprints, females ↑ later sprints)
Trust score:5/5

NaHCO3 and caffeine each improved some aspects of repeated-sprint performance, but their coingestion did not produce a synergistic benefit.

Trust comment: Randomized double-blind placebo-controlled crossover with objective performance measures but modest sample size.

Study Details

PMID:38335952
Participants:25
Impact:increase (NaHCO3+CAF and NaHCO3 vs placebo: +3% in Wt3; +4.5% in Wt4; p≤0.047)
Trust score:4/5

costly avoidance behavior (AACT)

1 evidences

In 29 patients with panic disorder and 53 healthy controls (n=82), 150 mg caffeine did not increase subjective anxiety but did raise physiological arousal (SCR), increase costly avoidance behavior, and impair exteroceptive attention.

Trust comment: Well-powered randomized, double-blind, placebo-controlled crossover with clear pre-registered outcomes and robust mixed-model analyses.

Study Details

PMID:40577029
Participants:82
Impact:increase (caffeine associated with greater avoidance; p<0.001)
Trust score:5/5

hypertension

1 evidences

In preterm infants (n=78) comparing high-dose versus lower-dose caffeine citrate, there was no difference in frequency or days with apnoea; side-effect rates showed non-significant trends toward being higher with the higher dose.

Trust comment: Parallel randomized, blinded RCT with appropriate methods and completed sample size for planned power, though some outcomes may be under-reported and long-term effects were not assessed.

Study Details

PMID:33922783
Participants:78
Impact:trend higher in high-dose group (40% vs 29%; not statistically significant)
Trust score:4/5

sustained attention (sequential reaction time)

1 evidences

In fasted young adults, combined caffeine (75 mg) + glucose (75 g) improved sustained attention and verbal memory consolidation beyond either substance alone; caffeine alone improved simple reaction time.

Trust comment: Double‑blind randomized design with moderate sample (n=72) and multiple cognitive measures; results need replication and dose/effort control.

Study Details

PMID:20521321
Participants:72
Impact:improved with combined caffeine + glucose (synergistic benefit)
Trust score:4/5

RSVP (attentional blink) dual vs single task performance

1 evidences

In older adults (42) and Parkinson's patients (24) who abstained from caffeine for a week, a single 100 mg caffeine dose improved response selection (accuracy) on choice reaction and Stroop tasks, sped Stroop RTs, improved dual-task (RSVP) performance via better T1 identification but impaired single-task RSVP performance; effects did not differ by disease.

Trust comment: Randomized single‑blind crossover with full 7‑day withdrawal, adequate sample for older/Parkinson groups and appropriate statistics, though modest dose and multiple comparisons limit certainty.

Study Details

PMID:35006304
Participants:66
Impact:dual-task accuracy improved (p=0.037) while single-task accuracy impaired (p=0.044); T1 identification improved (p=0.042), T2 not improved
Trust score:4/5

marker of poor diet / nutrient displacement

1 evidences

In a cohort of infants of Latina mothers followed to 18–36 months (106 children with follow-up), days when children consumed caffeine were associated with higher calorie intake and lower intake of key nutrients; the educational intervention did not prevent overweight.

Trust comment: Longitudinal dietary recall data with modest sample and secondary analyses; associations plausible but observational and subject to dietary recall and confounding.

Study Details

PMID:32081767
Participants:106
Impact:caffeine consumption correlated with higher added sugar and lower protein, fiber, dairy (associations reported)
Trust score:3/5

individual alpha frequency (IAF)

1 evidences

In 37 healthy adults undergoing total sleep deprivation with crossover acute caffeine/placebo, acute caffeine improved PVT reaction time, but higher habitual caffeine intake (>50 mg/day) was associated with worse vigilant attention (longer RT) and lower individual alpha frequency (IAF).

Trust comment: Controlled crossover sleep‑deprivation protocol with EEG and mixed‑model analyses; modest sample but well‑described methods and clear effects.

Study Details

PMID:36981883
Participants:37
Impact:IAF lower in high habitual caffeine consumers versus low/moderate (group effect p=0.002); IAF negatively correlated with daily caffeine intake
Trust score:4/5

P100 latency (PR‑VEP)

1 evidences

In 40 adults randomized to ~216 mg caffeine vs placebo, pattern‑reversal VEP P100 latency and amplitude measured at baseline and 1 h post‑dose were unchanged after caffeine.

Trust comment: Randomized controlled design with adequate sample for electrophysiology endpoints; single acute dose and single post‑test timepoint limit scope.

Study Details

PMID:30793994
Participants:40
Impact:no significant change 1 h after ~216 mg caffeine (no difference from baseline)
Trust score:4/5

SRT intra-individual variability (IIV-I)

1 evidences

In a crossover trial comparing guarana, caffeine (5 mg/kg) and placebo, caffeine showed no clear improvement in reaction time or memory versus placebo but did prevent post-exercise increases in simple reaction time variability.

Trust comment: Randomized double-blind crossover with 25 participants and objective cognitive measures; primary focus on guarana but included matched caffeine arm.

Study Details

PMID:36146946
Participants:25
Impact:prevented post-exercise increase (placebo increased; caffeine no change)
Trust score:4/5

strength endurance (repetitions to failure, RTF)

1 evidences

Resistance-trained men completed multiple caffeine and placebo trials; caffeine often increased arousal and dynamic muscle-power measures but effects varied across repeated trials.

Trust comment: Within-subject, double-blind randomized design with repeated measures and objective performance tests, but small completed sample (n=22) and variable repeatability.

Study Details

PMID:36297102
Participants:22
Impact:increased (e.g., SQ RTF higher with caffeine)
Trust score:4/5

pulmonary ventilation (steady-state)

1 evidences

Active adults performed cycling in normoxia and simulated altitude after 6 mg/kg caffeine; caffeine did not improve exercise capacity but changed some physiological and perceptual responses during steady-state.

Trust comment: Randomized controlled crossover with 29 participants and clear physiological outcomes; null effect on capacity reduces risk of overclaim.

Study Details

PMID:40675560
Participants:29
Impact:increased
Trust score:4/5

motor-unit recruitment (%ACT)

1 evidences

Two experiments showed 5 mg/kg caffeine increased knee-extensor strength and motor-unit recruitment and improved leg-cycling time-trial performance while reducing pain and perceived effort in some conditions.

Trust comment: Controlled experimental studies with objective neuromuscular and performance outcomes; modest sample sizes but clear percent effect estimates reported.

Study Details

PMID:25211364
Participants:26
Impact:increased (+5.5%)
Trust score:4/5

state mood (vigor, tension/anxiety, anger)

1 evidences

Post-hoc analysis of a randomized crossover trial (placebo vs ~98 mg caffeine) showing that individual trait mental/physical energy and fatigue modify caffeine's effects on mood, cognitive (serial subtraction) and fine-motor (9‑hole peg) performance—people with higher trait fatigue often gained more benefit.

Trust comment: Moderate-sized (n=30) randomized crossover parent trial but current analyses are post-hoc with multiple interactions and some effect estimates having wide CIs.

Study Details

PMID:33525438
Participants:30
Impact:observed increases with caffeine (vigor β=+1.30; tension/anxiety β=+0.63; anger β=+0.40) and trait low physical fatigue amplified anxiety response to caffeine
Trust score:3/5

selective attention speed (Stroop completion time)

1 evidences

Randomized double-blind crossover in recreational males showed dose-dependent benefits of caffeine mouth rinse on selective attention: faster completion time with 300 mg, fewer errors with 150 mg, and reduced perceived difficulty at 150 and 300 mg vs placebo.

Trust comment: Randomized double-blind crossover with objective cognitive tests and clear dose-response effects; sample limited to recreational males.

Study Details

PMID:39495309
Participants:30
Impact:−5.92 s (Part D completion time decreased from 62.93±19.07 to 57.01±16.74 s with 300 mg; p=0.002)
Trust score:4/5

laparoscopic manual dexterity (simulator total effect score)

1 evidences

Randomized double-blind placebo-controlled parallel trial in surgeons/attendees (n=107) found no significant effect of caffeinated coffee (≈230 mg from 340 mL) vs decaffeinated coffee on laparoscopic simulator performance (fine motor dexterity).

Trust comment: Large sample for this question, randomized double-blind design with validated simulator outcomes; pragmatic sample from a surgical congress may limit generalizability to clinical operations.

Study Details

PMID:34459976
Participants:107
Impact:no significant difference between caffeinated and decaffeinated coffee groups (p>0.05)
Trust score:4/5

blood pressure

14 evidences

Acute caffeine (50–450 mg) produced stimulant-like effects: increased blood pressure and arousal, improved vigilance, but worsened short-term memory in light nondependent users.

Trust comment: Well-powered within-subject double-blind design (n=102) showing consistent subjective and behavioral effects across doses.

Study Details

PMID:16541243
Participants:102
Impact:increase (significant)
Trust score:4/5

Caffeine increased blood pressure; expectancy/placebo effects influenced subjective alertness in one experiment, while reaction time showed no consistent change.

Trust comment: Two randomized experiments (N=45 each) with controls for expectancy; robust design shows pharmacologic and expectancy effects though some outcomes were null.

Study Details

PMID:17228991
Participants:90
Impact:increase with caffeine (large effect)
Trust score:4/5

Caffeine increased self-rated alertness, jitteriness, and blood pressure in healthy adults; theanine opposed caffeine's blood pressure rise.

Trust comment: Well-powered randomized double-blind placebo-controlled study with clear subjective and physiological endpoints.

Study Details

PMID:17891480
Participants:48
Impact:increased after caffeine; effect antagonized by co-administered theanine
Trust score:4/5

In 7- to 9-year-old children, moderate caffeine lowered heart rate and raised blood pressure during rest and low-moderate exercise but did not change VO2 or RER.

Trust comment: Randomized double-blind crossover in a defined pediatric sample (n=52) with clear physiological measures.

Study Details

PMID:16540840
Participants:52
Impact:increase (systolic and diastolic higher at rest and at some exercise intensities)
Trust score:4/5

A single caffeinated coffee dose increased blood pressure and made participants more cooperative in a social game versus decaffeinated coffee.

Trust comment: Randomized, double-blind, crossover study with a relatively large sample for behavioral research, though effects were assessed acutely.

Study Details

PMID:19178788
Participants:77
Impact:Significantly higher after caffeinated coffee
Trust score:4/5

In 22 resistance-trained men, acute caffeine (6 mg/kg) taken before resistance exercise raised blood-pressure-related measures compared with placebo and may increase cardiovascular load during/after heavy lifting.

Trust comment: Randomized crossover in trained men but small sample and limited reporting of effect magnitudes; high caffeine dose may limit generalizability.

Study Details

PMID:18046056
Participants:22
Impact:Increased with caffeine during/after exercise (statistically significant effect reported)
Trust score:3/5

In 49 moderate–high habitual consumers, a second 1.2 mg/kg caffeine dose improved cognitive performance and mood only after 8 h abstinence and raised blood pressure after 8 h; shorter abstinence produced some adverse effects on hand steadiness.

Trust comment: Larger, randomized placebo-controlled design with dose/abstinence manipulation (n=49); results depend on abstinence interval which was well tested.

Study Details

PMID:15696321
Participants:49
Impact:increase (after 8 h abstinence)
Trust score:4/5

Daily caffeine 250 mg (alone or with DMAA) for 12 weeks produced no statistically significant adverse changes in measured clinical or laboratory outcomes.

Trust comment: Randomized 12-week supplementation with comprehensive safety measures in 50 completing subjects; limited to healthy young men.

Study Details

PMID:23424215
Participants:50
Impact:no significant change (12-week supplementation vs baseline)
Trust score:4/5

In a double-blind crossover study of 23 mildly overweight adults, an acute multi-ingredient supplement containing high caffeine did not change heart rate or blood pressure but reduced RER in low-caffeine users.

Trust comment: Double-blind, placebo-controlled crossover with complete follow-up (n=23) but small sample and multi-ingredient product limits attribution to caffeine alone.

Study Details

PMID:21448304
Participants:23
Impact:no change
Trust score:4/5

Brief caffeine deprivation in habitual coffee drinkers caused decreased vigor, increased fatigue and sleepiness, and a modest drop in blood pressure; psychomotor performance unchanged.

Trust comment: Double-blind within-subject design with clear outcome measures and n=31; results are directly reported and interpretable.

Study Details

PMID:9402612
Participants:31
Impact:-5 to -6 mm Hg
Trust score:4/5

Over 8 weeks, the caffeine arm showed no statistically significant changes in vital signs or routine lab safety measures compared with other groups.

Trust comment: Controlled supplementation study including a caffeine arm, but modest sample size and short duration limit detection of uncommon/long-term effects.

Study Details

PMID:25591969
Participants:48
Impact:no significant change (8-week supplementation)
Trust score:3/5

In obese adults after weight loss, rye bread enriched with green tea extract (providing ~123–158 mg caffeine/day) did not improve weight-loss maintenance but was associated with slightly better blood pressure control and a marginally smaller waist circumference.

Trust comment: Randomized single-blind pilot with moderate sample size; results suggest modest BP effects but limited clinical impact and pilot design.

Study Details

PMID:25494205
Participants:55
Impact:maintained lower BP in intervention group (significant)
Trust score:3/5

In 40 habitual coffee consumers in a randomized crossover design, single servings of coffee (160 mg caffeine) increased salivary alpha-amylase and transiently increased salivary gastrin and blood pressure, but did not change salivary cortisol or self-reported GI symptoms.

Trust comment: Randomized double-blind crossover with objective biochemical measures, though modest sample and short-term assessments.

Study Details

PMID:26979712
Participants:40
Impact:increased within physiological range post-consumption (time effect)
Trust score:4/5

A bioactive combination including caffeine increased resting metabolic rate (thermogenesis) in men, and propranolol (beta-blocker) reduced about half of that thermogenic response.

Trust comment: Randomized double-blind crossover study with objective metabolic measures, but caffeine was part of a multi-ingredient mix so attribution to caffeine alone is indirect.

Study Details

PMID:19497591
Participants:22
Impact:Systolic BP increased ~3% (~4 mm Hg) and diastolic BP increased ~6% (~4 mm Hg) with the bioactive combination vs placebo.
Trust score:3/5

AUC (exposure)

2 evidences

Single 200 mg caffeine given overtly or covertly to healthy adults; large within-person variability in PK measures but no average covert vs overt difference.

Trust comment: Randomized crossover in healthy humans with standard PK methods; small sample (n=28 analysed) limits precision but design and methods are sound.

Study Details

PMID:28561231
Participants:28
Impact:23–30% of individuals had covert/overt ratios outside ±25%; mean absolute deviation 3.31–6.29%; 90% CI within 80–125% (no significant covert-vs-overt difference)
Trust score:4/5

Multiple-dose caffeine chewing gum produces dose-proportional plasma caffeine levels with maintained linear pharmacokinetics, supporting its use to sustain alertness.

Trust comment: Randomized, double-blind, parallel design with validated assays and 48 healthy volunteers gives reasonably high internal validity.

Study Details

PMID:16158445
Participants:48
Impact:33.2 / 46.94 / 86.94 mg·h/L (50 / 100 / 200 mg); dose-proportionate increase
Trust score:4/5

Side effects (activeness, nervousness)

1 evidences

Crossover trial in active young adults: 6 mg/kg caffeine acutely improved reaction time but did not change attention or memory and increased some side effects.

Trust comment: Randomized crossover with objective cognitive tests in healthy adults; modest sample size but clear within-subject comparisons and reported CIs/P values.

Study Details

PMID:39231871
Participants:29
Impact:Occurrence increased after 6 mg/kg (statistically significant increases)
Trust score:4/5

Time in activity intensities / short bouts

1 evidences

Double-blind crossover in active males given ~5 mg/kg/day caffeine for 4 days: caffeine did not change resting, total, or physical-activity energy expenditure or accelerometer-measured activity patterns.

Trust comment: Well-controlled double-blind crossover using doubly labelled water and accelerometry (gold standards); small sample (n=21) limits generalisability.

Study Details

PMID:23869233
Participants:21
Impact:No significant differences in steps, sedentary, LIPA, MVPA or short-bout frequencies (all p≥0.05); short-bout frequency predicted PAEE but caffeine did not alter frequencies
Trust score:4/5

systolic blood pressure (SBP)

6 evidences

A single cup of coffee (80 mg caffeine) produced a small rise in systolic BP but overall no statistically significant effect on BP at one hour in healthy young adults.

Trust comment: Randomized controlled trial with adequate sample size and objective BP measures; effect sizes small and not clearly clinically significant.

Study Details

PMID:27051992
Participants:104
Impact:+2.77 mmHg (P = 0.05) after a single 80 mg caffeine cup (borderline)
Trust score:4/5

In tactical males, 300 mg caffeine and a 150 mg caffeine + methylliberine + theacrine combo similarly improved vigilance reaction time; caffeine raised DBP vs placebo while the combo raised SBP but not DBP.

Trust comment: Randomized, placebo-controlled trial with moderate sample (n=48 completed) and appropriate measures; between-group design limits within-subject sensitivity but overall reliable.

Study Details

PMID:36016763
Participants:48
Impact:increase in CAF and CMT vs PLA (large effect; CAF P=0.003, CMT P=0.007)
Trust score:4/5

In 165 healthy men and women across age/hormonal-status groups, acute caffeine increased systolic and diastolic blood pressure by a few mmHg.

Trust comment: Well-powered randomized crossover with clear, consistent BP increases, though single-dose challenge design limits long-term inference.

Study Details

PMID:20500126
Participants:165
Impact:+4.0 mmHg (±0.6)
Trust score:4/5

Acute consumption of large-volume caffeinated energy drinks (two 16-oz bottles; ~304–320 mg caffeine) in healthy adults increased QTc and raised brachial and central blood pressure compared with placebo.

Trust comment: Randomized, double-masked, placebo-controlled crossover with adequate sample for ECG endpoints and clear numeric changes, though acute single-exposure limits long-term conclusions.

Study Details

PMID:31137991
Participants:34
Impact:Maximum change from baseline: Drink A +15.9±5.0 mm Hg, Drink B +14.4±4.8 mm Hg, Placebo +9.8±4.8 mm Hg (P<0.001)
Trust score:4/5

In undergraduates, 5 mg/kg caffeine increased systolic blood pressure and altered heart rate/HRV measures and subjective experience 40 minutes after ingestion; expectancies contributed to subjective effects but not objective measures.

Trust comment: Well-powered double-blind placebo-controlled design (n=107) with objective and subjective endpoints and control for expectancies, supporting credible differentiation of pharmacologic vs expectancy effects.

Study Details

PMID:25481367
Participants:107
Impact:increased after 5 mg/kg caffeine (magnitude not specified in provided text)
Trust score:4/5

Acute ingestion of various energy drinks (contain caffeine plus blends) produced group-specific increases in blood pressure, heart rate, cortisol, and mixed effects on anxiety and working memory.

Trust comment: Moderate-sized acute study (n=80) but tested commercial energy drinks with multiple active ingredients, so effects cannot be attributed to caffeine alone.

Study Details

PMID:27312565
Participants:80
Impact:significant 30-min increase in groups A and C
Trust score:3/5

Habitual caffeine use (tolerance)

1 evidences

Randomized, placebo-controlled trial in 80 men: acute pre-exercise 3 mg/kg caffeine improved 3-km running time and Wingate mean power output across groups; habitual caffeine use attenuated ergogenicity.

Trust comment: Large randomized controlled design with repeated testing and counterbalancing; effects reported across groups though exact effect sizes not provided in excerpt.

Study Details

PMID:39905628
Participants:80
Impact:Regular consumption reduced ergogenic effect of acute caffeine; adjustments (higher dose or withdrawal) can partially restore effect (authors' reported observation)
Trust score:4/5

Responder rate (≥50% SPRID)

1 evidences

Phase III double-blind randomized trial in dental pain: ibuprofen 400 mg + caffeine 100 mg provided superior and faster analgesia versus ibuprofen alone, caffeine alone, and placebo over 8 h with acceptable tolerability.

Trust comment: Large, phase III randomized double-blind trial (n=562) with validated dental pain model and robust statistical analyses; high internal validity.

Study Details

PMID:28805281
Participants:562
Impact:67.8% responders for ibuprofen/caffeine vs 49.7% for ibuprofen (ARR 18.1% vs ibuprofen; NNT ≈5.5)
Trust score:5/5

Combat activity (total attacks)

1 evidences

Randomized double-blind crossover in trained judoists: acute 6 and 9 mg/kg caffeine improved judo-specific performance (throws) and increased heart rate; habitual caffeine consumers were less responsive.

Trust comment: Well-controlled randomized double-blind crossover in trained athletes with discipline-specific tests; small sample (n=22) limits precision and generalisability.

Study Details

PMID:31488190
Participants:22
Impact:9 mg/kg increased total number of attacks compared to baseline/placebo (statistically significant); habitual caffeine use reduced responsiveness to supplementation
Trust score:4/5

mood (hedonic tone, anxiety)

1 evidences

In young adults consuming combinations of beer and caffeine (various doses), alcohol decreased alertness and increased hedonic tone; high caffeine doses counteracted alcohol-related decreases in subjective alertness but did not reverse alcohol-induced performance impairments.

Trust comment: Large randomized double-blind design (n=146) with multiple doses and repeated measures; robust sample and methods support moderate–high trust.

Study Details

PMID:23377024
Participants:146
Impact:Alcohol ↑ hedonic tone (p<0.005) and ↓ anxiety (p<0.05); caffeine had no effect on hedonic tone or anxiety
Trust score:4/5

Stroop response speed

1 evidences

In 150 healthy adults, a drink with 40 mg caffeine + 60 g glucose improved overall multi-tasking performance and speed on some tasks versus placebo or glucose alone, without changing mood.

Trust comment: Large randomized, double-blind, placebo-controlled trial with objective cognitive endpoints, though some authors had industry ties.

Study Details

PMID:25196040
Participants:150
Impact:↑ trend/greater speed with caffeine–glucose vs placebo and 60 g glucose (p≈0.011–0.027)
Trust score:4/5

Fatigue following cessation (caffeine abstainers)

1 evidences

Among 162 caffeine-using smokers in cessation programs, continuing caffeine use after quitting raised plasma caffeine to ~203% of baseline by 3 weeks; abstainers reported transient increased fatigue and decreased stimulation but cessation rates were similar.

Trust comment: Randomized assignment within cessation programs and large sample, but older study and secondary measures limit modern generalizability.

Study Details

PMID:9022872
Participants:162
Impact:Increased fatigue during first 3 days
Trust score:3/5

caffeine withdrawal symptoms

1 evidences

Open-label decaf reduced withdrawal ratings in abstinent heavy coffee drinkers compared to water and to deceptively-treated decaf.

Trust comment: Randomized comparison with adequate sample (n=61) and clear, statistically reported effects; open-label design limits mechanistic inference but result is robust.

Study Details

PMID:36628993
Participants:61
Impact:Open-label decaf reduced withdrawal by 9.5 points (95% CI 4.7 to 14.3); significantly different vs deceptive and control groups
Trust score:4/5

salivary caffeine concentration

1 evidences

Ingesting coffee providing 3 mg/kg caffeine improved 5 km cycling time (~9 s faster, ≈1.9% vs placebo) in both men and women.

Trust comment: Well-powered, double-blind crossover with objective performance and biochemical measures; modest sample but rigorous design.

Study Details

PMID:31731467
Participants:38
Impact:increased markedly post-drink
Trust score:4/5

total throws / SJFT performance

1 evidences

In elite jiu-jitsu athletes, 3 mg/kg caffeine increased throws in later SJFT sets, raised heart rate slightly, improved strength/endurance perception, and reduced fatigue perception, but did not change technical actions during real combat.

Trust comment: Randomized double-blind placebo-controlled trial in 22 elite athletes with objective performance and perceptual measures; moderate sample and some methodological limitations noted by authors.

Study Details

PMID:35277034
Participants:22
Impact:significant increase (overall)
Trust score:4/5

intraocular pressure (IOP)

2 evidences

In a crossover RCT including people with or at risk for glaucoma, one cup of caffeinated coffee (182 mg) produced small but statistically significant increases in intraocular pressure (IOP), ocular perfusion pressure and ocular pulse amplitude at 60–90 min vs decaffeinated coffee.

Trust comment: Prospective, double-masked crossover RCT with 106 participants and objective ophthalmic measures; small absolute changes likely of limited clinical relevance.

Study Details

PMID:22678051
Participants:106
Impact:+ ~1.0 mm Hg at 60 and 90 min (statistically significant)
Trust score:4/5

Drinking caffeinated coffee raised eye pressure transiently in patients with glaucoma or ocular hypertension.

Trust comment: Crossover human study with objective IOP measures but small sample (n=28) limits generalizability.

Study Details

PMID:12022898
Participants:28
Impact:+~3.4 mmHg at 60 min and +~2.3–3.0 mmHg at 90 min after 180 mg caffeine vs decaf (difference vs decaf significant at 60 and 90 min)
Trust score:4/5

serum FGF-21

1 evidences

Caffeine plus heat exposure increased body and skin temperatures and amplified thermogenesis-related biomarkers (FGF‑21 and irisin).

Trust comment: Randomized trial with a fairly large male sample and quantified biomarker changes, though limited to healthy males and acute exposure.

Study Details

PMID:40635261
Participants:87
Impact:+22.93% vs control after thermotherapy (P < 0.001)
Trust score:4/5

blood pressure / baroreflex sensitivity

1 evidences

Caffeine in hot drinks produced dose-dependent autonomic/cardio responses (e.g., changes in heart rate, blood pressure and baroreflex measures) during ingestion.

Trust comment: Controlled experimental design with multiple doses and repeated measures in healthy women (n=21), but subgroup dosing and small groups limit power.

Study Details

PMID:22614720
Participants:21
Impact:+ increased diastolic pressure with 134 mg (phases 2–3) and decreased baroreflex sensitivity (phase1)
Trust score:4/5

flavour preference expression

1 evidences

Moderate caffeine users developed increased liking for a novel caffeinated flavour when tested in a caffeine-deprived state; liking extinguished if caffeine was removed or deprivation changed.

Trust comment: Controlled human experimental study with moderate sample size; psychological conditioning outcomes are internally valid but specialized.

Study Details

PMID:10986106
Participants:36
Impact:decreased (extinction) when caffeine contingent relation or deprivation state removed
Trust score:3/5

Ten-second frequency speed of kick (FSKT-10s)

1 evidences

Double-blind randomized placebo-controlled crossover in 52 taekwondo athletes (elite and sub-elite) showed that 3 mg/kg caffeine acutely improved agility and kicking performance and reduced session RPE, with effects varying by sex and competitive level.

Trust comment: Well-powered (a priori), double-blind randomized placebo-controlled crossover with sport-specific tests and objective measures; good internal validity.

Study Details

PMID:37612360
Participants:52
Impact:Overall CAF 28 vs CON 25 kicks (~+3 kicks, ~+12%)
Trust score:5/5

Extrafoveal choroidal thickness

1 evidences

In healthy young adults, a single 200 mg oral caffeine dose caused a significant decrease in choroidal thickness measured by OCT at 1 and 3 hours post-ingestion compared with placebo.

Trust comment: Objective OCT measurements and placebo control strengthen validity, but modest sample size (n=36) limits precision.

Study Details

PMID:24861902
Participants:36
Impact:Significant decreases at five extrafoveal points (p<0.05) at 1 and 3 h vs baseline
Trust score:4/5

Serum/urine osmolality and renal markers

1 evidences

Controlled dosing over 11 days in healthy males showed no evidence that daily caffeine (up to 6 mg/kg/day) produced hypohydration or altered renal electrolyte measures compared with placebo.

Trust comment: Controlled dosing with multiple objective hydration and renal measures and reasonable sample size, but limited to young males.

Study Details

PMID:16131696
Participants:59
Impact:No significant change; values remained within normal clinical ranges
Trust score:4/5

reaction time / performance

1 evidences

In regular caffeine consumers tested when fatigued, repeated low doses of caffeine improved subjective mood/alertness and enhanced several performance measures, with dose‑dependent effects.

Trust comment: Well-controlled double‑blind study with objective assays and balanced conditions, though some details of effect sizes are not reported in the summary.

Study Details

PMID:16272184
Participants:60
Impact:Improved performance and reaction time (dose-dependent)
Trust score:4/5

time to exhaustion (nonusers)

1 evidences

A 5 mg/kg dose of caffeine increased cycling time-to-exhaustion in both users and nonusers, with larger and longer-lasting effects in nonusers.

Trust comment: Randomized crossover with clear outcome but small sample and subgroup sizes (13 users, 8 nonusers) limit generalizability.

Study Details

PMID:12235019
Participants:21
Impact:+8.5 min at 1 h; +6.3 min at 3 h; +8.5 min at 6 h vs placebo (all significant)
Trust score:3/5

caffeinated coffee consumption

1 evidences

In older women with vascular disease/risks, higher usual caffeine intake (mainly caffeinated coffee) was associated with slower cognitive decline over ~5 years.

Trust comment: Large prospective cohort with repeated cognitive testing and covariate adjustment, but observational design cannot prove causation and residual confounding is possible.

Study Details

PMID:23422357
Participants:2475
Impact:Consumption associated with slower cognitive decline (p-trend 0.05); other caffeine sources not associated
Trust score:3/5

maximal strength (1RM)

1 evidences

In trained women habituated to caffeine, acute caffeine (3 and 6 mg/kg) increased 1RM strength (dose-response) and 6 mg/kg increased time under tension; no clear change in repetitions or power measures.

Trust comment: Randomized double-blind crossover with direct performance measures in a specific trained female sample but small n (21) limits generalizability.

Study Details

PMID:33781269
Participants:21
Impact:PLAC 40.48 kg → CAF-3 41.68 kg (+3.5%); CAF-6 42.98 kg (+6.9%)
Trust score:4/5

COP frequency (anteroposterior)

1 evidences

In healthy older adults, a caffeinated coffee dose (~3 mg/kg) produced limited effects on balance metrics and did not change functional physical performance measures.

Trust comment: Randomized crossover in older adults with objective balance measures; moderate sample size and limited to healthy volunteers.

Study Details

PMID:39321752
Participants:22
Impact:increased after caffeinated coffee vs decaffeinated (p=0.047)
Trust score:4/5

fatigue (subjective)

1 evidences

In rested young male habitual caffeine consumers, individualized morning caffeine doses reduced fatigue and improved simple and sustained attention and the executive updating domain, independent of meal ingestion.

Trust comment: Double-blind placebo-controlled trial with a relatively large sample (n=60) and thorough cognitive testing; males only which limits generalizability.

Study Details

PMID:26621326
Participants:60
Impact:decreased after habitual personalized caffeine dose
Trust score:4/5

aerodynamic voice measures

1 evidences

In 58 adult females given 100 mg caffeine vs placebo after 24-h caffeine abstinence, no differences were found in acoustic or aerodynamic voice measures 30 minutes post-ingestion.

Trust comment: Moderate-sized randomized comparison with controlled abstinence; single conservative dose (100 mg) limits generalization to higher doses or habitual users.

Study Details

PMID:24408336
Participants:58
Impact:no change (100 mg caffeine vs placebo)
Trust score:3/5

urinary urgency

2 evidences

In a randomized trial of 95 patients with urinary symptoms, an education intervention reduced caffeine intake and produced significant improvements in urinary urgency and frequency at one month.

Trust comment: Prospective randomized trial with a reasonable sample (n=95) showing significant symptom changes after caffeine reduction education.

Study Details

PMID:11979209
Participants:95
Impact:improved (significant; p=0.002)
Trust score:4/5

Regular coffee (450 mg/day) increased urinary urgency and frequency in young healthy volunteers, especially in prior low coffee users.

Trust comment: Double-blinded parallel human trial with standardized exposure and validated symptom indices; modest sample (n=49).

Study Details

PMID:26703981
Participants:49
Impact:significant increase with regular coffee (450 mg/day) vs decaf/abstinence (P < 0.05)
Trust score:4/5

withdrawal symptoms (abrupt)

1 evidences

In a population survey and a controlled blinded experiment (57 regular users enrolled), abrupt caffeine withdrawal produced symptomatic withdrawal in a subset (e.g., headaches/tiredness), whereas gradual withdrawal produced minimal symptoms.

Trust comment: Community survey plus randomized, double-blind controlled pilot with clear outcome reporting but modest sample for the controlled arm.

Study Details

PMID:10586387
Participants:57
Impact:reported by 33.3% in abrupt group (6/18); overall clinically significant symptoms uncommon
Trust score:4/5

belief/experience influence

1 evidences

In 29 healthy adults given sham low or high caffeine doses, belief/expectation did not change choice reaction time or 10 km running performance.

Trust comment: Within-subject sham-controlled design with adequate sample for the questions about expectancy; outcomes clearly null.

Study Details

PMID:33939237
Participants:29
Impact:no effect of belief or belief+experience on outcomes
Trust score:4/5

EEG delta and beta spectral power

1 evidences

Evening 200 mg caffeine worsened objective sleep: longer time to fall asleep, lower sleep efficiency and shorter total sleep time in both age groups.

Trust comment: Double-blind crossover with polysomnography and EEG in 24 participants; objective high-quality sleep measures.

Study Details

PMID:16704567
Participants:24
Impact:delta power decreased (frontal/central/parietal); beta power increased (frontal/central)
Trust score:5/5

blood pressure and pulse rate

1 evidences

Caffeinated coffee improved encoding of new information and reduced fatigue over the morning, but raised blood pressure and pulse; breakfast improved mood and some memory measures.

Trust comment: Large sample (n=144) and controlled conditions; between-group design but with valid behavioral and cardiovascular measures.

Study Details

PMID:10463623
Participants:144
Impact:increased after caffeinated coffee
Trust score:4/5

reactive and sustained attention/performance (simple/choice reaction, vigilance, dual task)

1 evidences

Realistic multi-dose caffeine intake (4×65 mg) and a single 200 mg dose both increased alertness and anxiety and improved several task-performance measures.

Trust comment: Double-blind, within-subjects design mimicking real-world intake; modest sample (n=24) but well-controlled.

Study Details

PMID:12404081
Participants:24
Impact:improved with caffeine (both regimens)
Trust score:4/5

perceived fatigue (VAS)

1 evidences

Repeated coffee mouth-rinses (dose-related) increased futsal-specific endurance distance and improved/accelerated recovery of vertical jump performance versus control.

Trust comment: Randomized, double-blind crossover in 24 elite players with objective performance tests though placebo effects noted and plasma caffeine not measured.

Study Details

PMID:37190757
Participants:24
Impact:no consistent condition effect; main effect of time only (fatigue increased with exercise)
Trust score:4/5

attentional task performance

1 evidences

Participants given 200 mg caffeinated gum showed better sustained attention, reported being more on-task and had less mind-wandering versus placebo.

Trust comment: Large sample with placebo comparison and behavioral measures, though effect sizes not fully quantified in abstract.

Study Details

PMID:39098270
Participants:127
Impact:improved (performance benefit reported)
Trust score:4/5

systolic blood pressure (safety)

1 evidences

In a crossover pilot trial with a caffeine active control, caffeine improved post-lunch rapid visual information processing and some multitasking measures versus placebo.

Trust comment: Randomized crossover pilot with active caffeine control, moderate sample but multiple interventions and pilot design limit strength.

Study Details

PMID:38367243
Participants:30
Impact:no increase versus caffeine control
Trust score:3/5

plasma calcium concentration

1 evidences

High-dose caffeine (8 mg/kg) increased maximal strength in bench press, deadlift, and squat and raised plasma Ca2+ compared with placebo or lower dose.

Trust comment: Randomized double-blind crossover with mechanistic measures but limited to 21 recreational young men, restricting broader applicability.

Study Details

PMID:36432607
Participants:21
Impact:pre 8.5 mg/dL → post CF8 10.4 mg/dL (+1.9 mg/dL)
Trust score:4/5

Urine metabolite ratio AAMU+1U+1X/17U as CYP1A2 activity marker

1 evidences

In smokers and nonsmokers, the urine metabolite ratio AAMU+1U+1X/17U from a spot urine correlated with measured caffeine clearance (CYP1A2 activity) across dosing conditions except at very high caffeine doses.

Trust comment: Mechanistic human pharmacokinetic study using stable isotopes and multiple conditions; sample size small (n=21) but methods are rigorous for validation.

Study Details

PMID:8653991
Participants:21
Impact:correlated with caffeine clearance (gamma² range 0.4–0.9) across conditions except at high dose (12 mg·kg⁻¹)
Trust score:4/5

adverse events

1 evidences

Caffeine citrate reduced apnea episodes and eliminated apnea faster than placebo in preterm infants and was well tolerated.

Trust comment: Large multicenter randomized double-blind placebo-controlled trial in the target population with clear endpoints and adequate sample size.

Study Details

PMID:10853619
Participants:85
Impact:No significant difference in adverse events vs placebo
Trust score:5/5

sleep quality

1 evidences

In 27 participants across three groups, slow-release caffeine reduced daytime sleepiness after an eastbound 7-time-zone flight but tended to affect sleep quality.

Trust comment: Double-blind randomized placebo-controlled study with objective sleep measures; group sizes small (n=9 per arm) but design is robust.

Study Details

PMID:12959951
Participants:27
Impact:tended to be affected (some disruption) with slow-release caffeine during treatment days
Trust score:4/5

Reaction time / attention lapses

1 evidences

In sleep-restricted participants, a 200 mg caffeine capsule improved subjective mood and sped reaction times compared with placebo.

Trust comment: Double-blind crossover in a relevant fatigued population with a moderate sample (n=35); outcomes are behavioral and consistent with known caffeine effects.

Study Details

PMID:18266548
Participants:35
Impact:Faster reaction times and fewer attentional lapses after caffeine
Trust score:4/5

post-exercise blood lactate

1 evidences

In moderately trained CrossFit athletes, different acute caffeine doses (3, 6, 9 mg/kg) did not produce consistent statistically superior performance vs placebo, though 6 mg/kg showed the largest practical improvement in some measures.

Trust comment: Well-controlled randomized double-blind crossover (n=26) but practice effects and small sample reduce certainty of dose effects.

Study Details

PMID:38226646
Participants:26
Impact:increased with caffeine; highest at 9 mg/kg (~17.69 mmol/L vs placebo 15.34 mmol/L)
Trust score:4/5

Cmax

1 evidences

Multiple-dose caffeine chewing gum produces dose-proportional plasma caffeine levels with maintained linear pharmacokinetics, supporting its use to sustain alertness.

Trust comment: Randomized, double-blind, parallel design with validated assays and 48 healthy volunteers gives reasonably high internal validity.

Study Details

PMID:16158445
Participants:48
Impact:2.69 / 3.45 / 6.33 mg/L (50 / 100 / 200 mg)
Trust score:4/5

Linearity of pharmacokinetics

1 evidences

Multiple-dose caffeine chewing gum produces dose-proportional plasma caffeine levels with maintained linear pharmacokinetics, supporting its use to sustain alertness.

Trust comment: Randomized, double-blind, parallel design with validated assays and 48 healthy volunteers gives reasonably high internal validity.

Study Details

PMID:16158445
Participants:48
Impact:Maintained after multiple doses (no significant dose-normalized differences)
Trust score:4/5

decaffeinated coffee effect

1 evidences

Caffeinated coffee increased alertness and psychomotor performance in people with colds (restoring them to healthy levels); decaffeinated coffee also produced improvements.

Trust comment: Relatively old study with partial reporting (only subset returned with colds) and placebo-like effects from decaf reduce specificity of caffeine effect.

Study Details

PMID:9443519
Participants:46
Impact:improved alertness/performance (also produced benefit)
Trust score:3/5

days of respiratory support

1 evidences

In this subgroup analysis of the CAP trial, caffeine reduced death/disability and shortened time on respiratory support mainly in infants who were receiving ventilatory support or who started caffeine early.

Trust comment: Large randomized trial data but current results are from post-hoc subgroup analyses which lowers causal certainty for subgroup differences.

Study Details

PMID:19926098
Participants:2006
Impact:reduction with early caffeine (mean difference ≈ -1.35 weeks early vs -0.55 weeks late)
Trust score:4/5

subjective activation/alertness

1 evidences

A single 100 mg caffeine dose produced rapid arousal (less sleepiness, greater activation) within 10–30 min in healthy undergraduates, with larger effects in men.

Trust comment: Large, randomized double-blind placebo-controlled study (n=688) with repeated measures, giving high confidence in subjective-effect findings.

Study Details

PMID:18675877
Participants:688
Impact:increased at 10–30 min after 100 mg caffeine
Trust score:5/5

one-repetition maximum (1RM) strength

1 evidences

In resistance-trained women, 6 mg/kg caffeine improved leg-press muscular endurance (especially in fast CYP1A2 metabolizers) and affected subjective mood differently by genotype.

Trust comment: Randomized double-blind crossover with genotype stratification in humans but modest sample (n=36) and underpowered relative to planned size.

Study Details

PMID:39203905
Participants:36
Impact:no change with caffeine
Trust score:4/5

Total body water (TBW)

1 evidences

In 30 active young men, a moderate dose of caffeine over 4 days did not change total body water or its intracellular/extracellular compartments.

Trust comment: Direct physiological measures with a moderate sample size and appropriate methodology; findings specific to healthy active young men.

Study Details

PMID:23724879
Participants:30
Impact:no change
Trust score:4/5

cognitive control (Simon effect)

1 evidences

In 24 active participants, a caffeine mouth rinse during 40-min submaximal cycling likely improved certain aspects of cognitive control and time perception compared with placebo.

Trust comment: Controlled crossover design but small sample and use of mouth-rinse (not ingestion) limit generalizability to typical caffeine use.

Study Details

PMID:28598402
Participants:24
Impact:likely decreased with CAF mouth rinse (CAF: 24 ms vs PL: 30 ms; improvement in interference)
Trust score:3/5

parasympathetic activity (heart rate variability)

1 evidences

In acute STEMI patients, regular (caffeinated) coffee increased parasympathetic activity by up to 96% at 5 days without short-term adverse cardiac rhythm effects.

Trust comment: Randomized double-blind trial in a clinical STEMI population with a reasonable sample (n=103); clinically relevant endpoints.

Study Details

PMID:19531728
Participants:103
Impact:increase (up to +96% at 5 days; P = 0.04)
Trust score:4/5

Relative bioavailability (%)

1 evidences

In healthy men, caffeine in gum was absorbed faster than capsules and delivered similar total amounts systemically at higher doses.

Trust comment: Randomized, double-blind pharmacokinetic study with dense sampling and adequate sample size but limited to healthy male volunteers.

Study Details

PMID:11839447
Participants:84
Impact:50/100/200 mg gum: 64/74/77% raw; normalized to release: 75/87/90%
Trust score:4/5

Exercising systolic blood pressure

1 evidences

In young women, habitual preexercise caffeine supplementation (120 mg) prevented the exercise-training–induced reductions in exercising systolic blood pressure and double product seen in placebo group after 6 weeks.

Trust comment: Randomized study in young women (n≈33) showing an adverse effect of habitual preexercise caffeine on hemodynamic training adaptations; moderate sample and specifics may limit broader inference.

Study Details

PMID:39726136
Participants:33
Impact:no reduction PRE→POST with habitual caffeine (whereas placebo group showed decreases)
Trust score:3/5

caffeine clearance

1 evidences

In sleep-deprived healthy men, higher oral caffeine doses produced non-linear pharmacokinetics with slower metabolism.

Trust comment: Randomized double-blind human study with 37 subjects and clear pharmacokinetic measurements, though specific metabolic mechanism inference is moderate.

Study Details

PMID:7599918
Participants:37
Impact:decrease with increasing dose
Trust score:4/5

marksmanship accuracy

1 evidences

In sleep-deprived trainees, 200–300 mg caffeine made sighting and trigger-pull faster without reducing shooting accuracy.

Trust comment: Randomized dosing in a realistic, stressful field setting with objective simulator measures; moderate sample (n=62).

Study Details

PMID:12688447
Participants:62
Impact:no compromise in accuracy measures with 200–300 mg caffeine (accuracy unchanged)
Trust score:4/5

saliva-to-serum caffeine ratio

1 evidences

Salivary caffeine concentrations closely matched serum concentrations, so saliva can substitute for blood sampling in monitoring.

Trust comment: Randomized, parallel design in 59 premature infants with paired serum–saliva HPLC assays supports reliability.

Study Details

PMID:8738770
Participants:59
Impact:0.924 (mean)
Trust score:4/5

time to running exhaustion (TRE) at 85% VO2peak

1 evidences

A 201 mg caffeine-containing supplement had no effect on 1-RM bench press strength or time to exhaustion at 85% VO2peak in these men.

Trust comment: Double-blind, placebo-controlled crossover with a reasonable sample (n=31) though limited to men of modest training status.

Study Details

PMID:18714218
Participants:31
Impact:no change
Trust score:4/5

blood pressure (pressor effect)

1 evidences

Acute ingestion of black tea increased aortic stiffness briefly and both black and green tea raised wave reflections; effects were smaller than those produced by isolated caffeine.

Trust comment: Randomized crossover with objective vascular measures but modest sample size and acute setting; single-blind design reduces strength of inference about caffeine alone.

Study Details

PMID:16766780
Participants:29
Impact:acute pressor effect observed (increase vs baseline)
Trust score:3/5

subjective sedation

1 evidences

Repeated day-long administration of tea or coffee sustained aspects of alertness and psychomotor performance but caused dose-dependent worsening of sleep onset, sleep time, and sleep quality.

Trust comment: Randomized five-way crossover with n=30 and objective/subjective measures supports reliability, though naturalistic dosing adds variability.

Study Details

PMID:10823400
Participants:30
Impact:reduced subjective sedation after caffeinated drinks during acute phases
Trust score:4/5

augmentation index (AIx)

1 evidences

Coffee (caffeinated and decaffeinated) increased arterial stiffness measures more in non-habitual than habitual drinkers; caffeine alone also raised stiffness measures in both groups.

Trust comment: Crossover acute study with repeated measures but small sample (n=24); some effects reported for coffee and decaf with mixed significance for caffeine alone.

Study Details

PMID:29318895
Participants:24
Impact:increased (between-group maximal change for coffee: non-habitual > habitual by +4.5–5.3%)
Trust score:3/5

Self-perceived muscle power during exercise

1 evidences

Ingestion of an energy drink with 3 mg/kg caffeine increased perceived muscle power during exercise and raised the prevalence of side effects (e.g., insomnia).

Trust comment: Double-blind, placebo-controlled crossover with a large sample (n=90) though outcomes are self-reported and short-term.

Study Details

PMID:25212095
Participants:90
Impact:+0.75 units (6.41 vs 5.66; ≈+13.2%; P=0.001)
Trust score:4/5

conditioned performance (context-elicited)

1 evidences

Caffeine improved reaction time during administration and a conditioned context elicited similar improvement when placebo was given.

Trust comment: Controlled experimental design with small samples across two experiments; effects replicated within study but limited sample sizes.

Study Details

PMID:19931288
Participants:28
Impact:improved RT in CS+ context with placebo (conditioned response)
Trust score:3/5

executive function (JEF total and subcomponents: planning, creative thinking, prospective memory)

1 evidences

A normal dose of caffeinated coffee improved several executive function domains on the JEF and reduced Stroop reaction times compared to decaf.

Trust comment: Within-subject double-blind design with a reasonably large sample and multiple validated cognitive measures supports reliability of findings.

Study Details

PMID:27215836
Participants:43
Impact:improved (significant) after caffeinated coffee
Trust score:4/5

left ventricular ejection fraction

1 evidences

Over 14 days, an ephedra‑caffeine weight‑loss product produced no significant changes in measured cardiovascular parameters versus placebo in healthy overweight adults.

Trust comment: Randomized double‑blind trial in humans but product contained ephedra plus caffeine and duration was short (14 days); modest sample size (n=27).

Study Details

PMID:12355332
Participants:27
Impact:no change
Trust score:3/5

positive affect/arousal

1 evidences

Participants given 200 mg caffeinated gum showed better sustained attention, reported being more on-task and had less mind-wandering versus placebo.

Trust comment: Large sample with placebo comparison and behavioral measures, though effect sizes not fully quantified in abstract.

Study Details

PMID:39098270
Participants:127
Impact:increased; boredom and sleepiness decreased
Trust score:4/5

sleepiness level (AUC4 total effect)

1 evidences

In a large balanced placebo crossover, both caffeine (300 mg) and expectancy produced similar subjective effects (energy, reduced sleepiness); placebo altered caffeine pharmacokinetics.

Trust comment: Large, well-controlled randomized balanced placebo crossover with objective and subjective outcomes and solid statistical analysis.

Study Details

PMID:21092089
Participants:168
Impact:ratio 0.37 (reduction)
Trust score:5/5

1-RM bench press

1 evidences

High-dose caffeine (8 mg/kg) increased maximal strength in bench press, deadlift, and squat and raised plasma Ca2+ compared with placebo or lower dose.

Trust comment: Randomized double-blind crossover with mechanistic measures but limited to 21 recreational young men, restricting broader applicability.

Study Details

PMID:36432607
Participants:21
Impact:PLA 94.2 kg → CF8 101.1 kg (+6.9 kg)
Trust score:4/5

salivary alpha-amylase activity

1 evidences

In habitual caffeine-using young men, 200–400 mg caffeine combined with a mental stressor increased salivary alpha-amylase activity; placebo with stress did not.

Trust comment: Double-blind, placebo-controlled human study with adequate sample for the question but limited to young male habitual caffeine users.

Study Details

PMID:20589924
Participants:45
Impact:increased with 200 mg and 400 mg caffeine + stress (placebo + stress: no significant increase)
Trust score:4/5

effect modification by habitual caffeine intake

1 evidences

Caffeinated coffee (3 mg/kg) improved 5-km cycling time (~8 seconds) and habitual caffeine intake level did not modify this ergogenic effect.

Trust comment: Moderate-sized double-blind randomized crossover with clear outcome and appropriate analysis; results generalize to recreationally active adults.

Study Details

PMID:33260141
Participants:46
Impact:no effect (high vs low habitual users improved similarly)
Trust score:4/5

working memory accuracy (3-back ACC)

1 evidences

In healthy young women, caffeine alone improved working memory accuracy at ~T2 and combined tDCS+caffeine improved working memory accuracy (T1 and T2) and Stroop accuracy (T1) versus sham; caffeine alone did not improve inhibitory control and neither intervention affected cognitive flexibility.

Trust comment: Randomized, sham-controlled parallel design with adequate N (80) and task-based outcomes; single-blind and female-only sample limit generalizability.

Study Details

PMID:40888092
Participants:80
Impact:increase (caffeine alone: significant at T2 vs sham; tDCS+caffeine: significant at T1 and T2 vs sham)
Trust score:4/5

alpha1 power (8–10 Hz)

1 evidences

200 mg caffeine reduced lower-alpha (alpha1, 8–10 Hz) power primarily in participants with higher habitual caffeine consumption; overall caffeine effects did not differ reliably across menstrual phases.

Trust comment: Well-controlled randomized crossover design with EEG and hormone assays; moderate analyzed sample (n=56) after dropouts and effects moderated by habitual caffeine consumption.

Study Details

PMID:35904580
Participants:56
Impact:decrease in high habitual caffeine consumers (Caffeine-Placebo difference correlated with CCQ; r = -0.36, p = 0.007)
Trust score:4/5

bone mineral content (BMC)

1 evidences

In 625 young women, habitual caffeine intake was not associated with bone mass overall, but among users of DMPA there was a modest reduction in bone mineral content.

Trust comment: Prospective, population-based cohort with repeated DXA measures and adjustment for confounders, but observational design limits causality.

Study Details

PMID:18004611
Participants:625
Impact:No association overall; modest inverse association among DMPA users (lower BMC)
Trust score:4/5

Elimination of apnea

1 evidences

Caffeine citrate reduced apnea episodes and eliminated apnea faster than placebo in preterm infants and was well tolerated.

Trust comment: Large multicenter randomized double-blind placebo-controlled trial in the target population with clear endpoints and adequate sample size.

Study Details

PMID:10853619
Participants:85
Impact:Higher rate of apnea elimination in caffeine group (significant by day 5)
Trust score:5/5

Mood / subjective energy

1 evidences

In sleep-restricted participants, a 200 mg caffeine capsule improved subjective mood and sped reaction times compared with placebo.

Trust comment: Double-blind crossover in a relevant fatigued population with a moderate sample (n=35); outcomes are behavioral and consistent with known caffeine effects.

Study Details

PMID:18266548
Participants:35
Impact:Improved subjective mood/energy after caffeine (stimulant-like effects)
Trust score:4/5

time to recovery

1 evidences

In ambulatory surgical patients at risk for caffeine withdrawal, a 200 mg IV dose reduced postoperative headache incidence but did not shorten recovery time.

Trust comment: Prospective randomized double-blind trial with large enrollment and clear outcome, but analysis based on completed questionnaires (n=234).

Study Details

PMID:9212763
Participants:234
Impact:No significant difference
Trust score:4/5

finger skin temperature

1 evidences

In 36 healthy adults, moderate acute caffeine (2.5 mg/kg doses) improved finger temperature and some perfusion measures during cold exposure and rewarming, especially after total sleep deprivation, but altered pain responses.

Trust comment: Controlled double-blind crossover with n=36 and comprehensive physiological measures; findings robust though some effects vary by habitual use and TSD.

Study Details

PMID:40150834
Participants:36
Impact:After TSD, caffeine increased mean/min/max finger temperatures by ~+0.61–+2.28°C (e.g., Tfi4 mean +1.3°C; rewarming mean +2.28°C)
Trust score:4/5

sodium clearance

1 evidences

Double-blind study (12 caffeine, 12 placebo) found high acute caffeine intake increased renal calcium clearance markedly over 6 hours.

Trust comment: Double-blind clinical crossover with clear quantitative result but small sample (n=24).

Study Details

PMID:33852164
Participants:24
Impact:positively correlated with calcium clearance (increased)
Trust score:4/5

force fluctuation variability

1 evidences

Adding 6 mg/kg caffeine before low-load BFR training did not increase maximal strength more than BFR alone but improved precision of force release and reduced motor unit discharge variability.

Trust comment: Controlled 4-week training study with measurable neuromuscular outcomes and a moderate sample (n=28).

Study Details

PMID:40954555
Participants:28
Impact:reduced with caffeine during training (significant decline, P=0.002)
Trust score:4/5

grip strength

1 evidences

Chewing gum with 200 mg caffeine improved grip strength and some jumping and softball-specific performance measures in trained female players.

Trust comment: Randomized crossover in trained athletes with sport-specific objective measures but modest sample size and single-blind design.

Study Details

PMID:39225020
Participants:24
Impact:increase (P<0.05)
Trust score:4/5

Duration of oxygen and NCPAP support

1 evidences

Randomized trial in preterm infants with apnea: caffeine citrate vs aminophylline (both with NCPAP) showed improved early pulmonary function, shorter oxygen/NCPAP support times, and fewer apnea events with caffeine citrate.

Trust comment: Randomized clinical comparison in infants (N=40) with clinically relevant endpoints but limited sample size and single-country report.

Study Details

PMID:26975815
Participants:40
Impact:Shorter with caffeine citrate (P < 0.01)
Trust score:3/5

cocaine-like effects / desire for cocaine

1 evidences

In formerly cocaine-dependent adults, cumulative caffeine increased feelings of jitteriness and anxiety more than in controls but did not produce cocaine-like effects or greater reinforcement.

Trust comment: Double-blind randomized crossover design but small groups (n=11 per group) limit statistical power.

Study Details

PMID:9476695
Participants:22
Impact:no increase with caffeine in formerly cocaine-dependent subjects
Trust score:3/5

Working memory (Trails B)

1 evidences

In 25 healthy young men, a 50 mg caffeine drink reduced resting EEG alpha power and improved cognitive test performance (including working memory) about 30 minutes after ingestion.

Trust comment: Randomized double-blind crossover with objective EEG and cognitive endpoints in a homogeneous sample of young men.

Study Details

PMID:36055414
Participants:25
Impact:improved (significant improvement after 30 min)
Trust score:4/5

Intracellular water (ICW)

1 evidences

In 30 active young men, a moderate dose of caffeine over 4 days did not change total body water or its intracellular/extracellular compartments.

Trust comment: Direct physiological measures with a moderate sample size and appropriate methodology; findings specific to healthy active young men.

Study Details

PMID:23724879
Participants:30
Impact:no change
Trust score:4/5

Coincidence anticipation timing error (absolute and variable)

1 evidences

In 13 younger and 13 older habitual moderate caffeine consumers, a single 3 mg/kg dose improved coincidence anticipation timing (reduced error) in both age groups.

Trust comment: Double-blind randomized crossover with both younger and older participants; small sample but clear within-subject effects.

Study Details

PMID:24192642
Participants:26
Impact:improved pre-to-post after 3 mg/kg caffeine (significant); no age difference
Trust score:4/5

peak power (Wingate)

2 evidences

In 21 active adults, 3 mg/kg caffeine increased Wingate mean and peak power versus placebo without affecting visual attention; CYP1A2 genotype did not alter these effects.

Trust comment: Double-blind randomized crossover with genotyping and objective performance measures; moderate sample size for a pilot study.

Study Details

PMID:28287486
Participants:21
Impact:680 ±146 W (caffeine) vs 663 ±143 W (placebo), p=0.01 (~+~2.6%)
Trust score:4/5

In trained male boxers, adding 3 mg/kg caffeine to a PAPE protocol increased the magnitude of Wingate performance gains and uniquely increased peak power and perceived power versus control.

Trust comment: Randomized crossover with well-controlled protocol in 25 completers; limitation: no caffeine-only arm, limiting isolation of caffeine effect.

Study Details

PMID:38257128
Participants:25
Impact:increased (significant for PAPE+CAF vs CON; P=0.013)
Trust score:4/5

sustained attention / reaction time (PVT)

1 evidences

In 127 young heavy episodic drinkers, alcohol impaired simulated driving and vigilance; adding caffeine to alcoholic beverage did not improve driving or attention performance.

Trust comment: Large randomized between-groups trial with real-world relevance; caffeine dose matched commercial products and null effect is well supported.

Study Details

PMID:21134017
Participants:127
Impact:impaired by alcohol; addition of caffeine had no main or interaction effects
Trust score:4/5

temporal variability

1 evidences

In 24 active participants, a caffeine mouth rinse during 40-min submaximal cycling likely improved certain aspects of cognitive control and time perception compared with placebo.

Trust comment: Controlled crossover design but small sample and use of mouth-rinse (not ingestion) limit generalizability to typical caffeine use.

Study Details

PMID:28598402
Participants:24
Impact:likely decreased with CAF mouth rinse vs placebo
Trust score:3/5

vigilance

1 evidences

In habitual caffeine consumers, only the highest acute dose (400 mg) improved vigilance and executive control of visual attention.

Trust comment: Well-powered repeated-measures, double-blind design in habitual consumers with clear dose–response finding at 400 mg.

Study Details

PMID:20832925
Participants:36
Impact:improved at 400 mg dose
Trust score:4/5

choice reaction time

2 evidences

Five days of controlled caffeine intake produced few cognitive or psychomotor changes; only the Vigor-Activity mood subset increased in the 3 mg/kg/day group.

Trust comment: Randomized double-blind controlled design with three parallel groups (total n=60), appropriate for cognitive endpoints.

Study Details

PMID:16043199
Participants:60
Impact:no significant change
Trust score:4/5

In 68 SEAL trainees after 72 h sleep deprivation and stress, 200–300 mg caffeine improved vigilance, reaction time, learning, and reduced fatigue/sleepiness vs placebo.

Trust comment: Randomized allocation in a realistic stress model with measurable cognitive outcomes, moderate sample size (n=68).

Study Details

PMID:12424548
Participants:68
Impact:improvement (200 and 300 mg)
Trust score:4/5

Morning alertness

1 evidences

After drinking to intoxication, adding caffeine to beer improved perceived sleep quality and morning alertness but did not affect hangover or sleep duration.

Trust comment: Randomized human study with reasonable sample but mostly student population and single laboratory dosing session.

Study Details

PMID:24090620
Participants:64
Impact:Improved (effect size larger than sleep-quality improvement)
Trust score:3/5

Secretory IgA (SIgA)

1 evidences

In a VR stress task, caffeine increased salivary alpha-amylase after the task versus placebo; the task itself raised multiple stress markers.

Trust comment: Randomized, pre-registered human study with objective biomarkers but single acute exposure and limited detail on dosing/participant characteristics.

Study Details

PMID:38142605
Participants:53
Impact:SIgA increased after MST (no caffeine-specific difference reported)
Trust score:3/5

ACTH

1 evidences

Oral caffeine (3.3 mg/kg) at rest increased ACTH and cortisol in healthy young men.

Trust comment: Double-blind, placebo-controlled crossover in 47 healthy men with clear quantitative hormonal changes; reasonably high internal validity.

Study Details

PMID:8951977
Participants:47
Impact:+33% (+5.2 pg/ml peak vs placebo)
Trust score:4/5

peripheral awareness (hand–eye coordination)

1 evidences

An acute 5 mg/kg caffeine dose slightly improved a peripheral awareness (hand–eye) task but raised state anxiety; other low-intensity task performance was unchanged.

Trust comment: Randomized crossover with adequate sample for acute effects but limited to low-intensity tasks and low habitual consumers.

Study Details

PMID:12027348
Participants:31
Impact:improved (significant)
Trust score:4/5

urinary calcium excretion

1 evidences

After a high caffeine dose, women not using oral contraceptives had much larger increases in urinary calcium and some other minerals than oral contraceptive users, suggesting OCs blunt caffeine's calciuric effect.

Trust comment: Randomized crossover in 30 women with clear biochemical outcomes; sample limited to ages 20–29 and specific calcium intake.

Study Details

PMID:12566473
Participants:30
Impact:net increase after caffeine ~9-fold higher in non-OC vs OC (P<0.05)
Trust score:4/5

caffeine self-administration (cola-only drinkers)

1 evidences

Participants given concurrent caffeinated and noncaffeinated cola showed limited but reliable self-administration in a subset (~25%) of individuals.

Trust comment: Controlled double-blind crossover design but small sample sizes and heterogeneous participant groups limit generalizability.

Study Details

PMID:9260077
Participants:24
Impact:2/8 participants self-administered caffeinated cola (25%)
Trust score:3/5

mean salivary caffeine concentration

1 evidences

Salivary caffeine concentrations closely matched serum concentrations, so saliva can substitute for blood sampling in monitoring.

Trust comment: Randomized, parallel design in 59 premature infants with paired serum–saliva HPLC assays supports reliability.

Study Details

PMID:8738770
Participants:59
Impact:27.7 mg/L
Trust score:4/5

encoding of new information

1 evidences

A 2 mg/kg dose of caffeine made people react faster, detect more targets, and encode new information faster compared with placebo/withdrawal.

Trust comment: Controlled between-group design with adequate sample size (70) and objective performance measures, though specific effect magnitudes are not given.

Study Details

PMID:22992376
Participants:70
Impact:improved (faster encoding) on caffeine
Trust score:4/5

Error rate to positive items (accuracy)

1 evidences

A single 200 mg dose of caffeine enhanced left-hemisphere recognition of positive words compared with placebo.

Trust comment: Randomized placebo-controlled single-blind study with appropriate analyses but modest final sample (50) after exclusions.

Study Details

PMID:23144893
Participants:50
Impact:decreased (fewer errors to positive items in caffeine group; significant, p≈0.022)
Trust score:4/5

volume of distribution (Vd)

1 evidences

In extremely premature infants, caffeine clearance and volume of distribution change with age and weight; caffeine is well absorbed and has prolonged elimination.

Trust comment: Large neonatal PK dataset (n=110) with population modeling and bootstrap validation supports high reliability for PK findings.

Study Details

PMID:19057373
Participants:110
Impact:increases linearly with weight
Trust score:5/5

anaerobic power

1 evidences

Acute multi-ingredient preworkout supplements (one formulation contained caffeine) modestly improved anaerobic power and some endurance and vascular measures versus placebo; caffeine was one of several active ingredients.

Trust comment: Randomized crossover with n=30 but multi-ingredient formulations make isolating caffeine-specific effects uncertain.

Study Details

PMID:32569125
Participants:30
Impact:+0.3–0.4 W·kg⁻¹ (~+3%) (NBAC 10.7 & BAC 10.8 vs PLA 10.4 W·kg⁻¹, p≤0.022)
Trust score:3/5

lane keeping (standard deviation of lateral position, SDLP)

1 evidences

One cup of coffee (80 mg caffeine) taken during a break improved lane keeping and speed control and reduced subjective sleepiness for up to 2 hours.

Trust comment: Double-blind, randomized crossover with objective and subjective measures in 24 healthy drivers; well-controlled and directly applicable.

Study Details

PMID:22315048
Participants:24
Impact:reduced (~1.8 cm in hour 3; ~1.3 cm in hour 4) - improved
Trust score:4/5

peak heart rate

1 evidences

In 8–10‑year‑old boys, a single dose of caffeine (5 mg/kg) increased mean (average) power on a Wingate test and raised peak heart rate, without affecting peak power or static hand-grip strength.

Trust comment: Randomized, double‑blind, double‑crossover pediatric trial with clear measured outcomes; moderate sample size (n=24).

Study Details

PMID:22728413
Participants:24
Impact:+5 bpm (185 → 190 bpm; ≈+2.7%)
Trust score:4/5

Subcutaneous fat thickness

1 evidences

A liposome-encapsulated caffeine-based topical cream reduced subcutaneous fat thickness over 2 months compared with placebo.

Trust comment: Double-blind placebo-controlled trial with completed N=41 but single-center and limited reporting of absolute effect sizes.

Study Details

PMID:10469092
Participants:41
Impact:Significant reduction over 2 months; higher concentration more effective in hips and triceps (no absolute values reported)
Trust score:3/5

LF power (ANS measure)

1 evidences

A single dose of a multi-ingredient supplement containing 55 mg caffeine altered ECG intervals and autonomic (LF) measures in mentally fatigued adults.

Trust comment: Double-blind, placebo-controlled human study with N=47 showing physiological ECG/ANS changes, but effect sizes not fully reported in the extract.

Study Details

PMID:40562227
Participants:47
Impact:Changed and correlated with resting-state EEG; magnitude/direction not reported
Trust score:4/5

Other caffeine metabolite ratios

1 evidences

In smokers and nonsmokers, the urine metabolite ratio AAMU+1U+1X/17U from a spot urine correlated with measured caffeine clearance (CYP1A2 activity) across dosing conditions except at very high caffeine doses.

Trust comment: Mechanistic human pharmacokinetic study using stable isotopes and multiple conditions; sample size small (n=21) but methods are rigorous for validation.

Study Details

PMID:8653991
Participants:21
Impact:did not show robust correlation with caffeine clearance across conditions
Trust score:4/5

time‑trial performance (cycling)

1 evidences

In 42 trained cyclists, 6 mg/kg caffeine improved ~30‑min time‑trial performance versus placebo and control; correct identification of caffeine further increased the observed benefit.

Trust comment: Adequately powered randomized study with control and placebo arms and clear effects, though subjective identification influenced outcomes.

Study Details

PMID:27882605
Participants:42
Impact:+4.1% (overall improvement vs control; p≤0.001)
Trust score:4/5

Cardiovascular measures

1 evidences

In sleep-restricted participants, a 200 mg caffeine capsule improved subjective mood and sped reaction times compared with placebo.

Trust comment: Double-blind crossover in a relevant fatigued population with a moderate sample (n=35); outcomes are behavioral and consistent with known caffeine effects.

Study Details

PMID:18266548
Participants:35
Impact:Monitored but no problematic changes reported
Trust score:4/5

postoperative headache (at-risk patients)

1 evidences

In ambulatory surgical patients at risk for caffeine withdrawal, a 200 mg IV dose reduced postoperative headache incidence but did not shorten recovery time.

Trust comment: Prospective randomized double-blind trial with large enrollment and clear outcome, but analysis based on completed questionnaires (n=234).

Study Details

PMID:9212763
Participants:234
Impact:Reduced from 23% (placebo) to 10% (caffeine); absolute −13 percentage points
Trust score:4/5

renal calcium clearance

1 evidences

Double-blind study (12 caffeine, 12 placebo) found high acute caffeine intake increased renal calcium clearance markedly over 6 hours.

Trust comment: Double-blind clinical crossover with clear quantitative result but small sample (n=24).

Study Details

PMID:33852164
Participants:24
Impact:+77%
Trust score:4/5

skin conductance level (SCL)

3 evidences

In 30 children (8–13 y), a single 80 mg oral caffeine dose increased physiological arousal (skin conductance) and altered EEG indices versus placebo.

Trust comment: Randomized double-blind crossover with objective EEG and electrodermal measures in 30 children; moderate sample size.

Study Details

PMID:19486913
Participants:30
Impact:Increased (indicative of higher arousal)
Trust score:4/5

Caffeine increases physiological arousal (higher skin conductance) and reduces EEG alpha; these effects add to those of opening the eyes.

Trust comment: Randomized, counterbalanced double-blind within-subject study in 22 humans; moderate sample but good design.

Study Details

PMID:21489866
Participants:22
Impact:increase (caffeine > placebo)
Trust score:4/5

Caffeine increased skin conductance (arousal) in children, but dose-response differed between AD/HD and control groups.

Trust comment: Randomized double-blind crossover with matched controls but small sample and outcomes reported with limited quantitative detail.

Study Details

PMID:22266163
Participants:36
Impact:increase after caffeine (magnitude not reported)
Trust score:3/5

Maximal voluntary contraction (MVC)

1 evidences

Adding 6 mg/kg caffeine before low-load BFR training did not increase maximal strength more than BFR alone but improved precision of force release and reduced motor unit discharge variability.

Trust comment: Controlled 4-week training study with measurable neuromuscular outcomes and a moderate sample (n=28).

Study Details

PMID:40954555
Participants:28
Impact:increased with training but no additional benefit from caffeine (no significant difference between groups)
Trust score:4/5

cerebral blood flow (CBF)

1 evidences

Caffeine substantially reduced cerebral blood flow and middle cerebral artery velocity, implying narrowing of cerebral arterioles and the MCA.

Trust comment: Direct physiological measurements but small combined sample (14 patients + 9 controls = 23) and specific population (post-stroke recovery).

Study Details

PMID:15132312
Participants:23
Impact:reduced by 22% (95% CI 17–28%)
Trust score:3/5

peak power

3 evidences

In 8–10‑year‑old boys, a single dose of caffeine (5 mg/kg) increased mean (average) power on a Wingate test and raised peak heart rate, without affecting peak power or static hand-grip strength.

Trust comment: Randomized, double‑blind, double‑crossover pediatric trial with clear measured outcomes; moderate sample size (n=24).

Study Details

PMID:22728413
Participants:24
Impact:no change
Trust score:4/5

Acute caffeine (5 mg/kg) increased peak anaerobic power and reduced perceived exertion for upper-body exercise in men.

Trust comment: Double-blind crossover with clearly reported outcomes but limited to males and moderate sample size.

Study Details

PMID:31013204
Participants:22
Impact:significantly increased (P = .001)
Trust score:4/5

Caffeine improved short-duration arm-crank power in paraplegic participants but showed no clear ergogenic effect in tetraplegic or able-bodied groups.

Trust comment: Randomized, double-blind, placebo-controlled crossover trial with clearly reported subgroup results but modest sample size.

Study Details

PMID:26132642
Participants:34
Impact:increased: AB +46 W, P +21 W (not statistically significant vs placebo; AB p=0.10, P p=0.17)
Trust score:4/5

ECG intervals (PR, QRS, QT/QTc)

1 evidences

A single caffeinated energy shot acutely raised systolic and diastolic blood pressure, but these elevations were not sustained after repeated daily use; ECG intervals were unchanged.

Trust comment: Randomized double-blind crossover with objective cardiovascular measures but small sample and limited chronic-phase effects.

Study Details

PMID:26708636
Participants:26
Impact:no change
Trust score:4/5

postmenstrual age at discontinuation of PPV

1 evidences

In this subgroup analysis of the CAP trial, caffeine reduced death/disability and shortened time on respiratory support mainly in infants who were receiving ventilatory support or who started caffeine early.

Trust comment: Large randomized trial data but current results are from post-hoc subgroup analyses which lowers causal certainty for subgroup differences.

Study Details

PMID:19926098
Participants:2006
Impact:earlier discontinuation with early caffeine (mean ≈ -1.35 weeks)
Trust score:4/5

Pulmonary function (tidal volume, minute ventilation, peak flows)

1 evidences

Randomized trial in preterm infants with apnea: caffeine citrate vs aminophylline (both with NCPAP) showed improved early pulmonary function, shorter oxygen/NCPAP support times, and fewer apnea events with caffeine citrate.

Trust comment: Randomized clinical comparison in infants (N=40) with clinically relevant endpoints but limited sample size and single-country report.

Study Details

PMID:26975815
Participants:40
Impact:Improved in caffeine citrate group versus aminophylline (P < 0.05)
Trust score:3/5

gender differences in response

1 evidences

A single 100 mg caffeine dose produced rapid arousal (less sleepiness, greater activation) within 10–30 min in healthy undergraduates, with larger effects in men.

Trust comment: Large, randomized double-blind placebo-controlled study (n=688) with repeated measures, giving high confidence in subjective-effect findings.

Study Details

PMID:18675877
Participants:688
Impact:effects larger in men; decaffeinated beverage effects only at 10 min and greater in women
Trust score:5/5

subjective mood/energy (subjective outcome index)

1 evidences

In resistance-trained women, 6 mg/kg caffeine improved leg-press muscular endurance (especially in fast CYP1A2 metabolizers) and affected subjective mood differently by genotype.

Trust comment: Randomized double-blind crossover with genotype stratification in humans but modest sample (n=36) and underpowered relative to planned size.

Study Details

PMID:39203905
Participants:36
Impact:increased in FAST genotype with caffeine (P = 0.028) and decreased in SLOW genotype (P < 0.01)
Trust score:4/5

Resting EEG alpha power (midline frontal/central/occipital)

1 evidences

In 25 healthy young men, a 50 mg caffeine drink reduced resting EEG alpha power and improved cognitive test performance (including working memory) about 30 minutes after ingestion.

Trust comment: Randomized double-blind crossover with objective EEG and cognitive endpoints in a homogeneous sample of young men.

Study Details

PMID:36055414
Participants:25
Impact:decrease (significant %Δ from baseline after 30 min)
Trust score:4/5

Extracellular water (ECW)

1 evidences

In 30 active young men, a moderate dose of caffeine over 4 days did not change total body water or its intracellular/extracellular compartments.

Trust comment: Direct physiological measures with a moderate sample size and appropriate methodology; findings specific to healthy active young men.

Study Details

PMID:23724879
Participants:30
Impact:no change
Trust score:4/5

mean power (Wingate)

3 evidences

In 21 active adults, 3 mg/kg caffeine increased Wingate mean and peak power versus placebo without affecting visual attention; CYP1A2 genotype did not alter these effects.

Trust comment: Double-blind randomized crossover with genotyping and objective performance measures; moderate sample size for a pilot study.

Study Details

PMID:28287486
Participants:21
Impact:521 ±115 W (caffeine) vs 511 ±113 W (placebo), p<0.001 (~+~2%)
Trust score:4/5

In 26 boys (8–10 y), 3 mg/kg caffeine increased peak power and both 3 and 5 mg/kg doses increased maximal grip strength; 5 mg/kg increased mean power and peak heart rate during Wingate.

Trust comment: Double-blind, crossover design in children with objective performance measures; sample size modest but design strong.

Study Details

PMID:25051124
Participants:26
Impact:CAF-5: 153 vs PL 146 W (+7 W)
Trust score:4/5

In trained male boxers, adding 3 mg/kg caffeine to a PAPE protocol increased the magnitude of Wingate performance gains and uniquely increased peak power and perceived power versus control.

Trust comment: Randomized crossover with well-controlled protocol in 25 completers; limitation: no caffeine-only arm, limiting isolation of caffeine effect.

Study Details

PMID:38257128
Participants:25
Impact:increased (PAPE+PLA and PAPE+CAF vs CON; larger effect with CAF)
Trust score:4/5

driving performance

1 evidences

In 127 young heavy episodic drinkers, alcohol impaired simulated driving and vigilance; adding caffeine to alcoholic beverage did not improve driving or attention performance.

Trust comment: Large randomized between-groups trial with real-world relevance; caffeine dose matched commercial products and null effect is well supported.

Study Details

PMID:21134017
Participants:127
Impact:impaired by alcohol; addition of caffeine had no main or interaction effects
Trust score:4/5

mean produced duration (time estimation)

1 evidences

In 24 active participants, a caffeine mouth rinse during 40-min submaximal cycling likely improved certain aspects of cognitive control and time perception compared with placebo.

Trust comment: Controlled crossover design but small sample and use of mouth-rinse (not ingestion) limit generalizability to typical caffeine use.

Study Details

PMID:28598402
Participants:24
Impact:likely decreased (underproduction) with CAF mouth rinse vs placebo
Trust score:3/5

psychomotor vigilance upon awakening

1 evidences

Caffeine given during extended wakefulness prevented the usual drop in alertness immediately after awakening (sleep inertia) in adults.

Trust comment: Randomized double-blind study with objective psychomotor vigilance testing and polysomnography, moderate sample size (n=28).

Study Details

PMID:11683484
Participants:28
Impact:sleep-inertia impairment abolished with caffeine (impaired after naps in placebo; absent with caffeine)
Trust score:4/5

cardiac rhythm/adverse outcomes

1 evidences

In acute STEMI patients, regular (caffeinated) coffee increased parasympathetic activity by up to 96% at 5 days without short-term adverse cardiac rhythm effects.

Trust comment: Randomized double-blind trial in a clinical STEMI population with a reasonable sample (n=103); clinically relevant endpoints.

Study Details

PMID:19531728
Participants:103
Impact:no detrimental effect observed in short term
Trust score:4/5

perceived sleep quality

1 evidences

After drinking to intoxication, adding caffeine to beer improved perceived sleep quality and morning alertness but did not affect hangover or sleep duration.

Trust comment: Randomized human study with reasonable sample but mostly student population and single laboratory dosing session.

Study Details

PMID:24090620
Participants:64
Impact:Improved with caffeinated beer vs non-caffeinated beer
Trust score:3/5

Salivary alpha-amylase (sAA)

2 evidences

In a VR stress task, caffeine increased salivary alpha-amylase after the task versus placebo; the task itself raised multiple stress markers.

Trust comment: Randomized, pre-registered human study with objective biomarkers but single acute exposure and limited detail on dosing/participant characteristics.

Study Details

PMID:38142605
Participants:53
Impact:sAA increased after MST; post-MST sAA significantly higher with caffeine vs placebo
Trust score:3/5

In 40 habitual coffee consumers in a randomized crossover design, single servings of coffee (160 mg caffeine) increased salivary alpha-amylase and transiently increased salivary gastrin and blood pressure, but did not change salivary cortisol or self-reported GI symptoms.

Trust comment: Randomized double-blind crossover with objective biochemical measures, though modest sample and short-term assessments.

Study Details

PMID:26979712
Participants:40
Impact:increased after coffee (peaked ~30 min); cold instant > filter (P < 0.05)
Trust score:4/5

Cooperative behavior (allocations)

1 evidences

A single caffeinated coffee dose increased blood pressure and made participants more cooperative in a social game versus decaffeinated coffee.

Trust comment: Randomized, double-blind, crossover study with a relatively large sample for behavioral research, though effects were assessed acutely.

Study Details

PMID:19178788
Participants:77
Impact:Participants allocated fewer points to themselves (more cooperative) after caffeinated coffee
Trust score:4/5

Affective social signaling

1 evidences

A single caffeinated coffee dose increased blood pressure and made participants more cooperative in a social game versus decaffeinated coffee.

Trust comment: Randomized, double-blind, crossover study with a relatively large sample for behavioral research, though effects were assessed acutely.

Study Details

PMID:19178788
Participants:77
Impact:Participants sent more 'sadness' messages after caffeinated coffee
Trust score:4/5

Exercise-induced muscle pain (MPR)

1 evidences

In people with fibromyalgia, a 100 mg caffeinated chewing gum did not reduce exercise-induced muscle pain compared to placebo.

Trust comment: Double-blind crossover in 23 patients with fibromyalgia; outcome null but sample modest and specific population limits generalizability.

Study Details

PMID:26855267
Participants:23
Impact:no attenuation vs placebo (no significant difference)
Trust score:3/5

Double product (SBP×HR) during exercise

1 evidences

In young women, habitual preexercise caffeine supplementation (120 mg) prevented the exercise-training–induced reductions in exercising systolic blood pressure and double product seen in placebo group after 6 weeks.

Trust comment: Randomized study in young women (n≈33) showing an adverse effect of habitual preexercise caffeine on hemodynamic training adaptations; moderate sample and specifics may limit broader inference.

Study Details

PMID:39726136
Participants:33
Impact:prevented training-induced decrease with habitual caffeine (no PRE→POST change vs decreases in placebo)
Trust score:3/5

paraxanthine-to-caffeine ratio (metabolism rate)

1 evidences

In sleep-deprived healthy men, higher oral caffeine doses produced non-linear pharmacokinetics with slower metabolism.

Trust comment: Randomized double-blind human study with 37 subjects and clear pharmacokinetic measurements, though specific metabolic mechanism inference is moderate.

Study Details

PMID:7599918
Participants:37
Impact:decrease with increasing dose
Trust score:4/5

EEG-measured central arousal

1 evidences

Caffeine (200 mg) increased EEG arousal; a valerian/hop extract reduced or blocked that arousal at 60 minutes.

Trust comment: Human volunteer EEG study with clear pharmacodynamic findings; group sizes modest (16 per group assumed).

Study Details

PMID:15254851
Participants:48
Impact:caffeine induced EEG arousal; valerian/hop (verum) reduced or inhibited this arousal at 60 min
Trust score:4/5

mean serum caffeine concentration

1 evidences

Salivary caffeine concentrations closely matched serum concentrations, so saliva can substitute for blood sampling in monitoring.

Trust comment: Randomized, parallel design in 59 premature infants with paired serum–saliva HPLC assays supports reliability.

Study Details

PMID:8738770
Participants:59
Impact:29.9 mg/L
Trust score:4/5

sleep onset/time/quality

1 evidences

Repeated day-long administration of tea or coffee sustained aspects of alertness and psychomotor performance but caused dose-dependent worsening of sleep onset, sleep time, and sleep quality.

Trust comment: Randomized five-way crossover with n=30 and objective/subjective measures supports reliability, though naturalistic dosing adds variability.

Study Details

PMID:10823400
Participants:30
Impact:dose-dependent negative effects on sleep onset, total sleep time, and sleep quality (P<0.001)
Trust score:4/5

target detection (vigilance)

1 evidences

A 2 mg/kg dose of caffeine made people react faster, detect more targets, and encode new information faster compared with placebo/withdrawal.

Trust comment: Controlled between-group design with adequate sample size (70) and objective performance measures, though specific effect magnitudes are not given.

Study Details

PMID:22992376
Participants:70
Impact:improved (greater detection) on caffeine
Trust score:4/5

augmented pressure (AP)

1 evidences

Coffee (caffeinated and decaffeinated) increased arterial stiffness measures more in non-habitual than habitual drinkers; caffeine alone also raised stiffness measures in both groups.

Trust comment: Crossover acute study with repeated measures but small sample (n=24); some effects reported for coffee and decaf with mixed significance for caffeine alone.

Study Details

PMID:29318895
Participants:24
Impact:increased (between-group maximal change for coffee: non-habitual > habitual by +1.9–2.1 mmHg)
Trust score:3/5

Left-hemisphere performance for positive words (Performance P)

1 evidences

A single 200 mg dose of caffeine enhanced left-hemisphere recognition of positive words compared with placebo.

Trust comment: Randomized placebo-controlled single-blind study with appropriate analyses but modest final sample (50) after exclusions.

Study Details

PMID:23144893
Participants:50
Impact:+0.08 (from 0.37 to 0.45; ≈+21.6%; p<0.001)
Trust score:4/5

Insomnia prevalence

1 evidences

Ingestion of an energy drink with 3 mg/kg caffeine increased perceived muscle power during exercise and raised the prevalence of side effects (e.g., insomnia).

Trust comment: Double-blind, placebo-controlled crossover with a large sample (n=90) though outcomes are self-reported and short-term.

Study Details

PMID:25212095
Participants:90
Impact:+20.8 percentage points (31.2% vs 10.4%; P<0.05)
Trust score:4/5

handgrip strength

1 evidences

In 90 male adolescent athletes, acute caffeine (6 mg/kg) improved several performance measures (strength, jump height, sit-ups, and Yo-Yo endurance) versus placebo; these ergogenic effects were independent of ADORA2A and CYP1A2 genotypes.

Trust comment: Large (n=90) double-blind, randomized crossover in athletes; robust design supports findings though limited to adolescent male athletes.

Study Details

PMID:36385314
Participants:90
Impact:+1.5 kg (35.0 vs 33.5 kg)
Trust score:4/5

clearance (CL)

1 evidences

In extremely premature infants, caffeine clearance and volume of distribution change with age and weight; caffeine is well absorbed and has prolonged elimination.

Trust comment: Large neonatal PK dataset (n=110) with population modeling and bootstrap validation supports high reliability for PK findings.

Study Details

PMID:19057373
Participants:110
Impact:increases nonlinearly with postnatal age
Trust score:5/5

Stroop reaction time

1 evidences

A normal dose of caffeinated coffee improved several executive function domains on the JEF and reduced Stroop reaction times compared to decaf.

Trust comment: Within-subject double-blind design with a reasonably large sample and multiple validated cognitive measures supports reliability of findings.

Study Details

PMID:27215836
Participants:43
Impact:decreased (faster RT) with caffeinated coffee
Trust score:4/5

mean (average) Wingate power

1 evidences

In 8–10‑year‑old boys, a single dose of caffeine (5 mg/kg) increased mean (average) power on a Wingate test and raised peak heart rate, without affecting peak power or static hand-grip strength.

Trust comment: Randomized, double‑blind, double‑crossover pediatric trial with clear measured outcomes; moderate sample size (n=24).

Study Details

PMID:22728413
Participants:24
Impact:+7 W (173 → 180 W; ≈+4.0%)
Trust score:4/5

PRQ interval

1 evidences

A single dose of a multi-ingredient supplement containing 55 mg caffeine altered ECG intervals and autonomic (LF) measures in mentally fatigued adults.

Trust comment: Double-blind, placebo-controlled human study with N=47 showing physiological ECG/ANS changes, but effect sizes not fully reported in the extract.

Study Details

PMID:40562227
Participants:47
Impact:Changed (statistically significant); magnitude not reported
Trust score:4/5

bone mineral density (BMD)

1 evidences

In 625 young women, habitual caffeine intake was not associated with bone mass overall, but among users of DMPA there was a modest reduction in bone mineral content.

Trust comment: Prospective, population-based cohort with repeated DXA measures and adjustment for confounders, but observational design limits causality.

Study Details

PMID:18004611
Participants:625
Impact:No significant association with habitual caffeine intake
Trust score:4/5

Tear secretion (Schirmer 1)

1 evidences

In 41 healthy volunteers, orally ingested caffeine (5 mg/kg) increased tear secretion measured by Schirmer 1 at 45 and 90 minutes after intake.

Trust comment: Examiner-masked, placebo-controlled crossover with adequate sample for physiological measurement; clear short-term effect on tears.

Study Details

PMID:24240351
Participants:41
Impact:Increased at 45 and 90 minutes after caffeine ingestion (statistically significant, p<0.05)
Trust score:4/5

placebo identification effect

1 evidences

In 42 trained cyclists, 6 mg/kg caffeine improved ~30‑min time‑trial performance versus placebo and control; correct identification of caffeine further increased the observed benefit.

Trust comment: Adequately powered randomized study with control and placebo arms and clear effects, though subjective identification influenced outcomes.

Study Details

PMID:27882605
Participants:42
Impact:belief about supplement influenced performance (bias source)
Trust score:4/5

Reduction in apnea episodes

1 evidences

Caffeine citrate reduced apnea episodes and eliminated apnea faster than placebo in preterm infants and was well tolerated.

Trust comment: Large multicenter randomized double-blind placebo-controlled trial in the target population with clear endpoints and adequate sample size.

Study Details

PMID:10853619
Participants:85
Impact:Increased proportion of infants achieving ≥50% reduction or elimination of apnea (significant; faster improvement by day 5–6)
Trust score:5/5

Mean power

1 evidences

Acute caffeine (5 mg/kg) increased peak anaerobic power and reduced perceived exertion for upper-body exercise in men.

Trust comment: Double-blind crossover with clearly reported outcomes but limited to males and moderate sample size.

Study Details

PMID:31013204
Participants:22
Impact:no significant change
Trust score:4/5

skin blood flow (SkBF)

1 evidences

In 36 healthy adults, moderate acute caffeine (2.5 mg/kg doses) improved finger temperature and some perfusion measures during cold exposure and rewarming, especially after total sleep deprivation, but altered pain responses.

Trust comment: Controlled double-blind crossover with n=36 and comprehensive physiological measures; findings robust though some effects vary by habitual use and TSD.

Study Details

PMID:40150834
Participants:36
Impact:Increased at early rewarming (1–5 min) with caffeine; reduced variance between fingers at some timepoints
Trust score:4/5

urine volume

1 evidences

Double-blind study (12 caffeine, 12 placebo) found high acute caffeine intake increased renal calcium clearance markedly over 6 hours.

Trust comment: Double-blind clinical crossover with clear quantitative result but small sample (n=24).

Study Details

PMID:33852164
Participants:24
Impact:positively correlated with calcium clearance (increased)
Trust score:4/5

EEG alpha power

1 evidences

Bright light combined with 100 mg caffeine gum improved driving performance and subjective sleepiness more than caffeine alone in sleep-restricted young drivers.

Trust comment: Randomized simulator study with objective and subjective measures but limited to a simulator setting and moderate sample size.

Study Details

PMID:35398627
Participants:30
Impact:reduced (Light+Caffeine reduced alpha more than Light or Caffeine; P<0.0006)
Trust score:3/5

motor unit discharge variability

1 evidences

Adding 6 mg/kg caffeine before low-load BFR training did not increase maximal strength more than BFR alone but improved precision of force release and reduced motor unit discharge variability.

Trust comment: Controlled 4-week training study with measurable neuromuscular outcomes and a moderate sample (n=28).

Study Details

PMID:40954555
Participants:28
Impact:reduced variability and higher mean frequency with caffeine (P=0.002 and P=0.023)
Trust score:4/5

countermovement jump height (fielders)

1 evidences

Chewing gum with 200 mg caffeine improved grip strength and some jumping and softball-specific performance measures in trained female players.

Trust comment: Randomized crossover in trained athletes with sport-specific objective measures but modest sample size and single-blind design.

Study Details

PMID:39225020
Participants:24
Impact:increase (P<0.05)
Trust score:4/5

Correct choice rate (recognition accuracy)

1 evidences

Randomized double-blind placebo-controlled study: 200 mg caffeine given after learning reduced later face-recognition accuracy and increased false alarms compared with placebo.

Trust comment: Well-powered (N=97), randomized double-blind placebo-controlled human trial with clear outcome measures and appropriate analyses.

Study Details

PMID:40670616
Participants:97
Impact:-8.4 percentage points (caffeine vs placebo; Present hits 50.71% vs 59.13%; Absent correct rejections 29.57% vs 37.92%)
Trust score:4/5

Frequency of apnea attacks

1 evidences

Randomized trial in preterm infants with apnea: caffeine citrate vs aminophylline (both with NCPAP) showed improved early pulmonary function, shorter oxygen/NCPAP support times, and fewer apnea events with caffeine citrate.

Trust comment: Randomized clinical comparison in infants (N=40) with clinically relevant endpoints but limited sample size and single-country report.

Study Details

PMID:26975815
Participants:40
Impact:Reduced with caffeine citrate (P < 0.01)
Trust score:3/5

jitteriness and anxious/tense feelings

1 evidences

In formerly cocaine-dependent adults, cumulative caffeine increased feelings of jitteriness and anxiety more than in controls but did not produce cocaine-like effects or greater reinforcement.

Trust comment: Double-blind randomized crossover design but small groups (n=11 per group) limit statistical power.

Study Details

PMID:9476695
Participants:22
Impact:increased more with caffeine in formerly cocaine-dependent group vs controls (jittery P < 0.05)
Trust score:3/5

Visuomotor processing speed / attention (Trails A / Digit span)

1 evidences

In 25 healthy young men, a 50 mg caffeine drink reduced resting EEG alpha power and improved cognitive test performance (including working memory) about 30 minutes after ingestion.

Trust comment: Randomized double-blind crossover with objective EEG and cognitive endpoints in a homogeneous sample of young men.

Study Details

PMID:36055414
Participants:25
Impact:improved (significant after 30 min)
Trust score:4/5

Liking of paired novel-flavored food

1 evidences

In 62 adults, pairing a caffeinated beverage with a novel yogurt increased liking and consumption of that yogurt, especially for low-energy-density yogurts.

Trust comment: Randomized experiment with a moderate sample and behavioral endpoints; applicable to food preference contexts.

Study Details

PMID:23354532
Participants:62
Impact:increased when paired with caffeine (significant)
Trust score:4/5

visual attention (reaction time)

1 evidences

In 21 active adults, 3 mg/kg caffeine increased Wingate mean and peak power versus placebo without affecting visual attention; CYP1A2 genotype did not alter these effects.

Trust comment: Double-blind randomized crossover with genotyping and objective performance measures; moderate sample size for a pilot study.

Study Details

PMID:28287486
Participants:21
Impact:no significant change (reaction time ~282 vs 275 ms, p=0.31)
Trust score:4/5

executive control of visual attention

1 evidences

In habitual caffeine consumers, only the highest acute dose (400 mg) improved vigilance and executive control of visual attention.

Trust comment: Well-powered repeated-measures, double-blind design in habitual consumers with clear dose–response finding at 400 mg.

Study Details

PMID:20832925
Participants:36
Impact:improved at 400 mg dose
Trust score:4/5

pulse rate

1 evidences

In 100 male undergraduates, both actual caffeine and the expectation of caffeine affected mood and performance; caffeine increased BP, pulse, and reduced fatigue.

Trust comment: Well-powered balanced-placebo design (n=100) separating pharmacological and expectancy effects; clear internal validity.

Study Details

PMID:8991966
Participants:100
Impact:increase (significant; main effect of caffeine vs no caffeine)
Trust score:4/5

visual vigilance

2 evidences

Five days of controlled caffeine intake produced few cognitive or psychomotor changes; only the Vigor-Activity mood subset increased in the 3 mg/kg/day group.

Trust comment: Randomized double-blind controlled design with three parallel groups (total n=60), appropriate for cognitive endpoints.

Study Details

PMID:16043199
Participants:60
Impact:no significant change
Trust score:4/5

In 68 SEAL trainees after 72 h sleep deprivation and stress, 200–300 mg caffeine improved vigilance, reaction time, learning, and reduced fatigue/sleepiness vs placebo.

Trust comment: Randomized allocation in a realistic stress model with measurable cognitive outcomes, moderate sample size (n=68).

Study Details

PMID:12424548
Participants:68
Impact:improvement (dose-dependent; significant at 200 and 300 mg)
Trust score:4/5

Tmax (gum vs capsule)

1 evidences

In healthy men, caffeine in gum was absorbed faster than capsules and delivered similar total amounts systemically at higher doses.

Trust comment: Randomized, double-blind pharmacokinetic study with dense sampling and adequate sample size but limited to healthy male volunteers.

Study Details

PMID:11839447
Participants:84
Impact:Gum 44.2–80.4 min vs capsule 84.0–120.0 min; Tmax significantly shorter for gum (P<0.05)
Trust score:4/5

Hangover incidence/severity

1 evidences

After drinking to intoxication, adding caffeine to beer improved perceived sleep quality and morning alertness but did not affect hangover or sleep duration.

Trust comment: Randomized human study with reasonable sample but mostly student population and single laboratory dosing session.

Study Details

PMID:24090620
Participants:64
Impact:No effect (no difference between caffeinated and non-caffeinated beer)
Trust score:3/5

Heart rate (HR)

3 evidences

In a VR stress task, caffeine increased salivary alpha-amylase after the task versus placebo; the task itself raised multiple stress markers.

Trust comment: Randomized, pre-registered human study with objective biomarkers but single acute exposure and limited detail on dosing/participant characteristics.

Study Details

PMID:38142605
Participants:53
Impact:HR increased after MST (no caffeine-specific difference reported)
Trust score:3/5

In undergraduates, 5 mg/kg caffeine increased systolic blood pressure and altered heart rate/HRV measures and subjective experience 40 minutes after ingestion; expectancies contributed to subjective effects but not objective measures.

Trust comment: Well-powered double-blind placebo-controlled design (n=107) with objective and subjective endpoints and control for expectancies, supporting credible differentiation of pharmacologic vs expectancy effects.

Study Details

PMID:25481367
Participants:107
Impact:decreased after caffeine (magnitude not specified) and HRV (SDNN) changed
Trust score:4/5

Acute ingestion of various energy drinks (contain caffeine plus blends) produced group-specific increases in blood pressure, heart rate, cortisol, and mixed effects on anxiety and working memory.

Trust comment: Moderate-sized acute study (n=80) but tested commercial energy drinks with multiple active ingredients, so effects cannot be attributed to caffeine alone.

Study Details

PMID:27312565
Participants:80
Impact:percent increase in groups A and C
Trust score:3/5

cortisol

2 evidences

Oral caffeine (3.3 mg/kg) at rest increased ACTH and cortisol in healthy young men.

Trust comment: Double-blind, placebo-controlled crossover in 47 healthy men with clear quantitative hormonal changes; reasonably high internal validity.

Study Details

PMID:8951977
Participants:47
Impact:+30% (+2.7 μg/dl peak vs placebo)
Trust score:4/5

In healthy adults undergoing prolonged wakefulness, acute caffeine altered IGF-1 responses depending on COMT genotype and reduced the drop in testosterone during sleep deprivation.

Trust comment: Randomized crossover human study with hormonal measures and genotyping (n=37); moderate sample but well-controlled.

Study Details

PMID:37279709
Participants:37
Impact:Decreased during wakefulness (no clear caffeine main-effect reported)
Trust score:4/5

Heart rate variability (vagal activity)

1 evidences

Short-term HRV increased after drinking caffeinated espresso, decaf, or water; no clear specific short-term vagal effect of caffeine overall, though non-habitual consumers showed systolic BP increases.

Trust comment: Randomized crossover with a relatively large sample (n=77) and appropriate comparisons (caffeinated, decaf, water); outcomes short-term and population young/healthy.

Study Details

PMID:25850440
Participants:77
Impact:increased after all beverages; no specific short-term effect attributable to caffeinated espresso overall
Trust score:4/5

state anxiety (Spielberger)

1 evidences

An acute 5 mg/kg caffeine dose slightly improved a peripheral awareness (hand–eye) task but raised state anxiety; other low-intensity task performance was unchanged.

Trust comment: Randomized crossover with adequate sample for acute effects but limited to low-intensity tasks and low habitual consumers.

Study Details

PMID:12027348
Participants:31
Impact:increased (significant)
Trust score:4/5

vagal (parasympathetic) recovery (RMSSD, SD1)

1 evidences

In healthy young men, 300 mg caffeine before moderate exercise delayed vagal (parasympathetic) heart-rate recovery after exercise in men with lower cardiorespiratory fitness.

Trust comment: Randomized crossover single-blind trial with reasonable sample (n=40) and objective HRV metrics though limited to young men.

Study Details

PMID:31126123
Participants:40
Impact:delayed by ~10 min in lower VO2 group (recovery shifted from Rec2 to Rec3)
Trust score:4/5

urinary magnesium excretion

1 evidences

After a high caffeine dose, women not using oral contraceptives had much larger increases in urinary calcium and some other minerals than oral contraceptive users, suggesting OCs blunt caffeine's calciuric effect.

Trust comment: Randomized crossover in 30 women with clear biochemical outcomes; sample limited to ages 20–29 and specific calcium intake.

Study Details

PMID:12566473
Participants:30
Impact:net increase ~2-fold higher in non-OC vs OC (P<0.05)
Trust score:4/5

caffeine self-administration (cola+coffee drinkers)

1 evidences

Participants given concurrent caffeinated and noncaffeinated cola showed limited but reliable self-administration in a subset (~25%) of individuals.

Trust comment: Controlled double-blind crossover design but small sample sizes and heterogeneous participant groups limit generalizability.

Study Details

PMID:9260077
Participants:24
Impact:4/16 participants self-administered caffeinated cola (25%)
Trust score:3/5

heart rate variability (HRV)

2 evidences

Moderate caffeine (100–200 mg) did not change heart rate variability in young habitual male users within 90 minutes.

Trust comment: Randomized double-blind crossover with objective HRV measures in habitual users; moderate sample size (n=30).

Study Details

PMID:16640511
Participants:30
Impact:no significant change up to 90 min after 100–200 mg caffeine
Trust score:4/5

In people with and without long-standing type 1 diabetes, two weeks of moderate caffeine increased heart rate variability (a marker of autonomic function).

Trust comment: Randomized, blinded, placebo-controlled crossover in human subjects with clear quantitative HRV results, but modest sample size.

Study Details

PMID:15111532
Participants:30
Impact:+103% (type 1 diabetes), +38% (healthy controls)
Trust score:4/5

cognitive/managerial performance

1 evidences

Managers deprived of their usual caffeine showed withdrawal discomfort and decreased performance on several complex task measures.

Trust comment: Double-blind crossover in habitual high-caffeine consumers; decent design but specific population and high baseline intake limit broad applicability.

Study Details

PMID:7568623
Participants:25
Impact:decreased with caffeine deprivation (i.e., caffeine presence maintained performance)
Trust score:3/5

withdrawal symptoms

1 evidences

Managers deprived of their usual caffeine showed withdrawal discomfort and decreased performance on several complex task measures.

Trust comment: Double-blind crossover in habitual high-caffeine consumers; decent design but specific population and high baseline intake limit broad applicability.

Study Details

PMID:7568623
Participants:25
Impact:increased discomfort on deprivation
Trust score:3/5

elimination half-life

1 evidences

In extremely premature infants, caffeine clearance and volume of distribution change with age and weight; caffeine is well absorbed and has prolonged elimination.

Trust comment: Large neonatal PK dataset (n=110) with population modeling and bootstrap validation supports high reliability for PK findings.

Study Details

PMID:19057373
Participants:110
Impact:prolonged in extremely premature infants (mean ~101)
Trust score:5/5

flavour preference for caffeine-paired drink

1 evidences

Habitual postlunch caffeine users developed increased preference for a flavor paired with caffeine and had improved postlunch mood.

Trust comment: Randomized conditioning paradigm with moderate sample size and clear effects in habitual users, though self-report measures may bias results.

Study Details

PMID:8804673
Participants:44
Impact:increased in habitual postlunch users
Trust score:3/5

speed variability (standard deviation of speed, SDS)

1 evidences

One cup of coffee (80 mg caffeine) taken during a break improved lane keeping and speed control and reduced subjective sleepiness for up to 2 hours.

Trust comment: Double-blind, randomized crossover with objective and subjective measures in 24 healthy drivers; well-controlled and directly applicable.

Study Details

PMID:22315048
Participants:24
Impact:reduced (~0.25–0.30 km/h in hours 3–4) - improved
Trust score:4/5

subjective intoxication / masking effect

1 evidences

In a within‑subjects study of healthy men, adding caffeine or energy drink to alcohol did not reduce subjective intoxication (no reproducible 'masking effect') and did not alter breath alcohol concentrations.

Trust comment: Well‑powered within‑subject randomized, double‑blind design (n=52) with appropriate statistical corrections; conclusions robust for subjective measures.

Study Details

PMID:24178765
Participants:52
Impact:no change (no masking effect vs alcohol alone)
Trust score:4/5

perceived pain during cold exposure

1 evidences

In 36 healthy adults, moderate acute caffeine (2.5 mg/kg doses) improved finger temperature and some perfusion measures during cold exposure and rewarming, especially after total sleep deprivation, but altered pain responses.

Trust comment: Controlled double-blind crossover with n=36 and comprehensive physiological measures; findings robust though some effects vary by habitual use and TSD.

Study Details

PMID:40150834
Participants:36
Impact:Before TSD: decreased with caffeine; after TSD: increased with caffeine (significant, p<0.05)
Trust score:4/5

neurobehavioral performance

1 evidences

Repeated nighttime caffeine gum improved objective performance during 50 h wakefulness but did not change overall self-reported sleepiness or fatigue.

Trust comment: Controlled laboratory, randomized administration with repeated measures; moderate sample size and objective outcomes support credibility.

Study Details

PMID:27061779
Participants:24
Impact:improved / impairment mitigated (performance better than placebo after 50 h)
Trust score:4/5

subjective fatigue

3 evidences

Repeated nighttime caffeine gum improved objective performance during 50 h wakefulness but did not change overall self-reported sleepiness or fatigue.

Trust comment: Controlled laboratory, randomized administration with repeated measures; moderate sample size and objective outcomes support credibility.

Study Details

PMID:27061779
Participants:24
Impact:no change (overall)
Trust score:4/5

In healthy young males, 200 mg caffeine improved sustained attention (shorter reaction time) but showed no robust effects on most other cognitive domains or subjective fatigue.

Trust comment: Randomized, double-blind, within-subject trial (48 males) with rigorous corrections for multiple comparisons; limited by moderate per-arm sample size and male-only participants.

Study Details

PMID:33201262
Participants:48
Impact:no significant change with caffeine
Trust score:4/5

Two-week daily matcha (contains caffeine) preserved attention after mild stress in young adults.

Trust comment: Randomized placebo-controlled trial in 42 participants; multi-constituent intervention (matcha) so caffeine-specific attribution limited.

Study Details

PMID:33744591
Participants:42
Impact:No change
Trust score:4/5

batting exit speed / pitching fastball speed

1 evidences

Chewing gum with 200 mg caffeine improved grip strength and some jumping and softball-specific performance measures in trained female players.

Trust comment: Randomized crossover in trained athletes with sport-specific objective measures but modest sample size and single-blind design.

Study Details

PMID:39225020
Participants:24
Impact:increase (P<0.05)
Trust score:4/5

death or disability

1 evidences

In this subgroup analysis of the CAP trial, caffeine reduced death/disability and shortened time on respiratory support mainly in infants who were receiving ventilatory support or who started caffeine early.

Trust comment: Large randomized trial data but current results are from post-hoc subgroup analyses which lowers causal certainty for subgroup differences.

Study Details

PMID:19926098
Participants:2006
Impact:reduced in ventilated infants (ETT subgroup OR 0.73, 95% CI 0.57–0.94); no benefit in infants without support (OR 1.32)
Trust score:4/5

False alarm rate

1 evidences

Randomized double-blind placebo-controlled study: 200 mg caffeine given after learning reduced later face-recognition accuracy and increased false alarms compared with placebo.

Trust comment: Well-powered (N=97), randomized double-blind placebo-controlled human trial with clear outcome measures and appropriate analyses.

Study Details

PMID:40670616
Participants:97
Impact:Increased (Present: +12.14 percentage points; Absent: +7.92 percentage points versus placebo)
Trust score:4/5

somnolence (sleepiness)

1 evidences

A single 100 mg caffeine dose produced rapid arousal (less sleepiness, greater activation) within 10–30 min in healthy undergraduates, with larger effects in men.

Trust comment: Large, randomized double-blind placebo-controlled study (n=688) with repeated measures, giving high confidence in subjective-effect findings.

Study Details

PMID:18675877
Participants:688
Impact:decreased at 10–30 min after 100 mg caffeine
Trust score:5/5

leg press repetitions to failure (muscular endurance)

1 evidences

In resistance-trained women, 6 mg/kg caffeine improved leg-press muscular endurance (especially in fast CYP1A2 metabolizers) and affected subjective mood differently by genotype.

Trust comment: Randomized double-blind crossover with genotype stratification in humans but modest sample (n=36) and underpowered relative to planned size.

Study Details

PMID:39203905
Participants:36
Impact:increased with caffeine (main effect P = 0.038); significant in FAST genotype (P = 0.027)
Trust score:4/5

caffeine reinforcement

1 evidences

In formerly cocaine-dependent adults, cumulative caffeine increased feelings of jitteriness and anxiety more than in controls but did not produce cocaine-like effects or greater reinforcement.

Trust comment: Double-blind randomized crossover design but small groups (n=11 per group) limit statistical power.

Study Details

PMID:9476695
Participants:22
Impact:no difference between formerly cocaine-dependent and control groups
Trust score:3/5

Consumption of paired yogurt

1 evidences

In 62 adults, pairing a caffeinated beverage with a novel yogurt increased liking and consumption of that yogurt, especially for low-energy-density yogurts.

Trust comment: Randomized experiment with a moderate sample and behavioral endpoints; applicable to food preference contexts.

Study Details

PMID:23354532
Participants:62
Impact:increased for caffeine-paired yogurt, especially low-energy-density variety
Trust score:4/5

oxygen consumption (VO2) / RER

1 evidences

In 7- to 9-year-old children, moderate caffeine lowered heart rate and raised blood pressure during rest and low-moderate exercise but did not change VO2 or RER.

Trust comment: Randomized double-blind crossover in a defined pediatric sample (n=52) with clear physiological measures.

Study Details

PMID:16540840
Participants:52
Impact:no change
Trust score:4/5

vigor-activity (mood subset)

1 evidences

Five days of controlled caffeine intake produced few cognitive or psychomotor changes; only the Vigor-Activity mood subset increased in the 3 mg/kg/day group.

Trust comment: Randomized double-blind controlled design with three parallel groups (total n=60), appropriate for cognitive endpoints.

Study Details

PMID:16043199
Participants:60
Impact:increase in 3 mg/kg/day group versus 0 or 6 mg/kg/day
Trust score:4/5

Absorption rate constant (ka)

1 evidences

In healthy men, caffeine in gum was absorbed faster than capsules and delivered similar total amounts systemically at higher doses.

Trust comment: Randomized, double-blind pharmacokinetic study with dense sampling and adequate sample size but limited to healthy male volunteers.

Study Details

PMID:11839447
Participants:84
Impact:Gum 3.21–3.96 h^-1 vs capsule 1.29–2.36 h^-1 (higher for gum)
Trust score:4/5

Systolic blood pressure (non-habitual consumers)

1 evidences

Short-term HRV increased after drinking caffeinated espresso, decaf, or water; no clear specific short-term vagal effect of caffeine overall, though non-habitual consumers showed systolic BP increases.

Trust comment: Randomized crossover with a relatively large sample (n=77) and appropriate comparisons (caffeinated, decaf, water); outcomes short-term and population young/healthy.

Study Details

PMID:25850440
Participants:77
Impact:increased after caffeinated espresso (observed only in non-habitual consumers)
Trust score:4/5

other low-intensity task performance (math, reasoning, etc.)

1 evidences

An acute 5 mg/kg caffeine dose slightly improved a peripheral awareness (hand–eye) task but raised state anxiety; other low-intensity task performance was unchanged.

Trust comment: Randomized crossover with adequate sample for acute effects but limited to low-intensity tasks and low habitual consumers.

Study Details

PMID:12027348
Participants:31
Impact:no significant change
Trust score:4/5

frequency-domain HRV (LF, HF, LF/HF)

1 evidences

In healthy young men, 300 mg caffeine before moderate exercise delayed vagal (parasympathetic) heart-rate recovery after exercise in men with lower cardiorespiratory fitness.

Trust comment: Randomized crossover single-blind trial with reasonable sample (n=40) and objective HRV metrics though limited to young men.

Study Details

PMID:31126123
Participants:40
Impact:no consistent change among protocols; LF/HF showed protocol interaction (p=0.031)
Trust score:4/5

urinary caffeine metabolites (paraxanthine, 1-methylurate, AFMU, 1,7-dimethylurate)

1 evidences

After a high caffeine dose, women not using oral contraceptives had much larger increases in urinary calcium and some other minerals than oral contraceptive users, suggesting OCs blunt caffeine's calciuric effect.

Trust comment: Randomized crossover in 30 women with clear biochemical outcomes; sample limited to ages 20–29 and specific calcium intake.

Study Details

PMID:12566473
Participants:30
Impact:paraxanthine and 1-methylurate increases ~3x and ~5x higher in non-OC; AFMU and 1,7-dimethylurate higher in OC (P<0.05)
Trust score:4/5

dose-normalized caffeine AUC

1 evidences

In sleep-deprived healthy men, higher oral caffeine doses produced non-linear pharmacokinetics with slower metabolism.

Trust comment: Randomized double-blind human study with 37 subjects and clear pharmacokinetic measurements, though specific metabolic mechanism inference is moderate.

Study Details

PMID:7599918
Participants:37
Impact:disproportional increase with increasing dose
Trust score:4/5

preexercise blood pressure

1 evidences

In healthy children, low–moderate caffeine doses raised preexercise blood pressure and lowered heart rate by ~5–6 bpm; metabolic measures were largely unchanged.

Trust comment: Randomized, double-blind, counterbalanced study with 40 participants and clear physiologic measures; applicable to children but limited to acute responses.

Study Details

PMID:18408611
Participants:40
Impact:SBP/DBP increased with 5 mg/kg; DBP increased also with 1 and 3 mg/kg (P<0.05)
Trust score:4/5

substrate use (RER/VO2)

1 evidences

In healthy children, low–moderate caffeine doses raised preexercise blood pressure and lowered heart rate by ~5–6 bpm; metabolic measures were largely unchanged.

Trust comment: Randomized, double-blind, counterbalanced study with 40 participants and clear physiologic measures; applicable to children but limited to acute responses.

Study Details

PMID:18408611
Participants:40
Impact:no meaningful change (one small difference: lower RER CAF-1 vs CAF-5 at 60% VO2peak)
Trust score:4/5

subjective withdrawal-like symptoms when placebo only

1 evidences

Participants given concurrent caffeinated and noncaffeinated cola showed limited but reliable self-administration in a subset (~25%) of individuals.

Trust comment: Controlled double-blind crossover design but small sample sizes and heterogeneous participant groups limit generalizability.

Study Details

PMID:9260077
Participants:24
Impact:increased drowsiness, fatigue, and headache in Experiment 2 when only placebo presented
Trust score:3/5

sighting time

1 evidences

In sleep-deprived trainees, 200–300 mg caffeine made sighting and trigger-pull faster without reducing shooting accuracy.

Trust comment: Randomized dosing in a realistic, stressful field setting with objective simulator measures; moderate sample (n=62).

Study Details

PMID:12688447
Participants:62
Impact:decreased (faster) with 200–300 mg caffeine versus placebo/100 mg (significant)
Trust score:4/5

one-repetition maximum (1-RM) bench press strength

1 evidences

A 201 mg caffeine-containing supplement had no effect on 1-RM bench press strength or time to exhaustion at 85% VO2peak in these men.

Trust comment: Double-blind, placebo-controlled crossover with a reasonable sample (n=31) though limited to men of modest training status.

Study Details

PMID:18714218
Participants:31
Impact:no change
Trust score:4/5

cognitive/psychomotor performance (CFF, CRT)

1 evidences

Repeated day-long administration of tea or coffee sustained aspects of alertness and psychomotor performance but caused dose-dependent worsening of sleep onset, sleep time, and sleep quality.

Trust comment: Randomized five-way crossover with n=30 and objective/subjective measures supports reliability, though naturalistic dosing adds variability.

Study Details

PMID:10823400
Participants:30
Impact:sustained CFF and improved some CRT components vs water during the day (acute alerting effects)
Trust score:4/5

pulse wave velocity (PWV)

1 evidences

Coffee (caffeinated and decaffeinated) increased arterial stiffness measures more in non-habitual than habitual drinkers; caffeine alone also raised stiffness measures in both groups.

Trust comment: Crossover acute study with repeated measures but small sample (n=24); some effects reported for coffee and decaf with mixed significance for caffeine alone.

Study Details

PMID:29318895
Participants:24
Impact:increased (between-group maximal change for coffee: non-habitual > habitual by +0.34–0.39 m/s)
Trust score:3/5

repetitions (exercise performance)

1 evidences

Acute caffeine (6 mg/kg) increased repetitions to failure across sets, raised post-exercise blood lactate, and reduced perceived pain during low-load knee-extension with blood-flow restriction.

Trust comment: Double-blind crossover in trained men (n=22) with clear statistically significant performance and physiological differences; moderate sample size.

Study Details

PMID:30039986
Participants:22
Impact:first set +4.6 reps (28.3 vs 23.7); second set +2.7 reps (11.6 vs 8.9); total +9.5 reps (44.5 vs 35.0)
Trust score:4/5

postlunch mood dip

1 evidences

Habitual postlunch caffeine users developed increased preference for a flavor paired with caffeine and had improved postlunch mood.

Trust comment: Randomized conditioning paradigm with moderate sample size and clear effects in habitual users, though self-report measures may bias results.

Study Details

PMID:8804673
Participants:44
Impact:alleviated in habitual users after caffeine
Trust score:3/5

subjective sleepiness (Karolinska Sleepiness Scale)

1 evidences

One cup of coffee (80 mg caffeine) taken during a break improved lane keeping and speed control and reduced subjective sleepiness for up to 2 hours.

Trust comment: Double-blind, randomized crossover with objective and subjective measures in 24 healthy drivers; well-controlled and directly applicable.

Study Details

PMID:22315048
Participants:24
Impact:decreased (~1.9 points in hour 3; ~1.3 points in hour 4)
Trust score:4/5

breath alcohol concentration

1 evidences

In a within‑subjects study of healthy men, adding caffeine or energy drink to alcohol did not reduce subjective intoxication (no reproducible 'masking effect') and did not alter breath alcohol concentrations.

Trust comment: Well‑powered within‑subject randomized, double‑blind design (n=52) with appropriate statistical corrections; conclusions robust for subjective measures.

Study Details

PMID:24178765
Participants:52
Impact:no change
Trust score:4/5

QTc interval

3 evidences

One cup of caffeinated espresso acutely raised blood pressure and heart rate but did not change QTc in healthy adults.

Trust comment: Randomized, double-blind crossover with objective ECG/BP measures and N=40, though limited to healthy adults and short-term effects.

Study Details

PMID:21288364
Participants:40
Impact:No significant change
Trust score:4/5

A single dose of a multi-ingredient supplement containing 55 mg caffeine altered ECG intervals and autonomic (LF) measures in mentally fatigued adults.

Trust comment: Double-blind, placebo-controlled human study with N=47 showing physiological ECG/ANS changes, but effect sizes not fully reported in the extract.

Study Details

PMID:40562227
Participants:47
Impact:Changed (statistically significant); magnitude not reported
Trust score:4/5

In patients with familial LQTS, an energy drink containing caffeine acutely raised blood pressure and in some individuals caused large QTc prolongation.

Trust comment: Randomized double-blind crossover in a clinical LQTS cohort (n=24) with clinically relevant hemodynamic and safety findings.

Study Details

PMID:28189188
Participants:24
Impact:no significant mean change (ED 12±28 ms vs CD 16±27 ms, p=0.71); but 3 patients had ≥+50 ms prolongation
Trust score:4/5

perseverative errors (executive function)

1 evidences

Experienced gamers who took a microalgae extract combined with guarana (natural caffeine) showed some improvements in reaction time and certain cognitive tests after acute and 30-day supplementation, while gaming scores did not significantly change.

Trust comment: Randomized, double-blind, placebo-controlled human trial with 61 completers and multiple validated cognitive outcomes; some outcomes reported as trends and variability limited gaming effects.

Study Details

PMID:37111136
Participants:61
Impact:decreased with high-dose (acute and remained lower after 30 days)
Trust score:4/5

reaction time (Go/No-Go and Sternberg tasks)

1 evidences

Experienced gamers who took a microalgae extract combined with guarana (natural caffeine) showed some improvements in reaction time and certain cognitive tests after acute and 30-day supplementation, while gaming scores did not significantly change.

Trust comment: Randomized, double-blind, placebo-controlled human trial with 61 completers and multiple validated cognitive outcomes; some outcomes reported as trends and variability limited gaming effects.

Study Details

PMID:37111136
Participants:61
Impact:faster with high-dose acutely (15 min) and some faster reaction times after 30 days
Trust score:4/5

gaming performance (normalized scores)

1 evidences

Experienced gamers who took a microalgae extract combined with guarana (natural caffeine) showed some improvements in reaction time and certain cognitive tests after acute and 30-day supplementation, while gaming scores did not significantly change.

Trust comment: Randomized, double-blind, placebo-controlled human trial with 61 completers and multiple validated cognitive outcomes; some outcomes reported as trends and variability limited gaming effects.

Study Details

PMID:37111136
Participants:61
Impact:no significant change versus placebo
Trust score:4/5

vigilance (wakefulness)

1 evidences

In 24 healthy volunteers undergoing 32-hour sleep deprivation, single doses of slow-release caffeine (notably 300 mg) improved vigilance and performance for up to 13 hours compared with placebo.

Trust comment: Controlled human sleep-deprivation study with 24 participants and objective/subjective vigilance and performance measures; methodology described but details on blinding/dosing schedule limited in the summary.

Study Details

PMID:10947033
Participants:24
Impact:improved versus placebo; effects lasted up to 13 hours
Trust score:4/5

cognitive/performance tests (attention, memory, tracking)

1 evidences

In 24 healthy volunteers undergoing 32-hour sleep deprivation, single doses of slow-release caffeine (notably 300 mg) improved vigilance and performance for up to 13 hours compared with placebo.

Trust comment: Controlled human sleep-deprivation study with 24 participants and objective/subjective vigilance and performance measures; methodology described but details on blinding/dosing schedule limited in the summary.

Study Details

PMID:10947033
Participants:24
Impact:improved versus placebo, with 300 mg identified as optimal dose
Trust score:4/5

contraction time (Tc)

1 evidences

A single high dose of caffeine (9 mg/kg) shortened muscle contraction time and reduced maximal displacement in professional handball players.

Trust comment: Randomized double-blind placebo-controlled trial (N=40) with objective TMG measures; high caffeine dose and habitual caffeine use of participants may limit generalizability.

Study Details

PMID:33801251
Participants:40
Impact:-10.5% (20.60 -> 18.43 ms)
Trust score:4/5

maximal displacement (Dm)

1 evidences

A single high dose of caffeine (9 mg/kg) shortened muscle contraction time and reduced maximal displacement in professional handball players.

Trust comment: Randomized double-blind placebo-controlled trial (N=40) with objective TMG measures; high caffeine dose and habitual caffeine use of participants may limit generalizability.

Study Details

PMID:33801251
Participants:40
Impact:-27.2% (2.32 -> 1.69 mm)
Trust score:4/5

reactive agility time

1 evidences

A caffeine-based multi-ingredient supplement improved reactive agility (~3.4% faster) but did not significantly change jump height in recreational male handball players.

Trust comment: Randomized crossover in 24 players showing MS improved agility; small sample and multi-ingredient formulation limit attribution of effect solely to caffeine.

Study Details

PMID:35458131
Participants:24
Impact:-3.4% vs placebo (time shorter)
Trust score:3/5

jump height (CMJ)

1 evidences

A caffeine-based multi-ingredient supplement improved reactive agility (~3.4% faster) but did not significantly change jump height in recreational male handball players.

Trust comment: Randomized crossover in 24 players showing MS improved agility; small sample and multi-ingredient formulation limit attribution of effect solely to caffeine.

Study Details

PMID:35458131
Participants:24
Impact:no significant change
Trust score:3/5

slow-wave sleep (SWS)

1 evidences

Caffeine (200 mg) before sleep delayed sleep onset and reduced deep sleep, with stronger negative effects on daytime recovery sleep than nocturnal sleep.

Trust comment: Double-blind crossover study in 34 moderate caffeine consumers with polysomnography, providing objective sleep-stage data.

Study Details

PMID:16936703
Participants:34
Impact:reduced SWS
Trust score:4/5

ischemic preconditioning protection (annexin targeting)

1 evidences

Intravenous caffeine (4 mg/kg) abolished ischemic preconditioning protection in humans and eliminated the protective recovery seen in isolated human atrial tissue.

Trust comment: Randomized double-blind human study (N=42) with in vivo and in vitro endpoints showing caffeine (4 mg/kg IV) blocks ischemic preconditioning.

Study Details

PMID:16904537
Participants:42
Impact:abolished by caffeine; IP reduced annexin targeting without caffeine (13% -> 7%) but not after caffeine
Trust score:4/5

post-ischemic contractile recovery (atrial trabeculae)

1 evidences

Intravenous caffeine (4 mg/kg) abolished ischemic preconditioning protection in humans and eliminated the protective recovery seen in isolated human atrial tissue.

Trust comment: Randomized double-blind human study (N=42) with in vivo and in vitro endpoints showing caffeine (4 mg/kg IV) blocks ischemic preconditioning.

Study Details

PMID:16904537
Participants:42
Impact:IP improved recovery in control (+8%); with caffeine recovery was impaired (-8%)
Trust score:4/5

PVT lapses (sustained attention)

1 evidences

In sleep-deprived adults, 2.5 mg/kg caffeine reduced PVT lapses and increased reaction speed at several timepoints; genetic polymorphisms modulated the magnitude/timing of effects.

Trust comment: Double-blind crossover with objective PVT and EEG measures in 37 subjects; genetic analyses add depth though sample size modest for genotype subgroups.

Study Details

PMID:33920292
Participants:37
Impact:reduced (fewer lapses) from 14–32 h of awakening with 2.5 mg/kg caffeine
Trust score:4/5

PVT speed (reaction speed)

1 evidences

In sleep-deprived adults, 2.5 mg/kg caffeine reduced PVT lapses and increased reaction speed at several timepoints; genetic polymorphisms modulated the magnitude/timing of effects.

Trust comment: Double-blind crossover with objective PVT and EEG measures in 37 subjects; genetic analyses add depth though sample size modest for genotype subgroups.

Study Details

PMID:33920292
Participants:37
Impact:increased at 8, 26, and 32 h with caffeine
Trust score:4/5

Karolinska Sleepiness Scale (KSS)

1 evidences

In sleep-deprived adults, 2.5 mg/kg caffeine reduced PVT lapses and increased reaction speed at several timepoints; genetic polymorphisms modulated the magnitude/timing of effects.

Trust comment: Double-blind crossover with objective PVT and EEG measures in 37 subjects; genetic analyses add depth though sample size modest for genotype subgroups.

Study Details

PMID:33920292
Participants:37
Impact:no significant difference vs placebo
Trust score:4/5

3-km cycling mean power (Ingestion+Rinse)

1 evidences

Caffeine ingestion and mouth rinse produced small improvements in 3-km cycling performance; benefits varied by CYP1A2 genotype and were greater in early-day trials.

Trust comment: Crossover study (N=38) with genotype stratification and multiple conditions; moderate sample and population (recreational cyclists) limit generalizability.

Study Details

PMID:26062916
Participants:38
Impact:+3.4–4.1% improvement depending on genotype (AA ~3.4%, AC ~4.1%)
Trust score:4/5

3-km cycling mean power (Ingestion only)

1 evidences

Caffeine ingestion and mouth rinse produced small improvements in 3-km cycling performance; benefits varied by CYP1A2 genotype and were greater in early-day trials.

Trust comment: Crossover study (N=38) with genotype stratification and multiple conditions; moderate sample and population (recreational cyclists) limit generalizability.

Study Details

PMID:26062916
Participants:38
Impact:AC genotype benefited (~+6.0%); AA did not
Trust score:4/5

time-of-day effect

1 evidences

Caffeine ingestion and mouth rinse produced small improvements in 3-km cycling performance; benefits varied by CYP1A2 genotype and were greater in early-day trials.

Trust comment: Crossover study (N=38) with genotype stratification and multiple conditions; moderate sample and population (recreational cyclists) limit generalizability.

Study Details

PMID:26062916
Participants:38
Impact:Rinse and Ingestion+Rinse produced greater benefits when trials were performed before 10:00 vs after
Trust score:4/5

plantarflexor peak torque

1 evidences

In 43 men, 3 mg/kg caffeine acutely did not change plantarflexor peak torque or rate of torque development.

Trust comment: Double-blind, controlled human trial with objective torque measures but moderate sample size and limited to men.

Study Details

PMID:36640779
Participants:43
Impact:no change
Trust score:4/5

rate of torque development

1 evidences

In 43 men, 3 mg/kg caffeine acutely did not change plantarflexor peak torque or rate of torque development.

Trust comment: Double-blind, controlled human trial with objective torque measures but moderate sample size and limited to men.

Study Details

PMID:36640779
Participants:43
Impact:no change
Trust score:4/5

maximal grip strength

1 evidences

In 26 boys (8–10 y), 3 mg/kg caffeine increased peak power and both 3 and 5 mg/kg doses increased maximal grip strength; 5 mg/kg increased mean power and peak heart rate during Wingate.

Trust comment: Double-blind, crossover design in children with objective performance measures; sample size modest but design strong.

Study Details

PMID:25051124
Participants:26
Impact:CAF-3: 21.6 vs PL 20.4 kg (≈+1.2 kg); CAF-5: 21.5 vs PL 20.4 kg (≈+1.1 kg)
Trust score:4/5

absolute peak power (Wingate)

1 evidences

In 26 boys (8–10 y), 3 mg/kg caffeine increased peak power and both 3 and 5 mg/kg doses increased maximal grip strength; 5 mg/kg increased mean power and peak heart rate during Wingate.

Trust comment: Double-blind, crossover design in children with objective performance measures; sample size modest but design strong.

Study Details

PMID:25051124
Participants:26
Impact:CAF-3: 287 vs PL 281 W (+6 W)
Trust score:4/5

superficial macular whole-image vessel density (wiVD)

1 evidences

In 120 healthy adults, a single 200 mg caffeine dose acutely decreased macular (superficial and deep) and radial peripapillary vessel densities and reduced FD-300, without changing FAZ area/perimeter or IOP/BP.

Trust comment: Prospective, randomized, double-masked, placebo-controlled study with n=120 and repeatable OCTA measures, supporting internal validity.

Study Details

PMID:35225536
Participants:120
Impact:decreased: baseline 53.00 → 1 h after 51.10 (P < 0.001)
Trust score:4/5

deep macular whole-image vessel density (wiVD)

1 evidences

In 120 healthy adults, a single 200 mg caffeine dose acutely decreased macular (superficial and deep) and radial peripapillary vessel densities and reduced FD-300, without changing FAZ area/perimeter or IOP/BP.

Trust comment: Prospective, randomized, double-masked, placebo-controlled study with n=120 and repeatable OCTA measures, supporting internal validity.

Study Details

PMID:35225536
Participants:120
Impact:decreased: 58.44 ± 3.99 → 54.07 ± 5.03 (P < 0.001)
Trust score:4/5

radial peripapillary capillary whole papillary VD (wpVD)

1 evidences

In 120 healthy adults, a single 200 mg caffeine dose acutely decreased macular (superficial and deep) and radial peripapillary vessel densities and reduced FD-300, without changing FAZ area/perimeter or IOP/BP.

Trust comment: Prospective, randomized, double-masked, placebo-controlled study with n=120 and repeatable OCTA measures, supporting internal validity.

Study Details

PMID:35225536
Participants:120
Impact:decreased: 50.48 ± 2.06 → 48.99 ± 2.12 (P < 0.001)
Trust score:4/5

overall effective clinical rate

1 evidences

In 128 preterm infants randomized to prophylactic caffeine citrate or control, early caffeine was associated with higher overall effectiveness, fewer apneas, shorter ventilation and hospitalization, lower inflammatory markers, better growth and neurodevelopment scores, and reduced BPD incidence.

Trust comment: Randomized clinical report with multiple positive outcomes but limited methodological detail and potential reporting bias.

Study Details

PMID:37078543
Participants:128
Impact:increased: 95.31% (observation) vs 84.38% (control)
Trust score:3/5

incidence of bronchopulmonary dysplasia (BPD)

1 evidences

In 128 preterm infants randomized to prophylactic caffeine citrate or control, early caffeine was associated with higher overall effectiveness, fewer apneas, shorter ventilation and hospitalization, lower inflammatory markers, better growth and neurodevelopment scores, and reduced BPD incidence.

Trust comment: Randomized clinical report with multiple positive outcomes but limited methodological detail and potential reporting bias.

Study Details

PMID:37078543
Participants:128
Impact:reduced (P < 0.05)
Trust score:3/5

inflammatory markers (MMP-9, TNF-α, TLR-4)

1 evidences

In 128 preterm infants randomized to prophylactic caffeine citrate or control, early caffeine was associated with higher overall effectiveness, fewer apneas, shorter ventilation and hospitalization, lower inflammatory markers, better growth and neurodevelopment scores, and reduced BPD incidence.

Trust comment: Randomized clinical report with multiple positive outcomes but limited methodological detail and potential reporting bias.

Study Details

PMID:37078543
Participants:128
Impact:downregulated post-therapy (P < 0.05)
Trust score:3/5

24-hour retention of mean tracking performance (RMSE)

1 evidences

A single 200 mg dose of caffeine given immediately after practice did not improve 24-hour retention of a visuomotor tracking skill compared with placebo.

Trust comment: Double-blind placebo-controlled trial with adequate sample (n=26) and detailed behavioral measures; results are clearly reported though limited to low-caffeine consumers.

Study Details

PMID:26053288
Participants:26
Impact:no significant difference vs placebo (retention magnitudes similar; p > 0.05)
Trust score:4/5

performance variability

1 evidences

A single 200 mg dose of caffeine given immediately after practice did not improve 24-hour retention of a visuomotor tracking skill compared with placebo.

Trust comment: Double-blind placebo-controlled trial with adequate sample (n=26) and detailed behavioral measures; results are clearly reported though limited to low-caffeine consumers.

Study Details

PMID:26053288
Participants:26
Impact:both groups reduced variability with practice; caffeine group showed a non-significant trend toward greater within-subject variability on Day 2
Trust score:4/5

learning rates/magnitudes

1 evidences

A single 200 mg dose of caffeine given immediately after practice did not improve 24-hour retention of a visuomotor tracking skill compared with placebo.

Trust comment: Double-blind placebo-controlled trial with adequate sample (n=26) and detailed behavioral measures; results are clearly reported though limited to low-caffeine consumers.

Study Details

PMID:26053288
Participants:26
Impact:no significant differences between caffeine and placebo groups
Trust score:4/5

global cerebral perfusion

1 evidences

A 3 mg/kg caffeine dose produced a small (6–8%) nonsignificant global perfusion decrease and selective regional activations (inferior frontal gyrus/anterior insula, hypothalamus) but no activation of nucleus accumbens.

Trust comment: Well-controlled double-blind randomized counterbalanced SPECT study with defined consumer groups and controls (n=14 caffeine group vs n=12 controls), though imaging studies have known variability.

Study Details

PMID:20623930
Participants:26
Impact:generalized decrease ~6–8% (not statistically significant)
Trust score:4/5

nucleus accumbens perfusion

1 evidences

A 3 mg/kg caffeine dose produced a small (6–8%) nonsignificant global perfusion decrease and selective regional activations (inferior frontal gyrus/anterior insula, hypothalamus) but no activation of nucleus accumbens.

Trust comment: Well-controlled double-blind randomized counterbalanced SPECT study with defined consumer groups and controls (n=14 caffeine group vs n=12 controls), though imaging studies have known variability.

Study Details

PMID:20623930
Participants:26
Impact:no change (0%); no activation of reward/dependence circuit
Trust score:4/5

regional activation (inferior frontal gyrus/anterior insula, hypothalamus)

1 evidences

A 3 mg/kg caffeine dose produced a small (6–8%) nonsignificant global perfusion decrease and selective regional activations (inferior frontal gyrus/anterior insula, hypothalamus) but no activation of nucleus accumbens.

Trust comment: Well-controlled double-blind randomized counterbalanced SPECT study with defined consumer groups and controls (n=14 caffeine group vs n=12 controls), though imaging studies have known variability.

Study Details

PMID:20623930
Participants:26
Impact:discrete perfusion increases in these regions (statistically significant in group comparisons)
Trust score:4/5

Anagen hair ratio

1 evidences

In 210 men with androgenetic alopecia, topical 0.2% caffeine for 6 months increased anagen hair ratio (~+10.6%) and was noninferior to 5% minoxidil (~+11.7%).

Trust comment: Large randomized multicenter noninferiority trial with objective trichogram endpoint but open-label design may introduce bias.

Study Details

PMID:29055953
Participants:210
Impact:+10.59% anagen improvement at 6 months (caffeine) vs +11.68% (minoxidil); difference 1.09% (noninferior)
Trust score:4/5

Heart rate / rate-pressure product

1 evidences

In 22 resistance-trained men, acute caffeine (6 mg/kg) taken before resistance exercise raised blood-pressure-related measures compared with placebo and may increase cardiovascular load during/after heavy lifting.

Trust comment: Randomized crossover in trained men but small sample and limited reporting of effect magnitudes; high caffeine dose may limit generalizability.

Study Details

PMID:18046056
Participants:22
Impact:Elevated cardiovascular workload after caffeine (significant)
Trust score:3/5

Heart rate recovery

1 evidences

In a crossover trial, 300 mg caffeine given before resistance exercise delayed autonomic (HRV) recovery and slowed heart rate and blood pressure recovery after exercise.

Trust comment: Prospective, crossover, controlled clinical trial with objective cardiac measures and clear effects, though sample size moderate.

Study Details

PMID:34274079
Participants:30
Impact:- slowed recovery after exercise
Trust score:4/5

EEG delta power (NREM)

1 evidences

In 21 healthy young men given bedtime caffeine (160 mg delayed-release), higher plasma caffeine reduced NREM EEG delta power, lowered heart rate (~−3.24 bpm average) and increased high-frequency HRV during sleep.

Trust comment: Randomized double-blind crossover with simultaneous plasma caffeine measurement, polysomnography and HRV; good sample size for sleep physiology (n=21).

Study Details

PMID:38221756
Participants:21
Impact:Dose-dependent reduction in delta activity (threshold ~7.4 μmol·L⁻¹; significant)
Trust score:5/5

Heart rate during NREM sleep

1 evidences

In 21 healthy young men given bedtime caffeine (160 mg delayed-release), higher plasma caffeine reduced NREM EEG delta power, lowered heart rate (~−3.24 bpm average) and increased high-frequency HRV during sleep.

Trust comment: Randomized double-blind crossover with simultaneous plasma caffeine measurement, polysomnography and HRV; good sample size for sleep physiology (n=21).

Study Details

PMID:38221756
Participants:21
Impact:Average reduction −3.24 ± 0.77 beats per minute (dose-dependent)
Trust score:5/5

High-frequency HRV (parasympathetic activity)

1 evidences

In 21 healthy young men given bedtime caffeine (160 mg delayed-release), higher plasma caffeine reduced NREM EEG delta power, lowered heart rate (~−3.24 bpm average) and increased high-frequency HRV during sleep.

Trust comment: Randomized double-blind crossover with simultaneous plasma caffeine measurement, polysomnography and HRV; good sample size for sleep physiology (n=21).

Study Details

PMID:38221756
Participants:21
Impact:Increased HF HRV during NREM sleep (dose-dependent; significant)
Trust score:5/5

BMS symptom severity (VAS)

1 evidences

Daily 120–150 mg caffeine for 2 weeks reduced burning mouth syndrome symptoms (VAS) versus control; 65.1% of caffeine-treated patients reported symptom relief versus 12.5% in controls.

Trust comment: Randomized controlled trial with 118 patients and clinically relevant endpoints, though short (2-week) follow-up.

Study Details

PMID:40084800
Participants:118
Impact:significant reduction (p < 0.0005)
Trust score:4/5

symptom relief rate

1 evidences

Daily 120–150 mg caffeine for 2 weeks reduced burning mouth syndrome symptoms (VAS) versus control; 65.1% of caffeine-treated patients reported symptom relief versus 12.5% in controls.

Trust comment: Randomized controlled trial with 118 patients and clinically relevant endpoints, though short (2-week) follow-up.

Study Details

PMID:40084800
Participants:118
Impact:65.1% responders (caffeine) vs 46.5% (ALA) vs 12.5% (control)
Trust score:4/5

vasovagal reaction score

1 evidences

A single 250 mg dose of caffeine before donation reduced vasovagal reaction scores, required fewer interventions, and increased reported likelihood of repeat donation in first-time female donors.

Trust comment: Randomized double-blind design with 62 participants; clear clinical outcomes though sample limited to female undergraduate donors.

Study Details

PMID:10431942
Participants:62
Impact:decreased (250 mg vs placebo)
Trust score:4/5

phlebotomist interventions for negative reactions

1 evidences

A single 250 mg dose of caffeine before donation reduced vasovagal reaction scores, required fewer interventions, and increased reported likelihood of repeat donation in first-time female donors.

Trust comment: Randomized double-blind design with 62 participants; clear clinical outcomes though sample limited to female undergraduate donors.

Study Details

PMID:10431942
Participants:62
Impact:fewer required (250 mg group)
Trust score:4/5

likelihood of repeat donation (self-report)

1 evidences

A single 250 mg dose of caffeine before donation reduced vasovagal reaction scores, required fewer interventions, and increased reported likelihood of repeat donation in first-time female donors.

Trust comment: Randomized double-blind design with 62 participants; clear clinical outcomes though sample limited to female undergraduate donors.

Study Details

PMID:10431942
Participants:62
Impact:increased (250 mg group)
Trust score:4/5

salivary cortisol response to caffeine

1 evidences

Acute caffeine doses strongly increased salivary cortisol after abstinence; after 5 days of daily caffeine (300 or 600 mg/day) the morning cortisol response to a 9:00 AM caffeine challenge was blunted, indicating partial tolerance, with some cortisol elevation returning after later doses.

Trust comment: Large double-blind crossover with repeated within-subject measures and clear pharmacologic dosing—strong design to assess tolerance.

Study Details

PMID:16204431
Participants:96
Impact:robust increase after abstinence (p < 0.0001); morning response attenuated/abolished after 5 days daily intake at 300–600 mg/day; partial return after afternoon dose
Trust score:5/5

treatment response rate for apnea

1 evidences

Randomized trial in 78 very low birth weight preterm infants: higher maintenance caffeine citrate dose (10 mg/kg) improved apnea response rate versus lower dose (5 mg/kg) without increasing adverse events or mortality.

Trust comment: Prospective randomized controlled trial with adequate sample for neonatal setting and clear outcome reporting, though single-centre and short-term outcomes limit broader certainty.

Study Details

PMID:31208509
Participants:78
Impact:higher with high-dose maintenance caffeine (71% vs 48%; +23 percentage points)
Trust score:4/5

adverse event incidence

1 evidences

Randomized trial in 78 very low birth weight preterm infants: higher maintenance caffeine citrate dose (10 mg/kg) improved apnea response rate versus lower dose (5 mg/kg) without increasing adverse events or mortality.

Trust comment: Prospective randomized controlled trial with adequate sample for neonatal setting and clear outcome reporting, though single-centre and short-term outcomes limit broader certainty.

Study Details

PMID:31208509
Participants:78
Impact:no significant difference between high- and low-dose groups
Trust score:4/5

task completion time

1 evidences

Randomized crossover in 50 surgical trainees: acute 200 mg caffeine did not change laparoscopic task times or OSATS scores overall, but one error (tissue dislocation in circle cutting) was more frequent after caffeine; systolic BP rose slightly and more participants felt uncomfortable after caffeine.

Trust comment: Well-designed randomized, blinded crossover with objective motion-tracking and rater assessment (n=50); single rater and trainee sample restrict external validity.

Study Details

PMID:34782961
Participants:50
Impact:no significant change with caffeine (times comparable to placebo)
Trust score:4/5

OSATS performance score

1 evidences

Randomized crossover in 50 surgical trainees: acute 200 mg caffeine did not change laparoscopic task times or OSATS scores overall, but one error (tissue dislocation in circle cutting) was more frequent after caffeine; systolic BP rose slightly and more participants felt uncomfortable after caffeine.

Trust comment: Well-designed randomized, blinded crossover with objective motion-tracking and rater assessment (n=50); single rater and trainee sample restrict external validity.

Study Details

PMID:34782961
Participants:50
Impact:no significant change with caffeine
Trust score:4/5

tissue dislocation (circle cutting major error)

1 evidences

Randomized crossover in 50 surgical trainees: acute 200 mg caffeine did not change laparoscopic task times or OSATS scores overall, but one error (tissue dislocation in circle cutting) was more frequent after caffeine; systolic BP rose slightly and more participants felt uncomfortable after caffeine.

Trust comment: Well-designed randomized, blinded crossover with objective motion-tracking and rater assessment (n=50); single rater and trainee sample restrict external validity.

Study Details

PMID:34782961
Participants:50
Impact:increased after caffeine (34% vs 16%; +18 percentage points; p=0.049)
Trust score:4/5

coronary flow capacity (CFC) classification

1 evidences

Large PET imaging series (6087 scans) showed that even low serum caffeine reduces quantitative myocardial stress perfusion and coronary flow reserve during vasodilator stress, and in a small fraction alters coronary flow capacity interpretation (possible false negatives/positives).

Trust comment: Very large clinical dataset with quantitative PET measures and long follow-up; observational nature but robust imaging data support reliability of the reported associations.

Study Details

PMID:31056681
Participants:6087
Impact:altered in a small percent of caffeine-positive scans (2.1% false negatives, 5.5% false positives among caffeine-positives)
Trust score:4/5

headache (withdrawal)

1 evidences

In children who habitually consume caffeine, a 50 mg dose after overnight abstinence restored cognitive accuracy, prevented withdrawal headache, and increased alertness; non/low-consumers showed no clear benefit.

Trust comment: Randomized double-blind placebo-controlled trial in children (n=26); small sample but appropriate design.

Study Details

PMID:16423144
Participants:26
Impact:prevented increase (in habitual consumers vs placebo)
Trust score:4/5

15-s sprint mean power

1 evidences

In endurance-trained adults, 3 mg/kg caffeine increased mean power in a 6-min time trial (~+12 W) but did not add to creatine effects on 15-s sprint power.

Trust comment: Randomized crossover with measured performance outcomes in 23 trained athletes; small sample but objective measures and CIs reported.

Study Details

PMID:38646853
Participants:23
Impact:+10 W vs placebo (not statistically significant, p=0.156)
Trust score:4/5

type 2 diabetes risk

1 evidences

Higher caffeinated coffee/caffeine intake was associated with higher plasma SHBG and lower type 2 diabetes risk; adjustment for SHBG attenuated the diabetes association.

Trust comment: Large prospective nested case-control with biomarker and genotype data; observational design means residual confounding possible.

Study Details

PMID:21030499
Participants:718
Impact:reduced risk for high caffeinated coffee intake (OR 0.47 for ≥4 cups/day vs 0; categorical model) — association attenuated after adjusting for SHBG (OR 0.71)
Trust score:4/5

Tachycardia risk

1 evidences

In 240 preterm neonates with apnea, caffeine citrate was similarly effective to aminophylline overall, with caffeine showing a lower risk of tachycardia and lower mean heart rate.

Trust comment: Well-powered randomized controlled trial in the target population with clinically relevant endpoints.

Study Details

PMID:28474588
Participants:240
Impact:Reduced risk with caffeine vs aminophylline (RR 0.30; 95% CI 0.15–0.60; P<0.001)
Trust score:5/5

time to meaningful relief

1 evidences

Large randomized double-blind trial showing that adding caffeine to ibuprofen improved relief of tension-type headache vs components or placebo.

Trust comment: Large (n=301), randomized, double-blind, placebo- and active-controlled trial with clear positive effects of caffeine as an adjuvant to ibuprofen.

Study Details

PMID:11014413
Participants:301
Impact:significantly shorter with ibuprofen+caffeine vs ibuprofen, caffeine, or placebo (p<0.05)
Trust score:5/5

beverage liking

1 evidences

Adolescents exposed to a novel soda with 2 mg/kg caffeine showed increased liking over repeated exposures and reduced bitterness perception.

Trust comment: Controlled randomized exposure in adolescents with adequate sample size and clear within-group effects at the 2 mg/kg dose.

Study Details

PMID:22427020
Participants:99
Impact:increase in liking over exposure in the 2 mg/kg caffeine group (after initial decrease)
Trust score:4/5

feeling-of-knowing (FOK) resolution

1 evidences

Experimental induction of caffeine craving impaired memory performance and some metacognitive judgments compared to control.

Trust comment: Experimental human study (n=55) manipulating craving state; applicable to craving-related cognitive effects but not acute caffeine ingestion effects per se.

Study Details

PMID:28276980
Participants:55
Impact:reduced resolution for FOK judgements during craving
Trust score:3/5

simple reaction time and vigilance reaction time

1 evidences

In 24 habitual caffeine consumers and 24 non-consumers, acute caffeine (75 or 150 mg) improved reaction times, vigilance and working memory and reduced self-rated mental fatigue and increased alertness regardless of habitual use.

Trust comment: Well-powered (for acute effects), double-blind crossover in humans with clear cognitive and mood endpoints; overnight withdrawal may influence magnitude but design addresses withdrawal.

Study Details

PMID:15678363
Participants:48
Impact:improved (significant reductions in reaction times vs placebo)
Trust score:4/5

energy expenditure after ingestion

1 evidences

In middle-aged adults, 2-week intake of a tea catechin beverage (containing ~88 mg caffeine) increased energy expenditure after ingestion by ~96 kJ/day (~1.7%) versus a caffeinated placebo beverage; fasting RMR did not change.

Trust comment: Randomized double-blind crossover with objective metabolic measures and per-protocol n=26; however effect likely attributable to catechins and both beverages contained similar caffeine, limiting attribution to caffeine alone.

Study Details

PMID:31062079
Participants:26
Impact:+96 kJ/day (placebo 5502 ± 757 vs catechin 5598 ± 800 kJ/day; p=0.041)
Trust score:4/5

incidence of apnea

1 evidences

Both domestic and imported caffeine citrate were similarly safe and effective for treating apnea in preterm infants.

Trust comment: Prospective randomized double-blind RCT in 98 preterm infants with clinical endpoints reported; reasonable quality.

Study Details

PMID:32669161
Participants:98
Impact:no significant difference between domestic and imported caffeine citrate (P>0.05)
Trust score:4/5

motor steadiness error time

1 evidences

300 mg caffeine worsened motor steadiness (more errors) in healthy adult females.

Trust comment: Randomized double-blind crossover design but small sample (n=24) and limited to females.

Study Details

PMID:7650108
Participants:24
Impact:increased after 300 mg caffeine (significant)
Trust score:3/5

serum caffeine half-life

1 evidences

Caffeine has a long half-life in preterm infants and many infants had pathologic apnea days after stopping caffeine.

Trust comment: Prospective cohort with measured drug levels and clinical monitoring in 50 preterm infants; clear pharmacokinetic data.

Study Details

PMID:26562367
Participants:50
Impact:mean 87 ± 25 hours
Trust score:4/5

energetic mood

1 evidences

A single cup-equivalent dose after overnight abstinence increased energetic mood and improved psychomotor performance; additional spaced doses added little.

Trust comment: Double-blind randomized design with 64 moderate caffeine consumers; well-controlled behavioral measures.

Study Details

PMID:9862086
Participants:64
Impact:increased after caffeine (relative to placebo)
Trust score:4/5

compliance of the respiratory system (CRS)

1 evidences

Caffeine improved neonatal respiratory compliance and reduced oxygen needs earlier than theophylline.

Trust comment: Randomized neonatal study with protocol completion in 45 infants and objective respiratory measures; solid but pediatric-specific.

Study Details

PMID:9483391
Participants:45
Impact:improved after caffeine (significant at 24 h and 7 days)
Trust score:4/5

sustained attention performance

1 evidences

Combined caffeine and glucose did not change behavioral sustained attention but reduced activation in attention-related brain regions, suggesting increased neural efficiency.

Trust comment: Double-blind randomized fMRI study (n=40) exploratory in nature; neural changes reported without behavioral gains.

Study Details

PMID:21312288
Participants:40
Impact:behavioral performance similar across treatments (no improvement)
Trust score:3/5

deoxygenated haemoglobin (deoxy-Hb)

1 evidences

In healthy young adults, 75 mg caffeine reduced prefrontal oxygenated haemoglobin and increased deoxygenated haemoglobin and improved some reaction-time and mood measures; co‑administration with L‑theanine abolished the oxy‑Hb reduction and removed the behavioural benefits.

Trust comment: Well-controlled double-blind, within-subjects study with NIRS and behavioral measures but modest sample size (n=24).

Study Details

PMID:25761837
Participants:24
Impact:increase during tasks (significant; larger in non-habitual consumers)
Trust score:4/5

cardiac conduction / refractory periods / SVT inducibility

1 evidences

In patients undergoing EPS, oral caffeine (5 mg/kg) increased systolic and diastolic blood pressure but did not affect cardiac conduction parameters or SVT inducibility.

Trust comment: Prospective randomized placebo-controlled study in a clinical population with adequate sample (n=80).

Study Details

PMID:25081280
Participants:80
Impact:no significant change
Trust score:4/5

neonatal hypertonia (NNNS)

1 evidences

In very preterm infants randomized to early high- vs standard-dose caffeine, high-dose was associated with higher rates of cerebellar hemorrhage and subtle neonatal neurobehavioral differences but no detectable 2-year developmental differences in this pilot trial.

Trust comment: Pilot randomized trial with clinically important safety signals but single-center and limited power for long-term outcomes.

Study Details

PMID:25856169
Participants:74
Impact:higher hypertonia scores in high-dose group (2.3 vs 1.5, p=0.02)
Trust score:3/5

HRV threshold

1 evidences

About 3 mg/kg caffeine increased parasympathetic reactivation after submaximal exercise (60–300 s post-exercise) but did not alter resting cardiac parasympathetic modulation or HRV threshold.

Trust comment: Balanced-placebo, crossover design with n=21 and objective HRV metrics; reasonably robust though sample modest.

Study Details

PMID:30326789
Participants:21
Impact:no change
Trust score:4/5

body fat

3 evidences

In obese adolescents on a calorie-restricted diet, an ephedrine+caffeine pill produced much larger weight, BMI, and body-fat loss over 20 weeks than placebo.

Trust comment: Randomized double-blind placebo-controlled trial in adolescents with clear outcome differences, but pilot size and combined ephedrine+caffeine limit attribution to caffeine alone.

Study Details

PMID:11126208
Participants:29
Impact:-6.6 kg (CE group mean vs -0.5 kg in placebo; P < 0.05)
Trust score:4/5

A 6-month randomized trial of an herbal ephedra/caffeine product produced greater weight loss than placebo and increased some GI and sleep-related side effects.

Trust comment: Large randomized double-blind trial with 6-month follow-up, but intervention combines ephedra and caffeine so effects are not due to caffeine alone.

Study Details

PMID:12032741
Participants:167
Impact:decreased (magnitude not provided in excerpt)
Trust score:4/5

Combination treatment including ephedrine plus caffeine reduced body fat and altered lipid-related gene expression; caffeine was given as part of a multi-drug regimen so individual caffeine effects are not isolated.

Trust comment: Randomized trial with moderate sample size but caffeine was administered with ephedrine (and/or pioglitazone), so effects cannot be attributed solely to caffeine.

Study Details

PMID:17351280
Participants:57
Impact:-6.0% (ECP group)
Trust score:3/5

alcohol-related adverse consequences

1 evidences

Survey of 4,271 US college students found that mixing energy drinks with alcohol was common and associated with higher heavy drinking and more alcohol-related harms.

Trust comment: Large, multicenter web-based cross-sectional survey with clear associations but subject to confounding and self-report biases.

Study Details

PMID:18439201
Participants:4271
Impact:increased prevalence (e.g., sexual victimization, injury, need for medical treatment; p < 0.05)
Trust score:3/5

sleep continuity/fragmentation (WASO / awakenings)

1 evidences

In a double-blind crossover study, moderate caffeine during 38 h wakefulness reduced recovery-night total sleep time and N3 sleep and worsened sleep continuity and EEG slow-wave power.

Trust comment: Well-controlled double-blind crossover trial with objective sleep EEG measures and adequate sample for a demanding protocol (n=41).

Study Details

PMID:39458438
Participants:41
Impact:worse with caffeine (increase in number of WASO periods; +61.0% ± 12.3% in caffeine condition)
Trust score:5/5

intensity of tooth sensitivity (VAS/NRS)

1 evidences

In 84 patients, coadministration of ibuprofen plus caffeine did not reduce the risk or intensity of bleaching-induced tooth sensitivity compared with placebo.

Trust comment: Triple-blind randomized clinical trial with adequate sample size and direct patient-reported outcomes; caffeine was combined with ibuprofen so effect not isolated to caffeine alone.

Study Details

PMID:34755785
Participants:84
Impact:no significant change (p>0.05)
Trust score:4/5

body weight/body composition

1 evidences

In 58 adults, 12 weeks of catechin- and caffeine-containing green tea supplementation did not change gut microbiota composition or diversity nor body composition versus placebo.

Trust comment: Randomized single-blind placebo-controlled study but intervention combined catechins and small amounts of caffeine, so caffeine-specific effects cannot be isolated.

Study Details

PMID:27054321
Participants:58
Impact:no significant change over 12 weeks
Trust score:3/5

Blood pressure response to exercise

1 evidences

In 20 mild hypertensive and 12 normotensive men (total 32), caffeine increased blood pressure and rate-pressure product at rest and during exercise, raising cardiac workload in hypertensives.

Trust comment: Controlled study showing consistent hemodynamic effects, but older work and modest sample sizes (particularly per subgroup) moderate confidence.

Study Details

PMID:8998252
Participants:32
Impact:increase (greater BP during exercise after caffeine)
Trust score:3/5

Vigor (self-report)

1 evidences

Knowing about a possible placebo had limited effect overall; uninformed participants showed some caffeine-induced increases in diastolic blood pressure and vigor and impaired hand steadiness at higher dose.

Trust comment: Relatively large randomized sample with dose comparisons and objective measures, though effects depended on instruction subgroups and some outcomes non-significant.

Study Details

PMID:12021824
Participants:52
Impact:increased with 125 mg and 325 mg caffeine in uninformed participants
Trust score:4/5

18-km run time (performance)

1 evidences

During an 18-km run, sports drinks increased gastrointestinal complaint incidence versus water; adding caffeine (150 mg/L) to the sports drink did not affect running performance or GI complaints compared with the sports drink without caffeine.

Trust comment: Large randomized crossover field study with controlled intake and good external validity for runners; outcomes are self-reported GI symptoms which may be subjective.

Study Details

PMID:15795812
Participants:98
Impact:no significant difference between water, CES, and CES+150 mg/L caffeine
Trust score:4/5

Systolic blood pressure (waking)

1 evidences

Daily caffeine challenges produced small but persistent increases in ambulatory blood pressure in some habitual consumers after repeated intake.

Trust comment: Randomized double‑blind crossover with objective ambulatory BP measurement and n=85, though subgroup analyses of tolerance reduce generalizability.

Study Details

PMID:15882556
Participants:85
Impact:+2.8 mmHg
Trust score:4/5

Hair density

1 evidences

Daily use of a shampoo containing caffeine plus DMG‑Na reduced hair shedding and improved hair growth measures versus placebo after 6 months.

Trust comment: Large randomized double‑blind placebo‑controlled trial (n=154) with objective phototrichogram measures, though some authors are industry employees (COI).

Study Details

PMID:40820949
Participants:154
Impact:+47.3 (units reported as hair/cm²) mean change at 6 months (active)
Trust score:4/5

general cognitive quotient (Griffiths at 12 months)

1 evidences

In very preterm infants randomized to higher vs lower caffeine citrate dosing, there was a borderline higher mean cognitive score at 1 year in the high-dose group but no clear adverse developmental, temperament, or behavior effects.

Trust comment: Large multicentre randomized trial with substantial follow-up but primary outcome data missing for some randomized infants and effect was borderline/statistically sensitive.

Study Details

PMID:21244548
Participants:190
Impact:98.0 ± 13.8 (high-dose) vs 93.6 ± 16.5 (low-dose); mean difference ≈ +4.4 points, p = 0.048 (borderline; non-significant in sensitivity analysis)
Trust score:4/5

Fetuin-A

1 evidences

In overweight adults, 8 weeks of caffeinated coffee increased adiponectin and IL‑6 while decaffeinated coffee lowered fetuin‑A; no change in glucose tolerance.

Trust comment: Randomized, blinded 8-week trial measuring objective biomarkers but limited by small sample size (n=41 completed).

Study Details

PMID:21914162
Participants:41
Impact:-20% (decaffeinated vs no coffee)
Trust score:4/5

Obstructive sleep apnea prevalence

1 evidences

Neonatal caffeine therapy was not associated with differences in sleep duration or sleep-disordered breathing at school age.

Trust comment: Long-term follow-up of a randomized neonatal trial with objective sleep measures in a large sample (n=201).

Study Details

PMID:25171195
Participants:201
Impact:No significant difference (8.2% caffeine vs 11.0% placebo)
Trust score:5/5

Mood elevation

1 evidences

Adding caffeine to ibuprofen sped pain relief onset and increased analgesic effect at 45–60 minutes after single-dose administration, with few adverse events.

Trust comment: Randomized, double-blind, placebo-controlled single-dose trial (n=161) showing caffeine enhances ibuprofen analgesia with limited adverse events.

Study Details

PMID:8880847
Participants:161
Impact:All active treatments (including caffeine combination) produced significant mood elevation vs placebo
Trust score:4/5

heart rate response

2 evidences

In 101 children/adolescents, caffeine produced larger cardiovascular responses in boys than girls after puberty and responses varied across the menstrual cycle in postpubertal girls.

Trust comment: Double-blind, placebo-controlled dose-response design with adequate sample (n=101) and clear sex/puberty analyses.

Study Details

PMID:24935999
Participants:101
Impact:gender- and pubertal stage-dependent (greater response in postpubertal boys)
Trust score:4/5

A 480 mg oral caffeine challenge induced panic attacks in a higher proportion of patients with panic disorder and depression with panic attacks than in depressed-only patients or healthy controls.

Trust comment: Randomized double-blind human challenge (n=109) with clear clinically relevant group differences and objective anxiety assessments.

Study Details

PMID:17445520
Participants:109
Impact:patients with MD had lower heart rate response than other groups (statistically significant)
Trust score:4/5

physiological sleep tendency (MSLT)

1 evidences

Night-shift simulation: caffeine (2 mg/kg at two nighttime points) reduced physiological sleep tendency at night but did not change task performance or daytime sleep measures.

Trust comment: Randomized controlled trial with objective sleep measures but modest sample size (N=30).

Study Details

PMID:7761739
Participants:30
Impact:decreased during night shift (caffeine vs placebo)
Trust score:4/5

resting metabolic rate (RMR)

1 evidences

A combined caffeine+ephedra supplement raised resting metabolic rate and produced greater weight and fat loss than placebo over 12 weeks.

Trust comment: Randomized double-blind trial but supplement combined caffeine with ephedra, so effects cannot be attributed to caffeine alone.

Study Details

PMID:15292480
Participants:40
Impact:+8% over 2 hours (C&E vs placebo, phase I)
Trust score:3/5

Number of options generated

1 evidences

In a double-blind trial, 300 mg caffeine caused people to generate fewer options but to start generating options faster; caffeine did not affect subsequent choice selection.

Trust comment: Double-blind, placebo-controlled experiment with a moderate sample (n=47) and clear behavioral outcomes.

Study Details

PMID:24682504
Participants:47
Impact:Decreased (significant fewer options generated with caffeine vs placebo)
Trust score:4/5

Spherical equivalent (SE) change at 12 months

1 evidences

Topical 2% caffeine alone did not slow myopia progression over 12 months; atropine (0.02%) slowed progression and caffeine did not alter atropine's efficacy when combined.

Trust comment: Prospective randomized clinical trial with reasonable sample size; outcomes clinically measured but topical caffeine showed no benefit.

Study Details

PMID:39824253
Participants:182
Impact:2% caffeine: −0.70 ± 0.55 D (no slower than single-vision −0.76 ± 0.51 D); atropine groups ≈−0.46 D (slower progression)
Trust score:4/5

CrossFit FGB total repetitions

1 evidences

In moderately trained CrossFit athletes, different acute caffeine doses (3, 6, 9 mg/kg) did not produce consistent statistically superior performance vs placebo, though 6 mg/kg showed the largest practical improvement in some measures.

Trust comment: Well-controlled randomized double-blind crossover (n=26) but practice effects and small sample reduce certainty of dose effects.

Study Details

PMID:38226646
Participants:26
Impact:mean 271 → 294 reps at 6 mg/kg vs baseline (+8.5%); no clear significant difference vs placebo (placebo 289)
Trust score:4/5

length of critical care stay (PICU/step-down)

1 evidences

In infants with bronchiolitis-associated apnea, a single IV caffeine dose did not shorten time to a 24-hour apnea-free period compared with placebo.

Trust comment: Double-blind randomized parallel trial in infants with objective monitoring, but single-dose design and sample-size/power limitations noted.

Study Details

PMID:27189681
Participants:85
Impact:longer in caffeine group by mean 68.2 h (P=0.04)
Trust score:4/5

Rating of perceived exertion (RPE) — upper body

1 evidences

Acute caffeine (5 mg/kg) increased peak anaerobic power and reduced perceived exertion for upper-body exercise in men.

Trust comment: Double-blind crossover with clearly reported outcomes but limited to males and moderate sample size.

Study Details

PMID:31013204
Participants:22
Impact:significantly decreased (P = .014)
Trust score:4/5

Incidence of moderate/severe PDPH

1 evidences

IV caffeine after spinal anesthesia reduced headache severity, fewer moderate/severe headaches, and reduced analgesic needs.

Trust comment: Double-blind, placebo-controlled RCT with clear clinical endpoints and adequate sample size for perioperative context.

Study Details

PMID:9952095
Participants:60
Impact:group S: 11 patients vs group C: 3 patients (reduced with caffeine)
Trust score:4/5

Paracetamol absorption rate (Ka) and Tmax

1 evidences

Adding caffeine to paracetamol sped absorption (shorter Tmax), increased Cmax and Ka, and prolonged t1/2—effects greater in hepatic patients.

Trust comment: Human PK study including healthy and hepatic patients with clear measurements but modest sample sizes per subgroup.

Study Details

PMID:26888096
Participants:40
Impact:caffeine increased Ka and shortened Tmax (faster absorption)
Trust score:3/5

white matter fractional anisotropy (FA)

1 evidences

Early prophylactic caffeine in very preterm infants improved white-matter microstructure on MRI and reduced apnea/ventilation needs versus placebo.

Trust comment: Checklist: confirm human caffeine effect; identify outcomes (FA, ADC, apnea/ventilation); determine participants; rate quality; document changes; short summary | Large randomized trial with objective MRI endpoints and clear randomized allocation; high trust.

Study Details

PMID:32679370
Participants:160
Impact:increased in multiple white-matter regions (caffeine vs placebo, p<0.05)
Trust score:5/5

blood pressure (pressor response)

1 evidences

Caffeine combined with work stress produced additive increases in blood pressure in medical students, especially those at high familial risk for hypertension.

Trust comment: Checklist: confirm human caffeine effect; identify outcomes (BP, cortisol); determine participants; rate quality; document changes; short summary | Repeated-measures study with defined risk groups (n=31) showing interactive effect of stress and caffeine on BP; moderate trust given sample and generalizability limits.

Study Details

PMID:10826397
Participants:31
Impact:caffeine plus stress produced additive increases in BP, greater in high-risk individuals
Trust score:3/5

Retrospective liking change

1 evidences

Over six pairings, drinks paired with 19 mg caffeine + 250 mg theobromine became liked more than placebo‑paired drinks, suggesting methylxanthines increase acquired liking.

Trust comment: Randomized double-blind placebo-controlled design with adequate sample (n=64); outcome is subjective liking.

Study Details

PMID:15772863
Participants:64
Impact:increased (subjective confirmation)
Trust score:4/5

vitamin B6

1 evidences

In 36 volunteers, drinking unfiltered natural coffee for 4 weeks raised plasma homocysteine, whereas modified (filtered/treated) coffee tended to lower it; other vitamins not notably reported.

Trust comment: Randomized crossover in 36 people with repeated measures; effect reported clearly for homocysteine though mechanism may involve coffee constituents beyond caffeine.

Study Details

PMID:16708634
Participants:36
Impact:no significant change reported
Trust score:4/5

blood pressure response to stress

1 evidences

In a double-blind crossover trial, caffeine taken before a mental stressor amplified cardiovascular/hemodynamic stress responses in both men and women.

Trust comment: Well-controlled double-blind, placebo-controlled crossover in 47 humans showing consistent hemodynamic effects; moderate sample size.

Study Details

PMID:16916429
Participants:47
Impact:enhanced increase during stress
Trust score:4/5

visual analog scale (VAS) for tinnitus

1 evidences

In adults with tinnitus, a single 300 mg caffeine dose did not produce clinically meaningful changes in tinnitus-related discomfort or psychoacoustic measures compared to placebo.

Trust comment: Well-powered (n=80), triple-blind randomized placebo-controlled trial with appropriate outcome measures and analyses.

Study Details

PMID:34543285
Participants:80
Impact:No significant between-group change
Trust score:5/5

whole-body sweat loss

1 evidences

In 28 participants (14 habituated, 14 non-habituated), 5 mg/kg caffeine increased end-exercise esophageal temperature and attenuated skin blood flow responses in caffeine-habituated individuals but had no effect in non-habituated participants or on sweating.

Trust comment: Randomized, double-blind, crossover with clear habituation stratification and physiological measures; sample size adequate for mechanistic outcomes.

Study Details

PMID:34435513
Participants:28
Impact:no significant change
Trust score:5/5

postoperative headache incidence (caffeine substitution)

1 evidences

Perioperative substitution of patients' usual caffeine intake prevented postoperative headaches compared with placebo in habitual consumers.

Trust comment: Randomized allocation with objective compliance checks but modest sample size and older single-center study limits strength.

Study Details

PMID:7497559
Participants:40
Impact:0% reported headache immediately after surgery; 2.5% (1/40) on postoperative day 1
Trust score:3/5

ventricular premature beats

1 evidences

In 51 patients with systolic heart failure, acute high-dose caffeine (total 500 mg) did not increase ventricular or supraventricular premature beats or exercise-derived arrhythmias compared with placebo.

Trust comment: Randomized double-blind crossover clinical trial in a relevant patient population with objective ECG monitoring; adequately powered for primary outcomes.

Study Details

PMID:27749954
Participants:51
Impact:no significant change (185 vs 239 beats; P=.47)
Trust score:5/5

attention-switching performance

1 evidences

In 27 healthy volunteers, 50 mg caffeine improved alertness and attention-switching accuracy; combined L-theanine (100 mg) plus caffeine improved speed and accuracy on attention-switching and reduced distraction in memory tasks.

Trust comment: Placebo-controlled crossover with adequate sample for cognitive testing (n=27); results are consistent and specific to combined treatment effects.

Study Details

PMID:18681988
Participants:27
Impact:improved speed and accuracy with L-theanine + caffeine (at 60 min) and accuracy improved with caffeine alone (at 90 min)
Trust score:4/5

Uchida–Kraepelin Test (UKT) performance

1 evidences

In adults 50–69, single-dose caffeine shortened reaction times on several cognitive tasks and 12-week caffeine or matcha intake preserved MMSE-J scores versus placebo; matcha additionally improved work on a stress task with continuous intake.

Trust comment: Randomized double-blind placebo-controlled parallel study with reasonable sample (n=51) and multiple cognitive endpoints; some outcomes task-specific.

Study Details

PMID:34067795
Participants:51
Impact:increase (caffeine: higher first-block score single dose; matcha: higher total/first-block after 12 weeks; p values reported)
Trust score:4/5

body weight (45 days)

1 evidences

A mixed herbal preparation containing Yerba Maté and Guarana (sources of caffeine) delayed gastric emptying and produced greater short-term weight loss versus placebo over 45 days.

Trust comment: Human placebo-controlled trials but intervention was a multi-ingredient herbal mix (not isolated caffeine), so effects cannot be attributed solely to caffeine.

Study Details

PMID:11424516
Participants:47
Impact:-5.1 ± 0.5 kg (YGD) vs -0.3 ± 0.08 kg (placebo) over 45 days)
Trust score:3/5

body weight and composition

1 evidences

Daily ingestion of a caffeine-containing supplement (≈201 mg/day) during 8 weeks of aerobic training produced no additional improvements in VO2peak, time to exhaustion, or body composition versus placebo.

Trust comment: Randomized placebo-controlled trial with moderate sample size, but supplement composition and dosing limits specificity to caffeine alone.

Study Details

PMID:17149989
Participants:36
Impact:no significant change between groups
Trust score:4/5

GLP-1 (postprandial)

1 evidences

Two randomized crossover trials in men showed beverages containing green tea catechins and coffee chlorogenic acids (with matched caffeine) raised postprandial GLP-1, lowered GIP, and reduced post-meal blood glucose compared to placebo.

Trust comment: Well-controlled randomized crossover trials with relevant biochemical endpoints and complete reporting, but modest sample sizes and male-only participants limit generalizability.

Study Details

PMID:36771483
Participants:34
Impact:increase
Trust score:4/5

acute systolic blood pressure

1 evidences

Acute ingestion of green or black tea produced larger short-term increases in clinic systolic and diastolic blood pressure than caffeine-matched water, but regular 7-day tea consumption did not significantly change 24-h ambulatory blood pressure.

Trust comment: Crossover designs and objective BP measures are strengths, but small samples in two separate cohorts and limited intervention duration reduce confidence.

Study Details

PMID:10404946
Participants:33
Impact:increase (greater with tea vs caffeine at 30 min)
Trust score:3/5

80 mg caffeine effect on accuracy

1 evidences

Sleep restriction (5 h) impaired tennis serving accuracy; a single 80 mg caffeine dose did not restore accuracy in semi-professional players.

Trust comment: Field-relevant design with two small counterbalanced studies and double-blind caffeine testing, but limited sample sizes and single caffeine dose limit conclusions.

Study Details

PMID:23916998
Participants:28
Impact:no beneficial effect
Trust score:3/5

days of apnea

1 evidences

Higher maintenance caffeine citrate dose (10 mg/kg/day vs 5 mg/kg/day) reduced extubation failure, apnea days and shortened time to extubation in very preterm infants.

Trust comment: Randomized trial in preterm infants with clear clinically relevant endpoints and adequate sample size (n=111).

Study Details

PMID:32639634
Participants:111
Impact:−1.4 days (3.2 → 1.8 days)
Trust score:5/5

postprandial glucose incremental AUC

1 evidences

In healthy adults, caffeinated coffee acutely delayed insulin rise and increased postprandial glucose exposure compared with water; effects varied by sex and BMI.

Trust comment: Randomized crossover clinical trial with measured glucose/insulin outcomes but modest sample size and subgroup findings were secondary/nominal.

Study Details

PMID:23498899
Participants:33
Impact:increase (greater IAUC vs water; P=0.009)
Trust score:4/5

Mortality

2 evidences

Early caffeine did not shorten time to first successful extubation in ventilated preterm infants and showed a non-significant trend toward higher mortality in the caffeine group.

Trust comment: Randomized, placebo-controlled neonatal trial stopped early for safety signals; adequate design but limited by early termination and sample size.

Study Details

PMID:29519541
Participants:83
Impact:higher in early caffeine group (9/41 [22%] vs 5/42 [12%], P=0.22, not statistically significant)
Trust score:3/5

Randomized comparison of caffeine versus aminophylline for apnea of prematurity showed trends toward lower risks of cognitive, motor, and language impairments with caffeine but differences were not statistically significant.

Trust comment: Randomized trial with 240 infants and objective neurodevelopmental assessment, but reported differences were not statistically significant.

Study Details

PMID:29286928
Participants:240
Impact:risk reduced (RR 0.92; 9% lower) but not statistically significant (p=0.81)
Trust score:4/5

Pressor effect consistency

1 evidences

In 165 healthy men and women across age/hormonal-status groups, acute caffeine increased systolic and diastolic blood pressure by a few mmHg.

Trust comment: Well-powered randomized crossover with clear, consistent BP increases, though single-dose challenge design limits long-term inference.

Study Details

PMID:20500126
Participants:165
Impact:Increase observed across age and sex groups
Trust score:4/5

time with SaO2 <90%

1 evidences

Extending caffeine treatment in preterm infants reduced time spent with oxygen saturation <90% (intermittent hypoxia) compared with usual care.

Trust comment: Multicenter randomized clinical trial with masked oximeter analysis and clinically relevant, objectively measured outcomes.

Study Details

PMID:24445955
Participants:95
Impact:reduced by 47% at 35 wks PMA and 45% at 36 wks PMA (to ~50 s/h)
Trust score:5/5

visual memory (24‑h delayed recall)

1 evidences

In healthy male adults, single doses of stimulants (including caffeine 200 mg as one arm) improved multiple memory measures and altered resting‑state functional connectivity; changes in connectivity related to memory enhancement.

Trust comment: Double‑blind, placebo‑controlled within‑subject fMRI study with rigorous analysis, though stimulant effects were pooled across three drugs and per‑drug group sizes were modest (≈16 each).

Study Details

PMID:35670369
Participants:48
Impact:stimulant: 21.53 ± 17.61 vs placebo: 16.77 ± 13.33 (significant improvement)
Trust score:4/5

perceived activation

1 evidences

In a double-blind crossover, 4 mg/kg caffeine increased perceived activation and pupil size and reduced variability of accommodative response, without altering accommodation accuracy.

Trust comment: Placebo-controlled, double-blind crossover with reported statistics in a defined sample (n=22), supporting internal validity.

Study Details

PMID:32011181
Participants:22
Impact:+ increased (p = .047, d = 0.48)
Trust score:4/5

Skin intrinsic fluorescence (SIF14, 456 nm)

1 evidences

In people with type 1 diabetes, habitual caffeine intake was positively associated with skin intrinsic fluorescence (SIF) measures, and this was replicated in an independent cohort.

Trust comment: Large well-characterized cohort with replication; observational design limits causal inference but associations are consistent and statistically robust.

Study Details

PMID:26192006
Participants:1185
Impact:Positive association with mean caffeine intake; caffeine explained ≈4.2% of variance in adjusted models (≈10.7% unadjusted)
Trust score:4/5

stress myocardial blood flow

1 evidences

Large PET imaging series (6087 scans) showed that even low serum caffeine reduces quantitative myocardial stress perfusion and coronary flow reserve during vasodilator stress, and in a small fraction alters coronary flow capacity interpretation (possible false negatives/positives).

Trust comment: Very large clinical dataset with quantitative PET measures and long follow-up; observational nature but robust imaging data support reliability of the reported associations.

Study Details

PMID:31056681
Participants:6087
Impact:reduced with caffeine (dipyridamole: 1.74 vs 2.14 mL/min/g; regadenoson: 1.82 vs 2.33 mL/min/g)
Trust score:4/5

post-spinal hypotension (≥20% MAP drop)

1 evidences

Preoperative 200 mg oral caffeine reduced the incidence of post-spinal hypotension and lowered vasopressor (ephedrine) requirements in adults undergoing lower limb orthopedic surgery.

Trust comment: Randomized, placebo-controlled, double-blind trial with clinically significant, clearly reported outcomes (n=79 analyzed).

Study Details

PMID:40318850
Participants:79
Impact:-27.2 percentage points (15.3% vs 42.5%)
Trust score:5/5

apnea of prematurity incidence

1 evidences

In 90 preterm neonates (1250–2000 g), prophylactic caffeine reduced duration of NCPAP and lowered apnea and IVH incidence compared to control.

Trust comment: Randomized neonatal trial with clinically meaningful reductions (n=90) though control arm lacked placebo and some outcomes have wide variance.

Study Details

PMID:35429946
Participants:90
Impact:-15.6 percentage points (4.4% vs 20%; P=0.02)
Trust score:4/5

simulated driving performance

1 evidences

During 50 h sleep deprivation, strategic caffeine gum maintained neurobehavioural performance; higher salivary alpha-amylase (sAA) was associated with better PVT response speed in the caffeine group, though the association was weaker than in placebo.

Trust comment: Double-blind placebo-controlled sleep-deprivation study with physiological and performance measures (n=23); moderate sample size but robust protocol.

Study Details

PMID:29402402
Participants:23
Impact:association with sAA not consistent across days
Trust score:4/5

driving performance (lateral lane variability)

1 evidences

Bright light combined with 100 mg caffeine gum improved driving performance and subjective sleepiness more than caffeine alone in sleep-restricted young drivers.

Trust comment: Randomized simulator study with objective and subjective measures but limited to a simulator setting and moderate sample size.

Study Details

PMID:35398627
Participants:30
Impact:improved vs placebo for Light, Caffeine, and Light+Caffeine (all P<0.0001); Light+Caffeine > Caffeine
Trust score:3/5

Adverse cardiac outcomes (combined endpoint)

1 evidences

Among 194 patients undergoing dipyridamole stress testing, ~19% who denied caffeine exposure had detectable serum caffeine; detectable caffeine was associated with higher 24-month adverse cardiac events.

Trust comment: Prospective randomized screening study with objective serum measures, but associations with outcomes may be confounded and sample size modest for outcome subgroup analyses.

Study Details

PMID:20451698
Participants:194
Impact:Detectable serum caffeine associated with higher combined endpoint incidence: 22.9% vs 7.3% (p=0.01)
Trust score:3/5

fat oxidation rate during exercise

1 evidences

In healthy young adults, single doses of caffeine (3 and 6 mg/kg) increased fat oxidation during moderate-intensity cycling, and this effect did not differ by CYP1A2 genotype.

Trust comment: Randomized double-blind crossover in humans with direct measurement of fat oxidation; pilot sample size limits precision but methods are appropriate.

Study Details

PMID:39007997
Participants:32
Impact:increase (3 and 6 mg/kg vs placebo; p<0.05 at 40–50% VO2max)
Trust score:4/5

foot reaction time

1 evidences

In trained male athletes, caffeine mouth rinse improved hand and foot reaction time, with the highest concentration (2.4%) giving the largest benefit.

Trust comment: Double-blind, randomized crossover with a reasonable sample (n=45) in trained athletes; clear effect sizes reported.

Study Details

PMID:35193478
Participants:45
Impact:+21% (2.4% CAF-MR vs placebo)
Trust score:4/5

alpha power (EEG)

1 evidences

In adults given caffeine vs placebo across weeks, caffeine produced few modest EEG changes (theta and alpha) and evidence of withdrawal/withdrawal reversal effects on EEG and mood.

Trust comment: Within-subjects controlled design addressing withdrawal but small sample and modest effects limit generalizability.

Study Details

PMID:18337638
Participants:22
Impact:modest increase across conditions (linked to withdrawal/withdrawal reversal)
Trust score:3/5

oxygenation and heart rate (subgroup)

1 evidences

In ventilated preterm infants, higher caffeine doses reduced short-term apnoea and improved oxygenation metrics but did not change extubation failure rates.

Trust comment: Randomized double-blind trial with adequate sample (n=127) though some physiological data derive from a smaller subgroup (n=37).

Study Details

PMID:12969204
Participants:127
Impact:↑ mean SpO2 and HR; ↓ time with SpO2<85% in higher-dose subgroup
Trust score:4/5

accuracy (cognitive)

1 evidences

A 3 mg/kg dose of caffeine improved reaction times on a cognitive task, including during a fatiguing motor dual-task, without changing motor force or endurance.

Trust comment: Semi-randomized double-blind crossover with n=23 and clear cognitive outcome measures; moderate sample size.

Study Details

PMID:15723227
Participants:23
Impact:no change
Trust score:4/5

post-exercise parasympathetic reactivation (SD1)

1 evidences

About 3 mg/kg caffeine increased parasympathetic reactivation after submaximal exercise (60–300 s post-exercise) but did not alter resting cardiac parasympathetic modulation or HRV threshold.

Trust comment: Balanced-placebo, crossover design with n=21 and objective HRV metrics; reasonably robust though sample modest.

Study Details

PMID:30326789
Participants:21
Impact:increased from 60 to 300 s post-exercise (p=0.01–0.05)
Trust score:4/5

relative body weight

1 evidences

In obese adolescents on a calorie-restricted diet, an ephedrine+caffeine pill produced much larger weight, BMI, and body-fat loss over 20 weeks than placebo.

Trust comment: Randomized double-blind placebo-controlled trial in adolescents with clear outcome differences, but pilot size and combined ephedrine+caffeine limit attribution to caffeine alone.

Study Details

PMID:11126208
Participants:29
Impact:-14.4% (CE group mean weight loss over 20 weeks vs -2.2% in placebo; P < 0.05)
Trust score:4/5

heavy episodic drinking

1 evidences

Survey of 4,271 US college students found that mixing energy drinks with alcohol was common and associated with higher heavy drinking and more alcohol-related harms.

Trust comment: Large, multicenter web-based cross-sectional survey with clear associations but subject to confounding and self-report biases.

Study Details

PMID:18439201
Participants:4271
Impact:higher in AmED users (6.4 days vs 3.4 days on average in past period; p < 0.001)
Trust score:3/5

total sleep time (TST) during recovery night

1 evidences

In a double-blind crossover study, moderate caffeine during 38 h wakefulness reduced recovery-night total sleep time and N3 sleep and worsened sleep continuity and EEG slow-wave power.

Trust comment: Well-controlled double-blind crossover trial with objective sleep EEG measures and adequate sample for a demanding protocol (n=41).

Study Details

PMID:39458438
Participants:41
Impact:-30.2 ± 8.2 min (acute caffeine vs placebo; significant decrease)
Trust score:5/5

gut microbiota alpha diversity (Shannon index)

1 evidences

In 58 adults, 12 weeks of catechin- and caffeine-containing green tea supplementation did not change gut microbiota composition or diversity nor body composition versus placebo.

Trust comment: Randomized single-blind placebo-controlled study but intervention combined catechins and small amounts of caffeine, so caffeine-specific effects cannot be isolated.

Study Details

PMID:27054321
Participants:58
Impact:no significant change (baseline vs week 12 vs placebo)
Trust score:3/5

cognitive performance

1 evidences

Adding low-dose caffeine (60 mg) to patients' antidepressant regimens reduced depression scores, improved cognition, and normalized stress-hormone response.

Trust comment: Clinical 4-week study with 95 inpatients showing symptomatic and biomarker changes, but results reported for males only and exact magnitudes not provided in the extract.

Study Details

PMID:28054436
Participants:95
Impact:improvement (60 mg caffeine)
Trust score:4/5

Glucose area under the curve (AUC)

1 evidences

In 27 pregnant women (19 controls, 8 with GDM) in a randomized crossover trial, acute caffeine (3 mg/kg) impaired insulin sensitivity and raised glucose and C-peptide AUCs in women with gestational diabetes but not in controls.

Trust comment: Double-blind randomized crossover design but small subgroup sizes, limiting generalizability.

Study Details

PMID:19497149
Participants:27
Impact:increased in GDM group after caffeine (P < 0.01)
Trust score:3/5

augmentation index (wave reflections)

1 evidences

Acute ingestion of black tea increased aortic stiffness briefly and both black and green tea raised wave reflections; effects were smaller than those produced by isolated caffeine.

Trust comment: Randomized crossover with objective vascular measures but modest sample size and acute setting; single-blind design reduces strength of inference about caffeine alone.

Study Details

PMID:16766780
Participants:29
Impact:augmentation index +5.0% (black tea) and +6.6% (green tea)
Trust score:3/5

Plasma adrenaline

1 evidences

In 110 men, acute caffeine raised systolic and diastolic blood pressure modestly (~+4 mmHg and +3 mmHg) and increased plasma adrenaline.

Trust comment: Well-controlled double-blind crossover with objective BP and genetic analyses; sample size moderate and measures robust.

Study Details

PMID:22170367
Participants:110
Impact:increased (after caffeine)
Trust score:4/5

Postoperative pain severity (VRS 1 day)

1 evidences

Preoperative Novafen (acetaminophen + ibuprofen + 40 mg caffeine) produced small reductions in postoperative pain scores at several timepoints versus placebo.

Trust comment: Randomized double‑blind trial (n=70) with standard pain scales, but reporting contains internal inconsistencies and the analgesic combines multiple drugs including caffeine.

Study Details

PMID:28616088
Participants:70
Impact:−0.26 (VRS; 2.94 vs 3.20)
Trust score:3/5

pain intensity

2 evidences

A nonprescription combination including caffeine (with acetaminophen and aspirin) provided greater pain relief and functional improvement than placebo in OTC-appropriate migraine sufferers.

Trust comment: Large randomized placebo-controlled trials, but caffeine was part of a multi-ingredient combination so effects cannot be attributed to caffeine alone.

Study Details

PMID:10524663
Participants:1220
Impact:greater reduction with AAC (significant from 0.5–6 h)
Trust score:3/5

After outpatient general surgery, analgesia was similar between the codeine+acetaminophen+caffeine regimen and acetaminophen+ibuprofen, but the codeine+caffeine group had more side effects and lower satisfaction.

Trust comment: Double-blind randomized trial with high completion (95%); results are credible though effects reflect a combination product rather than caffeine alone.

Study Details

PMID:18308218
Participants:139
Impact:No significant difference overall; acetaminophen+ibuprofen had modestly lower mean VAS over the week (p=0.018) and lower pain on postop day 2 (p=0.025).
Trust score:4/5

cardiac and inflammatory biomarkers

1 evidences

Daily caffeine 250 mg (alone or with DMAA) for 12 weeks produced no statistically significant adverse changes in measured clinical or laboratory outcomes.

Trust comment: Randomized 12-week supplementation with comprehensive safety measures in 50 completing subjects; limited to healthy young men.

Study Details

PMID:23424215
Participants:50
Impact:no significant change (12-week supplementation vs baseline)
Trust score:4/5

Digit–Symbol accuracy

1 evidences

An 80 mg-caffeine energy drink improved some working-memory and attention measures and partially antagonised alcohol-induced errors on select tasks at specific timepoints.

Trust comment: Crossover, double-blind within-subject design (n=24) with repeated measures and effect sizes reported, but small sample limits power for multiple comparisons.

Study Details

PMID:30625179
Participants:24
Impact:fewer errors with ED (significant ED main effects; fewer errors at 45 and 90 min vs some conditions)
Trust score:4/5

adiponectin

1 evidences

In overweight adults, 8 weeks of caffeinated coffee increased adiponectin and IL‑6 while decaffeinated coffee lowered fetuin‑A; no change in glucose tolerance.

Trust comment: Randomized, blinded 8-week trial measuring objective biomarkers but limited by small sample size (n=41 completed).

Study Details

PMID:21914162
Participants:41
Impact:+1.44 μg/mL (caffeinated vs no coffee)
Trust score:4/5

Total sleep time (actigraphy)

1 evidences

Neonatal caffeine therapy was not associated with differences in sleep duration or sleep-disordered breathing at school age.

Trust comment: Long-term follow-up of a randomized neonatal trial with objective sleep measures in a large sample (n=201).

Study Details

PMID:25171195
Participants:201
Impact:No significant difference (adjusted mean difference -6.7 min; P=0.13)
Trust score:5/5

Analgesic effect (pain relief)

1 evidences

Adding caffeine to ibuprofen sped pain relief onset and increased analgesic effect at 45–60 minutes after single-dose administration, with few adverse events.

Trust comment: Randomized, double-blind, placebo-controlled single-dose trial (n=161) showing caffeine enhances ibuprofen analgesia with limited adverse events.

Study Details

PMID:8880847
Participants:161
Impact:Increased analgesia when caffeine added to ibuprofen 200 mg (significant at 45 and 60 min vs ibuprofen 200 mg alone)
Trust score:4/5

Global cognitive scores (MoCA-J, ADCS-MCI-ADL)

1 evidences

In older adults with SCD or MCI, daily matcha (contains caffeine, theanine, catechins) for 12 months improved emotional perception/social acuity and showed a trend toward better sleep quality, but did not change primary global cognitive scores.

Trust comment: 12-month randomized, double-blind trial (n≈99 randomized; ~91 completed questionnaires) with good compliance and objective neurocognitive measures.

Study Details

PMID:39213264
Participants:91
Impact:No significant change vs placebo
Trust score:4/5

duration of respiratory support (intubation, NCPAP, oxygen)

1 evidences

Early caffeine in 59 preterm infants reduced ventilator needs, shortened respiratory support times, lowered VAP, and reduced post-extubation apnea.

Trust comment: Prospective controlled clinical trial with clinically relevant neonatal outcomes in 59 infants; moderate sample size.

Study Details

PMID:27974112
Participants:59
Impact:shorter duration
Trust score:4/5

plasma epinephrine

2 evidences

Single 6 mg/kg caffeine increased blood pressure and tidal volume and raised plasma caffeine concentrations; epinephrine rose in able-bodied and paraplegic but not tetraplegic participants, with limited HRV changes.

Trust comment: Randomized, double‑blind, placebo‑controlled crossover with objective physiological measures, but subgroup sizes are small (n per subgroup limited).

Study Details

PMID:27776149
Participants:28
Impact:increased significantly in able‑bodied and paraplegic participants, not in tetraplegic
Trust score:4/5

In healthy elderly adults, 6 mg/kg caffeine increased plasma epinephrine, free fatty acids, and lactate (percent increases consistent at rest, 5 min, and exhaustion), and increased insulin-resistance measures.

Trust comment: Randomized double-blind crossover in 30 elderly subjects with clear metabolic measures; moderate sample size but robust findings.

Study Details

PMID:16886964
Participants:30
Impact:+~42% (rest), +39% (5 min), +49% (exhaustion)
Trust score:4/5

Recovery sleep architecture

1 evidences

During 40.5 h sleep deprivation, caffeine reduced sleep drive compared with placebo but did not improve sleep-related recovery measures; other stimulants had differing effects.

Trust comment: Well-powered randomized double-blind pharmacologic comparison in humans (n=76), though specific numeric sleep metrics for caffeine are not reported here.

Study Details

PMID:12887139
Participants:76
Impact:Caffeine did not significantly improve recovery sleep measures; phentermine impaired REM recovery sleep
Trust score:4/5

Acute post-consumption homocysteine (4 h)

1 evidences

Two-week ingestion of caffeine capsules (≈870 mg/day) produced a small but significant increase in fasting plasma homocysteine (~+0.4 µmol/L, ≈+5%), indicating caffeine partly contributes to coffee's homocysteine-raising effect.

Trust comment: Randomized crossover (n=48) with clear biochemical endpoints; results consistent though effects are modest.

Study Details

PMID:12450889
Participants:48
Impact:Caffeine had a weak acute effect (+4%, P=0.09) while coffee showed a larger acute rise (~+19% at 4 h)
Trust score:4/5

C-peptide AUC

2 evidences

In healthy adults, increasing caffeine doses impaired insulin sensitivity and raised insulin, C-peptide, and glucose responses in a dose-dependent way.

Trust comment: Randomized double-blind crossover study in 24 healthy volunteers with dose-response modelling supports internal validity.

Study Details

PMID:23438224
Participants:24
Impact:+8.7% per 1 mg/kg
Trust score:5/5

In 27 pregnant women (19 controls, 8 with GDM) in a randomized crossover trial, acute caffeine (3 mg/kg) impaired insulin sensitivity and raised glucose and C-peptide AUCs in women with gestational diabetes but not in controls.

Trust comment: Double-blind randomized crossover design but small subgroup sizes, limiting generalizability.

Study Details

PMID:19497149
Participants:27
Impact:increased in GDM group after caffeine (P < 0.05)
Trust score:3/5

time to 24-hour apnea-free period

1 evidences

In infants with bronchiolitis-associated apnea, a single IV caffeine dose did not shorten time to a 24-hour apnea-free period compared with placebo.

Trust comment: Double-blind randomized parallel trial in infants with objective monitoring, but single-dose design and sample-size/power limitations noted.

Study Details

PMID:27189681
Participants:85
Impact:geometric mean 28.7 h (caffeine) vs 29.1 h (placebo); OR 0.99, P=0.88 (no difference)
Trust score:4/5

tachycardia / heart rate

1 evidences

Late preterm infants were randomized to placebo or varying doses of caffeine citrate; overnight oximetry measured intermittent hypoxaemia and cardiorespiratory outcomes.

Trust comment: Large randomized, double-blind, placebo-controlled dosage trial with objective oximetry outcomes, though some attrition and dose-comparison limits exist.

Study Details

PMID:36038256
Participants:107
Impact:time with HR>180 and mean HR increased (any caffeine: increased tachycardia and mean HR change ~+4.6 bpm at 2 weeks)
Trust score:5/5

subjective sleepiness (KSS)

1 evidences

A 250-ml Red Bull (80 mg caffeine) consumed during a short break improved driving stability and reduced sleepiness for about 2 hours compared with placebo or no break.

Trust comment: Well-controlled double-blind crossover simulator study with objective and subjective endpoints, moderate sample (n=21) and some simulator limitations.

Study Details

PMID:21063868
Participants:21
Impact:decrease (hour 3: −2.14 points; hour 4: −1.24 points vs placebo)
Trust score:4/5

V̇o2peak time to exhaustion (BAC)

1 evidences

Acute multi-ingredient preworkout supplements (one formulation contained caffeine) modestly improved anaerobic power and some endurance and vascular measures versus placebo; caffeine was one of several active ingredients.

Trust comment: Randomized crossover with n=30 but multi-ingredient formulations make isolating caffeine-specific effects uncertain.

Study Details

PMID:32569125
Participants:30
Impact:increase (p=0.006) with BAC formulation containing caffeine
Trust score:3/5

vertical jump performance

1 evidences

In competitive male athletes, caffeine had no overall effect on strength/power, but 4 mg/kg caffeine reduced handgrip strength by ~12.8% in individuals with the CYP1A2 CC genotype.

Trust comment: Well-powered randomized controlled trial with genotype stratification revealing a genotype-dependent adverse effect; good internal validity.

Study Details

PMID:34284351
Participants:102
Impact:no change overall (no differences between caffeine doses and placebo)
Trust score:4/5

plasma potassium

1 evidences

In 30 resistance-trained men, acute caffeine (6 mg/kg) increased blood lactate during resistance exercise, with greater lactate elevations in carriers of the MCT1 A allele (TA+AA) versus TT genotype; potassium responses varied by genotype and intervention.

Trust comment: Controlled crossover genetic study with objective measures but small, specific athletic sample limiting broad applicability.

Study Details

PMID:39771017
Participants:30
Impact:increased after exercise (time effect); caffeine moderated post-exercise K+ rise in TT genotype
Trust score:3/5

muscle strength (1-RM)

1 evidences

In 28 trained young adults randomized to creatine, caffeine, creatine+caffeine, or placebo during 6 weeks training, creatine increased knee extensor thickness but caffeine produced no clear benefits.

Trust comment: Randomized trial but small group sizes per arm and modest duration; findings reliable for lack of caffeine effect within this sample.

Study Details

PMID:33759701
Participants:28
Impact:no between-group differences including caffeine
Trust score:3/5

psychomotor performance (finger tapping)

1 evidences

Sixty abstinent coffee drinkers received decaf with 0 or 280 mg caffeine crossed with expectancy instructions; caffeine improved vigilance and psychomotor speed and expectancy altered subjective and some behavioral outcomes.

Trust comment: Well-powered (n=60) factorial, double-blind design assessing both pharmacology and expectancy; conclusions on behavioral effects are robust.

Study Details

PMID:19760283
Participants:60
Impact:improved with caffeine
Trust score:4/5

plasma homocysteine

1 evidences

In 36 volunteers, drinking unfiltered natural coffee for 4 weeks raised plasma homocysteine, whereas modified (filtered/treated) coffee tended to lower it; other vitamins not notably reported.

Trust comment: Randomized crossover in 36 people with repeated measures; effect reported clearly for homocysteine though mechanism may involve coffee constituents beyond caffeine.

Study Details

PMID:16708634
Participants:36
Impact:increased from 9.6 to 11.4 µmol/L (+1.8 µmol/L, +18.8%) with natural coffee
Trust score:4/5

Backache

1 evidences

In 320 women with moderate-to-severe dysmenorrhoea, paracetamol (1 g) plus caffeine (130 mg) provided greater pain relief at 2 hours and better relief of cramping and backache than paracetamol alone, caffeine alone, or placebo.

Trust comment: Large (n=320), randomized double-blind crossover with clinically relevant endpoints and clear significant differences.

Study Details

PMID:17407641
Participants:320
Impact:greater relief with combination vs comparators
Trust score:5/5

liking of SSB

1 evidences

In a 6-week double-blind randomized free-living trial, adding caffeine to a sugar-sweetened beverage increased ad libitum consumption compared with the non-caffeinated version.

Trust comment: Large randomized double-blind free-living trial with 99 completers and objective consumption records, supporting ecological validity.

Study Details

PMID:25567475
Participants:99
Impact:slightly higher liking (6.3 vs 6.0)
Trust score:4/5

extended learning / retention

1 evidences

In 93 college-age moderate caffeine users, caffeine improved initial acquisition (accuracy and latency) on a proprioceptive force-discrimination learning task but did not improve performance beyond normal practice.

Trust comment: Large sample and multiple measured outcomes but single-session laboratory task in moderate users limits ecological validity for broader claims.

Study Details

PMID:8774028
Participants:93
Impact:No improvement beyond normal practice
Trust score:3/5

average power (first 30s and 60s, paraplegic)

1 evidences

Caffeine improved short-duration arm-crank power in paraplegic participants but showed no clear ergogenic effect in tetraplegic or able-bodied groups.

Trust comment: Randomized, double-blind, placebo-controlled crossover trial with clearly reported subgroup results but modest sample size.

Study Details

PMID:26132642
Participants:34
Impact:increased (significant in paraplegic group; p=0.028 and p=0.005)
Trust score:4/5

catecholamines (plasma epinephrine/norepinephrine)

1 evidences

Caffeine improved short-duration arm-crank power in paraplegic participants but showed no clear ergogenic effect in tetraplegic or able-bodied groups.

Trust comment: Randomized, double-blind, placebo-controlled crossover trial with clearly reported subgroup results but modest sample size.

Study Details

PMID:26132642
Participants:34
Impact:epinephrine increased (AB p=0.002; P p=0.018); norepinephrine increased in AB (p=0.018)
Trust score:4/5

10-km cycling time (endurance performance)

1 evidences

In 100 male athletes performing 10-km cycling trials, 4 mg/kg caffeine improved endurance time selectively in individuals with HTR2A CC genotype who were also CYP1A2 fast metabolizers.

Trust comment: Randomized, double-blind, placebo-controlled design with a large overall sample, but key effects are from genotype-defined subgroups of limited size.

Study Details

PMID:32569126
Participants:100
Impact:-2.4 minutes improvement with 4 mg·kg⁻¹ caffeine in HTR2A CC genotype among CYP1A2 fast metabolizers (subgroup)
Trust score:4/5

cognition (MoCA)

1 evidences

In a multicenter RCT of 200 mg twice daily caffeine vs placebo in Parkinson’s disease (n=121), caffeine did not improve motor scores and had minor adverse effects on cognition and dyskinesia.

Trust comment: Well-powered, multicenter randomized controlled trial (Class I evidence) with clear primary and secondary outcome reporting.

Study Details

PMID:28954882
Participants:121
Impact:worse by 0.66 points on average versus placebo
Trust score:5/5

MMSE-J score (12 weeks)

1 evidences

In adults 50–69, single-dose caffeine shortened reaction times on several cognitive tasks and 12-week caffeine or matcha intake preserved MMSE-J scores versus placebo; matcha additionally improved work on a stress task with continuous intake.

Trust comment: Randomized double-blind placebo-controlled parallel study with reasonable sample (n=51) and multiple cognitive endpoints; some outcomes task-specific.

Study Details

PMID:34067795
Participants:51
Impact:increase (caffeine and matcha > placebo at 12 weeks; caffeine p=0.016)
Trust score:4/5

procedure and ablation times

1 evidences

Preprocedural oral caffeine (5 mg/kg) increased PVC counts during isoproterenol washout, increased PVC count fluctuation, and shortened procedure and ablation times during catheter ablation.

Trust comment: Randomized clinical study in 70 patients with clear ECG/ procedural endpoints; moderate sample and clinically relevant findings.

Study Details

PMID:32500131
Participants:70
Impact:decrease (procedure time 105.0 ± 23.4 vs 136.9 ± 43.2 min; ablation time 219.1 ± 104.7 vs 283.5 ± 136.0 sec; both p<0.01)
Trust score:4/5

postexercise cortisol

1 evidences

Single 6 mg/kg caffeine dose before a triathlon slightly improved swim and overall completion times and increased postexercise cortisol and peak blood lactate.

Trust comment: Well-designed double-blind randomized crossover field trial in trained triathletes with objective performance and biochemical outcomes.

Study Details

PMID:29345161
Participants:26
Impact:+122 nmol/L (665 ± 200 vs 543 ± 169 nmol/L, p<0.0001)
Trust score:5/5

complex reaction time (COGRT) at halftime

1 evidences

A single 275 mg caffeine dose (or 150 mg caffeine + 125 mg theacrine) produced modest improvements in some reaction-time measures and trended to increase time-to-exhaustion versus placebo.

Trust comment: Within-subject, double-blind design in trained athletes with objective endpoints, though some effects were small or only trending and sample is modest.

Study Details

PMID:30999897
Participants:24
Impact:faster: CAF 0.658 ± 0.047 s vs PL 0.676 ± 0.059 s (difference ≈ -0.018 s, p=0.049)
Trust score:4/5

VO2peak

1 evidences

Daily ingestion of a caffeine-containing supplement (≈201 mg/day) during 8 weeks of aerobic training produced no additional improvements in VO2peak, time to exhaustion, or body composition versus placebo.

Trust comment: Randomized placebo-controlled trial with moderate sample size, but supplement composition and dosing limits specificity to caffeine alone.

Study Details

PMID:17149989
Participants:36
Impact:no significant change between groups (no ergogenic effect)
Trust score:4/5

strength endurance (total repetitions)

1 evidences

Acute caffeine (6 mg/kg) improved countermovement jump performance and total repetitions in strength endurance tests regardless of habitual caffeine intake level.

Trust comment: Double-blind crossover with reasonable sample (n=36) and stratification by habitual intake; credible results though specific to trained individuals.

Study Details

PMID:34010807
Participants:36
Impact:significant increase vs placebo (p = 0.004)
Trust score:4/5

rule violations

1 evidences

During 40-h sleep deprivation, caffeine preserved simple response output but did not prevent many executive-function deficits on a random number task.

Trust comment: Well-controlled randomized crossover sleep-deprivation study with objective cognitive measures, moderate sample size.

Study Details

PMID:16490000
Participants:21
Impact:3-fold increase with sleep deprivation; caffeine had no effect
Trust score:4/5

phenotypic metabolic indices

1 evidences

Adding caffeine to a multi-drug probe cocktail did not produce meaningful metabolic interactions for measured enzyme probe drugs, though a small increase in one flurbiprofen metric occurred.

Trust comment: Well-controlled randomized crossover in healthy adults with appropriate pharmacokinetic endpoints, moderate sample size.

Study Details

PMID:16952492
Participants:24
Impact:no significant change (within 80–125% bioequivalence range)
Trust score:4/5

20-m sprint and Illinois change-of-direction speed (CODS)

1 evidences

Male collegiate basketball players doing 6 weeks of plyometric training improved performance and physiology; ingesting caffeine 1 h before sessions (especially 6 mg/kg) produced slightly larger and more uniform adaptations than placebo.

Trust comment: Randomized double-blind placebo-controlled trial with clear methods and complete follow-up but small sample (n=24) and male-only participants.

Study Details

PMID:38971848
Participants:24
Impact:improved in all groups; CAF3 & CAF6 showed medium-large effects (e.g., CAF6 20-m ES=–0.61, p=0.026)
Trust score:4/5

Tachycardia episodes

1 evidences

In 120 preterm infants, higher-dose caffeine citrate reduced extubation failure and apnea frequency/duration but increased episodes of tachycardia.

Trust comment: Double-blind RCT in a relevant neonatal population with clear clinical endpoints, though age-specific safety monitoring required.

Study Details

PMID:25644724
Participants:120
Impact:Significant increase (p<0.05)
Trust score:4/5

Systolic blood pressure (post-regadenoson)

1 evidences

In patients undergoing regadenoson-stress SPECT MPI, ingestion of caffeine (200–400 mg) 90 minutes before testing reduced the number and severity of detected reversible perfusion defects and altered BP/HR responses.

Trust comment: Large, multicenter, randomized placebo-controlled trial with blinded core lab reads and robust analyses.

Study Details

PMID:24737255
Participants:207
Impact:Approx. +9 mmHg (caffeine vs placebo at certain timepoints)
Trust score:5/5

sleep duration

2 evidences

A brief school-based intervention modestly reduced electronic media use at night but did not change adolescents' caffeine consumption, sleep duration, or secondary outcomes.

Trust comment: Pilot cluster-randomized design with reasonable sample size but limited effect sizes and short follow-up, reducing strength of conclusions.

Study Details

PMID:30611715
Participants:352
Impact:No change
Trust score:3/5

Stopping coffee in iron-deficient Guatemalan toddlers increased night and total sleep but did not change cognitive test scores.

Trust comment: Randomized assignment with masked testers in 132 toddlers and repeated sleep assessments; reasonable quality.

Study Details

PMID:10088991
Participants:132
Impact:increased (Substitute group slept more at final visit vs Coffee)
Trust score:4/5

exercise heat tolerance time (EHT)

1 evidences

Chronic (3 or 6 mg/kg/day) and acute caffeine did not alter most fluid-electrolyte, thermoregulatory or cardiovascular responses during a heat exercise test, though one treatment group had longer tolerance time.

Trust comment: Moderately sized randomized, stratified study (n=59) with controlled dosing and objective physiological measures.

Study Details

PMID:16491580
Participants:59
Impact:G3: 86 ± 2.0 min vs G0: 75 ± 3.3 min (G3 > G0, P<0.05)
Trust score:4/5

index of sexual satisfaction (ISS)

1 evidences

On-demand 100 mg caffeine before intercourse increased ejaculation latency and sexual satisfaction versus placebo.

Trust comment: Double-blind RCT but small sample and some ambiguity in reported p-values, limiting certainty.

Study Details

PMID:25601604
Participants:40
Impact:significant increase (post-treatment vs pre-treatment in caffeine group)
Trust score:3/5

ibuprofen pharmacokinetics (Cmax, AUC, tmax)

1 evidences

Caffeine 100 mg in the fixed-dose combination was rapidly absorbed and did not alter ibuprofen pharmacokinetics; ibuprofen PK comparable with/without caffeine.

Trust comment: Two well-controlled randomized crossover PK studies in healthy volunteers with validated bioanalytical methods; moderate sample size for PK studies.

Study Details

PMID:30897305
Participants:72
Impact:no relevant effect from co-administered caffeine (100 mg)
Trust score:4/5

voiding frequency

1 evidences

In women with urinary incontinence, reducing fluid intake improved some symptoms, but switching from caffeinated to decaffeinated drinks did not improve urinary symptoms.

Trust comment: Randomized crossover trial with objective diary measures and 69 completers, though effects of caffeine restriction were negative while fluid changes showed benefit.

Study Details

PMID:15947624
Participants:69
Impact:decreased (significant) with decreased fluid intake (IDO group)
Trust score:4/5

coronary flow reserve (CFR)

1 evidences

Large PET imaging series (6087 scans) showed that even low serum caffeine reduces quantitative myocardial stress perfusion and coronary flow reserve during vasodilator stress, and in a small fraction alters coronary flow capacity interpretation (possible false negatives/positives).

Trust comment: Very large clinical dataset with quantitative PET measures and long follow-up; observational nature but robust imaging data support reliability of the reported associations.

Study Details

PMID:31056681
Participants:6087
Impact:reduced with caffeine (dipyridamole: 2.26 vs 2.67; regadenoson: 1.84 vs 2.31)
Trust score:4/5

ephedrine requirement (number of patients and dose)

1 evidences

Preoperative 200 mg oral caffeine reduced the incidence of post-spinal hypotension and lowered vasopressor (ephedrine) requirements in adults undergoing lower limb orthopedic surgery.

Trust comment: Randomized, placebo-controlled, double-blind trial with clinically significant, clearly reported outcomes (n=79 analyzed).

Study Details

PMID:40318850
Participants:79
Impact:decreased (fewer patients required ephedrine and lower amount per patient)
Trust score:5/5

cognitive performance (task-based)

1 evidences

In a randomized crossover trial, a 75 mg caffeine positive-control produced consistent alerting and performance-enhancing effects versus placebo in healthy adults (n=72).

Trust comment: Well-powered, pre-registered, randomized double-blind crossover with clear positive-control effects (n=72), supporting internal validity.

Study Details

PMID:37299382
Participants:72
Impact:improved (performance-enhancing effects across multiple outcomes vs placebo)
Trust score:5/5

intraventricular hemorrhage (IVH) incidence

1 evidences

In 90 preterm neonates (1250–2000 g), prophylactic caffeine reduced duration of NCPAP and lowered apnea and IVH incidence compared to control.

Trust comment: Randomized neonatal trial with clinically meaningful reductions (n=90) though control arm lacked placebo and some outcomes have wide variance.

Study Details

PMID:35429946
Participants:90
Impact:decreased in caffeine group (P=0.03)
Trust score:4/5

cognitive accuracy

1 evidences

In children who habitually consume caffeine, a 50 mg dose after overnight abstinence restored cognitive accuracy, prevented withdrawal headache, and increased alertness; non/low-consumers showed no clear benefit.

Trust comment: Randomized double-blind placebo-controlled trial in children (n=26); small sample but appropriate design.

Study Details

PMID:16423144
Participants:26
Impact:improved to near non/low-consumer baseline (in habitual consumers)
Trust score:4/5

apnea frequency

2 evidences

In preterm infants <33 weeks, caffeine reduced apnea frequency during the first week of therapy and appeared advantageous over theophylline early on.

Trust comment: Randomized controlled trial in 70 neonates showing early benefit of caffeine; open-label design and limited sustained effect reduce certainty slightly.

Study Details

PMID:19751376
Participants:70
Impact:decreased with caffeine (significant in first week; combined data P=0.001)
Trust score:4/5

In preterm infants with primary apnea, a higher maintenance dose of caffeine citrate improved apnea control and ventilator weaning success without increasing measured side effects.

Trust comment: Prospective randomized allocation with moderate-to-large sample (n=164); outcomes and safety reported, though single-center.

Study Details

PMID:26791921
Participants:164
Impact:median 10 (8,15) vs 18 (13,22); lower in high-dose group
Trust score:4/5

plasma SHBG levels

1 evidences

Higher caffeinated coffee/caffeine intake was associated with higher plasma SHBG and lower type 2 diabetes risk; adjustment for SHBG attenuated the diabetes association.

Trust comment: Large prospective nested case-control with biomarker and genotype data; observational design means residual confounding possible.

Study Details

PMID:21030499
Participants:718
Impact:higher with caffeinated coffee/caffeine (e.g., 26.6 vs 23.0 nmol/L for ≥4 cups/day vs nondrinkers; P for trend=0.01)
Trust score:4/5

Apnea prevention (overall)

1 evidences

In 240 preterm neonates with apnea, caffeine citrate was similarly effective to aminophylline overall, with caffeine showing a lower risk of tachycardia and lower mean heart rate.

Trust comment: Well-powered randomized controlled trial in the target population with clinically relevant endpoints.

Study Details

PMID:28474588
Participants:240
Impact:No significant difference in mean apnea rate between caffeine and aminophylline (similar efficacy)
Trust score:5/5

Intensive vs routine screening efficacy

1 evidences

Among 194 patients undergoing dipyridamole stress testing, ~19% who denied caffeine exposure had detectable serum caffeine; detectable caffeine was associated with higher 24-month adverse cardiac events.

Trust comment: Prospective randomized screening study with objective serum measures, but associations with outcomes may be confounded and sample size modest for outcome subgroup analyses.

Study Details

PMID:20451698
Participants:194
Impact:No significant difference in screening-arm seropositivity (16% vs 22%, p=0.31)
Trust score:3/5

cued-recall and recognition memory

1 evidences

Experimental induction of caffeine craving impaired memory performance and some metacognitive judgments compared to control.

Trust comment: Experimental human study (n=55) manipulating craving state; applicable to craving-related cognitive effects but not acute caffeine ingestion effects per se.

Study Details

PMID:28276980
Participants:55
Impact:impaired performance under caffeine craving vs control (reduced recall and recognition)
Trust score:3/5

daily frequency of apnea

1 evidences

Both domestic and imported caffeine citrate were similarly safe and effective for treating apnea in preterm infants.

Trust comment: Prospective randomized double-blind RCT in 98 preterm infants with clinical endpoints reported; reasonable quality.

Study Details

PMID:32669161
Participants:98
Impact:no significant difference between groups (P>0.05)
Trust score:4/5

motor steadiness error count

1 evidences

300 mg caffeine worsened motor steadiness (more errors) in healthy adult females.

Trust comment: Randomized double-blind crossover design but small sample (n=24) and limited to females.

Study Details

PMID:7650108
Participants:24
Impact:increased after 300 mg caffeine (significant)
Trust score:3/5

serum caffeine concentration change

1 evidences

Caffeine has a long half-life in preterm infants and many infants had pathologic apnea days after stopping caffeine.

Trust comment: Prospective cohort with measured drug levels and clinical monitoring in 50 preterm infants; clear pharmacokinetic data.

Study Details

PMID:26562367
Participants:50
Impact:decreased from 13.3 ± 3.8 to 4.3 ± 2 mg/L (24 h to 168 h)
Trust score:4/5

psychomotor performance (simple reaction time)

1 evidences

A single cup-equivalent dose after overnight abstinence increased energetic mood and improved psychomotor performance; additional spaced doses added little.

Trust comment: Double-blind randomized design with 64 moderate caffeine consumers; well-controlled behavioral measures.

Study Details

PMID:9862086
Participants:64
Impact:improved; reduced time-on-task slowing and removed post-lunch dip
Trust score:4/5

supplementary inspired oxygen requirement

1 evidences

Caffeine improved neonatal respiratory compliance and reduced oxygen needs earlier than theophylline.

Trust comment: Randomized neonatal study with protocol completion in 45 infants and objective respiratory measures; solid but pediatric-specific.

Study Details

PMID:9483391
Participants:45
Impact:reduced; greater reduction at 24 h with caffeine vs theophylline (p<0.05)
Trust score:4/5

parietal and left prefrontal cortex activation

1 evidences

Combined caffeine and glucose did not change behavioral sustained attention but reduced activation in attention-related brain regions, suggesting increased neural efficiency.

Trust comment: Double-blind randomized fMRI study (n=40) exploratory in nature; neural changes reported without behavioral gains.

Study Details

PMID:21312288
Participants:40
Impact:decreased activation with combined caffeine + glucose (30 min post-dose)
Trust score:3/5

time to peak power

1 evidences

NaHCO3 and caffeine each improved some aspects of repeated-sprint performance, but their coingestion did not produce a synergistic benefit.

Trust comment: Randomized double-blind placebo-controlled crossover with objective performance measures but modest sample size.

Study Details

PMID:38335952
Participants:25
Impact:decrease (CAF in Wt1: −8.5%; p=0.008)
Trust score:4/5

Bayley-III developmental scores at 2 years

1 evidences

In very preterm infants randomized to early high- vs standard-dose caffeine, high-dose was associated with higher rates of cerebellar hemorrhage and subtle neonatal neurobehavioral differences but no detectable 2-year developmental differences in this pilot trial.

Trust comment: Pilot randomized trial with clinically important safety signals but single-center and limited power for long-term outcomes.

Study Details

PMID:25856169
Participants:74
Impact:no significant difference between groups
Trust score:3/5

extubation failure

3 evidences

In ventilated preterm infants, higher caffeine doses reduced short-term apnoea and improved oxygenation metrics but did not change extubation failure rates.

Trust comment: Randomized double-blind trial with adequate sample (n=127) though some physiological data derive from a smaller subgroup (n=37).

Study Details

PMID:12969204
Participants:127
Impact:no significant difference between doses
Trust score:4/5

Higher maintenance caffeine citrate dose (10 mg/kg/day vs 5 mg/kg/day) reduced extubation failure, apnea days and shortened time to extubation in very preterm infants.

Trust comment: Randomized trial in preterm infants with clear clinically relevant endpoints and adequate sample size (n=111).

Study Details

PMID:32639634
Participants:111
Impact:reduced from 36.8% to 16.7% (−20.1 percentage points)
Trust score:5/5

In 120 preterm infants, higher-dose caffeine citrate reduced extubation failure and apnea frequency/duration but increased episodes of tachycardia.

Trust comment: Double-blind RCT in a relevant neonatal population with clear clinical endpoints, though age-specific safety monitoring required.

Study Details

PMID:25644724
Participants:120
Impact:Significant reduction (p<0.05) with high-dose caffeine
Trust score:4/5

squat repetitions until failure (first set)

1 evidences

In 27 male rugby players, 3 mg/kg caffeine (capsule, gum, or mouth rinse) produced limited effects: a small increase in countermovement-jump height and one-set squat endurance, but most strength/power measures were unchanged.

Trust comment: Well-designed double-blind, mode-matched placebo crossover in athletes (n=27); effects were generally small and outcome-specific.

Study Details

PMID:39439175
Participants:27
Impact:+~1 repetition (13 → 14 reps in first set; significant, d ≈ 0.48)
Trust score:4/5

maximal power output (takeoff)

1 evidences

In 26 recreationally trained men, acute caffeine (6 mg/kg) increased countermovement jump height versus control and versus placebo; maximal power output was unchanged.

Trust comment: Randomized double-blind crossover in recreational athletes with clear performance measures; moderate sample size.

Study Details

PMID:32707561
Participants:26
Impact:no significant change
Trust score:4/5

recency (temporal) memory

1 evidences

In 40 young adults, 36 h sleep deprivation impaired temporal (recency) memory; a single 350 mg caffeine dose reduced subjective sleepiness but did not restore temporal memory performance.

Trust comment: Randomized placebo-controlled groups with neuropsychological endpoints; caffeine given acutely and effects on sleepiness measured, but cognitive remediation was not observed.

Study Details

PMID:10718074
Participants:40
Impact:impaired by sleep deprivation; no improvement with caffeine
Trust score:4/5

recognition memory

1 evidences

In 40 young adults, 36 h sleep deprivation impaired temporal (recency) memory; a single 350 mg caffeine dose reduced subjective sleepiness but did not restore temporal memory performance.

Trust comment: Randomized placebo-controlled groups with neuropsychological endpoints; caffeine given acutely and effects on sleepiness measured, but cognitive remediation was not observed.

Study Details

PMID:10718074
Participants:40
Impact:no significant impairment from sleep deprivation
Trust score:4/5

cognitive function

1 evidences

Amounts of caffeine plus theobromine present in normal portions of chocolate improved energetic arousal and cognitive function versus placebo/white chocolate.

Trust comment: Two double-blind placebo-controlled experiments (n=20 and n=22) showing consistent mood and cognitive effects at chocolate-equivalent methylxanthine doses.

Study Details

PMID:15549276
Participants:42
Impact:improved with cocoa/methylxanthine doses
Trust score:4/5

Rate–pressure product (cardiac workload)

1 evidences

In 20 mild hypertensive and 12 normotensive men (total 32), caffeine increased blood pressure and rate-pressure product at rest and during exercise, raising cardiac workload in hypertensives.

Trust comment: Controlled study showing consistent hemodynamic effects, but older work and modest sample sizes (particularly per subgroup) moderate confidence.

Study Details

PMID:8998252
Participants:32
Impact:increase
Trust score:3/5

GI complaint incidence (overall)

1 evidences

During an 18-km run, sports drinks increased gastrointestinal complaint incidence versus water; adding caffeine (150 mg/L) to the sports drink did not affect running performance or GI complaints compared with the sports drink without caffeine.

Trust comment: Large randomized crossover field study with controlled intake and good external validity for runners; outcomes are self-reported GI symptoms which may be subjective.

Study Details

PMID:15795812
Participants:98
Impact:increased with carbohydrate sports drinks vs water (e.g., flatulence and reflux higher with CES and CAF vs water)
Trust score:4/5

Diastolic blood pressure (waking)

1 evidences

Daily caffeine challenges produced small but persistent increases in ambulatory blood pressure in some habitual consumers after repeated intake.

Trust comment: Randomized double‑blind crossover with objective ambulatory BP measurement and n=85, though subgroup analyses of tolerance reduce generalizability.

Study Details

PMID:15882556
Participants:85
Impact:+2.2 mmHg
Trust score:4/5

Anagen hair percentage

1 evidences

Daily use of a shampoo containing caffeine plus DMG‑Na reduced hair shedding and improved hair growth measures versus placebo after 6 months.

Trust comment: Large randomized double‑blind placebo‑controlled trial (n=154) with objective phototrichogram measures, though some authors are industry employees (COI).

Study Details

PMID:40820949
Participants:154
Impact:+14.3 percentage points (active) at 6 months
Trust score:4/5

Postoperative pain severity (VAS 1 hour)

1 evidences

Preoperative Novafen (acetaminophen + ibuprofen + 40 mg caffeine) produced small reductions in postoperative pain scores at several timepoints versus placebo.

Trust comment: Randomized double‑blind trial (n=70) with standard pain scales, but reporting contains internal inconsistencies and the analgesic combines multiple drugs including caffeine.

Study Details

PMID:28616088
Participants:70
Impact:−0.28 (VAS; 2.74 vs 3.02)
Trust score:3/5

attention errors (composite)

1 evidences

An 80 mg-caffeine energy drink improved some working-memory and attention measures and partially antagonised alcohol-induced errors on select tasks at specific timepoints.

Trust comment: Crossover, double-blind within-subject design (n=24) with repeated measures and effect sizes reported, but small sample limits power for multiple comparisons.

Study Details

PMID:30625179
Participants:24
Impact:alcohol increased errors; ED reduced errors relative to alcohol at 45 and 90 min (significant contrasts; e.g., ALC vs ED d≈0.64 at 45 min)
Trust score:4/5

death or major disability

1 evidences

In very preterm infants randomized to higher vs lower caffeine citrate dosing, there was a borderline higher mean cognitive score at 1 year in the high-dose group but no clear adverse developmental, temperament, or behavior effects.

Trust comment: Large multicentre randomized trial with substantial follow-up but primary outcome data missing for some randomized infants and effect was borderline/statistically sensitive.

Study Details

PMID:21244548
Participants:190
Impact:trend toward lower composite outcome in high-dose (15.4% vs 24.2%); relative risk 0.75 (95% CI 0.49–1.14), not statistically significant
Trust score:4/5

Rescue medication use

2 evidences

A combination containing caffeine (AAC) provided faster and greater migraine pain relief and symptom improvement than placebo in both menstruation-associated and non-menstrual migraine.

Trust comment: Large pooled randomized, double-masked trials give robust evidence for the combination product, but caffeine was not tested alone.

Study Details

PMID:10321417
Participants:1220
Impact:reduced (menstruation-associated: AAC 6% vs placebo 15% at ≥3 h; ~9 percentage point reduction)
Trust score:4/5

Diclofenac softgel plus 100 mg caffeine provided greater headache relief at 60 minutes versus placebo in migraineurs; diclofenac alone showed non-significant differences (study underpowered).

Trust comment: Randomized crossover with positive signal for caffeine as an analgesic adjuvant but limited by smaller-than-planned sample and incomplete attack treatments.

Study Details

PMID:14756851
Participants:51
Impact:diclofenac+caffeine 30% vs placebo 63% (substantially lower; P=0.003)
Trust score:3/5

Social acuity (emotion perception)

1 evidences

In older adults with SCD or MCI, daily matcha (contains caffeine, theanine, catechins) for 12 months improved emotional perception/social acuity and showed a trend toward better sleep quality, but did not change primary global cognitive scores.

Trust comment: 12-month randomized, double-blind trial (n≈99 randomized; ~91 completed questionnaires) with good compliance and objective neurocognitive measures.

Study Details

PMID:39213264
Participants:91
Impact:Improved (difference between groups; reported significant, P=0.028)
Trust score:4/5

dribbling speed (total time, Dribble Deficit)

1 evidences

In 21 elite basketball players, 3 mg/kg caffeine did not improve dribbling speed; most players were non-responders.

Trust comment: Double-blind, randomized crossover in elite athletes with appropriate measures but modest sample size (n=21).

Study Details

PMID:30569790
Participants:21
Impact:no significant change
Trust score:4/5

blood pressure response

1 evidences

In 101 children/adolescents, caffeine produced larger cardiovascular responses in boys than girls after puberty and responses varied across the menstrual cycle in postpubertal girls.

Trust comment: Double-blind, placebo-controlled dose-response design with adequate sample (n=101) and clear sex/puberty analyses.

Study Details

PMID:24935999
Participants:101
Impact:gender- and pubertal stage-dependent; cycle-phase differences in postpubertal girls
Trust score:4/5

simulated assembly line performance (SALT)

1 evidences

Night-shift simulation: caffeine (2 mg/kg at two nighttime points) reduced physiological sleep tendency at night but did not change task performance or daytime sleep measures.

Trust comment: Randomized controlled trial with objective sleep measures but modest sample size (N=30).

Study Details

PMID:7761739
Participants:30
Impact:no change (equivalent performance vs placebo)
Trust score:4/5

systolic blood pressure (SBP) slope

1 evidences

Placebo-caffeine study (participants believed they drank caffeinated water): social influence moderated responses—confirming confederate increased subjective alertness, reduced cognitive interference and raised product endorsement; disconfirming confederate produced larger SBP decreases.

Trust comment: Well-powered randomized experiment with objective physiological and cognitive measures, though it tested placebo expectancy (female-only sample).

Study Details

PMID:27875567
Participants:99
Impact:disconfirming confederate: decrease -1.09 mmHg/min (minutes 19–24) vs confirming -0.19 mmHg/min (difference ~-0.90 mmHg/min; marginal P=0.072)
Trust score:4/5

Option generation onset time

1 evidences

In a double-blind trial, 300 mg caffeine caused people to generate fewer options but to start generating options faster; caffeine did not affect subsequent choice selection.

Trust comment: Double-blind, placebo-controlled experiment with a moderate sample (n=47) and clear behavioral outcomes.

Study Details

PMID:24682504
Participants:47
Impact:Decreased (faster first-option generation with caffeine vs placebo)
Trust score:4/5

Axial length (AL) change at 12 months

1 evidences

Topical 2% caffeine alone did not slow myopia progression over 12 months; atropine (0.02%) slowed progression and caffeine did not alter atropine's efficacy when combined.

Trust comment: Prospective randomized clinical trial with reasonable sample size; outcomes clinically measured but topical caffeine showed no benefit.

Study Details

PMID:39824253
Participants:182
Impact:2% caffeine: +0.35 ± 0.23 mm (no slower than single-vision +0.37 ± 0.20 mm); atropine groups ≈+0.24 mm (significantly less)
Trust score:4/5

reaction time (simple RTime)

1 evidences

In moderately trained CrossFit athletes, different acute caffeine doses (3, 6, 9 mg/kg) did not produce consistent statistically superior performance vs placebo, though 6 mg/kg showed the largest practical improvement in some measures.

Trust comment: Well-controlled randomized double-blind crossover (n=26) but practice effects and small sample reduce certainty of dose effects.

Study Details

PMID:38226646
Participants:26
Impact:no consistent significant improvement across doses; 6 mg/kg showed shortest pre-exercise values
Trust score:4/5

Plasma caffeine concentration (post-exercise)

1 evidences

A moderate caffeine dose (3 mg/kg) improved endurance cycling time similarly in women and men (~4–4.6% improvement).

Trust comment: Randomized, double-blind, placebo-controlled crossover with standardized controls and reported effect sizes.

Study Details

PMID:30629046
Participants:27
Impact:higher in women (P < 0.001)
Trust score:5/5

Analgesic requirement (days 1–4)

1 evidences

IV caffeine after spinal anesthesia reduced headache severity, fewer moderate/severe headaches, and reduced analgesic needs.

Trust comment: Double-blind, placebo-controlled RCT with clear clinical endpoints and adequate sample size for perioperative context.

Study Details

PMID:9952095
Participants:60
Impact:significantly lower with caffeine
Trust score:4/5

Paracetamol half-life (t1/2)

1 evidences

Adding caffeine to paracetamol sped absorption (shorter Tmax), increased Cmax and Ka, and prolonged t1/2—effects greater in hepatic patients.

Trust comment: Human PK study including healthy and hepatic patients with clear measurements but modest sample sizes per subgroup.

Study Details

PMID:26888096
Participants:40
Impact:prolonged with caffeine (greater effect in hepatic patients)
Trust score:3/5

rate of intermittent hypoxaemia

1 evidences

Late preterm infants were randomized to placebo or varying doses of caffeine citrate; overnight oximetry measured intermittent hypoxaemia and cardiorespiratory outcomes.

Trust comment: Large randomized, double-blind, placebo-controlled dosage trial with objective oximetry outcomes, though some attrition and dose-comparison limits exist.

Study Details

PMID:36038256
Participants:107
Impact:reduced: 10 mg/kg RGM 0.39 (≈−61%), 20 mg/kg RGM 0.33 (≈−67%) vs placebo at 2 weeks
Trust score:5/5

apparent diffusion coefficient (ADC)

2 evidences

Early prophylactic caffeine in very preterm infants improved white-matter microstructure on MRI and reduced apnea/ventilation needs versus placebo.

Trust comment: Checklist: confirm human caffeine effect; identify outcomes (FA, ADC, apnea/ventilation); determine participants; rate quality; document changes; short summary | Large randomized trial with objective MRI endpoints and clear randomized allocation; high trust.

Study Details

PMID:32679370
Participants:160
Impact:decreased in same white-matter regions (caffeine vs placebo, p<0.05)
Trust score:5/5

In very preterm infants, caffeine was linked to microstructural changes in white matter but not to changes in brain volumes.

Trust comment: Randomized trial with MRI outcomes supports moderate-high trust, though some diffusion data were only available in a subset (n=28).

Study Details

PMID:21031585
Participants:70
Impact:decrease (improved white matter microstructure)
Trust score:4/5

cortisol secretion

1 evidences

Caffeine combined with work stress produced additive increases in blood pressure in medical students, especially those at high familial risk for hypertension.

Trust comment: Checklist: confirm human caffeine effect; identify outcomes (BP, cortisol); determine participants; rate quality; document changes; short summary | Repeated-measures study with defined risk groups (n=31) showing interactive effect of stress and caffeine on BP; moderate trust given sample and generalizability limits.

Study Details

PMID:10826397
Participants:31
Impact:measured alongside BP; study assessed cortisol but primary reported effect was on BP (stress-related increases)
Trust score:3/5

executive control and working memory

1 evidences

In 48 habitual caffeine consumers deprived 24 h, caffeine (200 mg) improved aspects of cognition and reduced fatigue; taurine and glucose had different or no effects.

Trust comment: Randomized, double-blind mixed-design with 48 participants and multiple objective cognitive endpoints; reasonably reliable.

Study Details

PMID:22819803
Participants:48
Impact:improved with caffeine
Trust score:4/5

fatigue (mood)

1 evidences

In 48 habitual caffeine consumers deprived 24 h, caffeine (200 mg) improved aspects of cognition and reduced fatigue; taurine and glucose had different or no effects.

Trust comment: Randomized, double-blind mixed-design with 48 participants and multiple objective cognitive endpoints; reasonably reliable.

Study Details

PMID:22819803
Participants:48
Impact:feelings of fatigue reduced; tension and vigor increased with caffeine
Trust score:4/5

Overall pain relief at 2 hours

1 evidences

In 320 women with moderate-to-severe dysmenorrhoea, paracetamol (1 g) plus caffeine (130 mg) provided greater pain relief at 2 hours and better relief of cramping and backache than paracetamol alone, caffeine alone, or placebo.

Trust comment: Large (n=320), randomized double-blind crossover with clinically relevant endpoints and clear significant differences.

Study Details

PMID:17407641
Participants:320
Impact:greater relief vs paracetamol alone, caffeine alone, and placebo (p<0.05–0.01)
Trust score:5/5

cardiac index

1 evidences

In a double-blind crossover trial, caffeine taken before a mental stressor amplified cardiovascular/hemodynamic stress responses in both men and women.

Trust comment: Well-controlled double-blind, placebo-controlled crossover in 47 humans showing consistent hemodynamic effects; moderate sample size.

Study Details

PMID:16916429
Participants:47
Impact:increased
Trust score:4/5

SSB consumption (daily volume)

1 evidences

In a 6-week double-blind randomized free-living trial, adding caffeine to a sugar-sweetened beverage increased ad libitum consumption compared with the non-caffeinated version.

Trust comment: Large randomized double-blind free-living trial with 99 completers and objective consumption records, supporting ecological validity.

Study Details

PMID:25567475
Participants:99
Impact:+143 ml/day (419 vs 273 ml; C-SSB vs NC-SSB)
Trust score:4/5

mood (POMS: TMD, tension-anxiety)

1 evidences

In adults with tinnitus, a single 300 mg caffeine dose did not produce clinically meaningful changes in tinnitus-related discomfort or psychoacoustic measures compared to placebo.

Trust comment: Well-powered (n=80), triple-blind randomized placebo-controlled trial with appropriate outcome measures and analyses.

Study Details

PMID:34543285
Participants:80
Impact:Within-group mood improvements in caffeine group vs baseline, but no significant differences between caffeine and placebo groups
Trust score:5/5

initial motor learning accuracy

1 evidences

In 93 college-age moderate caffeine users, caffeine improved initial acquisition (accuracy and latency) on a proprioceptive force-discrimination learning task but did not improve performance beyond normal practice.

Trust comment: Large sample and multiple measured outcomes but single-session laboratory task in moderate users limits ecological validity for broader claims.

Study Details

PMID:8774028
Participants:93
Impact:Improved during initial learning with caffeine
Trust score:3/5

hallucination-like experiences (WCP)

1 evidences

In a double-blind experiment (regular n=92, low/non-consumers n=89), acute stress slightly increased hallucination-like experiences; 100 mg caffeine produced a small time-dependent effect on threat-related recall bias.

Trust comment: Relatively large sample and double-blind placebo-controlled design support moderate-high confidence; effects were small.

Study Details

PMID:34792804
Participants:181
Impact:+ (slight increase with acute stress)
Trust score:4/5

supraventricular premature beats

1 evidences

In 51 patients with systolic heart failure, acute high-dose caffeine (total 500 mg) did not increase ventricular or supraventricular premature beats or exercise-derived arrhythmias compared with placebo.

Trust comment: Randomized double-blind crossover clinical trial in a relevant patient population with objective ECG monitoring; adequately powered for primary outcomes.

Study Details

PMID:27749954
Participants:51
Impact:no significant change (6 vs 6 beats; P=.44)
Trust score:5/5

motor parkinsonism (MDS-UPDRS-III)

1 evidences

In a multicenter RCT of 200 mg twice daily caffeine vs placebo in Parkinson’s disease (n=121), caffeine did not improve motor scores and had minor adverse effects on cognition and dyskinesia.

Trust comment: Well-powered, multicenter randomized controlled trial (Class I evidence) with clear primary and secondary outcome reporting.

Study Details

PMID:28954882
Participants:121
Impact:no clinically important change (difference −0.48 points; 95% CI −3.21 to 2.25)
Trust score:5/5

memory susceptibility to distraction

1 evidences

In 27 healthy volunteers, 50 mg caffeine improved alertness and attention-switching accuracy; combined L-theanine (100 mg) plus caffeine improved speed and accuracy on attention-switching and reduced distraction in memory tasks.

Trust comment: Placebo-controlled crossover with adequate sample for cognitive testing (n=27); results are consistent and specific to combined treatment effects.

Study Details

PMID:18681988
Participants:27
Impact:reduced with L-theanine + caffeine at 60 and 90 minutes
Trust score:4/5

PVC count during isoproterenol washout

1 evidences

Preprocedural oral caffeine (5 mg/kg) increased PVC counts during isoproterenol washout, increased PVC count fluctuation, and shortened procedure and ablation times during catheter ablation.

Trust comment: Randomized clinical study in 70 patients with clear ECG/ procedural endpoints; moderate sample and clinically relevant findings.

Study Details

PMID:32500131
Participants:70
Impact:increase (73.1 ± 73.2 vs 38.9 ± 28.9 beats/5 min; p=0.012)
Trust score:4/5

swim time

1 evidences

Single 6 mg/kg caffeine dose before a triathlon slightly improved swim and overall completion times and increased postexercise cortisol and peak blood lactate.

Trust comment: Well-designed double-blind randomized crossover field trial in trained triathletes with objective performance and biochemical outcomes.

Study Details

PMID:29345161
Participants:26
Impact:-3.7% (33.5 ± 7.0 vs 34.8 ± 8.1 min, p<0.05)
Trust score:5/5

GIP (postprandial)

1 evidences

Two randomized crossover trials in men showed beverages containing green tea catechins and coffee chlorogenic acids (with matched caffeine) raised postprandial GLP-1, lowered GIP, and reduced post-meal blood glucose compared to placebo.

Trust comment: Well-controlled randomized crossover trials with relevant biochemical endpoints and complete reporting, but modest sample sizes and male-only participants limit generalizability.

Study Details

PMID:36771483
Participants:34
Impact:decrease
Trust score:4/5

acute diastolic blood pressure

1 evidences

Acute ingestion of green or black tea produced larger short-term increases in clinic systolic and diastolic blood pressure than caffeine-matched water, but regular 7-day tea consumption did not significantly change 24-h ambulatory blood pressure.

Trust comment: Crossover designs and objective BP measures are strengths, but small samples in two separate cohorts and limited intervention duration reduce confidence.

Study Details

PMID:10404946
Participants:33
Impact:increase (greater with tea vs caffeine at 30 min)
Trust score:3/5

age at extubation

1 evidences

Higher maintenance caffeine citrate dose (10 mg/kg/day vs 5 mg/kg/day) reduced extubation failure, apnea days and shortened time to extubation in very preterm infants.

Trust comment: Randomized trial in preterm infants with clear clinically relevant endpoints and adequate sample size (n=111).

Study Details

PMID:32639634
Participants:111
Impact:−2.5 days (10.7 ± 2.3 → 8.2 ± 2.1 days)
Trust score:5/5

insulin response timing/level

1 evidences

In healthy adults, caffeinated coffee acutely delayed insulin rise and increased postprandial glucose exposure compared with water; effects varied by sex and BMI.

Trust comment: Randomized crossover clinical trial with measured glucose/insulin outcomes but modest sample size and subgroup findings were secondary/nominal.

Study Details

PMID:23498899
Participants:33
Impact:delay in rise; 6 mg/kg dose lowered insulin in first 30 min in men and overweight (nominal subgroup effects)
Trust score:4/5

serum creatinine

1 evidences

In 54 active men, creatine loading with or without added caffeine (or coffee) did not provide additional improvements in strength or sprint performance compared with placebo over 5 days.

Trust comment: Randomized controlled design with moderate sample and objective performance measures but short (5-day) supplementation period.

Study Details

PMID:26439785
Participants:54
Impact:increased with creatine-containing groups (including CRE+CAF and CRE+COF), not with placebo
Trust score:4/5

Number of reversible perfusion defects

1 evidences

In patients undergoing regadenoson-stress SPECT MPI, ingestion of caffeine (200–400 mg) 90 minutes before testing reduced the number and severity of detected reversible perfusion defects and altered BP/HR responses.

Trust comment: Large, multicenter, randomized placebo-controlled trial with blinded core lab reads and robust analyses.

Study Details

PMID:24737255
Participants:207
Impact:Mean change −0.61 to −0.62 segments (caffeine vs placebo 0.12)
Trust score:5/5

Evening electronic media use

1 evidences

A brief school-based intervention modestly reduced electronic media use at night but did not change adolescents' caffeine consumption, sleep duration, or secondary outcomes.

Trust comment: Pilot cluster-randomized design with reasonable sample size but limited effect sizes and short follow-up, reducing strength of conclusions.

Study Details

PMID:30611715
Participants:352
Impact:Modest decrease (intervention vs control)
Trust score:3/5

panic attack incidence after 480 mg caffeine

2 evidences

A 480 mg oral caffeine challenge induced panic attacks in a higher proportion of patients with panic disorder and depression with panic attacks than in depressed-only patients or healthy controls.

Trust comment: Randomized double-blind human challenge (n=109) with clear clinically relevant group differences and objective anxiety assessments.

Study Details

PMID:17445520
Participants:109
Impact:PD 58.6% (17/29); MDP 44.4% (12/27); MD 12.0% (3/25); controls 7.1% (2/28)
Trust score:4/5

A 480 mg oral caffeine challenge induced panic attacks in a majority of panic disorder (60.7%) and performance social anxiety disorder (52.6%) patients, in fewer GSAD patients (16%), and in no controls.

Trust comment: Randomized double-blind challenge with adequate group sizes showing differential vulnerability, though diagnostic group sizes vary.

Study Details

PMID:19698996
Participants:98
Impact:PD: 60.7% induced; PSAD: 52.6% induced; GSAD: 16.0% induced; controls: 0% induced
Trust score:4/5

behavioral risk-taking (BART)

1 evidences

Caffeine gum prevented the rise in risky behaviour and reduced self-reported impulsivity during 75 hours of continuous sleep deprivation.

Trust comment: Controlled, double-blind administration during prolonged sleep deprivation with objective and subjective outcomes but modest sample size.

Study Details

PMID:20946437
Participants:25
Impact:prevented increase at 75 h (placebo increased; caffeine group remained at baseline)
Trust score:4/5

number of intermittent hypoxia events

1 evidences

Extending caffeine treatment in preterm infants reduced time spent with oxygen saturation <90% (intermittent hypoxia) compared with usual care.

Trust comment: Multicenter randomized clinical trial with masked oximeter analysis and clinically relevant, objectively measured outcomes.

Study Details

PMID:24445955
Participants:95
Impact:decreased from 35 to 39 weeks PMA (overall decrease over time)
Trust score:5/5

implicit memory (d')

1 evidences

In healthy male adults, single doses of stimulants (including caffeine 200 mg as one arm) improved multiple memory measures and altered resting‑state functional connectivity; changes in connectivity related to memory enhancement.

Trust comment: Double‑blind, placebo‑controlled within‑subject fMRI study with rigorous analysis, though stimulant effects were pooled across three drugs and per‑drug group sizes were modest (≈16 each).

Study Details

PMID:35670369
Participants:48
Impact:increased: 2.29 ± 0.76 (stimulant) vs 2.01 ± 0.71 (placebo) (significant)
Trust score:4/5

pupil size

2 evidences

In a double-blind crossover, 4 mg/kg caffeine increased perceived activation and pupil size and reduced variability of accommodative response, without altering accommodation accuracy.

Trust comment: Placebo-controlled, double-blind crossover with reported statistics in a defined sample (n=22), supporting internal validity.

Study Details

PMID:32011181
Participants:22
Impact:+ dilation (p = .011)
Trust score:4/5

A 250 mg caffeine drink increased pupil size and amplitude of accommodation over 90 minutes in young adults.

Trust comment: Double-masked crossover design with objective ocular measurements in a moderate sample size.

Study Details

PMID:27983733
Participants:50
Impact:+1.1 mm (from 3.4±0.4 mm to 4.5±0.72 mm; ≈+32%)
Trust score:4/5

Body weight (VLCD)

1 evidences

Overweight subjects lost weight on a very low energy diet then during 3-month maintenance received a green tea–caffeine mixture or placebo; effects depended on habitual caffeine intake.

Trust comment: Randomized, double-blind, placebo-controlled trial with moderate sample size; mixture contained caffeine but effects are influenced by habitual caffeine use.

Study Details

PMID:16076989
Participants:76
Impact:-5.9 ± 1.8 kg (overall weight loss during low-energy diet)
Trust score:4/5

Developmental coordination disorder (DCD) rate at 5 years

1 evidences

Follow-up of infants randomized to neonatal caffeine or placebo showed lower rates of developmental coordination disorder at age 5 in the caffeine group.

Trust comment: Large randomized trial with blinded follow-up assessment and robust sample size showing a clinically meaningful reduction in DCD.

Study Details

PMID:24840756
Participants:1433
Impact:11.3% (caffeine) vs 15.2% (placebo); absolute -3.9 percentage points; adjusted OR 0.71 (95% CI 0.52–0.97), P=0.032
Trust score:5/5

sleepiness

1 evidences

Caffeine reduced sleepiness and improved motor performance (tapping and reaction times); improvements in mental alertness and cognition were mainly seen in medium-high consumers and were limited in frequent consumers.

Trust comment: Large sample, double-blind treatment with behavioral and cognitive tasks; subgroup effects and tolerance discussed, increasing relevance.

Study Details

PMID:23108937
Participants:369
Impact:decreased after caffeine (improvement)
Trust score:4/5

postoperative pain

1 evidences

After implant surgery, acetaminophen+caffeine produced less early postoperative swelling but more pain at 3–12 h compared with acetaminophen+codeine.

Trust comment: Triple-blind randomized clinical trial with 76 completers showing clear differences for pain and swelling, though comparisons are against codeine-containing medication rather than placebo.

Study Details

PMID:28864284
Participants:76
Impact:greater in caffeine-containing analgesic vs codeine-containing at 3, 6, 12 h (p=0.001)
Trust score:4/5

Brake reaction time (BRT)

1 evidences

In 100 healthy drivers, a single 200 mg caffeine dose improved some executive/cognitive test performance and shortened brake reaction time versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with objective cognitive and driving outcomes in 100 healthy adults; some limitations noted by authors (washout/habit effects).

Study Details

PMID:30379815
Participants:100
Impact:-0.05 sec (0.89 → 0.84 s; p=0.048)
Trust score:4/5

VO2max

1 evidences

In adolescent male athletes, 6 mg/kg caffeine increased endurance performance (Yo-Yo IR1 distance) and VO2max in ACE II and DI genotype carriers but not in DD carriers; heart rate and perceived exertion also rose in I-allele carriers.

Trust comment: Randomized, double-blind crossover in 75 adolescents with genotyping and reported p-values; moderate sample and genotype subgroup sizes (II n=13) limit subgroup precision.

Study Details

PMID:38896643
Participants:75
Impact:ACE DI: 44.1→45.2 mL·kg⁻¹·min⁻¹ (+≈1.1, p=0.001); ACE II: 43.7→45.1 (+≈1.4, p=0.01); no change in DD
Trust score:4/5

NCPAP duration

1 evidences

In 90 preterm neonates (1250–2000 g), prophylactic caffeine reduced duration of NCPAP and lowered apnea and IVH incidence compared to control.

Trust comment: Randomized neonatal trial with clinically meaningful reductions (n=90) though control arm lacked placebo and some outcomes have wide variance.

Study Details

PMID:35429946
Participants:90
Impact:-36.95 hours (41.53 vs 78.48 h; mean difference -36.95; P=0.04)
Trust score:4/5

5-km running time

1 evidences

Ingesting 5 mg/kg caffeine produced small but statistically significant faster 5-km times in both well-trained and recreational runners (~1% improvement).

Trust comment: Double-blind placebo-controlled trial with 30 participants and clear effect sizes; modest sample limits generalizability.

Study Details

PMID:17544329
Participants:30
Impact:-1.1% (well-trained; 90% CI 0.4–1.6) and -1.0% (recreational; 90% CI 0.2–2) faster vs placebo
Trust score:4/5

psychomotor vigilance (response speed)

1 evidences

During 50 h sleep deprivation, strategic caffeine gum maintained neurobehavioural performance; higher salivary alpha-amylase (sAA) was associated with better PVT response speed in the caffeine group, though the association was weaker than in placebo.

Trust comment: Double-blind placebo-controlled sleep-deprivation study with physiological and performance measures (n=23); moderate sample size but robust protocol.

Study Details

PMID:29402402
Participants:23
Impact:maintained/improved performance in presence of caffeine during extended wakefulness
Trust score:4/5

Undisclosed detectable serum caffeine

1 evidences

Among 194 patients undergoing dipyridamole stress testing, ~19% who denied caffeine exposure had detectable serum caffeine; detectable caffeine was associated with higher 24-month adverse cardiac events.

Trust comment: Prospective randomized screening study with objective serum measures, but associations with outcomes may be confounded and sample size modest for outcome subgroup analyses.

Study Details

PMID:20451698
Participants:194
Impact:19% of patients who screened negative by history had detectable serum caffeine
Trust score:3/5

pain severity

1 evidences

A 7-day multi-ingredient supplement (including vitamin D) reduced pain severity and musculoskeletal discomfort vs baseline and performed similarly or better than acetaminophen in this small crossover trial.

Trust comment: Randomized double-blind crossover RCT with thorough outcome measures but small sample size limits generalizability; caffeine was one of multiple active ingredients.

Study Details

PMID:32575480
Participants:27
Impact:Pain Bloc-R reduced pain severity (~21.8% decrease from baseline after 7 days).
Trust score:4/5

depressive symptom improvement (MADRS-S)

1 evidences

In depressed patients receiving active or sham dmPFC iTBS, higher habitual caffeine intake was associated with greater symptom improvement in the active group.

Trust comment: Randomized sham-controlled trial but this is an observational follow-up on self-reported habitual caffeine with modest sample size and potential confounding.

Study Details

PMID:34872405
Participants:40
Impact:positive correlation with pretreatment caffeine in active iTBS (r=0.51, p=0.025); significant Caffeine×Group interaction (β=0.62, p=0.043)
Trust score:3/5

complete headache relief (responder rate)

1 evidences

Large randomized double-blind trial showing that adding caffeine to ibuprofen improved relief of tension-type headache vs components or placebo.

Trust comment: Large (n=301), randomized, double-blind, placebo- and active-controlled trial with clear positive effects of caffeine as an adjuvant to ibuprofen.

Study Details

PMID:11014413
Participants:301
Impact:more subjects obtained complete relief with ibuprofen+caffeine vs comparators (p<0.05)
Trust score:5/5

subjective mental fatigue / alertness

1 evidences

In 24 habitual caffeine consumers and 24 non-consumers, acute caffeine (75 or 150 mg) improved reaction times, vigilance and working memory and reduced self-rated mental fatigue and increased alertness regardless of habitual use.

Trust comment: Well-powered (for acute effects), double-blind crossover in humans with clear cognitive and mood endpoints; overnight withdrawal may influence magnitude but design addresses withdrawal.

Study Details

PMID:15678363
Participants:48
Impact:reduced mental fatigue and increased alertness (significant)
Trust score:4/5

time to apnea disappearance

1 evidences

Both domestic and imported caffeine citrate were similarly safe and effective for treating apnea in preterm infants.

Trust comment: Prospective randomized double-blind RCT in 98 preterm infants with clinical endpoints reported; reasonable quality.

Study Details

PMID:32669161
Participants:98
Impact:no significant difference between groups (P>0.05)
Trust score:4/5

maze coordination

1 evidences

300 mg caffeine worsened motor steadiness (more errors) in healthy adult females.

Trust comment: Randomized double-blind crossover design but small sample (n=24) and limited to females.

Study Details

PMID:7650108
Participants:24
Impact:tended to decrease after caffeine
Trust score:3/5

pathologic apnea after discontinuation

1 evidences

Caffeine has a long half-life in preterm infants and many infants had pathologic apnea days after stopping caffeine.

Trust comment: Prospective cohort with measured drug levels and clinical monitoring in 50 preterm infants; clear pharmacokinetic data.

Study Details

PMID:26562367
Participants:50
Impact:64% had pathologic apnea 7 days after stopping caffeine
Trust score:4/5

Dose-response

1 evidences

A single cup-equivalent dose after overnight abstinence increased energetic mood and improved psychomotor performance; additional spaced doses added little.

Trust comment: Double-blind randomized design with 64 moderate caffeine consumers; well-controlled behavioral measures.

Study Details

PMID:9862086
Participants:64
Impact:one dose as effective as two or three spaced doses (flat response)
Trust score:4/5

Hering Breuer reflex strength

1 evidences

Caffeine improved neonatal respiratory compliance and reduced oxygen needs earlier than theophylline.

Trust comment: Randomized neonatal study with protocol completion in 45 infants and objective respiratory measures; solid but pediatric-specific.

Study Details

PMID:9483391
Participants:45
Impact:reduced (significant only in caffeine group)
Trust score:4/5

hand reaction time

1 evidences

In trained male athletes, caffeine mouth rinse improved hand and foot reaction time, with the highest concentration (2.4%) giving the largest benefit.

Trust comment: Double-blind, randomized crossover with a reasonable sample (n=45) in trained athletes; clear effect sizes reported.

Study Details

PMID:35193478
Participants:45
Impact:+22% (2.4% CAF-MR vs placebo)
Trust score:4/5

theta power (EEG)

1 evidences

In adults given caffeine vs placebo across weeks, caffeine produced few modest EEG changes (theta and alpha) and evidence of withdrawal/withdrawal reversal effects on EEG and mood.

Trust comment: Within-subjects controlled design addressing withdrawal but small sample and modest effects limit generalizability.

Study Details

PMID:18337638
Participants:22
Impact:modest increase during task performance (associated with withdrawal/withdrawal reversal/tolerance)
Trust score:3/5

apnoea incidence

1 evidences

In ventilated preterm infants, higher caffeine doses reduced short-term apnoea and improved oxygenation metrics but did not change extubation failure rates.

Trust comment: Randomized double-blind trial with adequate sample (n=127) though some physiological data derive from a smaller subgroup (n=37).

Study Details

PMID:12969204
Participants:127
Impact:reduced in higher-dose groups (15 and 30 mg/kg vs 3 mg/kg)
Trust score:4/5

reaction time (cognitive)

1 evidences

A 3 mg/kg dose of caffeine improved reaction times on a cognitive task, including during a fatiguing motor dual-task, without changing motor force or endurance.

Trust comment: Semi-randomized double-blind crossover with n=23 and clear cognitive outcome measures; moderate sample size.

Study Details

PMID:15723227
Participants:23
Impact:decreased (improved) with caffeine in single and dual tasks
Trust score:4/5

other strength/power measures (DJ, IMTP, most force-time metrics)

1 evidences

In 27 male rugby players, 3 mg/kg caffeine (capsule, gum, or mouth rinse) produced limited effects: a small increase in countermovement-jump height and one-set squat endurance, but most strength/power measures were unchanged.

Trust comment: Well-designed double-blind, mode-matched placebo crossover in athletes (n=27); effects were generally small and outcome-specific.

Study Details

PMID:39439175
Participants:27
Impact:no significant change (no effect of caffeine across modes for most outcomes)
Trust score:4/5

depressive symptom score

1 evidences

Adding low-dose caffeine (60 mg) to patients' antidepressant regimens reduced depression scores, improved cognition, and normalized stress-hormone response.

Trust comment: Clinical 4-week study with 95 inpatients showing symptomatic and biomarker changes, but results reported for males only and exact magnitudes not provided in the extract.

Study Details

PMID:28054436
Participants:95
Impact:reduction in depressive scores (60 mg caffeine; magnitude not reported)
Trust score:4/5

white chocolate vs methylxanthine effects

1 evidences

Amounts of caffeine plus theobromine present in normal portions of chocolate improved energetic arousal and cognitive function versus placebo/white chocolate.

Trust comment: Two double-blind placebo-controlled experiments (n=20 and n=22) showing consistent mood and cognitive effects at chocolate-equivalent methylxanthine doses.

Study Details

PMID:15549276
Participants:42
Impact:white chocolate showed no effect versus water; effects attributable to methylxanthines
Trust score:4/5

Cognitive performance and mood

1 evidences

In 49 moderate–high habitual consumers, a second 1.2 mg/kg caffeine dose improved cognitive performance and mood only after 8 h abstinence and raised blood pressure after 8 h; shorter abstinence produced some adverse effects on hand steadiness.

Trust comment: Larger, randomized placebo-controlled design with dose/abstinence manipulation (n=49); results depend on abstinence interval which was well tested.

Study Details

PMID:15696321
Participants:49
Impact:improved (only after 8 h abstinence)
Trust score:4/5

Hand steadiness

2 evidences

In 49 moderate–high habitual consumers, a second 1.2 mg/kg caffeine dose improved cognitive performance and mood only after 8 h abstinence and raised blood pressure after 8 h; shorter abstinence produced some adverse effects on hand steadiness.

Trust comment: Larger, randomized placebo-controlled design with dose/abstinence manipulation (n=49); results depend on abstinence interval which was well tested.

Study Details

PMID:15696321
Participants:49
Impact:decrease (impaired after 4 h abstinence)
Trust score:4/5

Knowing about a possible placebo had limited effect overall; uninformed participants showed some caffeine-induced increases in diastolic blood pressure and vigor and impaired hand steadiness at higher dose.

Trust comment: Relatively large randomized sample with dose comparisons and objective measures, though effects depended on instruction subgroups and some outcomes non-significant.

Study Details

PMID:12021824
Participants:52
Impact:impaired with 325 mg caffeine in uninformed participants
Trust score:4/5

carotid-femoral pulse wave velocity (aortic stiffness)

1 evidences

Acute ingestion of black tea increased aortic stiffness briefly and both black and green tea raised wave reflections; effects were smaller than those produced by isolated caffeine.

Trust comment: Randomized crossover with objective vascular measures but modest sample size and acute setting; single-blind design reduces strength of inference about caffeine alone.

Study Details

PMID:16766780
Participants:29
Impact:PWV +0.49 m/s (black tea, first 90 min)
Trust score:3/5

effect of added caffeine on GI complaints

1 evidences

During an 18-km run, sports drinks increased gastrointestinal complaint incidence versus water; adding caffeine (150 mg/L) to the sports drink did not affect running performance or GI complaints compared with the sports drink without caffeine.

Trust comment: Large randomized crossover field study with controlled intake and good external validity for runners; outcomes are self-reported GI symptoms which may be subjective.

Study Details

PMID:15795812
Participants:98
Impact:no additional effect of caffeine added to CES (CAF vs CES: no significant change)
Trust score:4/5

BMI

1 evidences

A multi-ingredient product (including caffeine and ephedrine) produced modest additional weight loss (~1.5 kg) and greater reductions in BMI and waist circumference versus placebo over 12 weeks; no BP or pulse increases were observed.

Trust comment: Large randomized placebo-controlled trial but attribution to caffeine is limited because the active product contained ephedrine and other ingredients and actual caffeine dose was lower than intended.

Study Details

PMID:15356670
Participants:102
Impact:decreased (greater reduction vs placebo)
Trust score:3/5

insulin AUC

1 evidences

In healthy adults, increasing caffeine doses impaired insulin sensitivity and raised insulin, C-peptide, and glucose responses in a dose-dependent way.

Trust comment: Randomized double-blind crossover study in 24 healthy volunteers with dose-response modelling supports internal validity.

Study Details

PMID:23438224
Participants:24
Impact:+5.8% per 1 mg/kg
Trust score:5/5

Systolic blood pressure (sleep)

1 evidences

Daily caffeine challenges produced small but persistent increases in ambulatory blood pressure in some habitual consumers after repeated intake.

Trust comment: Randomized double‑blind crossover with objective ambulatory BP measurement and n=85, though subgroup analyses of tolerance reduce generalizability.

Study Details

PMID:15882556
Participants:85
Impact:+2.3 mmHg
Trust score:4/5

Postoperative pain severity (VAS 3 hours)

1 evidences

Preoperative Novafen (acetaminophen + ibuprofen + 40 mg caffeine) produced small reductions in postoperative pain scores at several timepoints versus placebo.

Trust comment: Randomized double‑blind trial (n=70) with standard pain scales, but reporting contains internal inconsistencies and the analgesic combines multiple drugs including caffeine.

Study Details

PMID:28616088
Participants:70
Impact:−0.11 (VAS; 3.60 vs 3.71)
Trust score:3/5

metabolic panel / clinical chemistry

1 evidences

Daily caffeine 250 mg (alone or with DMAA) for 12 weeks produced no statistically significant adverse changes in measured clinical or laboratory outcomes.

Trust comment: Randomized 12-week supplementation with comprehensive safety measures in 50 completing subjects; limited to healthy young men.

Study Details

PMID:23424215
Participants:50
Impact:no significant change (12-week supplementation vs baseline)
Trust score:4/5

working memory reaction time

1 evidences

An 80 mg-caffeine energy drink improved some working-memory and attention measures and partially antagonised alcohol-induced errors on select tasks at specific timepoints.

Trust comment: Crossover, double-blind within-subject design (n=24) with repeated measures and effect sizes reported, but small sample limits power for multiple comparisons.

Study Details

PMID:30625179
Participants:24
Impact:faster RT at 90 min with ED vs placebo (t(23)=2.17, p=0.040; d=0.444)
Trust score:4/5

squat jump height

1 evidences

Acute caffeine (5 mg/kg) increased squat- and countermovement-jump heights and improved some force/velocity execution metrics in collegiate athletes.

Trust comment: Single-blind randomized crossover in 25 athletes with clear within-subject improvements and reported means/SDs for key outcomes.

Study Details

PMID:26626028
Participants:25
Impact:32.8 ± 6.2 cm (placebo) → 34.5 ± 6.7 cm (caffeine); p = 0.001 (≈+1.7 cm)
Trust score:4/5

peak force / rate of force development

1 evidences

Acute caffeine (5 mg/kg) increased squat- and countermovement-jump heights and improved some force/velocity execution metrics in collegiate athletes.

Trust comment: Single-blind randomized crossover in 25 athletes with clear within-subject improvements and reported means/SDs for key outcomes.

Study Details

PMID:26626028
Participants:25
Impact:peak force and average rate of force development increased (p = 0.032 and p = 0.037 respectively)
Trust score:4/5

temperament and behaviour

1 evidences

In very preterm infants randomized to higher vs lower caffeine citrate dosing, there was a borderline higher mean cognitive score at 1 year in the high-dose group but no clear adverse developmental, temperament, or behavior effects.

Trust comment: Large multicentre randomized trial with substantial follow-up but primary outcome data missing for some randomized infants and effect was borderline/statistically sensitive.

Study Details

PMID:21244548
Participants:190
Impact:no significant differences between dosage groups
Trust score:4/5

subjective sleepiness (SSS)

1 evidences

Repeated caffeine gum (up to 200 mg every 2 hours) reduced vigilance lapses during an extended wake period and 200 mg preserved baseline performance overnight.

Trust comment: Randomized groups with objective PVT measures and adequate sample size for performance effects.

Study Details

PMID:16313140
Participants:48
Impact:increased over time with no significant differences between groups
Trust score:4/5

Sleep quality (PSQI)

1 evidences

In older adults with SCD or MCI, daily matcha (contains caffeine, theanine, catechins) for 12 months improved emotional perception/social acuity and showed a trend toward better sleep quality, but did not change primary global cognitive scores.

Trust comment: 12-month randomized, double-blind trial (n≈99 randomized; ~91 completed questionnaires) with good compliance and objective neurocognitive measures.

Study Details

PMID:39213264
Participants:91
Impact:Trend toward improvement (difference ≈0.86 points; P=0.088)
Trust score:4/5

vigilance reaction time

1 evidences

In tactical males, 300 mg caffeine and a 150 mg caffeine + methylliberine + theacrine combo similarly improved vigilance reaction time; caffeine raised DBP vs placebo while the combo raised SBP but not DBP.

Trust comment: Randomized, placebo-controlled trial with moderate sample (n=48 completed) and appropriate measures; between-group design limits within-subject sensitivity but overall reliable.

Study Details

PMID:36016763
Participants:48
Impact:improvement from round1 to round2 in CAF (d=−0.37) and CMT (d=−0.32); no improvement in PLA
Trust score:4/5

ventilator parameters (PIP, FiO2)

1 evidences

Early caffeine in 59 preterm infants reduced ventilator needs, shortened respiratory support times, lowered VAP, and reduced post-extubation apnea.

Trust comment: Prospective controlled clinical trial with clinically relevant neonatal outcomes in 59 infants; moderate sample size.

Study Details

PMID:27974112
Participants:59
Impact:decreased
Trust score:4/5

individual response rate

1 evidences

In 21 elite basketball players, 3 mg/kg caffeine did not improve dribbling speed; most players were non-responders.

Trust comment: Double-blind, randomized crossover in elite athletes with appropriate measures but modest sample size (n=21).

Study Details

PMID:30569790
Participants:21
Impact:majority non-responders (20/21)
Trust score:4/5

time under tension (TUT)

1 evidences

In trained women habituated to caffeine, acute caffeine (3 and 6 mg/kg) increased 1RM strength (dose-response) and 6 mg/kg increased time under tension; no clear change in repetitions or power measures.

Trust comment: Randomized double-blind crossover with direct performance measures in a specific trained female sample but small n (21) limits generalizability.

Study Details

PMID:33781269
Participants:21
Impact:PLAC 53.52 s → CAF-6 61.76 s (+17.6%); CAF-3 no significant change
Trust score:4/5

daytime polysomnography

1 evidences

Night-shift simulation: caffeine (2 mg/kg at two nighttime points) reduced physiological sleep tendency at night but did not change task performance or daytime sleep measures.

Trust comment: Randomized controlled trial with objective sleep measures but modest sample size (N=30).

Study Details

PMID:7761739
Participants:30
Impact:no change between groups
Trust score:4/5

cognitive interference (Stroop)

1 evidences

Placebo-caffeine study (participants believed they drank caffeinated water): social influence moderated responses—confirming confederate increased subjective alertness, reduced cognitive interference and raised product endorsement; disconfirming confederate produced larger SBP decreases.

Trust comment: Well-powered randomized experiment with objective physiological and cognitive measures, though it tested placebo expectancy (female-only sample).

Study Details

PMID:27875567
Participants:99
Impact:less interference in confirming vs disconfirming (adj means 53.27 ms vs 99.59 ms; difference -46.32 ms; P=0.026)
Trust score:4/5

Body weight

4 evidences

A 6-month randomized trial of an herbal ephedra/caffeine product produced greater weight loss than placebo and increased some GI and sleep-related side effects.

Trust comment: Large randomized double-blind trial with 6-month follow-up, but intervention combines ephedra and caffeine so effects are not due to caffeine alone.

Study Details

PMID:12032741
Participants:167
Impact:-5.3 kg (herbal) vs -2.6 kg (placebo) over 6 months
Trust score:4/5

A combined caffeine+ephedra supplement raised resting metabolic rate and produced greater weight and fat loss than placebo over 12 weeks.

Trust comment: Randomized double-blind trial but supplement combined caffeine with ephedra, so effects cannot be attributed to caffeine alone.

Study Details

PMID:15292480
Participants:40
Impact:-3.5 ± 0.6 kg (C&E) vs -0.8 ± 0.5 kg (placebo) at 12 weeks)
Trust score:3/5

A multi-ingredient product (including caffeine and ephedrine) produced modest additional weight loss (~1.5 kg) and greater reductions in BMI and waist circumference versus placebo over 12 weeks; no BP or pulse increases were observed.

Trust comment: Large randomized placebo-controlled trial but attribution to caffeine is limited because the active product contained ephedrine and other ingredients and actual caffeine dose was lower than intended.

Study Details

PMID:15356670
Participants:102
Impact:decreased (active vs placebo: additional −1.5 kg over 12 weeks)
Trust score:3/5

An 8-week randomized trial of an herbal mix (includes 240 mg/day caffeine) produced greater short-term weight and fat loss but more withdrawals and side effects.

Trust comment: Randomized, double-blind, placebo-controlled RCT but small, short-term and multi-ingredient so effects cannot be attributed solely to caffeine.

Study Details

PMID:11319627
Participants:48
Impact:-4.0 kg (active) vs -0.8 kg (placebo) over 8 weeks
Trust score:4/5

Subsequent choice (take-the-first heuristic)

1 evidences

In a double-blind trial, 300 mg caffeine caused people to generate fewer options but to start generating options faster; caffeine did not affect subsequent choice selection.

Trust comment: Double-blind, placebo-controlled experiment with a moderate sample (n=47) and clear behavioral outcomes.

Study Details

PMID:24682504
Participants:47
Impact:No significant effect on tendency to select first-generated option
Trust score:4/5

Fasting plasma homocysteine (after 2 wk)

1 evidences

Two-week ingestion of caffeine capsules (≈870 mg/day) produced a small but significant increase in fasting plasma homocysteine (~+0.4 µmol/L, ≈+5%), indicating caffeine partly contributes to coffee's homocysteine-raising effect.

Trust comment: Randomized crossover (n=48) with clear biochemical endpoints; results consistent though effects are modest.

Study Details

PMID:12450889
Participants:48
Impact:+0.4 µmol/L (+5%) after caffeine capsules vs placebo; coffee increased +0.9 µmol/L (+11%)
Trust score:4/5

mean SpO2

1 evidences

Late preterm infants were randomized to placebo or varying doses of caffeine citrate; overnight oximetry measured intermittent hypoxaemia and cardiorespiratory outcomes.

Trust comment: Large randomized, double-blind, placebo-controlled dosage trial with objective oximetry outcomes, though some attrition and dose-comparison limits exist.

Study Details

PMID:36038256
Participants:107
Impact:increased at 2 weeks (10 mg/kg mean difference +0.68; 20 mg/kg +1.31 vs placebo)
Trust score:5/5

brachial artery diameter (post-workout)

1 evidences

Acute multi-ingredient preworkout supplements (one formulation contained caffeine) modestly improved anaerobic power and some endurance and vascular measures versus placebo; caffeine was one of several active ingredients.

Trust comment: Randomized crossover with n=30 but multi-ingredient formulations make isolating caffeine-specific effects uncertain.

Study Details

PMID:32569125
Participants:30
Impact:increase with NBAC and BAC (p=0.041 and p=0.005)
Trust score:3/5

muscular endurance (reps to fatigue)

1 evidences

In 28 trained young adults randomized to creatine, caffeine, creatine+caffeine, or placebo during 6 weeks training, creatine increased knee extensor thickness but caffeine produced no clear benefits.

Trust comment: Randomized trial but small group sizes per arm and modest duration; findings reliable for lack of caffeine effect within this sample.

Study Details

PMID:33759701
Participants:28
Impact:no between-group differences including caffeine
Trust score:3/5

negative somatic effects (subjective)

1 evidences

Sixty abstinent coffee drinkers received decaf with 0 or 280 mg caffeine crossed with expectancy instructions; caffeine improved vigilance and psychomotor speed and expectancy altered subjective and some behavioral outcomes.

Trust comment: Well-powered (n=60) factorial, double-blind design assessing both pharmacology and expectancy; conclusions on behavioral effects are robust.

Study Details

PMID:19760283
Participants:60
Impact:greater when 'impair' expectancy given, but only when caffeine administered
Trust score:4/5

Liking (palatability)

1 evidences

Over six pairings, drinks paired with 19 mg caffeine + 250 mg theobromine became liked more than placebo‑paired drinks, suggesting methylxanthines increase acquired liking.

Trust comment: Randomized double-blind placebo-controlled design with adequate sample (n=64); outcome is subjective liking.

Study Details

PMID:15772863
Participants:64
Impact:increased over time for drink paired with methylxanthines
Trust score:4/5

Folic acid

1 evidences

In 36 volunteers, drinking unfiltered natural coffee for 4 weeks raised plasma homocysteine, whereas modified (filtered/treated) coffee tended to lower it; other vitamins not notably reported.

Trust comment: Randomized crossover in 36 people with repeated measures; effect reported clearly for homocysteine though mechanism may involve coffee constituents beyond caffeine.

Study Details

PMID:16708634
Participants:36
Impact:no significant change reported
Trust score:4/5

tinnitus-related discomfort (THI)

1 evidences

In adults with tinnitus, a single 300 mg caffeine dose did not produce clinically meaningful changes in tinnitus-related discomfort or psychoacoustic measures compared to placebo.

Trust comment: Well-powered (n=80), triple-blind randomized placebo-controlled trial with appropriate outcome measures and analyses.

Study Details

PMID:34543285
Participants:80
Impact:No significant between-group change
Trust score:5/5

postoperative headache incidence (placebo)

1 evidences

Perioperative substitution of patients' usual caffeine intake prevented postoperative headaches compared with placebo in habitual consumers.

Trust comment: Randomized allocation with objective compliance checks but modest sample size and older single-center study limits strength.

Study Details

PMID:7497559
Participants:40
Impact:50% reported headache on placebo day; 35% persisted to next day
Trust score:3/5

dyskinesia (MDS-UPDRS 4.1+4.2)

1 evidences

In a multicenter RCT of 200 mg twice daily caffeine vs placebo in Parkinson’s disease (n=121), caffeine did not improve motor scores and had minor adverse effects on cognition and dyskinesia.

Trust comment: Well-powered, multicenter randomized controlled trial (Class I evidence) with clear primary and secondary outcome reporting.

Study Details

PMID:28954882
Participants:121
Impact:+0.25 points
Trust score:5/5

reaction time (attention/working memory tasks)

1 evidences

In adults 50–69, single-dose caffeine shortened reaction times on several cognitive tasks and 12-week caffeine or matcha intake preserved MMSE-J scores versus placebo; matcha additionally improved work on a stress task with continuous intake.

Trust comment: Randomized double-blind placebo-controlled parallel study with reasonable sample (n=51) and multiple cognitive endpoints; some outcomes task-specific.

Study Details

PMID:34067795
Participants:51
Impact:faster (single dose caffeine shortened reaction times on SAT, CPT, FPCPT parts; p<0.05)
Trust score:4/5

peak blood lactate

1 evidences

Single 6 mg/kg caffeine dose before a triathlon slightly improved swim and overall completion times and increased postexercise cortisol and peak blood lactate.

Trust comment: Well-designed double-blind randomized crossover field trial in trained triathletes with objective performance and biochemical outcomes.

Study Details

PMID:29345161
Participants:26
Impact:greater peak accumulation (ANOVA main effect p<0.05)
Trust score:5/5

run time-to-exhaustion (TTE)

1 evidences

A single 275 mg caffeine dose (or 150 mg caffeine + 125 mg theacrine) produced modest improvements in some reaction-time measures and trended to increase time-to-exhaustion versus placebo.

Trust comment: Within-subject, double-blind design in trained athletes with objective endpoints, though some effects were small or only trending and sample is modest.

Study Details

PMID:30999897
Participants:24
Impact:trend to increase: CAF +32% (255.4 ± 189.1 s vs PL 194.1 ± 96.9 s), TCr+CAF +38% (267.0 ± 175.7 s)
Trust score:4/5

gastric emptying time

1 evidences

A mixed herbal preparation containing Yerba Maté and Guarana (sources of caffeine) delayed gastric emptying and produced greater short-term weight loss versus placebo over 45 days.

Trust comment: Human placebo-controlled trials but intervention was a multi-ingredient herbal mix (not isolated caffeine), so effects cannot be attributed solely to caffeine.

Study Details

PMID:11424516
Participants:47
Impact:prolonged: 58 ± 15 min (YGD) vs 38 ± 7.6 min (placebo), p=0.025
Trust score:3/5

time to exhaustion at 90% VO2peak

1 evidences

Daily ingestion of a caffeine-containing supplement (≈201 mg/day) during 8 weeks of aerobic training produced no additional improvements in VO2peak, time to exhaustion, or body composition versus placebo.

Trust comment: Randomized placebo-controlled trial with moderate sample size, but supplement composition and dosing limits specificity to caffeine alone.

Study Details

PMID:17149989
Participants:36
Impact:no significant change between groups
Trust score:4/5

serving accuracy

1 evidences

Sleep restriction (5 h) impaired tennis serving accuracy; a single 80 mg caffeine dose did not restore accuracy in semi-professional players.

Trust comment: Field-relevant design with two small counterbalanced studies and double-blind caffeine testing, but limited sample sizes and single caffeine dose limit conclusions.

Study Details

PMID:23916998
Participants:28
Impact:decrease after sleep restriction
Trust score:3/5

ratings of perceived exertion / pain

1 evidences

Acute caffeine (6 mg/kg) improved countermovement jump performance and total repetitions in strength endurance tests regardless of habitual caffeine intake level.

Trust comment: Double-blind crossover with reasonable sample (n=36) and stratification by habitual intake; credible results though specific to trained individuals.

Study Details

PMID:34010807
Participants:36
Impact:no change
Trust score:4/5

response redundancy and stereotypy

1 evidences

During 40-h sleep deprivation, caffeine preserved simple response output but did not prevent many executive-function deficits on a random number task.

Trust comment: Well-controlled randomized crossover sleep-deprivation study with objective cognitive measures, moderate sample size.

Study Details

PMID:16490000
Participants:21
Impact:redundancy +59%, stereotypy +20% with sleep deprivation; caffeine had no effect
Trust score:4/5

age at first successful extubation

1 evidences

Early caffeine did not shorten time to first successful extubation in ventilated preterm infants and showed a non-significant trend toward higher mortality in the caffeine group.

Trust comment: Randomized, placebo-controlled neonatal trial stopped early for safety signals; adequate design but limited by early termination and sample size.

Study Details

PMID:29519541
Participants:83
Impact:no significant difference (median 24 vs 20 days; P=0.7)
Trust score:3/5

8-hour urinary flurbiprofen recovery ratio

1 evidences

Adding caffeine to a multi-drug probe cocktail did not produce meaningful metabolic interactions for measured enzyme probe drugs, though a small increase in one flurbiprofen metric occurred.

Trust comment: Well-controlled randomized crossover in healthy adults with appropriate pharmacokinetic endpoints, moderate sample size.

Study Details

PMID:16952492
Participants:24
Impact:small increase (7.5%, P=0.03) when in 6-drug cocktail
Trust score:4/5

maximal strength and VO2max

1 evidences

Male collegiate basketball players doing 6 weeks of plyometric training improved performance and physiology; ingesting caffeine 1 h before sessions (especially 6 mg/kg) produced slightly larger and more uniform adaptations than placebo.

Trust comment: Randomized double-blind placebo-controlled trial with clear methods and complete follow-up but small sample (n=24) and male-only participants.

Study Details

PMID:38971848
Participants:24
Impact:improved in all groups; CAF6 showed very large effects for strength (ES=2.29, p=0.001) and VO2max (ES=1.59, p=0.001) compared to pre-training
Trust score:4/5

countermovement jump performance

1 evidences

In resistance-trained males, acute caffeine (3 mg/kg) produced no significant changes in bench-press, jump, or Wingate outcomes related to habitual caffeine intake.

Trust comment: Controlled crossover-style testing in trained participants with reported p-values, but small sample size limits generalizability.

Study Details

PMID:32859145
Participants:24
Impact:no significant change (p > 0.05)
Trust score:3/5

plasma/urinary/thermoregulatory variables

1 evidences

Chronic (3 or 6 mg/kg/day) and acute caffeine did not alter most fluid-electrolyte, thermoregulatory or cardiovascular responses during a heat exercise test, though one treatment group had longer tolerance time.

Trust comment: Moderately sized randomized, stratified study (n=59) with controlled dosing and objective physiological measures.

Study Details

PMID:16491580
Participants:59
Impact:no between-group differences (P>0.05)
Trust score:4/5

caffeine pharmacokinetics (tmax, Cmax)

1 evidences

Caffeine 100 mg in the fixed-dose combination was rapidly absorbed and did not alter ibuprofen pharmacokinetics; ibuprofen PK comparable with/without caffeine.

Trust comment: Two well-controlled randomized crossover PK studies in healthy volunteers with validated bioanalytical methods; moderate sample size for PK studies.

Study Details

PMID:30897305
Participants:72
Impact:rapid absorption; median tmax ~1.13 h, Cmax ~2.1 µg/mL
Trust score:4/5

wetting episodes

1 evidences

In women with urinary incontinence, reducing fluid intake improved some symptoms, but switching from caffeinated to decaffeinated drinks did not improve urinary symptoms.

Trust comment: Randomized crossover trial with objective diary measures and 69 completers, though effects of caffeine restriction were negative while fluid changes showed benefit.

Study Details

PMID:15947624
Participants:69
Impact:decreased (significant) with decreased fluid intake (USI and IDO groups)
Trust score:4/5

visual memory (early recall)

1 evidences

In healthy male adults, single doses of stimulants (including caffeine 200 mg as one arm) improved multiple memory measures and altered resting‑state functional connectivity; changes in connectivity related to memory enhancement.

Trust comment: Double‑blind, placebo‑controlled within‑subject fMRI study with rigorous analysis, though stimulant effects were pooled across three drugs and per‑drug group sizes were modest (≈16 each).

Study Details

PMID:35670369
Participants:48
Impact:stimulant: 35.21 ± 18.24 words vs placebo: 31.69 ± 16.88 (significant improvement)
Trust score:4/5

psychomotor response speed

1 evidences

In sleep-deprived adults, stimulants had different effects: caffeine improved alertness measures but did not enhance cartoon humor appreciation.

Trust comment: Randomized, double-blind sleep-deprivation study with specified sample size and clear outcome reporting, moderate-to-high quality.

Study Details

PMID:16796223
Participants:54
Impact:+ improved (vs placebo)
Trust score:4/5

cartoon humor appreciation

1 evidences

In sleep-deprived adults, stimulants had different effects: caffeine improved alertness measures but did not enhance cartoon humor appreciation.

Trust comment: Randomized, double-blind sleep-deprivation study with specified sample size and clear outcome reporting, moderate-to-high quality.

Study Details

PMID:16796223
Participants:54
Impact:no change (caffeine did not enhance vs placebo)
Trust score:4/5

bench press performance (velocity, power, endurance)

1 evidences

In resistance-trained males, acute caffeine (3 mg/kg) produced no significant changes in bench-press, jump, or Wingate outcomes related to habitual caffeine intake.

Trust comment: Controlled crossover-style testing in trained participants with reported p-values, but small sample size limits generalizability.

Study Details

PMID:32859145
Participants:24
Impact:no significant change (p > 0.05)
Trust score:3/5

Wingate test performance

1 evidences

In resistance-trained males, acute caffeine (3 mg/kg) produced no significant changes in bench-press, jump, or Wingate outcomes related to habitual caffeine intake.

Trust comment: Controlled crossover-style testing in trained participants with reported p-values, but small sample size limits generalizability.

Study Details

PMID:32859145
Participants:24
Impact:no significant change (p > 0.05)
Trust score:3/5

Skin intrinsic fluorescence (SIF1, 375 nm)

1 evidences

In people with type 1 diabetes, habitual caffeine intake was positively associated with skin intrinsic fluorescence (SIF) measures, and this was replicated in an independent cohort.

Trust comment: Large well-characterized cohort with replication; observational design limits causal inference but associations are consistent and statistically robust.

Study Details

PMID:26192006
Participants:1185
Impact:Positive association with mean caffeine intake; caffeine explained ≈3.8% of variance in adjusted models (≈11% unadjusted)
Trust score:4/5

oral health-related quality of life (OHIP-14)

1 evidences

Paracetamol-caffeine reduced separator-related pain compared with placebo but did not improve overall oral-health-related quality of life.

Trust comment: Randomized, placebo-controlled clinical trial with objective pain scales and clear group sizes, though sample size is modest.

Study Details

PMID:35110003
Participants:54
Impact:no improvement (median 25 drug vs 24 control)
Trust score:4/5

sleep onset latency

1 evidences

Single 600 mg slow-release caffeine decreased calmness and prolonged sleep onset but did not change alertness the next day.

Trust comment: Randomized double-blind parallel trial with a large sample (120) but limited to young males and single-dose testing.

Study Details

PMID:9025802
Participants:120
Impact:increased (p<0.01)
Trust score:4/5

sustained attention (PVT reaction time)

1 evidences

In healthy young males, 200 mg caffeine improved sustained attention (shorter reaction time) but showed no robust effects on most other cognitive domains or subjective fatigue.

Trust comment: Randomized, double-blind, within-subject trial (48 males) with rigorous corrections for multiple comparisons; limited by moderate per-arm sample size and male-only participants.

Study Details

PMID:33201262
Participants:48
Impact:improved with caffeine (shorter RT; p=0.002)
Trust score:4/5

6-min time trial mean power

1 evidences

In endurance-trained adults, 3 mg/kg caffeine increased mean power in a 6-min time trial (~+12 W) but did not add to creatine effects on 15-s sprint power.

Trust comment: Randomized crossover with measured performance outcomes in 23 trained athletes; small sample but objective measures and CIs reported.

Study Details

PMID:38646853
Participants:23
Impact:+12 W vs placebo (95% CI 5–18, p=0.001)
Trust score:4/5

salivary alpha-amylase (sAA) association

1 evidences

During 50 h sleep deprivation, strategic caffeine gum maintained neurobehavioural performance; higher salivary alpha-amylase (sAA) was associated with better PVT response speed in the caffeine group, though the association was weaker than in placebo.

Trust comment: Double-blind placebo-controlled sleep-deprivation study with physiological and performance measures (n=23); moderate sample size but robust protocol.

Study Details

PMID:29402402
Participants:23
Impact:higher sAA associated with improved PVT response speed during first 24 h in caffeine group (association weaker vs placebo)
Trust score:4/5

sex hormones (estradiol, testosterone, DHEAS)

1 evidences

Higher caffeinated coffee/caffeine intake was associated with higher plasma SHBG and lower type 2 diabetes risk; adjustment for SHBG attenuated the diabetes association.

Trust comment: Large prospective nested case-control with biomarker and genotype data; observational design means residual confounding possible.

Study Details

PMID:21030499
Participants:718
Impact:no consistent association (no meaningful change)
Trust score:4/5

total analgesia/peak relief

1 evidences

Large randomized double-blind trial showing that adding caffeine to ibuprofen improved relief of tension-type headache vs components or placebo.

Trust comment: Large (n=301), randomized, double-blind, placebo- and active-controlled trial with clear positive effects of caffeine as an adjuvant to ibuprofen.

Study Details

PMID:11014413
Participants:301
Impact:significantly greater with ibuprofen+caffeine vs ibuprofen, caffeine, or placebo (p<0.05)
Trust score:5/5

perceived bitterness

1 evidences

Adolescents exposed to a novel soda with 2 mg/kg caffeine showed increased liking over repeated exposures and reduced bitterness perception.

Trust comment: Controlled randomized exposure in adolescents with adequate sample size and clear within-group effects at the 2 mg/kg dose.

Study Details

PMID:22427020
Participants:99
Impact:decrease in perceived bitterness in the 2 mg/kg caffeine group
Trust score:4/5

judgements-of-learning (JOL) calibration

1 evidences

Experimental induction of caffeine craving impaired memory performance and some metacognitive judgments compared to control.

Trust comment: Experimental human study (n=55) manipulating craving state; applicable to craving-related cognitive effects but not acute caffeine ingestion effects per se.

Study Details

PMID:28276980
Participants:55
Impact:reduced calibration for JOLs during craving
Trust score:3/5

numeric working memory reaction time and sentence verification accuracy

1 evidences

In 24 habitual caffeine consumers and 24 non-consumers, acute caffeine (75 or 150 mg) improved reaction times, vigilance and working memory and reduced self-rated mental fatigue and increased alertness regardless of habitual use.

Trust comment: Well-powered (for acute effects), double-blind crossover in humans with clear cognitive and mood endpoints; overnight withdrawal may influence magnitude but design addresses withdrawal.

Study Details

PMID:15678363
Participants:48
Impact:reaction time improved and accuracy increased (significant)
Trust score:4/5

fasting resting metabolic rate (RMR)

1 evidences

In middle-aged adults, 2-week intake of a tea catechin beverage (containing ~88 mg caffeine) increased energy expenditure after ingestion by ~96 kJ/day (~1.7%) versus a caffeinated placebo beverage; fasting RMR did not change.

Trust comment: Randomized double-blind crossover with objective metabolic measures and per-protocol n=26; however effect likely attributable to catechins and both beverages contained similar caffeine, limiting attribution to caffeine alone.

Study Details

PMID:31062079
Participants:26
Impact:no significant change (placebo 5269 ± 781 vs catechin 5291 ± 780 kJ/day; p=0.681)
Trust score:4/5

prefrontal oxygenated haemoglobin (oxy-Hb)

1 evidences

In healthy young adults, 75 mg caffeine reduced prefrontal oxygenated haemoglobin and increased deoxygenated haemoglobin and improved some reaction-time and mood measures; co‑administration with L‑theanine abolished the oxy‑Hb reduction and removed the behavioural benefits.

Trust comment: Well-controlled double-blind, within-subjects study with NIRS and behavioral measures but modest sample size (n=24).

Study Details

PMID:25761837
Participants:24
Impact:decrease during absorption and tasks (significant)
Trust score:4/5

dose-response of CAF mouth rinse

1 evidences

In trained male athletes, caffeine mouth rinse improved hand and foot reaction time, with the highest concentration (2.4%) giving the largest benefit.

Trust comment: Double-blind, randomized crossover with a reasonable sample (n=45) in trained athletes; clear effect sizes reported.

Study Details

PMID:35193478
Participants:45
Impact:2.4% > 1.8% ≈ 1.2% (2.4% significantly superior)
Trust score:4/5

subjective mood (withdrawal-related)

1 evidences

In adults given caffeine vs placebo across weeks, caffeine produced few modest EEG changes (theta and alpha) and evidence of withdrawal/withdrawal reversal effects on EEG and mood.

Trust comment: Within-subjects controlled design addressing withdrawal but small sample and modest effects limit generalizability.

Study Details

PMID:18337638
Participants:22
Impact:adverse changes associated with withdrawal
Trust score:3/5

cerebellar hemorrhage

1 evidences

In very preterm infants randomized to early high- vs standard-dose caffeine, high-dose was associated with higher rates of cerebellar hemorrhage and subtle neonatal neurobehavioral differences but no detectable 2-year developmental differences in this pilot trial.

Trust comment: Pilot randomized trial with clinically important safety signals but single-center and limited power for long-term outcomes.

Study Details

PMID:25856169
Participants:74
Impact:increased incidence (36% high-dose vs 10% standard-dose; OR 5.0, p=0.03)
Trust score:3/5

total work (Wingate)

1 evidences

In trained male boxers, adding 3 mg/kg caffeine to a PAPE protocol increased the magnitude of Wingate performance gains and uniquely increased peak power and perceived power versus control.

Trust comment: Randomized crossover with well-controlled protocol in 25 completers; limitation: no caffeine-only arm, limiting isolation of caffeine effect.

Study Details

PMID:38257128
Participants:25
Impact:increased (PAPE+PLA and PAPE+CAF vs CON)
Trust score:4/5

motor parameters (force, endurance, EMG)

1 evidences

A 3 mg/kg dose of caffeine improved reaction times on a cognitive task, including during a fatiguing motor dual-task, without changing motor force or endurance.

Trust comment: Semi-randomized double-blind crossover with n=23 and clear cognitive outcome measures; moderate sample size.

Study Details

PMID:15723227
Participants:23
Impact:no change
Trust score:4/5

resting parasympathetic modulation

1 evidences

About 3 mg/kg caffeine increased parasympathetic reactivation after submaximal exercise (60–300 s post-exercise) but did not alter resting cardiac parasympathetic modulation or HRV threshold.

Trust comment: Balanced-placebo, crossover design with n=21 and objective HRV metrics; reasonably robust though sample modest.

Study Details

PMID:30326789
Participants:21
Impact:no change
Trust score:4/5

Body mass index (BMI)

1 evidences

In obese adolescents on a calorie-restricted diet, an ephedrine+caffeine pill produced much larger weight, BMI, and body-fat loss over 20 weeks than placebo.

Trust comment: Randomized double-blind placebo-controlled trial in adolescents with clear outcome differences, but pilot size and combined ephedrine+caffeine limit attribution to caffeine alone.

Study Details

PMID:11126208
Participants:29
Impact:-2.9 kg/m2 (CE group mean vs -0.5 kg/m2 in placebo; P < 0.05)
Trust score:4/5

episodes of weekly drunkenness

1 evidences

Survey of 4,271 US college students found that mixing energy drinks with alcohol was common and associated with higher heavy drinking and more alcohol-related harms.

Trust comment: Large, multicenter web-based cross-sectional survey with clear associations but subject to confounding and self-report biases.

Study Details

PMID:18439201
Participants:4271
Impact:about twice as many in AmED users (1.4 days/week vs 0.73 days/week; p < 0.001)
Trust score:3/5

N3 (deep sleep) duration

1 evidences

In a double-blind crossover study, moderate caffeine during 38 h wakefulness reduced recovery-night total sleep time and N3 sleep and worsened sleep continuity and EEG slow-wave power.

Trust comment: Well-controlled double-blind crossover trial with objective sleep EEG measures and adequate sample for a demanding protocol (n=41).

Study Details

PMID:39458438
Participants:41
Impact:-17% (caffeine-associated decrease in N3 during recovery night; interaction p = 0.04)
Trust score:5/5

absolute risk of tooth sensitivity

1 evidences

In 84 patients, coadministration of ibuprofen plus caffeine did not reduce the risk or intensity of bleaching-induced tooth sensitivity compared with placebo.

Trust comment: Triple-blind randomized clinical trial with adequate sample size and direct patient-reported outcomes; caffeine was combined with ibuprofen so effect not isolated to caffeine alone.

Study Details

PMID:34755785
Participants:84
Impact:no change (p=1.00 vs placebo)
Trust score:4/5

gut microbiota beta diversity (Bray–Curtis)

1 evidences

In 58 adults, 12 weeks of catechin- and caffeine-containing green tea supplementation did not change gut microbiota composition or diversity nor body composition versus placebo.

Trust comment: Randomized single-blind placebo-controlled study but intervention combined catechins and small amounts of caffeine, so caffeine-specific effects cannot be isolated.

Study Details

PMID:27054321
Participants:58
Impact:no significant change (baseline vs week 12 vs placebo)
Trust score:3/5

salivary cortisol response to stress

1 evidences

Adding low-dose caffeine (60 mg) to patients' antidepressant regimens reduced depression scores, improved cognition, and normalized stress-hormone response.

Trust comment: Clinical 4-week study with 95 inpatients showing symptomatic and biomarker changes, but results reported for males only and exact magnitudes not provided in the extract.

Study Details

PMID:28054436
Participants:95
Impact:normalization / inhibition of HPA activation
Trust score:4/5

sleep efficiency / duration / REM (daytime recovery)

1 evidences

Caffeine (200 mg) before sleep delayed sleep onset and reduced deep sleep, with stronger negative effects on daytime recovery sleep than nocturnal sleep.

Trust comment: Double-blind crossover study in 34 moderate caffeine consumers with polysomnography, providing objective sleep-stage data.

Study Details

PMID:16936703
Participants:34
Impact:reduced sleep efficiency (greater effect daytime); reduced sleep duration and REM only in daytime recovery
Trust score:4/5

Hair pull test (hair loss)

1 evidences

Daily use of a shampoo containing caffeine plus DMG‑Na reduced hair shedding and improved hair growth measures versus placebo after 6 months.

Trust comment: Large randomized double‑blind placebo‑controlled trial (n=154) with objective phototrichogram measures, though some authors are industry employees (COI).

Study Details

PMID:40820949
Participants:154
Impact:Mean change −2.8 hairs (active) vs +0.6 (placebo) at 6 months
Trust score:4/5

interleukin-6 (IL-6)

1 evidences

In overweight adults, 8 weeks of caffeinated coffee increased adiponectin and IL‑6 while decaffeinated coffee lowered fetuin‑A; no change in glucose tolerance.

Trust comment: Randomized, blinded 8-week trial measuring objective biomarkers but limited by small sample size (n=41 completed).

Study Details

PMID:21914162
Participants:41
Impact:+60% (caffeinated vs no coffee)
Trust score:4/5

Apnea–hypopnea index (polysomnography)

1 evidences

Neonatal caffeine therapy was not associated with differences in sleep duration or sleep-disordered breathing at school age.

Trust comment: Long-term follow-up of a randomized neonatal trial with objective sleep measures in a large sample (n=201).

Study Details

PMID:25171195
Participants:201
Impact:No significant difference (rate ratio 0.89; P=0.63)
Trust score:5/5

Onset of analgesia

1 evidences

Adding caffeine to ibuprofen sped pain relief onset and increased analgesic effect at 45–60 minutes after single-dose administration, with few adverse events.

Trust comment: Randomized, double-blind, placebo-controlled single-dose trial (n=161) showing caffeine enhances ibuprofen analgesia with limited adverse events.

Study Details

PMID:8880847
Participants:161
Impact:Earlier onset with ibuprofen plus caffeine
Trust score:4/5

apnea after extubation / VAP incidence

1 evidences

Early caffeine in 59 preterm infants reduced ventilator needs, shortened respiratory support times, lowered VAP, and reduced post-extubation apnea.

Trust comment: Prospective controlled clinical trial with clinically relevant neonatal outcomes in 59 infants; moderate sample size.

Study Details

PMID:27974112
Participants:59
Impact:fewer apneas; lower VAP incidence
Trust score:4/5

PASI score (psoriasis severity)

1 evidences

Randomized double-blind right/left comparison: topical 10% caffeine applied thrice daily produced greater reduction in PASI scores than placebo after 8 weeks (small but statistically significant effect).

Trust comment: Double-blind, placebo-controlled dermatology trial with objective clinical outcome but modest N and borderline P-value.

Study Details

PMID:16249145
Participants:39
Impact:greater reduction with topical caffeine at 8 weeks (caffeine mean reduction 6.58 vs placebo 4.43; difference ~2.15 points; P=0.047)
Trust score:4/5

glucose AUC

1 evidences

In healthy adults, increasing caffeine doses impaired insulin sensitivity and raised insulin, C-peptide, and glucose responses in a dose-dependent way.

Trust comment: Randomized double-blind crossover study in 24 healthy volunteers with dose-response modelling supports internal validity.

Study Details

PMID:23438224
Participants:24
Impact:+11.2 mmol per 120 min·L per 1 mg/kg
Trust score:5/5

duration of apnea episodes

1 evidences

In infants with bronchiolitis-associated apnea, a single IV caffeine dose did not shorten time to a 24-hour apnea-free period compared with placebo.

Trust comment: Double-blind randomized parallel trial in infants with objective monitoring, but single-dose design and sample-size/power limitations noted.

Study Details

PMID:27189681
Participants:85
Impact:mean shorter by 5.7 s in caffeine group (P=0.003)
Trust score:4/5

Headache severity (VAS)

2 evidences

IV caffeine after spinal anesthesia reduced headache severity, fewer moderate/severe headaches, and reduced analgesic needs.

Trust comment: Double-blind, placebo-controlled RCT with clear clinical endpoints and adequate sample size for perioperative context.

Study Details

PMID:9952095
Participants:60
Impact:significantly lower with caffeine
Trust score:4/5

A single 400 mg dose of caffeine before graded CO₂ exposure reduced CO₂ retention and substantially lowered headache ratings compared with placebo.

Trust comment: Randomized double-blind crossover with physiological and symptomatic endpoints (n=23) provides robust within-subject evidence.

Study Details

PMID:40019582
Participants:23
Impact:At 8% inspired CO₂: placebo 25 ±15 mm vs caffeine 13 ±12 mm (absolute reduction ≈12 mm)
Trust score:4/5

Paracetamol Cmax and AUC in hepatic vs healthy

1 evidences

Adding caffeine to paracetamol sped absorption (shorter Tmax), increased Cmax and Ka, and prolonged t1/2—effects greater in hepatic patients.

Trust comment: Human PK study including healthy and hepatic patients with clear measurements but modest sample sizes per subgroup.

Study Details

PMID:26888096
Participants:40
Impact:substantially increased in hepatic patients (Cmax ~+95–98%; AUC increases up to ~101% depending on treatment)
Trust score:3/5

clinical respiratory outcomes (apnea, assisted ventilation)

1 evidences

Early prophylactic caffeine in very preterm infants improved white-matter microstructure on MRI and reduced apnea/ventilation needs versus placebo.

Trust comment: Checklist: confirm human caffeine effect; identify outcomes (FA, ADC, apnea/ventilation); determine participants; rate quality; document changes; short summary | Large randomized trial with objective MRI endpoints and clear randomized allocation; high trust.

Study Details

PMID:32679370
Participants:160
Impact:fewer apnea events and shorter assisted ventilation times in caffeine group (p<0.05)
Trust score:5/5

handgrip strength (CYP1A2 CC genotype)

1 evidences

In competitive male athletes, caffeine had no overall effect on strength/power, but 4 mg/kg caffeine reduced handgrip strength by ~12.8% in individuals with the CYP1A2 CC genotype.

Trust comment: Well-powered randomized controlled trial with genotype stratification revealing a genotype-dependent adverse effect; good internal validity.

Study Details

PMID:34284351
Participants:102
Impact:-12.8% (53 ±11 kg vs 61 ±17 kg) with 4 mg/kg caffeine vs placebo
Trust score:4/5

knee extensor muscle thickness

1 evidences

In 28 trained young adults randomized to creatine, caffeine, creatine+caffeine, or placebo during 6 weeks training, creatine increased knee extensor thickness but caffeine produced no clear benefits.

Trust comment: Randomized trial but small group sizes per arm and modest duration; findings reliable for lack of caffeine effect within this sample.

Study Details

PMID:33759701
Participants:28
Impact:no change in caffeine-only group (increase observed with creatine only)
Trust score:3/5

vigilance (reaction time and accuracy)

1 evidences

Sixty abstinent coffee drinkers received decaf with 0 or 280 mg caffeine crossed with expectancy instructions; caffeine improved vigilance and psychomotor speed and expectancy altered subjective and some behavioral outcomes.

Trust comment: Well-powered (n=60) factorial, double-blind design assessing both pharmacology and expectancy; conclusions on behavioral effects are robust.

Study Details

PMID:19760283
Participants:60
Impact:improved with caffeine vs placebo
Trust score:4/5

Abdominal cramping

1 evidences

In 320 women with moderate-to-severe dysmenorrhoea, paracetamol (1 g) plus caffeine (130 mg) provided greater pain relief at 2 hours and better relief of cramping and backache than paracetamol alone, caffeine alone, or placebo.

Trust comment: Large (n=320), randomized double-blind crossover with clinically relevant endpoints and clear significant differences.

Study Details

PMID:17407641
Participants:320
Impact:greater relief with combination vs comparators
Trust score:5/5

peripheral resistance index

1 evidences

In a double-blind crossover trial, caffeine taken before a mental stressor amplified cardiovascular/hemodynamic stress responses in both men and women.

Trust comment: Well-controlled double-blind, placebo-controlled crossover in 47 humans showing consistent hemodynamic effects; moderate sample size.

Study Details

PMID:16916429
Participants:47
Impact:decreased
Trust score:4/5

energy from SSB

1 evidences

In a 6-week double-blind randomized free-living trial, adding caffeine to a sugar-sweetened beverage increased ad libitum consumption compared with the non-caffeinated version.

Trust comment: Large randomized double-blind free-living trial with 99 completers and objective consumption records, supporting ecological validity.

Study Details

PMID:25567475
Participants:99
Impact:+268 kJ/day (785 vs 512 kJ/day)
Trust score:4/5

number of repetitions / power output

1 evidences

In trained women habituated to caffeine, acute caffeine (3 and 6 mg/kg) increased 1RM strength (dose-response) and 6 mg/kg increased time under tension; no clear change in repetitions or power measures.

Trust comment: Randomized double-blind crossover with direct performance measures in a specific trained female sample but small n (21) limits generalizability.

Study Details

PMID:33781269
Participants:21
Impact:No significant change
Trust score:4/5

response latency (initial learning)

1 evidences

In 93 college-age moderate caffeine users, caffeine improved initial acquisition (accuracy and latency) on a proprioceptive force-discrimination learning task but did not improve performance beyond normal practice.

Trust comment: Large sample and multiple measured outcomes but single-session laboratory task in moderate users limits ecological validity for broader claims.

Study Details

PMID:8774028
Participants:93
Impact:Improved (reduced) during initial learning with caffeine
Trust score:3/5

recall bias towards threat-related words (persecutory ideation)

1 evidences

In a double-blind experiment (regular n=92, low/non-consumers n=89), acute stress slightly increased hallucination-like experiences; 100 mg caffeine produced a small time-dependent effect on threat-related recall bias.

Trust comment: Relatively large sample and double-blind placebo-controlled design support moderate-high confidence; effects were small.

Study Details

PMID:34792804
Participants:181
Impact:altered (small time-dependent effect of 100 mg caffeine)
Trust score:4/5

exercise-derived arrhythmia measures (duration, HR, estimated VO2peak)

1 evidences

In 51 patients with systolic heart failure, acute high-dose caffeine (total 500 mg) did not increase ventricular or supraventricular premature beats or exercise-derived arrhythmias compared with placebo.

Trust comment: Randomized double-blind crossover clinical trial in a relevant patient population with objective ECG monitoring; adequately powered for primary outcomes.

Study Details

PMID:27749954
Participants:51
Impact:no significant change
Trust score:5/5

somnolence

1 evidences

In a multicenter RCT of 200 mg twice daily caffeine vs placebo in Parkinson’s disease (n=121), caffeine did not improve motor scores and had minor adverse effects on cognition and dyskinesia.

Trust comment: Well-powered, multicenter randomized controlled trial (Class I evidence) with clear primary and secondary outcome reporting.

Study Details

PMID:28954882
Participants:121
Impact:slight improvement during first 6 months (magnitude not specified)
Trust score:5/5

PVC count fluctuation

1 evidences

Preprocedural oral caffeine (5 mg/kg) increased PVC counts during isoproterenol washout, increased PVC count fluctuation, and shortened procedure and ablation times during catheter ablation.

Trust comment: Randomized clinical study in 70 patients with clear ECG/ procedural endpoints; moderate sample and clinically relevant findings.

Study Details

PMID:32500131
Participants:70
Impact:increase (69.3 ± 61.3 vs 37.7 ± 30.9 beats/5 min; p=0.008)
Trust score:4/5

time to completion (triathlon)

1 evidences

Single 6 mg/kg caffeine dose before a triathlon slightly improved swim and overall completion times and increased postexercise cortisol and peak blood lactate.

Trust comment: Well-designed double-blind randomized crossover field trial in trained triathletes with objective performance and biochemical outcomes.

Study Details

PMID:29345161
Participants:26
Impact:-1.3% (149.6 ± 19.8 vs 151.5 ± 18.6 min, p<0.05)
Trust score:5/5

choice reaction time (CRT) at halftime

1 evidences

A single 275 mg caffeine dose (or 150 mg caffeine + 125 mg theacrine) produced modest improvements in some reaction-time measures and trended to increase time-to-exhaustion versus placebo.

Trust comment: Within-subject, double-blind design in trained athletes with objective endpoints, though some effects were small or only trending and sample is modest.

Study Details

PMID:30999897
Participants:24
Impact:faster: CAF 0.593 ± 0.054 s vs PL 0.614 ± 0.069 s (difference ≈ -0.021 s, p=0.012)
Trust score:4/5

postprandial blood glucose (tAUC)

1 evidences

Two randomized crossover trials in men showed beverages containing green tea catechins and coffee chlorogenic acids (with matched caffeine) raised postprandial GLP-1, lowered GIP, and reduced post-meal blood glucose compared to placebo.

Trust comment: Well-controlled randomized crossover trials with relevant biochemical endpoints and complete reporting, but modest sample sizes and male-only participants limit generalizability.

Study Details

PMID:36771483
Participants:34
Impact:decrease
Trust score:4/5

24 h ambulatory blood pressure

1 evidences

Acute ingestion of green or black tea produced larger short-term increases in clinic systolic and diastolic blood pressure than caffeine-matched water, but regular 7-day tea consumption did not significantly change 24-h ambulatory blood pressure.

Trust comment: Crossover designs and objective BP measures are strengths, but small samples in two separate cohorts and limited intervention duration reduce confidence.

Study Details

PMID:10404946
Participants:33
Impact:no significant change
Trust score:3/5

countermovement vertical jump

1 evidences

Acute caffeine (6 mg/kg) improved countermovement jump performance and total repetitions in strength endurance tests regardless of habitual caffeine intake level.

Trust comment: Double-blind crossover with reasonable sample (n=36) and stratification by habitual intake; credible results though specific to trained individuals.

Study Details

PMID:34010807
Participants:36
Impact:significant increase vs placebo (p = 0.001)
Trust score:4/5

number of responses

1 evidences

During 40-h sleep deprivation, caffeine preserved simple response output but did not prevent many executive-function deficits on a random number task.

Trust comment: Well-controlled randomized crossover sleep-deprivation study with objective cognitive measures, moderate sample size.

Study Details

PMID:16490000
Participants:21
Impact:decrease during sleep deprivation; caffeine ameliorated the decrease
Trust score:4/5

vertical jump (VJ)

1 evidences

Male collegiate basketball players doing 6 weeks of plyometric training improved performance and physiology; ingesting caffeine 1 h before sessions (especially 6 mg/kg) produced slightly larger and more uniform adaptations than placebo.

Trust comment: Randomized double-blind placebo-controlled trial with clear methods and complete follow-up but small sample (n=24) and male-only participants.

Study Details

PMID:38971848
Participants:24
Impact:pre-post increase in all groups; CAF6: very large effect (ES=1.45, p=0.002)
Trust score:4/5

Apnea frequency / days of apnea

1 evidences

In 120 preterm infants, higher-dose caffeine citrate reduced extubation failure and apnea frequency/duration but increased episodes of tachycardia.

Trust comment: Double-blind RCT in a relevant neonatal population with clear clinical endpoints, though age-specific safety monitoring required.

Study Details

PMID:25644724
Participants:120
Impact:Significant decrease (p<0.001)
Trust score:4/5

Summed difference score (SDS)

1 evidences

In patients undergoing regadenoson-stress SPECT MPI, ingestion of caffeine (200–400 mg) 90 minutes before testing reduced the number and severity of detected reversible perfusion defects and altered BP/HR responses.

Trust comment: Large, multicenter, randomized placebo-controlled trial with blinded core lab reads and robust analyses.

Study Details

PMID:24737255
Participants:207
Impact:Decrease −1.03 (200 mg) to −1.25 (400 mg) vs placebo
Trust score:5/5

Caffeine consumption (evening)

1 evidences

A brief school-based intervention modestly reduced electronic media use at night but did not change adolescents' caffeine consumption, sleep duration, or secondary outcomes.

Trust comment: Pilot cluster-randomized design with reasonable sample size but limited effect sizes and short follow-up, reducing strength of conclusions.

Study Details

PMID:30611715
Participants:352
Impact:No change
Trust score:3/5

intravaginal ejaculation latency time (IELT)

1 evidences

On-demand 100 mg caffeine before intercourse increased ejaculation latency and sexual satisfaction versus placebo.

Trust comment: Double-blind RCT but small sample and some ambiguity in reported p-values, limiting certainty.

Study Details

PMID:25601604
Participants:40
Impact:144 s → 312 s (increase)
Trust score:3/5

self-reported risk propensity (EVAR: total risk, impulsivity, risk/thrill seeking)

1 evidences

Caffeine gum prevented the rise in risky behaviour and reduced self-reported impulsivity during 75 hours of continuous sleep deprivation.

Trust comment: Controlled, double-blind administration during prolonged sleep deprivation with objective and subjective outcomes but modest sample size.

Study Details

PMID:20946437
Participants:25
Impact:reduced across 3 days with caffeine (remained baseline for placebo)
Trust score:4/5

Parkinson disease progression (UPDRS total score)

1 evidences

Overall caffeine intake was not linked to Parkinson progression, but among patients taking creatine higher caffeine intake was associated with faster disease progression.

Trust comment: Large phase 3 trial dataset but the caffeine analysis was observational/secondary with potential confounding; interaction finding requires cautious interpretation.

Study Details

PMID:26366971
Participants:1549
Impact:no association overall; faster progression with higher caffeine among creatine users (significant interaction)
Trust score:3/5

vigor

1 evidences

Brief caffeine deprivation in habitual coffee drinkers caused decreased vigor, increased fatigue and sleepiness, and a modest drop in blood pressure; psychomotor performance unchanged.

Trust comment: Double-blind within-subject design with clear outcome measures and n=31; results are directly reported and interpretable.

Study Details

PMID:9402612
Participants:31
Impact:- decreased
Trust score:4/5

variability of accommodative response

1 evidences

In a double-blind crossover, 4 mg/kg caffeine increased perceived activation and pupil size and reduced variability of accommodative response, without altering accommodation accuracy.

Trust comment: Placebo-controlled, double-blind crossover with reported statistics in a defined sample (n=22), supporting internal validity.

Study Details

PMID:32011181
Participants:22
Impact:- reduced variability (p = .027)
Trust score:4/5

Weight maintenance (low habitual caffeine consumers)

1 evidences

Overweight subjects lost weight on a very low energy diet then during 3-month maintenance received a green tea–caffeine mixture or placebo; effects depended on habitual caffeine intake.

Trust comment: Randomized, double-blind, placebo-controlled trial with moderate sample size; mixture contained caffeine but effects are influenced by habitual caffeine use.

Study Details

PMID:16076989
Participants:76
Impact:reduced body weight, waist and body fat; increased resting energy expenditure vs placebo (p<0.01)
Trust score:4/5

spontaneous pain

1 evidences

Paracetamol-caffeine reduced separator-related pain compared with placebo but did not improve overall oral-health-related quality of life.

Trust comment: Randomized, placebo-controlled clinical trial with objective pain scales and clear group sizes, though sample size is modest.

Study Details

PMID:35110003
Participants:54
Impact:median 3 (drug) vs 6.5 (control) at 24 h; reduction (~54%)
Trust score:4/5

simple and choice reaction time

1 evidences

Caffeine reduced sleepiness and improved motor performance (tapping and reaction times); improvements in mental alertness and cognition were mainly seen in medium-high consumers and were limited in frequent consumers.

Trust comment: Large sample, double-blind treatment with behavioral and cognitive tasks; subgroup effects and tolerance discussed, increasing relevance.

Study Details

PMID:23108937
Participants:369
Impact:improved (faster) in both medium-high and non-low consumers
Trust score:4/5

postoperative swelling

1 evidences

After implant surgery, acetaminophen+caffeine produced less early postoperative swelling but more pain at 3–12 h compared with acetaminophen+codeine.

Trust comment: Triple-blind randomized clinical trial with 76 completers showing clear differences for pain and swelling, though comparisons are against codeine-containing medication rather than placebo.

Study Details

PMID:28864284
Participants:76
Impact:reduced with caffeine-containing analgesic at days 1–3 (p=0.018)
Trust score:4/5

Subjective state (drowsiness/alertness)

1 evidences

Across three experiments, caffeine-related attentional biases were observed, but deprivation increased coffee consumption and subjective drowsiness without altering attentional bias.

Trust comment: Multiple experiments (between- and within-subject) showing consistent behavioural outcomes; sample sizes per experiment were modest.

Study Details

PMID:16170233
Participants:28
Impact:Deprivation increased drowsiness/headaches and reduced alertness
Trust score:3/5

microstate class B occurrence (in SZ)

1 evidences

In early-phase psychosis patients (vs controls), acute caffeine shifted EEG microstate dynamics: it reduced class D and increased classes A and B parameters in patients but had little effect in controls.

Trust comment: Randomized, double-blind within-subject EEG study with objective measures, but small sample and some reporting inconsistencies limit generalizability.

Study Details

PMID:35257622
Participants:25
Impact:increased with caffeine (5.47 vs 3.34 occurrences/s, caffeine vs placebo)
Trust score:3/5

plasma dopamine

1 evidences

In men, 3 mg/kg caffeine taken before treadmill running increased plasma dopamine and β-endorphin compared with control; serotonin rose with exercise regardless of caffeine.

Trust comment: Randomized acute exercise study with 30 male volunteers; moderate sample and clear biochemical outcomes but limited to acute setting.

Study Details

PMID:31793465
Participants:30
Impact:↑ (significant increase with caffeine vs control)
Trust score:3/5

distal tumor risk and water intake (men)

1 evidences

Case-control analysis found associations between coffee (methylxanthine) intake and colon cancer risk in men that varied by intake level and tumor location.

Trust comment: Large population-based case-control study (cases+controls=4,403) but observational design and potential confounding reduce causal certainty.

Study Details

PMID:10188719
Participants:4403
Impact:- decreased risk with high water intake (OR 0.68, 95% CI 0.49–0.96)
Trust score:3/5

plasma total homocysteine

1 evidences

Drinking 1 L/day of paper‑filtered coffee for 4 weeks raised fasting plasma homocysteine in healthy adults.

Trust comment: Randomized crossover trial in healthy volunteers with clear, statistically significant biochemical outcome measures.

Study Details

PMID:11063436
Participants:26
Impact:+1.5 µmol/L (+18%)
Trust score:4/5

tremor (tremor-specific score)

1 evidences

In novices, low-dose caffeine worsened simulator surgical performance and increased tremor; seniors showed mainly tremor changes without dexterity loss.

Trust comment: Self-controlled simulator study with repeated exposures and modest sample sizes (novices n=15, seniors n=11); internal control is strength but ecological validity limited.

Study Details

PMID:36782058
Participants:26
Impact:worsened (increased tremor) in novices; tremor affected in seniors without dexterity loss
Trust score:3/5

muscle endurance (repetitions at 85% 1RM)

1 evidences

A moderate dose of caffeine (3 mg/kg) acutely improved bench-press velocity/power, muscle endurance, vertical jump height, and Wingate power in resistance-trained men, with no clear genotype differences.

Trust comment: Randomized double-blind crossover, registered trial in trained men (n=22); robust within-subject design though moderate sample size.

Study Details

PMID:32295624
Participants:22
Impact:increased (more repetitions and higher quality output)
Trust score:4/5

spreading time (ST)

1 evidences

Topical caffeine combined with interferon shortened healing time of recurrent herpetic lesions more than either agent alone; caffeine alone shortened healing time in many patients but had little effect on lesion spread.

Trust comment: One-center randomized placebo-controlled clinical trial with clear group sizes (115 total) though methodological details and modern replication are limited.

Study Details

PMID:8578993
Participants:115
Impact:shortened with IFN and mixture; negligible effect with caffeine alone
Trust score:3/5

depression symptoms

1 evidences

In a crossover RCT of postmenopausal women with OAB, 400 mg/day caffeine for 7 days produced a small reduction in anxiety; depression, insomnia, and perceived stress showed no change.

Trust comment: Randomized double-blind crossover with 56 completers supports internal validity, but short 7-day exposures limit long-term conclusions.

Study Details

PMID:35363563
Participants:56
Impact:no change vs placebo over 7 days
Trust score:4/5

Dynamic visual acuity (DVA)

1 evidences

Acute caffeine (~4 mg/kg) improved dynamic visual acuity (horizontal and random paths), shortened horizontal reaction time, and increased subjective activation in low-caffeine consumers.

Trust comment: Double-blind, balanced crossover with validated measures and appropriate analyses but modest sample size (n=21).

Study Details

PMID:34420061
Participants:21
Impact:improved (statistically significant)
Trust score:4/5

dyspnea incidence on ticagrelor

1 evidences

In ~9,700 high-risk post‑MI patients, baseline caffeinated beverage intake was not associated with lower ticagrelor-related dyspnea but was associated with lower drug discontinuation for dyspnea and lower rates of MACE/MI in adjusted analyses.

Trust comment: Large, well-characterized randomized trial database but caffeine exposure was observational (baseline self-report) and analyses are nonrandomized, so residual confounding is possible.

Study Details

PMID:32410485
Participants:9694
Impact:No significant association: adjusted HR 0.91 (95% CI 0.76–1.10), P=0.34
Trust score:4/5

Quality of life

1 evidences

Self-monitoring (including advice on caffeine) reduced urine loss and improved quality of life; participants also reduced caffeine intake.

Trust comment: Large randomized clinical trial (n=224) with clear primary outcomes, though caffeine change was part of a multi-component intervention.

Study Details

PMID:17366526
Participants:224
Impact:+26.1 points (self-monitoring vs wait list)
Trust score:4/5

appetite sensations

1 evidences

In a double-blind crossover trial of 50 adults, 1 mg/kg caffeine transiently reduced laboratory breakfast intake by about 10% but did not change appetite ratings or free-living intake.

Trust comment: Double-blind randomized crossover design with complete reporting (n=50) supports moderate-high confidence; effects were small and transient.

Study Details

PMID:30033159
Participants:50
Impact:no significant change
Trust score:4/5

pleasant subjective effects

1 evidences

In 50 male smokers, an acute dose of caffeine increased subjective 'pleasant' effects and feeling 'high' but did not change cigarette consumption.

Trust comment: Randomized double-blind crossover with ecological setting and adequate sample, but outcomes are subjective self-reports.

Study Details

PMID:15001822
Participants:50
Impact:increased (p=0.008)
Trust score:3/5

Days to physiological maturity

1 evidences

Extending caffeine citrate in moderately preterm infants did not shorten hospital stay or time to physiological maturity but led to earlier resolution of apnea.

Trust comment: Large multicenter randomized clinical trial (n=827) with prespecified outcomes and stopping for futility, high-quality evidence.

Study Details

PMID:40294395
Participants:827
Impact:no significant difference (14.0 vs 15.0 days; adjusted median difference -1 day; 95% CI -2.4 to 0.4)
Trust score:5/5

foveal avascular zone (FAZ) area

1 evidences

A single 200 mg oral caffeine dose acutely reduced macular blood flow and vessel density measured by OCT-A at 1 hour.

Trust comment: Randomized allocation with objective OCT-A imaging and moderate sample size (n=52); acute study limits long-term inference.

Study Details

PMID:29401177
Participants:52
Impact:no significant change (P=0.063)
Trust score:4/5

Short Category Test errors (abstract reasoning)

1 evidences

During prolonged sleep deprivation, acute caffeine withdrawal worsened abstract reasoning/concept-formation performance (more errors) compared with placebo.

Trust comment: Double-blind experimental design but small sample (n=26) and specific to sleep-deprived withdrawal state, moderate quality.

Study Details

PMID:18380127
Participants:26
Impact:increased (~57% more errors in caffeine-withdrawal group vs placebo)
Trust score:3/5

mood (POMS)

1 evidences

Single-blind randomized study found small improvements in basic attention and psychomotor speed after matcha products; no significant mood changes.

Trust comment: Randomized, placebo-controlled single-blind study with small sample (n=23) and modest effects, moderate quality.

Study Details

PMID:28784536
Participants:23
Impact:no significant change
Trust score:3/5

attention (RVIP accuracy and speed)

1 evidences

A nutrient-enriched breakfast bar (containing a low caffeine dose of 21.5 mg among many other ingredients) produced acute improvements in alertness, attention and several cognitive tasks versus placebo on Day 1 and Day 56.

Trust comment: Well-designed randomized double-blind placebo-controlled trial with adequate sample (N=95) though many active ingredients and multiple outcomes limit attribution to caffeine alone.

Study Details

PMID:29215606
Participants:95
Impact:Accuracy and speed improved across post-dose assessments (RVIP accuracy F(1,87)=24.74, p<0.001; speed F(1,87)=10.29, p=0.002)
Trust score:4/5

exercise capacity (400-m walk time)

1 evidences

In prostate cancer survivors, a single dose of caffeine (~6 mg/kg) increased exercise capacity (faster 400-m walk) and tended to increase grip strength, without changing perceived exertion.

Trust comment: Randomized double-blind placebo-controlled crossover with clear numeric effects on exercise capacity, though modest sample size and single-dose design.

Study Details

PMID:24977700
Participants:30
Impact:Time improved by −7.93 s (−3.0%), P=0.010
Trust score:4/5

IL-6

1 evidences

In preterm infants at risk of recurrent apnea, early preventive caffeine citrate given within 8 h after birth was associated with larger decreases in IL-6 and IL-8 after therapy compared with later treatment; no significant difference in BPD incidence was demonstrated.

Trust comment: Randomized allocation described but limited reporting and modest sample size in neonatal population; results on cytokines are significant but clinical BPD outcome was not different.

Study Details

PMID:30961342
Participants:56
Impact:Significantly decreased in prevention group vs treatment group after therapy (P=0.001)
Trust score:3/5

QTc interval (Bazett corrected)

1 evidences

Acute consumption of large-volume caffeinated energy drinks (two 16-oz bottles; ~304–320 mg caffeine) in healthy adults increased QTc and raised brachial and central blood pressure compared with placebo.

Trust comment: Randomized, double-masked, placebo-controlled crossover with adequate sample for ECG endpoints and clear numeric changes, though acute single-exposure limits long-term conclusions.

Study Details

PMID:31137991
Participants:34
Impact:Maximum change from baseline: Drink A +17.9±13.9 ms, Drink B +19.6±15.8 ms, Placebo +11.9±11.1 ms (ANOVA P=0.005; drinks vs placebo significant at 180–240 min)
Trust score:4/5

central systolic/diastolic blood pressure

1 evidences

Acute consumption of large-volume caffeinated energy drinks (two 16-oz bottles; ~304–320 mg caffeine) in healthy adults increased QTc and raised brachial and central blood pressure compared with placebo.

Trust comment: Randomized, double-masked, placebo-controlled crossover with adequate sample for ECG endpoints and clear numeric changes, though acute single-exposure limits long-term conclusions.

Study Details

PMID:31137991
Participants:34
Impact:cSBP and cDBP increased after energy drinks vs placebo (cSBP max: Drink A +11.1±4.7 mm Hg, Drink B +10.1±4.8 mm Hg, Placebo +6.5±3.5 mm Hg; P<0.001)
Trust score:4/5

HRV recovery (RMSSD, SDNN, TINN, SD1, LF, HF)

1 evidences

In a crossover trial, 300 mg caffeine given before resistance exercise delayed autonomic (HRV) recovery and slowed heart rate and blood pressure recovery after exercise.

Trust comment: Prospective, crossover, controlled clinical trial with objective cardiac measures and clear effects, though sample size moderate.

Study Details

PMID:34274079
Participants:30
Impact:- delayed/impaired recovery (significant differences vs control)
Trust score:4/5

blood pressure recovery

1 evidences

In a crossover trial, 300 mg caffeine given before resistance exercise delayed autonomic (HRV) recovery and slowed heart rate and blood pressure recovery after exercise.

Trust comment: Prospective, crossover, controlled clinical trial with objective cardiac measures and clear effects, though sample size moderate.

Study Details

PMID:34274079
Participants:30
Impact:- slowed recovery after exercise
Trust score:4/5

white/gray matter abnormality

1 evidences

In very preterm infants, caffeine was linked to microstructural changes in white matter but not to changes in brain volumes.

Trust comment: Randomized trial with MRI outcomes supports moderate-high trust, though some diffusion data were only available in a subset (n=28).

Study Details

PMID:21031585
Participants:70
Impact:no change
Trust score:4/5

spontaneous DNA strand breaks (WBC)

1 evidences

In a randomized trial of 84 healthy men, daily consumption of a dark roast coffee for 4 weeks significantly reduced spontaneous DNA strand breaks in white blood cells compared with water (about 27% difference).

Trust comment: Randomized controlled trial with a relatively large sample for a molecular endpoint and clear statistical significance, though limited to men and one coffee blend.

Study Details

PMID:24740588
Participants:84
Impact:decrease (~27% difference between coffee and water; p=0.0002)
Trust score:4/5

Time to exhaustion at 80% VO2peak

1 evidences

A multi-ingredient caffeine supplement did not change strength or cycling time-to-exhaustion in untrained men.

Trust comment: Double-blind placebo crossover but small sample and supplement contained other ingredients (not caffeine-only), limiting causal attribution to caffeine.

Study Details

PMID:19834348
Participants:21
Impact:no change
Trust score:3/5

CYP1A2 genotype effect on TMH

1 evidences

Caffeine modestly increased tear volume; genetic variants in ADORA2A and CYP1A2 influenced the size of the increase.

Trust comment: Well-powered double-masked placebo crossover with objective measurement and genotyping, though effect size was small and of limited clinical significance.

Study Details

PMID:22336631
Participants:78
Impact:minor homozygous: net increase lower by 0.06 mm vs major homozygous
Trust score:4/5

adrenaline (epinephrine)

1 evidences

In sleep-deprived healthy men, higher caffeine doses (up to 8.6 mg/kg) increased adrenaline and produced dose-related improvements in alertness measures.

Trust comment: Randomized double-blind with a substantial sample (n=50) and objective/subjective alertness measures; good internal validity.

Study Details

PMID:11151742
Participants:50
Impact:significant increase between 1–4 h post-dose in high dose group (8.6 mg/kg) vs placebo
Trust score:4/5

re-intubation rate within 48 h after ventilator weaning

1 evidences

Higher maintenance caffeine dose after loading reduced re-intubation rate within 48 hours and apnea after ventilator weaning in very preterm infants.

Trust comment: Prospective randomized controlled trial with adequate sample (n=162) and clinically relevant outcomes; appears well conducted though full details not shown here.

Study Details

PMID:34753540
Participants:162
Impact:decreased (high-dose maintenance vs low-dose maintenance, P<0.05)
Trust score:4/5

fine motor coordination

1 evidences

At age 11, children randomized to neonatal caffeine therapy showed modest improvements in fine motor and visuomotor/visuospatial skills and no adverse effects on intelligence, attention, or behavior.

Trust comment: Large randomized placebo-controlled trial follow-up (n≈870) with consistent neurodevelopmental assessments and robust results for targeted outcomes.

Study Details

PMID:29643070
Participants:870
Impact:mean difference +2.9 points (95% CI 0.7 to 5.1; P=0.01)
Trust score:5/5

pain-free at 2 h (total attacks)

1 evidences

Multicentre randomized trial in adults comparing Indoprocaf (includes caffeine) vs sumatriptan: similar pain-free rates at 2 h, but Indoprocaf showed higher total pain-free rate at 5 h (including re-dosing).

Trust comment: Large multicentre randomized double-blind trial with appropriate endpoints and ITT analysis; high internal validity for clinical efficacy of the combination product.

Study Details

PMID:17627707
Participants:281
Impact:Indoprocaf 34% vs sumatriptan 37% (no significant difference)
Trust score:4/5

temporal attention (T2 RT)

1 evidences

In healthy young adults, 200 mg caffeine (alone or with cocoa flavanols) produced little-to-no acute benefits on temporal/spatial attention or working memory, aside from modest faster reaction times on some attention measures.

Trust comment: Well-powered randomized crossover with appropriate tasks and mixed-model analyses; results are largely null with a few modest RT effects.

Study Details

PMID:39607519
Participants:48
Impact:-25.3 ms (caffeine; LMM b = -25.26, p = 0.020)
Trust score:4/5

subjective intoxication symptoms (headache, weakness, dry mouth, perceived motor impairment)

1 evidences

In young adults, combining an energy drink with alcohol reduced some subjective symptoms of intoxication but did not improve objective motor coordination, reaction time, or breath alcohol.

Trust comment: Randomized crossover human study with objective and subjective measures but moderate sample and specificity to alcohol+energy drink context.

Study Details

PMID:16573577
Participants:26
Impact:reduced vs alcohol alone (significant)
Trust score:3/5

weight-loss maintenance

1 evidences

In obese adults after weight loss, rye bread enriched with green tea extract (providing ~123–158 mg caffeine/day) did not improve weight-loss maintenance but was associated with slightly better blood pressure control and a marginally smaller waist circumference.

Trust comment: Randomized single-blind pilot with moderate sample size; results suggest modest BP effects but limited clinical impact and pilot design.

Study Details

PMID:25494205
Participants:55
Impact:no significant change
Trust score:3/5

cognitive/language/motor scores

1 evidences

Follow-up of very preterm infants (randomized to high vs standard loading caffeine dose) found no clear differences in cognitive, language, motor, or socioemotional outcomes at age five, despite higher early cerebellar hemorrhage in the high-dose group.

Trust comment: Randomized double-blind trial with long-term follow-up but pilot-sized sample, attrition, and limited power reduce confidence in detecting small effects.

Study Details

PMID:35145209
Participants:46
Impact:similar on average between groups (no significant difference)
Trust score:3/5

Reaction time (vigilance)

1 evidences

A cup of coffee (100 mg caffeine) improved and stabilized reaction time across 120 min regardless of recent sleep quality, but in those with poor sleep it increased commission errors at 90 min and only partially reduced omission errors.

Trust comment: Randomized, counterbalanced trials with a moderate sample (n=69) and repeated objective vigilance measures; design appropriate for tested question.

Study Details

PMID:29866304
Participants:69
Impact:Improved and stabilized at 30, 90, 120 min with 100 mg caffeine
Trust score:4/5

parasympathetic heart rate control (RMSSD, SD1)

1 evidences

In healthy young men, 300 mg caffeine taken before moderate aerobic exercise delayed parasympathetic heart-rate recovery and slowed blood pressure return to baseline, without changing HR, respiratory rate or oxygen saturation.

Trust comment: Randomized crossover trial with objective measures and clear methods; moderate sample (32 completed) though limited to healthy young males and researcher was not blinded.

Study Details

PMID:29075019
Participants:32
Impact:delayed recovery (later return to baseline after exercise)
Trust score:4/5

apnea episodes (≥2/day) within 48 h

1 evidences

In preterm infants (≤32 weeks) on mechanical ventilation, an extra 5 mg/kg maintenance dose of caffeine 1 hour before weaning reduced reintubation and apnea episodes and lowered intraventricular hemorrhage incidence, with improved blood gas (higher pH, lower PaCO2) at 2 hours.

Trust comment: Prospective randomized controlled trial with sizeable sample (338) and statistically significant clinical outcomes, though full trial details (blinding, allocation concealment) not in excerpt.

Study Details

PMID:33476534
Participants:338
Impact:decreased (P = 0.015)
Trust score:4/5

onset of analgesia / analgesic effect at 1 h

1 evidences

Single-dose combinations containing caffeine (with paracetamol and opium) provided superior analgesia to placebo and were non-inferior to tramadol after third-molar extraction, with faster onset and greater analgesic effect at 1 hour for the stronger formulation and acceptable safety.

Trust comment: Well-conducted randomized double-blind multicenter trial, but caffeine was studied only as part of a combination product so isolated caffeine effects cannot be determined.

Study Details

PMID:20080382
Participants:228
Impact:faster onset and greater effect at 1 h (especially paracetamol+opium+caffeine with higher opium)
Trust score:3/5

cognitive and motor impairment rates

1 evidences

At 5-year follow-up of a large neonatal RCT, early caffeine therapy for apnea of prematurity did not significantly change the combined outcome of death or survival with disability compared with placebo (no lasting significant benefit on survival without disability).

Trust comment: Large multicenter randomized placebo-controlled trial with high follow-up rate and clinically important long-term outcomes.

Study Details

PMID:22253394
Participants:1640
Impact:no significant differences between groups
Trust score:5/5

BMNC cytokine levels

1 evidences

Caffeine (6 mg/kg) before a 15-km run increased plasma IL-10 and IL-6 responses after exercise versus placebo, but did not affect cytokines in blood mononuclear cells.

Trust comment: Randomized double-blind trial with direct cytokine measurements but small sample size (n=28).

Study Details

PMID:26132827
Participants:28
Impact:no effect of caffeine on BMNC cytokines
Trust score:4/5

pleasantness over training days

1 evidences

Caffeine-conditioned increases in drink pleasantness were expressed only when subjects were tested in the same caffeine-deprivation state as during conditioning.

Trust comment: Double-blind behavioral study with clear effects but modest sample size and subjective outcomes.

Study Details

PMID:10907674
Participants:44
Impact:increased across 4 days with caffeine during conditioning
Trust score:3/5

flavanol absorption

1 evidences

Taking green tea extract capsules led to better absorption of tea flavanols and a small increase in blood antioxidant activity compared with drinking green or black tea.

Trust comment: Randomized 3x3 crossover in 30 healthy subjects with direct biochemical measures; moderate-quality evidence.

Study Details

PMID:15585768
Participants:30
Impact:increased (enhanced with green tea supplement vs beverages)
Trust score:4/5

middle cerebral artery velocity (Vmca)

1 evidences

Caffeine substantially reduced cerebral blood flow and middle cerebral artery velocity, implying narrowing of cerebral arterioles and the MCA.

Trust comment: Direct physiological measurements but small combined sample (14 patients + 9 controls = 23) and specific population (post-stroke recovery).

Study Details

PMID:15132312
Participants:23
Impact:reduced by 13% (95% CI 10–17%)
Trust score:3/5

IGF-1

1 evidences

In healthy adults undergoing prolonged wakefulness, acute caffeine altered IGF-1 responses depending on COMT genotype and reduced the drop in testosterone during sleep deprivation.

Trust comment: Randomized crossover human study with hormonal measures and genotyping (n=37); moderate sample but well-controlled.

Study Details

PMID:37279709
Participants:37
Impact:-~10% (reduced with caffeine vs placebo at recovery; e.g., 102 vs 113 ng/mL)
Trust score:4/5

Pain reduction (>50% responders)

1 evidences

Adding 50 mg caffeine to paracetamol produced analgesia comparable to the tested comparator combination in patients with spinal osteoarthritis over one week.

Trust comment: Double-blind multicenter randomized trial (n=124 randomized; 112 per-protocol) showing equivalent analgesic efficacy and tolerability, but reported in a clinical medication-combination context.

Study Details

PMID:8949620
Participants:124
Impact:similar (51.2% paracetamol+caffeine vs 47.0% comparator)
Trust score:4/5

TBARS (oxidative stress)

1 evidences

In trained young adults, a single dose of caffeine before a maximal treadmill test reduced an oxidative stress marker and increased IL-6 after exercise, with no change in performance.

Trust comment: Randomized double‑blind crossover with relevant biomarkers but small sample and some exclusions limit generalizability.

Study Details

PMID:28480382
Participants:24
Impact:-52% (post‑exercise mean 11.4 vs 23.9 μM)
Trust score:3/5

1RM strength

1 evidences

In 54 active men, creatine loading with or without added caffeine (or coffee) did not provide additional improvements in strength or sprint performance compared with placebo over 5 days.

Trust comment: Randomized controlled design with moderate sample and objective performance measures but short (5-day) supplementation period.

Study Details

PMID:26439785
Participants:54
Impact:improved over time in all groups; no additional effect of caffeine vs placebo
Trust score:4/5

≥50% pain reduction at 4 h

1 evidences

A fixed-dose combination containing caffeine provided faster and greater short-term relief of episodic tension-type headache than nimesulide in compliant participants.

Trust comment: Double-blind multicentre RCT but outcome pertains to a multi-drug product (caffeine combined with other drugs) and only 40 completed per-protocol.

Study Details

PMID:16190913
Participants:40
Impact:IndoProCaf 90% vs nimesulide 58% (difference +32%)
Trust score:3/5

testosterone:cortisol ratio

1 evidences

In 24 professional rugby players, acute caffeine increased exercise-associated testosterone modestly and, at high dose (800 mg), substantially raised cortisol, slightly lowering the testosterone:cortisol ratio.

Trust comment: Well-controlled double-blind crossover in athletes with clear dose-response data, though high doses and wide confidence limits reduce generalizability.

Study Details

PMID:18458357
Participants:24
Impact:small decline ~-14% (±21%) with caffeine
Trust score:4/5

nausea incidence

1 evidences

Among ~296 migraine patients, the ergotamine+100 mg caffeine combination was less effective and had more gastrointestinal adverse effects than calcium carbasalate+metoclopramide.

Trust comment: Large randomized double-blind multicenter trial; robust design though caffeine was tested as part of a combination therapy.

Study Details

PMID:9885327
Participants:296
Impact:EC 63% vs CM 42% (difference +21%, p=0.007)
Trust score:4/5

effect of habitual caffeine intake within green tea group

1 evidences

In 104 overweight adults, green tea (containing 104 mg caffeine/day) did not significantly affect weight regain after weight loss overall, but habitual high caffeine consumers on green tea regained more weight.

Trust comment: Randomized placebo-controlled trial of green tea (contains caffeine and catechins); effects cannot be attributed solely to caffeine.

Study Details

PMID:15005829
Participants:104
Impact:habitual high caffeine consumers regained 39% vs low consumers 16% (P<0.05)
Trust score:4/5

fatigue / sleepiness (withdrawal symptoms)

1 evidences

Brief caffeine deprivation in habitual coffee drinkers caused decreased vigor, increased fatigue and sleepiness, and a modest drop in blood pressure; psychomotor performance unchanged.

Trust comment: Double-blind within-subject design with clear outcome measures and n=31; results are directly reported and interpretable.

Study Details

PMID:9402612
Participants:31
Impact:+ increased (sleepiness, yawning)
Trust score:4/5

Response by habitual caffeine intake

1 evidences

Overweight subjects lost weight on a very low energy diet then during 3-month maintenance received a green tea–caffeine mixture or placebo; effects depended on habitual caffeine intake.

Trust comment: Randomized, double-blind, placebo-controlled trial with moderate sample size; mixture contained caffeine but effects are influenced by habitual caffeine use.

Study Details

PMID:16076989
Participants:76
Impact:no WM effects of green tea–caffeine in high habitual caffeine consumers
Trust score:4/5

chewing pain

1 evidences

Paracetamol-caffeine reduced separator-related pain compared with placebo but did not improve overall oral-health-related quality of life.

Trust comment: Randomized, placebo-controlled clinical trial with objective pain scales and clear group sizes, though sample size is modest.

Study Details

PMID:35110003
Participants:54
Impact:median 6 (drug) vs 8 (control) at 24 h; reduction (~25%)
Trust score:4/5

mental alertness / recognition memory

1 evidences

Caffeine reduced sleepiness and improved motor performance (tapping and reaction times); improvements in mental alertness and cognition were mainly seen in medium-high consumers and were limited in frequent consumers.

Trust comment: Large sample, double-blind treatment with behavioral and cognitive tasks; subgroup effects and tolerance discussed, increasing relevance.

Study Details

PMID:23108937
Participants:369
Impact:improved mainly in medium-high consumers; little effect in frequent consumers
Trust score:4/5

calmness

1 evidences

Single 600 mg slow-release caffeine decreased calmness and prolonged sleep onset but did not change alertness the next day.

Trust comment: Randomized double-blind parallel trial with a large sample (120) but limited to young males and single-dose testing.

Study Details

PMID:9025802
Participants:120
Impact:decreased (p<0.01)
Trust score:4/5

EEG theta/alpha power

1 evidences

In 30 children (8–13 y), a single 80 mg oral caffeine dose increased physiological arousal (skin conductance) and altered EEG indices versus placebo.

Trust comment: Randomized double-blind crossover with objective EEG and electrodermal measures in 30 children; moderate sample size.

Study Details

PMID:19486913
Participants:30
Impact:Global reduction in theta and alpha power
Trust score:4/5

responder proportion (pain relief)

1 evidences

A nonprescription combination including caffeine (with acetaminophen and aspirin) provided greater pain relief and functional improvement than placebo in OTC-appropriate migraine sufferers.

Trust comment: Large randomized placebo-controlled trials, but caffeine was part of a multi-ingredient combination so effects cannot be attributed to caffeine alone.

Study Details

PMID:10524663
Participants:1220
Impact:increased (AAC > placebo from 1–6 h postdose)
Trust score:3/5

functional disability / photophobia / phonophobia

2 evidences

A nonprescription combination including caffeine (with acetaminophen and aspirin) provided greater pain relief and functional improvement than placebo in OTC-appropriate migraine sufferers.

Trust comment: Large randomized placebo-controlled trials, but caffeine was part of a multi-ingredient combination so effects cannot be attributed to caffeine alone.

Study Details

PMID:10524663
Participants:1220
Impact:improved more with AAC (significant from 2–6 h)
Trust score:3/5

A combination containing caffeine (AAC) provided faster and greater migraine pain relief and symptom improvement than placebo in both menstruation-associated and non-menstrual migraine.

Trust comment: Large pooled randomized, double-masked trials give robust evidence for the combination product, but caffeine was not tested alone.

Study Details

PMID:10321417
Participants:1220
Impact:significantly improved with AAC vs placebo at 1–6 h (P≤0.01)
Trust score:4/5

β-endorphin

1 evidences

In men, 3 mg/kg caffeine taken before treadmill running increased plasma dopamine and β-endorphin compared with control; serotonin rose with exercise regardless of caffeine.

Trust comment: Randomized acute exercise study with 30 male volunteers; moderate sample and clear biochemical outcomes but limited to acute setting.

Study Details

PMID:31793465
Participants:30
Impact:↑ (significant increase with caffeine vs control)
Trust score:3/5

psychomotor vigilance lapses

1 evidences

Repeated caffeine gum (up to 200 mg every 2 hours) reduced vigilance lapses during an extended wake period and 200 mg preserved baseline performance overnight.

Trust comment: Randomized groups with objective PVT measures and adequate sample size for performance effects.

Study Details

PMID:16313140
Participants:48
Impact:reduced in a dose-related manner; 200 mg maintained baseline performance across the night
Trust score:4/5

total repetitions (strength training performance)

1 evidences

Caffeine (6.5 mg/kg) improved total repetitions in resistance training compared with placebo in active women; no additional benefit from combining with carbohydrate rinse.

Trust comment: Double-blind, randomized, placebo-controlled crossover with objective performance outcomes though modest sample size.

Study Details

PMID:32851636
Participants:29
Impact:increased vs placebo
Trust score:4/5

average reflection time per game

1 evidences

Caffeine increased reflection time and games lost on time but did not improve overall chess performance under normal analysis of all games.

Trust comment: Well-designed double-blind randomized crossover (n=39) showing increased deliberation time and time-loss but no overall performance gain.

Study Details

PMID:28119083
Participants:39
Impact:increased with caffeine (significant)
Trust score:4/5

simulation time

1 evidences

In novices, low-dose caffeine worsened simulator surgical performance and increased tremor; seniors showed mainly tremor changes without dexterity loss.

Trust comment: Self-controlled simulator study with repeated exposures and modest sample sizes (novices n=15, seniors n=11); internal control is strength but ecological validity limited.

Study Details

PMID:36782058
Participants:26
Impact:increased (slower) in novices after caffeine
Trust score:3/5

Wingate peak/mean/minimum power

1 evidences

A moderate dose of caffeine (3 mg/kg) acutely improved bench-press velocity/power, muscle endurance, vertical jump height, and Wingate power in resistance-trained men, with no clear genotype differences.

Trust comment: Randomized double-blind crossover, registered trial in trained men (n=22); robust within-subject design though moderate sample size.

Study Details

PMID:32295624
Participants:22
Impact:increased
Trust score:4/5

insomnia severity

1 evidences

In a crossover RCT of postmenopausal women with OAB, 400 mg/day caffeine for 7 days produced a small reduction in anxiety; depression, insomnia, and perceived stress showed no change.

Trust comment: Randomized double-blind crossover with 56 completers supports internal validity, but short 7-day exposures limit long-term conclusions.

Study Details

PMID:35363563
Participants:56
Impact:no change vs placebo over 7 days
Trust score:4/5

Horizontal reaction time (RT)

1 evidences

Acute caffeine (~4 mg/kg) improved dynamic visual acuity (horizontal and random paths), shortened horizontal reaction time, and increased subjective activation in low-caffeine consumers.

Trust comment: Double-blind, balanced crossover with validated measures and appropriate analyses but modest sample size (n=21).

Study Details

PMID:34420061
Participants:21
Impact:decreased (e.g., -58 ms at velocity 0.34 m/s; significant)
Trust score:4/5

dyspnea leading to drug discontinuation

1 evidences

In ~9,700 high-risk post‑MI patients, baseline caffeinated beverage intake was not associated with lower ticagrelor-related dyspnea but was associated with lower drug discontinuation for dyspnea and lower rates of MACE/MI in adjusted analyses.

Trust comment: Large, well-characterized randomized trial database but caffeine exposure was observational (baseline self-report) and analyses are nonrandomized, so residual confounding is possible.

Study Details

PMID:32410485
Participants:9694
Impact:Lower with caffeine: adjusted HR 0.72 (95% CI 0.53–0.98), P=0.035
Trust score:4/5

OCD symptom severity (Y-BOCS) — early response

1 evidences

In 24 treatment-resistant OCD patients, caffeine 300 mg/day augmentation produced symptom improvements comparable to dextroamphetamine over 5 weeks in this small double-blind trial.

Trust comment: Double-blind randomized design but very small sample (n=24) and results reported for responders subset, limiting generalizability.

Study Details

PMID:19573497
Participants:24
Impact:Week 1 responders: caffeine 7/12 (58%) vs dextroamphetamine 6/12 (50%)
Trust score:3/5

Sustained attention (EEG P300 amplitude)

1 evidences

In a randomized double-blind placebo-controlled trial (n=60) a citicoline-caffeine beverage improved sustained attention, reaction time, and working memory measures and increased P300 amplitudes on EEG vs placebo.

Trust comment: Randomized double-blind placebo-controlled trial with EEG and neurocognitive outcomes and a moderate sample (n=60).

Study Details

PMID:25046515
Participants:60
Impact:increased P300 amplitude (improved sustained attention; significant)
Trust score:4/5

Working memory / learning

1 evidences

In a randomized double-blind placebo-controlled trial (n=60) a citicoline-caffeine beverage improved sustained attention, reaction time, and working memory measures and increased P300 amplitudes on EEG vs placebo.

Trust comment: Randomized double-blind placebo-controlled trial with EEG and neurocognitive outcomes and a moderate sample (n=60).

Study Details

PMID:25046515
Participants:60
Impact:faster maze learning times and fewer errors on go/no-go task (significant)
Trust score:4/5

Anxiety response to caffeine

1 evidences

In 379 participants, caffeine (100 mg then 150 mg) increased anxiety in genetically susceptible individuals (ADORA2A rs5751876 TT) especially among low habitual consumers; habitual consumption reduced anxiogenic response (tolerance) and no net alerting benefit was seen in some groups.

Trust comment: Large randomized double-blind design with genetic stratification and habitual-consumption groups (n=379); strong design for behavioral/genetic effects.

Study Details

PMID:20520601
Participants:379
Impact:greater caffeine-induced anxiety in rs5751876 TT genotype among low habitual consumers (significant)
Trust score:4/5

cardiovascular parameters

2 evidences

In 80 healthy volunteers, a 200 mg caffeine active control increased subjective alertness and affected cardiovascular measures.

Trust comment: Within-subjects placebo-controlled design with a large sample (n=80) gives moderate-high reliability though caffeine was an active control rather than the primary focus.

Study Details

PMID:23420115
Participants:80
Impact:altered (reported effects)
Trust score:4/5

In habitual coffee-drinking middle-aged women, caffeine (50–100 mg) reduced negative mood scores (notably anxiety/sadness); combining aspirin and caffeine did not increase positive mood or show clear abuse potential.

Trust comment: Randomized double-blind design with adequate sample (n=96) in habitual coffee drinkers; outcomes focused on mood scales.

Study Details

PMID:11486635
Participants:96
Impact:no clear change reported
Trust score:4/5

caffeine intake

1 evidences

Self-monitoring (including advice on caffeine) reduced urine loss and improved quality of life; participants also reduced caffeine intake.

Trust comment: Large randomized clinical trial (n=224) with clear primary outcomes, though caffeine change was part of a multi-component intervention.

Study Details

PMID:17366526
Participants:224
Impact:reduced (magnitude not specified)
Trust score:4/5

subjective 'high'

1 evidences

In 50 male smokers, an acute dose of caffeine increased subjective 'pleasant' effects and feeling 'high' but did not change cigarette consumption.

Trust comment: Randomized double-blind crossover with ecological setting and adequate sample, but outcomes are subjective self-reports.

Study Details

PMID:15001822
Participants:50
Impact:increased (p=0.03)
Trust score:3/5

Time to be apnea-free

1 evidences

Extending caffeine citrate in moderately preterm infants did not shorten hospital stay or time to physiological maturity but led to earlier resolution of apnea.

Trust comment: Large multicenter randomized clinical trial (n=827) with prespecified outcomes and stopping for futility, high-quality evidence.

Study Details

PMID:40294395
Participants:827
Impact:shorter with caffeine (6.0 vs 10.0 days; adjusted median difference -2.7 days; 95% CI -3.4 to -2.0)
Trust score:5/5

incident probable dementia

1 evidences

In this prospective cohort of older women, higher baseline caffeine intake was associated with lower incidence of probable dementia and cognitive impairment over follow-up.

Trust comment: Large prospective cohort with adjustment for confounders but observational design limits causal inference.

Study Details

PMID:27678290
Participants:6467
Impact:decreased (HR=0.74 vs below-median intake)
Trust score:3/5

mental fatigue

1 evidences

A nutrient-enriched breakfast bar (containing a low caffeine dose of 21.5 mg among many other ingredients) produced acute improvements in alertness, attention and several cognitive tasks versus placebo on Day 1 and Day 56.

Trust comment: Well-designed randomized double-blind placebo-controlled trial with adequate sample (N=95) though many active ingredients and multiple outcomes limit attribution to caffeine alone.

Study Details

PMID:29215606
Participants:95
Impact:Subjective mental fatigue reduced across assessments (Cognitive Demand Battery fatigue F(3,279)=22.5, p<0.001)
Trust score:4/5

isometric grip strength

1 evidences

In prostate cancer survivors, a single dose of caffeine (~6 mg/kg) increased exercise capacity (faster 400-m walk) and tended to increase grip strength, without changing perceived exertion.

Trust comment: Randomized double-blind placebo-controlled crossover with clear numeric effects on exercise capacity, though modest sample size and single-dose design.

Study Details

PMID:24977700
Participants:30
Impact:Trend to increase: dominant +2.9% (P=0.053), nondominant +2.1% (P=0.061)
Trust score:4/5

IL-8

1 evidences

In preterm infants at risk of recurrent apnea, early preventive caffeine citrate given within 8 h after birth was associated with larger decreases in IL-6 and IL-8 after therapy compared with later treatment; no significant difference in BPD incidence was demonstrated.

Trust comment: Randomized allocation described but limited reporting and modest sample size in neonatal population; results on cytokines are significant but clinical BPD outcome was not different.

Study Details

PMID:30961342
Participants:56
Impact:Significantly decreased in prevention group vs treatment group after therapy (P=0.001)
Trust score:3/5

mood and physiological state

1 evidences

In a single-blind crossover, breakfast including espresso plus either carbohydrate or protein improved mood, physiological state and short-term verbal memory; authors attribute effects to both croissants and caffeine.

Trust comment: Randomized counterbalanced crossover with reasonable sample, but interventions combined food and coffee so caffeine-specific effects are not isolated.

Study Details

PMID:33640376
Participants:40
Impact:+ improved self-reported mood and physiological measures after breakfast (significant)
Trust score:3/5

global and regional brain volumes

1 evidences

In very preterm infants, caffeine was linked to microstructural changes in white matter but not to changes in brain volumes.

Trust comment: Randomized trial with MRI outcomes supports moderate-high trust, though some diffusion data were only available in a subset (n=28).

Study Details

PMID:21031585
Participants:70
Impact:no change
Trust score:4/5

Global perfusion

1 evidences

Acute caffeine in elderly reduced global brain perfusion but enhanced working‑memory related fMRI activation and increased functional connectivity in task networks.

Trust comment: Placebo‑controlled crossover with multimodal MRI and behavioral correlation in a moderate sample of elderly subjects provides credible functional data.

Study Details

PMID:23876323
Participants:24
Impact:decreased −22.7% vs placebo
Trust score:4/5

Total repetitions (resistance exercise)

1 evidences

Caffeine (6 mg/kg) increased resistance-exercise repetitions in CYP1A2 AA homozygotes but not in C-allele carriers.

Trust comment: Randomized double-blind placebo crossover with genotype stratification and objective performance outcomes, but modest sample and subgroup sizes.

Study Details

PMID:29532291
Participants:30
Impact:increase under caffeine in AA homozygotes vs AC/CC (statistically significant)
Trust score:4/5

noradrenaline (norepinephrine)

1 evidences

In sleep-deprived healthy men, higher caffeine doses (up to 8.6 mg/kg) increased adrenaline and produced dose-related improvements in alertness measures.

Trust comment: Randomized double-blind with a substantial sample (n=50) and objective/subjective alertness measures; good internal validity.

Study Details

PMID:11151742
Participants:50
Impact:no significant effect
Trust score:4/5

incidence of apnea after weaning / ventilator weaning failure

1 evidences

Higher maintenance caffeine dose after loading reduced re-intubation rate within 48 hours and apnea after ventilator weaning in very preterm infants.

Trust comment: Prospective randomized controlled trial with adequate sample (n=162) and clinically relevant outcomes; appears well conducted though full details not shown here.

Study Details

PMID:34753540
Participants:162
Impact:reduced in high-dose group (significant)
Trust score:4/5

visuomotor integration

1 evidences

At age 11, children randomized to neonatal caffeine therapy showed modest improvements in fine motor and visuomotor/visuospatial skills and no adverse effects on intelligence, attention, or behavior.

Trust comment: Large randomized placebo-controlled trial follow-up (n≈870) with consistent neurodevelopmental assessments and robust results for targeted outcomes.

Study Details

PMID:29643070
Participants:870
Impact:mean difference +1.8 points (95% CI 0.0 to 3.7; P≈0.05)
Trust score:5/5

headache relief at 2 h

1 evidences

Multicentre randomized trial in adults comparing Indoprocaf (includes caffeine) vs sumatriptan: similar pain-free rates at 2 h, but Indoprocaf showed higher total pain-free rate at 5 h (including re-dosing).

Trust comment: Large multicentre randomized double-blind trial with appropriate endpoints and ITT analysis; high internal validity for clinical efficacy of the combination product.

Study Details

PMID:17627707
Participants:281
Impact:Indoprocaf 62% vs sumatriptan 56% (no significant difference)
Trust score:4/5

visual search reaction time

1 evidences

In healthy young adults, 200 mg caffeine (alone or with cocoa flavanols) produced little-to-no acute benefits on temporal/spatial attention or working memory, aside from modest faster reaction times on some attention measures.

Trust comment: Well-powered randomized crossover with appropriate tasks and mixed-model analyses; results are largely null with a few modest RT effects.

Study Details

PMID:39607519
Participants:48
Impact:-16.4 ms (caffeine; b = -16.42, p = 0.031)
Trust score:4/5

objective motor coordination

1 evidences

In young adults, combining an energy drink with alcohol reduced some subjective symptoms of intoxication but did not improve objective motor coordination, reaction time, or breath alcohol.

Trust comment: Randomized crossover human study with objective and subjective measures but moderate sample and specificity to alcohol+energy drink context.

Study Details

PMID:16573577
Participants:26
Impact:no significant change
Trust score:3/5

Commission errors (inhibitory control)

1 evidences

A cup of coffee (100 mg caffeine) improved and stabilized reaction time across 120 min regardless of recent sleep quality, but in those with poor sleep it increased commission errors at 90 min and only partially reduced omission errors.

Trust comment: Randomized, counterbalanced trials with a moderate sample (n=69) and repeated objective vigilance measures; design appropriate for tested question.

Study Details

PMID:29866304
Participants:69
Impact:Increased at 90 min in individuals reporting poor sleep quality
Trust score:4/5

intraventricular hemorrhage incidence

1 evidences

In preterm infants (≤32 weeks) on mechanical ventilation, an extra 5 mg/kg maintenance dose of caffeine 1 hour before weaning reduced reintubation and apnea episodes and lowered intraventricular hemorrhage incidence, with improved blood gas (higher pH, lower PaCO2) at 2 hours.

Trust comment: Prospective randomized controlled trial with sizeable sample (338) and statistically significant clinical outcomes, though full trial details (blinding, allocation concealment) not in excerpt.

Study Details

PMID:33476534
Participants:338
Impact:decreased during hospitalization (P = 0.048)
Trust score:4/5

safety profile / adverse events

1 evidences

Single-dose combinations containing caffeine (with paracetamol and opium) provided superior analgesia to placebo and were non-inferior to tramadol after third-molar extraction, with faster onset and greater analgesic effect at 1 hour for the stronger formulation and acceptable safety.

Trust comment: Well-conducted randomized double-blind multicenter trial, but caffeine was studied only as part of a combination product so isolated caffeine effects cannot be determined.

Study Details

PMID:20080382
Participants:228
Impact:no unexpected safety concerns; acceptable tolerability
Trust score:3/5

plasma antioxidant activity

1 evidences

Taking green tea extract capsules led to better absorption of tea flavanols and a small increase in blood antioxidant activity compared with drinking green or black tea.

Trust comment: Randomized 3x3 crossover in 30 healthy subjects with direct biochemical measures; moderate-quality evidence.

Study Details

PMID:15585768
Participants:30
Impact:small significant increase (vs green or black tea)
Trust score:4/5

arteriole and MCA diameter

1 evidences

Caffeine substantially reduced cerebral blood flow and middle cerebral artery velocity, implying narrowing of cerebral arterioles and the MCA.

Trust comment: Direct physiological measurements but small combined sample (14 patients + 9 controls = 23) and specific population (post-stroke recovery).

Study Details

PMID:15132312
Participants:23
Impact:arteriole diameter ≈ −5.9%; MCA diameter ≈ −4.3% (estimates)
Trust score:3/5

testosterone

2 evidences

In healthy adults undergoing prolonged wakefulness, acute caffeine altered IGF-1 responses depending on COMT genotype and reduced the drop in testosterone during sleep deprivation.

Trust comment: Randomized crossover human study with hormonal measures and genotyping (n=37); moderate sample but well-controlled.

Study Details

PMID:37279709
Participants:37
Impact:Caffeine attenuated the decrease during prolonged wakefulness (alleviated reduction vs placebo)
Trust score:4/5

In an 8-week randomized trial in overweight habitual coffee drinkers, caffeinated and decaffeinated coffee produced some short-term (week 4) changes in sex hormones that were not sustained at week 8.

Trust comment: Randomized controlled trial with biochemical outcomes but small sample (n=42) and transient effects limited to week 4.

Study Details

PMID:23078574
Participants:42
Impact:Men: +67% at week 4 with caffeinated coffee; Women: −47.8% at week 4 with caffeinated coffee (decaffeinated women −60% at week 4)
Trust score:3/5

adverse events/tolerability

1 evidences

Adding 50 mg caffeine to paracetamol produced analgesia comparable to the tested comparator combination in patients with spinal osteoarthritis over one week.

Trust comment: Double-blind multicenter randomized trial (n=124 randomized; 112 per-protocol) showing equivalent analgesic efficacy and tolerability, but reported in a clinical medication-combination context.

Study Details

PMID:8949620
Participants:124
Impact:no serious adverse events; similar frequency/intensity between groups
Trust score:4/5

≥50% pain reduction at 2 h

1 evidences

A fixed-dose combination containing caffeine provided faster and greater short-term relief of episodic tension-type headache than nimesulide in compliant participants.

Trust comment: Double-blind multicentre RCT but outcome pertains to a multi-drug product (caffeine combined with other drugs) and only 40 completed per-protocol.

Study Details

PMID:16190913
Participants:40
Impact:IndoProCaf 75% vs nimesulide 30% (difference +45%)
Trust score:3/5

sirtuin1 and CD36 mRNA

1 evidences

Combination treatment including ephedrine plus caffeine reduced body fat and altered lipid-related gene expression; caffeine was given as part of a multi-drug regimen so individual caffeine effects are not isolated.

Trust comment: Randomized trial with moderate sample size but caffeine was administered with ephedrine (and/or pioglitazone), so effects cannot be attributed solely to caffeine.

Study Details

PMID:17351280
Participants:57
Impact:increased (only in ECPio group)
Trust score:3/5

percentage body fat

1 evidences

A combined caffeine+ephedra supplement raised resting metabolic rate and produced greater weight and fat loss than placebo over 12 weeks.

Trust comment: Randomized double-blind trial but supplement combined caffeine with ephedra, so effects cannot be attributed to caffeine alone.

Study Details

PMID:15292480
Participants:40
Impact:-7.9% (C&E) vs -1.9% (placebo) in percent fat lost
Trust score:3/5

cortisol concentration

1 evidences

In 24 professional rugby players, acute caffeine increased exercise-associated testosterone modestly and, at high dose (800 mg), substantially raised cortisol, slightly lowering the testosterone:cortisol ratio.

Trust comment: Well-controlled double-blind crossover in athletes with clear dose-response data, though high doses and wide confidence limits reduce generalizability.

Study Details

PMID:18458357
Participants:24
Impact:800 mg caffeine produced ~+52% (±44%) increase
Trust score:4/5

complete headache relief

1 evidences

Among ~296 migraine patients, the ergotamine+100 mg caffeine combination was less effective and had more gastrointestinal adverse effects than calcium carbasalate+metoclopramide.

Trust comment: Large randomized double-blind multicenter trial; robust design though caffeine was tested as part of a combination therapy.

Study Details

PMID:9885327
Participants:296
Impact:EC 8% vs CM 20% (difference -12%, p=0.006)
Trust score:4/5

body-weight regain after weight loss

1 evidences

In 104 overweight adults, green tea (containing 104 mg caffeine/day) did not significantly affect weight regain after weight loss overall, but habitual high caffeine consumers on green tea regained more weight.

Trust comment: Randomized placebo-controlled trial of green tea (contains caffeine and catechins); effects cannot be attributed solely to caffeine.

Study Details

PMID:15005829
Participants:104
Impact:green tea 30.5% vs placebo 19.7% (no significant difference)
Trust score:4/5

Squat jump / dynamic performance

1 evidences

After eastbound travel across seven time zones, slow‑release caffeine (300 mg) prevented the post-travel decline in dominant-hand static strength seen with placebo, while dynamic measures were unchanged.

Trust comment: Randomized (three-arm) small trial with objective performance tests but limited sample and preliminary findings.

Study Details

PMID:11283440
Participants:27
Impact:No significant degradation or consistent change after travel (no benefit observed)
Trust score:3/5

pain relief

1 evidences

In a large multicenter RCT, the acetaminophen+aspirin+caffeine combination provided faster and greater pain relief than ibuprofen and placebo in patients with severe migraine.

Trust comment: Large, well-conducted RCT, but caffeine was given as part of a fixed combination so individual effect of caffeine cannot be isolated.

Study Details

PMID:24733408
Participants:1555
Impact:greater relief vs placebo and ibuprofen at multiple time points (p≤0.05)
Trust score:4/5

functional disability

1 evidences

In a large multicenter RCT, the acetaminophen+aspirin+caffeine combination provided faster and greater pain relief than ibuprofen and placebo in patients with severe migraine.

Trust comment: Large, well-conducted RCT, but caffeine was given as part of a fixed combination so individual effect of caffeine cannot be isolated.

Study Details

PMID:24733408
Participants:1555
Impact:reduced to little/none more often at 3 hours (p=0.013)
Trust score:4/5

nighttime diastolic blood pressure variation (rate)

1 evidences

Regular consumption of black tea (3 cups/day) reduced nighttime blood-pressure variability by about 10% compared with a flavonoid-free caffeine-matched control; effect appears independent of caffeine.

Trust comment: Large (n=111), randomized, double-blind, 6-month trial with appropriate control (caffeine-matched), supporting robustness of findings.

Study Details

PMID:23553154
Participants:111
Impact:decrease (~10% lower vs caffeine-matched control)
Trust score:5/5

early recall of audio material

1 evidences

In healthy young males, 200 mg caffeine improved sustained attention (shorter reaction time) but showed no robust effects on most other cognitive domains or subjective fatigue.

Trust comment: Randomized, double-blind, within-subject trial (48 males) with rigorous corrections for multiple comparisons; limited by moderate per-arm sample size and male-only participants.

Study Details

PMID:33201262
Participants:48
Impact:trend toward improvement with caffeine (p=0.044; not significant after multiple-comparison correction)
Trust score:4/5

Executive function (Shifting Attention Test correct responses/errors)

1 evidences

In 100 healthy drivers, a single 200 mg caffeine dose improved some executive/cognitive test performance and shortened brake reaction time versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with objective cognitive and driving outcomes in 100 healthy adults; some limitations noted by authors (washout/habit effects).

Study Details

PMID:30379815
Participants:100
Impact:+2.8 correct responses and -1.2 errors (55.0 vs 52.2; 2.5 vs 3.7; p=0.03 and p=0.02)
Trust score:4/5

Attentional bias for caffeine-related stimuli

1 evidences

Across three experiments, caffeine-related attentional biases were observed, but deprivation increased coffee consumption and subjective drowsiness without altering attentional bias.

Trust comment: Multiple experiments (between- and within-subject) showing consistent behavioural outcomes; sample sizes per experiment were modest.

Study Details

PMID:16170233
Participants:28
Impact:Present but not modulated by deprivation (no change)
Trust score:3/5

esophageal temperature rise (ΔTes)

1 evidences

In 28 participants (14 habituated, 14 non-habituated), 5 mg/kg caffeine increased end-exercise esophageal temperature and attenuated skin blood flow responses in caffeine-habituated individuals but had no effect in non-habituated participants or on sweating.

Trust comment: Randomized, double-blind, crossover with clear habituation stratification and physiological measures; sample size adequate for mechanistic outcomes.

Study Details

PMID:34435513
Participants:28
Impact:HAB: +0.88°C vs PLA +0.62°C (increase ≈+0.26°C with caffeine); NHAB: no change
Trust score:5/5

total sleep time (TST)

1 evidences

In 30 healthy physically active males, 5 mg/kg/day caffeine over 4 days did not change resting or activity-related energy expenditure but reduced total sleep time.

Trust comment: Well-controlled double-blind crossover with objective measures (accelerometry, calorimetry); moderate sample size and clear outcomes.

Study Details

PMID:23368828
Participants:30
Impact:decreased (p=0.022) over 4 days
Trust score:4/5

treatment effective rate

1 evidences

In preterm infants with primary apnea, a higher maintenance dose of caffeine citrate improved apnea control and ventilator weaning success without increasing measured side effects.

Trust comment: Prospective randomized allocation with moderate-to-large sample (n=164); outcomes and safety reported, though single-center.

Study Details

PMID:26791921
Participants:164
Impact:82% vs 61% (high-dose vs low-dose) increased
Trust score:4/5

microstate class D contribution/duration/occurrence (in SZ)

1 evidences

In early-phase psychosis patients (vs controls), acute caffeine shifted EEG microstate dynamics: it reduced class D and increased classes A and B parameters in patients but had little effect in controls.

Trust comment: Randomized, double-blind within-subject EEG study with objective measures, but small sample and some reporting inconsistencies limit generalizability.

Study Details

PMID:35257622
Participants:25
Impact:decreased with caffeine in patients (duration 0.045s vs 0.064s; occurrence 3.85 vs 5.36/s; contribution 17.3% vs 37.6% caffeine vs placebo)
Trust score:3/5

error rate (four-choice reaction task)

1 evidences

Caffeine counteracted some alcohol-induced slowing on psychomotor speed and partially reduced alcohol-related errors on specific tasks.

Trust comment: Randomized, double-blind, placebo-controlled design with a moderate sample (n=64); task-based outcomes are straightforward.

Study Details

PMID:12404692
Participants:64
Impact:increased with alcohol; caffeine showed weak antagonism for random-sequence errors
Trust score:4/5

insulin

1 evidences

200 mg oral caffeine before an OGTT shifted the glucose curve rightward with higher glucose at 2–4 hours without changing insulin levels.

Trust comment: Single-blind Latin-square crossover with 30 healthy subjects and standardized OGTT; well controlled for this outcome.

Study Details

PMID:9846599
Participants:30
Impact:no significant change during OGTT
Trust score:4/5

colon cancer risk (men, low coffee intake)

1 evidences

Case-control analysis found associations between coffee (methylxanthine) intake and colon cancer risk in men that varied by intake level and tumor location.

Trust comment: Large population-based case-control study (cases+controls=4,403) but observational design and potential confounding reduce causal certainty.

Study Details

PMID:10188719
Participants:4403
Impact:+ increased risk (OR 1.32, 95% CI 1.02–1.67)
Trust score:3/5

amplitude of accommodation

1 evidences

A 250 mg caffeine drink increased pupil size and amplitude of accommodation over 90 minutes in young adults.

Trust comment: Double-masked crossover design with objective ocular measurements in a moderate sample size.

Study Details

PMID:27983733
Participants:50
Impact:+3.4 D (from 12.4±2.2 D to 15.8±2.6 D; ≈+27%)
Trust score:4/5

chess performance (overall)

1 evidences

Caffeine increased reflection time and games lost on time but did not improve overall chess performance under normal analysis of all games.

Trust comment: Well-designed double-blind randomized crossover (n=39) showing increased deliberation time and time-loss but no overall performance gain.

Study Details

PMID:28119083
Participants:39
Impact:no improvement versus placebo when all games analyzed; no net performance benefit
Trust score:4/5

serum free fatty acids

1 evidences

In healthy elderly adults, 6 mg/kg caffeine increased plasma epinephrine, free fatty acids, and lactate (percent increases consistent at rest, 5 min, and exhaustion), and increased insulin-resistance measures.

Trust comment: Randomized double-blind crossover in 30 elderly subjects with clear metabolic measures; moderate sample size but robust findings.

Study Details

PMID:16886964
Participants:30
Impact:+~53% (rest), +44% (5 min), +50% (exhaustion)
Trust score:4/5

Cumulative duration of caffeine therapy

1 evidences

In preterm infants (26–32 wk) on caffeine therapy for apnea, stopping after 7 apnea-free days did not increase recurrence vs continuing until 34 wk PMA, and stopping earlier reduced cumulative therapy duration.

Trust comment: Randomized controlled trial with moderate sample size (n=120) and clear primary outcome, though further work in extremely preterm infants is advised.

Study Details

PMID:33625665
Participants:120
Impact:shorter when stopped at 7 d apnea-free (19.5 vs 33 days)
Trust score:4/5

cognitive ability correlation

1 evidences

In sleep-deprived healthy adults, caffeine (600 mg) did not meaningfully restore risk-taking propensity to rested baseline, whereas dextroamphetamine did.

Trust comment: Randomized double-blind sleep-deprivation study in humans but small caffeine group (N=12 on caffeine) limiting precision.

Study Details

PMID:18785355
Participants:54
Impact:Cognitive ability correlated with changes in some risk-taking indices after stimulant administration (association reported, no effect size provided)
Trust score:4/5

global EEG alpha amplitude

1 evidences

Caffeine increases physiological arousal (higher skin conductance) and reduces EEG alpha; these effects add to those of opening the eyes.

Trust comment: Randomized, counterbalanced double-blind within-subject study in 22 humans; moderate sample but good design.

Study Details

PMID:21489866
Participants:22
Impact:decrease (caffeine vs placebo)
Trust score:4/5

Urinary metabolomic profile

1 evidences

In a three-arm randomized crossover trial (n=21), different coffee intake patterns produced distinct urinary metabolomic changes implicating pathways (e.g., phenylalanine/tyrosine, energy metabolism, steroid and arginine biosynthesis), suggesting coffee (which contains caffeine) alters metabolic profiles.

Trust comment: Randomized crossover metabolomics in 21 volunteers; robust metabolite identification but effects are indirect measures of caffeine specifically (coffee is a complex mixture).

Study Details

PMID:33300301
Participants:21
Impact:153 discriminant metabolites identified; patterns changed with coffee intake (altered phenylalanine/tyrosine and energy metabolism pathways)
Trust score:3/5

Nausea and vomiting (PDPH)

1 evidences

In 42 PDPH patients, gabapentin reduced pain, nausea, and vomiting more than ergotamine/caffeine (Cafergot); Cafergot was less effective than gabapentin in this setting.

Trust comment: Randomized prospective controlled study in clinical patients (n=42); directly compares ergotamine/caffeine to gabapentin but results indicate Cafergot was less effective.

Study Details

PMID:21536541
Participants:42
Impact:gabapentin reduced nausea/vomiting more than Cafergot (significant)
Trust score:3/5

macular flow area

1 evidences

A single 200 mg oral caffeine dose acutely reduced macular blood flow and vessel density measured by OCT-A at 1 hour.

Trust comment: Randomized allocation with objective OCT-A imaging and moderate sample size (n=52); acute study limits long-term inference.

Study Details

PMID:29401177
Participants:52
Impact:decrease (superficial, deep, choriocapillaris; significant, P<0.05)
Trust score:4/5

speed of attention

1 evidences

Single-blind randomized study found small improvements in basic attention and psychomotor speed after matcha products; no significant mood changes.

Trust comment: Randomized, placebo-controlled single-blind study with small sample (n=23) and modest effects, moderate quality.

Study Details

PMID:28784536
Participants:23
Impact:improved (small, significant)
Trust score:3/5

dose-dependent uptake (pharmacokinetic slope)

1 evidences

Oral coffee with increasing caffeine doses raised measurable caffeine levels in the lens capsule/lens epithelial cells in cataract patients in a dose-dependent way.

Trust comment: Small randomized pilot in human cataract patients with direct GC-MS/MS measurements supports internal validity but sample size is limited.

Study Details

PMID:29677345
Participants:33
Impact:Linear increase estimated slope ~0.02 (95% CI ±0.0046), r=0.85
Trust score:3/5

radial diffusivity

1 evidences

In very preterm infants, caffeine was linked to microstructural changes in white matter but not to changes in brain volumes.

Trust comment: Randomized trial with MRI outcomes supports moderate-high trust, though some diffusion data were only available in a subset (n=28).

Study Details

PMID:21031585
Participants:70
Impact:decrease (improved white matter microstructure)
Trust score:4/5

leg extension 1RM

1 evidences

In resistance-trained men, a caffeine-containing supplement increased bench-press 1RM but did not affect leg strength, endurance, or Wingate power.

Trust comment: Randomized supplement vs placebo with moderate sample, but single-exercise benefit and lack of broader effects lower confidence.

Study Details

PMID:16937961
Participants:37
Impact:no change
Trust score:3/5

common cold symptom score

1 evidences

A multi‑component product that includes caffeine improved common‑cold symptom scores more than controls, though caffeine was not tested alone.

Trust comment: Large randomized double‑blind multicenter trial but caffeine was not isolated, so effects cannot be attributed solely to caffeine.

Study Details

PMID:12665160
Participants:1167
Impact:improved vs control (statistically significant)
Trust score:3/5

Functional connectivity (task network)

1 evidences

Acute caffeine in elderly reduced global brain perfusion but enhanced working‑memory related fMRI activation and increased functional connectivity in task networks.

Trust comment: Placebo‑controlled crossover with multimodal MRI and behavioral correlation in a moderate sample of elderly subjects provides credible functional data.

Study Details

PMID:23876323
Participants:24
Impact:increased +8.2% vs placebo
Trust score:4/5

Tear meniscus height (tear volume)

1 evidences

Caffeine modestly increased tear volume; genetic variants in ADORA2A and CYP1A2 influenced the size of the increase.

Trust comment: Well-powered double-masked placebo crossover with objective measurement and genotyping, though effect size was small and of limited clinical significance.

Study Details

PMID:22336631
Participants:78
Impact:net increase +0.08 mm (95% CI 0.05–0.10) vs placebo
Trust score:4/5

Relation to symptoms in AD/HD

1 evidences

Caffeine increased skin conductance (arousal) in children, but dose-response differed between AD/HD and control groups.

Trust comment: Randomized double-blind crossover with matched controls but small sample and outcomes reported with limited quantitative detail.

Study Details

PMID:22266163
Participants:36
Impact:caffeine-induced arousal increases positively correlated with hyperactivity/impulsivity
Trust score:3/5

neurodevelopmental delay/impairment at 5 years

1 evidences

Follow-up of very preterm infants (randomized to high vs standard loading caffeine dose) found no clear differences in cognitive, language, motor, or socioemotional outcomes at age five, despite higher early cerebellar hemorrhage in the high-dose group.

Trust comment: Randomized double-blind trial with long-term follow-up but pilot-sized sample, attrition, and limited power reduce confidence in detecting small effects.

Study Details

PMID:35145209
Participants:46
Impact:no significant difference (high-dose vs standard-dose)
Trust score:3/5

Total pain relief (TOTPAR)

1 evidences

Paracetamol 1000 mg + caffeine 130 mg relieved migraine pain as well as sumatriptan 50 mg with similar overall tolerability; fatigue was slightly more common with sumatriptan.

Trust comment: Randomized, double-blind, double-dummy cross-over vs active comparator with reasonable sample for a crossover (ITT n=92); moderate external generalizability.

Study Details

PMID:23054063
Participants:92
Impact:Mean TOTPAR 7.0 (PCF) vs 7.4 (SUM); no difference (p=0.48)
Trust score:4/5

plasma IL-10

1 evidences

Caffeine (6 mg/kg) before a 15-km run increased plasma IL-10 and IL-6 responses after exercise versus placebo, but did not affect cytokines in blood mononuclear cells.

Trust comment: Randomized double-blind trial with direct cytokine measurements but small sample size (n=28).

Study Details

PMID:26132827
Participants:28
Impact:greater postexercise increase with caffeine vs placebo
Trust score:4/5

conditioned flavour pleasantness

1 evidences

Caffeine-conditioned increases in drink pleasantness were expressed only when subjects were tested in the same caffeine-deprivation state as during conditioning.

Trust comment: Double-blind behavioral study with clear effects but modest sample size and subjective outcomes.

Study Details

PMID:10907674
Participants:44
Impact:increased during conditioning with caffeine (100 mg)
Trust score:3/5

incident atrial fibrillation

1 evidences

In a large prospective cohort of women, higher caffeine intake was not associated with an increased risk of developing atrial fibrillation.

Trust comment: Large prospective cohort (n=33,638) with long follow-up and adjusted analyses, providing high-quality observational evidence.

Study Details

PMID:20573799
Participants:33638
Impact:no association (no increased risk across caffeine intake quintiles; multivariable HRs not significant)
Trust score:5/5

SHBG

1 evidences

In an 8-week randomized trial in overweight habitual coffee drinkers, caffeinated and decaffeinated coffee produced some short-term (week 4) changes in sex hormones that were not sustained at week 8.

Trust comment: Randomized controlled trial with biochemical outcomes but small sample (n=42) and transient effects limited to week 4.

Study Details

PMID:23078574
Participants:42
Impact:No consistent effect at week 8; decaffeinated coffee showed a borderline ↑38% in women at week 4 (not sustained)
Trust score:3/5

sustained attention (mean response time)

1 evidences

In habitual caffeine consumers, the combination of Alpinia galanga extract with caffeine reduced mean response time (improved sustained attention) at 3 hours compared with placebo.

Trust comment: Well-controlled crossover trial with moderate sample size, but caffeine-alone effects are not clearly reported in the provided excerpt.

Study Details

PMID:28910196
Participants:59
Impact:-15.55 ms at 3 hours (E-AG-01 with caffeine vs placebo; p=0.026)
Trust score:3/5

salivary cortisol

3 evidences

In habitual male caffeine users, single-dose caffeine (200 or 400 mg) did not change salivary alpha-amylase, cortisol, or cardiovascular measures during a non-stressful task.

Trust comment: Randomized, double-blind, placebo-controlled design with adequate sample size (N=45) but limited to young habitual male caffeine users, limiting broader generalizability.

Study Details

PMID:24410993
Participants:45
Impact:no change (no caffeine effect)
Trust score:4/5

In 40 habitual coffee consumers in a randomized crossover design, single servings of coffee (160 mg caffeine) increased salivary alpha-amylase and transiently increased salivary gastrin and blood pressure, but did not change salivary cortisol or self-reported GI symptoms.

Trust comment: Randomized double-blind crossover with objective biochemical measures, though modest sample and short-term assessments.

Study Details

PMID:26979712
Participants:40
Impact:no significant change
Trust score:4/5

Acute ingestion of various energy drinks (contain caffeine plus blends) produced group-specific increases in blood pressure, heart rate, cortisol, and mixed effects on anxiety and working memory.

Trust comment: Moderate-sized acute study (n=80) but tested commercial energy drinks with multiple active ingredients, so effects cannot be attributed to caffeine alone.

Study Details

PMID:27312565
Participants:80
Impact:increased in group B
Trust score:3/5

skin conductance level

1 evidences

Caffeine-associated cues and information about caffeine content modulated physiological and subjective arousal; conditioned and expectancy effects both contributed.

Trust comment: Controlled experimental studies (two experiments) with modest sample sizes and mixed within- and between-subject designs; suitable for conditioning/expectancy effects but not large-scale inference.

Study Details

PMID:11605096
Participants:69
Impact:increased with caffeine-associated stimuli
Trust score:3/5

IC response density (inner retinal activity)

1 evidences

A single 300 mg oral caffeine dose acutely increased inner-retinal electrophysiological responses at high/medium contrast and increased subjective alertness in young adults.

Trust comment: Double-masked, placebo-controlled within-subject crossover (n=24) with objective electrophysiology and clear statistical reporting; sample limited to young adults.

Study Details

PMID:39230997
Participants:24
Impact:increased (+14.9% at 95% contrast; +13.7% at 50% contrast; significant vs placebo)
Trust score:4/5

Alertness and vigilance (psychomotor vigilance)

1 evidences

Caffeine, naps, and especially their combination improved alertness and vigilance in laboratory and field night-shift settings.

Trust comment: Large multi-part study (68 laboratory participants, 53 field participants; total n=121) with lab and real-world data showing consistent alertness/performance benefits, though shift-worker populations vary.

Study Details

PMID:16453980
Participants:121
Impact:improved (napping, caffeine, and combination; combination best)
Trust score:4/5

Threat‑selective attention (threat‑bias)

1 evidences

In 40 women, 200 mg caffeine altered threat‑selective attention in a manner that depended on baseline EEG theta/beta ratio and trait anxiety (no uniform directional effect).

Trust comment: Double‑blind crossover with mechanistic EEG and behavioral measures; moderate sample but limited to females which restricts generalizability.

Study Details

PMID:29792908
Participants:40
Impact:Effect moderated by baseline frontal theta/beta ratio and trait‑anxiety; opposite effects observed in low trait‑anxious groups with low vs high TBR
Trust score:4/5

pain-free at 2 h

1 evidences

A fixed-dose combination containing caffeine provided faster and greater short-term relief of episodic tension-type headache than nimesulide in compliant participants.

Trust comment: Double-blind multicentre RCT but outcome pertains to a multi-drug product (caffeine combined with other drugs) and only 40 completed per-protocol.

Study Details

PMID:16190913
Participants:40
Impact:IndoProCaf 45% vs nimesulide 10% (difference +35%)
Trust score:3/5

salivary α-amylase (morning)

1 evidences

Matcha (contains caffeine and theanine) modestly lowered anxiety and morning salivary stress marker in students, but baseline group differences and modest effects limit certainty.

Trust comment: Randomized double-blind trial but baseline group imbalance and modest sample size reduce confidence in isolating caffeine-specific effects.

Study Details

PMID:30308973
Participants:39
Impact:decrease (significant at university, p=0.03)
Trust score:3/5

Triglycerides

1 evidences

Combination treatment including ephedrine plus caffeine reduced body fat and altered lipid-related gene expression; caffeine was given as part of a multi-drug regimen so individual caffeine effects are not isolated.

Trust comment: Randomized trial with moderate sample size but caffeine was administered with ephedrine (and/or pioglitazone), so effects cannot be attributed solely to caffeine.

Study Details

PMID:17351280
Participants:57
Impact:decrease (ECP: -15.2 mg/dL; ECPio: -41 mg/dL)
Trust score:3/5

testosterone concentration

1 evidences

In 24 professional rugby players, acute caffeine increased exercise-associated testosterone modestly and, at high dose (800 mg), substantially raised cortisol, slightly lowering the testosterone:cortisol ratio.

Trust comment: Well-controlled double-blind crossover in athletes with clear dose-response data, though high doses and wide confidence limits reduce generalizability.

Study Details

PMID:18458357
Participants:24
Impact:exercise increased ~15%; additional increase with caffeine up to ~+21% at 800 mg
Trust score:4/5

headache relief (2 h)

1 evidences

Among ~296 migraine patients, the ergotamine+100 mg caffeine combination was less effective and had more gastrointestinal adverse effects than calcium carbasalate+metoclopramide.

Trust comment: Large randomized double-blind multicenter trial; robust design though caffeine was tested as part of a combination therapy.

Study Details

PMID:9885327
Participants:296
Impact:EC 36% vs CM 54% (difference -18%, p=0.003)
Trust score:4/5

headache relief at 60 min

1 evidences

Diclofenac softgel plus 100 mg caffeine provided greater headache relief at 60 minutes versus placebo in migraineurs; diclofenac alone showed non-significant differences (study underpowered).

Trust comment: Randomized crossover with positive signal for caffeine as an analgesic adjuvant but limited by smaller-than-planned sample and incomplete attack treatments.

Study Details

PMID:14756851
Participants:51
Impact:diclofenac+caffeine 41% vs placebo 14% (statistically significant; OR 4.2, 95% CI 1.3–13.7)
Trust score:3/5

Dominant-hand static strength (hand-grip)

1 evidences

After eastbound travel across seven time zones, slow‑release caffeine (300 mg) prevented the post-travel decline in dominant-hand static strength seen with placebo, while dynamic measures were unchanged.

Trust comment: Randomized (three-arm) small trial with objective performance tests but limited sample and preliminary findings.

Study Details

PMID:11283440
Participants:27
Impact:Improved in slow‑release caffeine group versus decline in placebo over the first three mornings (statistically significant)
Trust score:3/5

Speed of correct responses (working & episodic)

1 evidences

In a randomized, double-blind crossover study of healthy young adults, consumption of Red Bull (contains caffeine) improved working and episodic memory accuracy and speed compared with sugar-free and placebo drinks.

Trust comment: Well-controlled crossover design but tests an energy drink (multiple active ingredients) so effects cannot be attributed to caffeine alone.

Study Details

PMID:28168925
Participants:24
Impact:Significant improvement vs sugar-free and placebo (medium effect size)
Trust score:3/5

motor deficits

1 evidences

Randomized comparison of caffeine versus aminophylline for apnea of prematurity showed trends toward lower risks of cognitive, motor, and language impairments with caffeine but differences were not statistically significant.

Trust comment: Randomized trial with 240 infants and objective neurodevelopmental assessment, but reported differences were not statistically significant.

Study Details

PMID:29286928
Participants:240
Impact:risk reduced (RR 0.50; ~50% lower) but not statistically significant (CI 0.12–1.95)
Trust score:4/5

speed variability (SDS)

1 evidences

A 250-ml Red Bull (80 mg caffeine) consumed during a short break improved driving stability and reduced sleepiness for about 2 hours compared with placebo or no break.

Trust comment: Well-controlled double-blind crossover simulator study with objective and subjective endpoints, moderate sample (n=21) and some simulator limitations.

Study Details

PMID:21063868
Participants:21
Impact:decrease (significant in hour 3 and 4 vs placebo/no-break)
Trust score:4/5

nighttime systolic blood pressure variation (rate)

1 evidences

Regular consumption of black tea (3 cups/day) reduced nighttime blood-pressure variability by about 10% compared with a flavonoid-free caffeine-matched control; effect appears independent of caffeine.

Trust comment: Large (n=111), randomized, double-blind, 6-month trial with appropriate control (caffeine-matched), supporting robustness of findings.

Study Details

PMID:23553154
Participants:111
Impact:decrease (~10% lower vs caffeine-matched control)
Trust score:5/5

Alpha frequency

1 evidences

In 30 children (8–13 y), a single 80 mg oral caffeine dose increased physiological arousal (skin conductance) and altered EEG indices versus placebo.

Trust comment: Randomized double-blind crossover with objective EEG and electrodermal measures in 30 children; moderate sample size.

Study Details

PMID:19486913
Participants:30
Impact:Focal increase in alpha peak frequency
Trust score:4/5

ventilator removal success rate

1 evidences

In preterm infants with primary apnea, a higher maintenance dose of caffeine citrate improved apnea control and ventilator weaning success without increasing measured side effects.

Trust comment: Prospective randomized allocation with moderate-to-large sample (n=164); outcomes and safety reported, though single-center.

Study Details

PMID:26791921
Participants:164
Impact:85% vs 70% (high-dose vs low-dose) increased
Trust score:4/5

serotonin

1 evidences

In men, 3 mg/kg caffeine taken before treadmill running increased plasma dopamine and β-endorphin compared with control; serotonin rose with exercise regardless of caffeine.

Trust comment: Randomized acute exercise study with 30 male volunteers; moderate sample and clear biochemical outcomes but limited to acute setting.

Study Details

PMID:31793465
Participants:30
Impact:↑ with exercise (no significant caffeine effect)
Trust score:3/5

blood glucose (OGTT)

1 evidences

200 mg oral caffeine before an OGTT shifted the glucose curve rightward with higher glucose at 2–4 hours without changing insulin levels.

Trust comment: Single-blind Latin-square crossover with 30 healthy subjects and standardized OGTT; well controlled for this outcome.

Study Details

PMID:9846599
Participants:30
Impact:↑ at 2–4 hours after glucose load (right-shift of glycaemic curve)
Trust score:4/5

games lost on time

1 evidences

Caffeine increased reflection time and games lost on time but did not improve overall chess performance under normal analysis of all games.

Trust comment: Well-designed double-blind randomized crossover (n=39) showing increased deliberation time and time-loss but no overall performance gain.

Study Details

PMID:28119083
Participants:39
Impact:increased with caffeine (significant)
Trust score:4/5

severity of anxiety response

1 evidences

A 480 mg oral caffeine challenge induced panic attacks in a majority of panic disorder (60.7%) and performance social anxiety disorder (52.6%) patients, in fewer GSAD patients (16%), and in no controls.

Trust comment: Randomized double-blind challenge with adequate group sizes showing differential vulnerability, though diagnostic group sizes vary.

Study Details

PMID:19698996
Participants:98
Impact:patients (PD and PSAD) showed greater anxiety symptom increases versus GSAD and controls
Trust score:4/5

Subjective activation

1 evidences

Acute caffeine (~4 mg/kg) improved dynamic visual acuity (horizontal and random paths), shortened horizontal reaction time, and increased subjective activation in low-caffeine consumers.

Trust comment: Double-blind, balanced crossover with validated measures and appropriate analyses but modest sample size (n=21).

Study Details

PMID:34420061
Participants:21
Impact:increased (significant)
Trust score:4/5

Recurrence of apnea of prematurity (RAP)

1 evidences

In preterm infants (26–32 wk) on caffeine therapy for apnea, stopping after 7 apnea-free days did not increase recurrence vs continuing until 34 wk PMA, and stopping earlier reduced cumulative therapy duration.

Trust comment: Randomized controlled trial with moderate sample size (n=120) and clear primary outcome, though further work in extremely preterm infants is advised.

Study Details

PMID:33625665
Participants:120
Impact:no difference (15% vs 13%; OR 0.87, 95% CI 0.31–2.43)
Trust score:4/5

risk-taking propensity (BSSS / EVAR / BART)

1 evidences

In sleep-deprived healthy adults, caffeine (600 mg) did not meaningfully restore risk-taking propensity to rested baseline, whereas dextroamphetamine did.

Trust comment: Randomized double-blind sleep-deprivation study in humans but small caffeine group (N=12 on caffeine) limiting precision.

Study Details

PMID:18785355
Participants:54
Impact:No restoration to baseline after caffeine; less effect than dextroamphetamine (placebo showed 16–32% decline vs baseline)
Trust score:4/5

major adverse cardiovascular events (MACE) / MI

1 evidences

In ~9,700 high-risk post‑MI patients, baseline caffeinated beverage intake was not associated with lower ticagrelor-related dyspnea but was associated with lower drug discontinuation for dyspnea and lower rates of MACE/MI in adjusted analyses.

Trust comment: Large, well-characterized randomized trial database but caffeine exposure was observational (baseline self-report) and analyses are nonrandomized, so residual confounding is possible.

Study Details

PMID:32410485
Participants:9694
Impact:Lower MACE with caffeine: adjusted HR 0.78 (95% CI 0.63–0.98), P=0.031; MI adjusted HR 0.70 (95% CI 0.53–0.93), P=0.013
Trust score:4/5

OCD symptom reduction among responders at week 5

1 evidences

In 24 treatment-resistant OCD patients, caffeine 300 mg/day augmentation produced symptom improvements comparable to dextroamphetamine over 5 weeks in this small double-blind trial.

Trust comment: Double-blind randomized design but very small sample (n=24) and results reported for responders subset, limiting generalizability.

Study Details

PMID:19573497
Participants:24
Impact:Responders' mean Y-BOCS decrease: caffeine 55% vs dextroamphetamine 48% (reported among responders)
Trust score:3/5

clinical laboratory panels (metabolic/liver/etc.)

1 evidences

Over 8 weeks, the caffeine arm showed no statistically significant changes in vital signs or routine lab safety measures compared with other groups.

Trust comment: Controlled supplementation study including a caffeine arm, but modest sample size and short duration limit detection of uncommon/long-term effects.

Study Details

PMID:25591969
Participants:48
Impact:no significant change (8-week supplementation)
Trust score:3/5

Headache pain severity (PDPH)

1 evidences

In 42 PDPH patients, gabapentin reduced pain, nausea, and vomiting more than ergotamine/caffeine (Cafergot); Cafergot was less effective than gabapentin in this setting.

Trust comment: Randomized prospective controlled study in clinical patients (n=42); directly compares ergotamine/caffeine to gabapentin but results indicate Cafergot was less effective.

Study Details

PMID:21536541
Participants:42
Impact:gabapentin reduced pain more than ergotamine/caffeine (Cafergot) (significant)
Trust score:3/5

self-reported caffeine craving

1 evidences

Thinking/talking about caffeine made students report stronger cravings for caffeine.

Trust comment: Large randomized behavioral study with self-reported outcomes in undergraduates; subjective measure limits objective inference.

Study Details

PMID:36595573
Participants:346
Impact:increased (no magnitude reported)
Trust score:3/5

cigarette consumption

1 evidences

In 50 male smokers, an acute dose of caffeine increased subjective 'pleasant' effects and feeling 'high' but did not change cigarette consumption.

Trust comment: Randomized double-blind crossover with ecological setting and adequate sample, but outcomes are subjective self-reports.

Study Details

PMID:15001822
Participants:50
Impact:no change
Trust score:3/5

incident any cognitive impairment

1 evidences

In this prospective cohort of older women, higher baseline caffeine intake was associated with lower incidence of probable dementia and cognitive impairment over follow-up.

Trust comment: Large prospective cohort with adjustment for confounders but observational design limits causal inference.

Study Details

PMID:27678290
Participants:6467
Impact:decreased (HR=0.74 vs below-median intake)
Trust score:3/5

lens capsule/epithelium caffeine concentration

1 evidences

Oral coffee with increasing caffeine doses raised measurable caffeine levels in the lens capsule/lens epithelial cells in cataract patients in a dose-dependent way.

Trust comment: Small randomized pilot in human cataract patients with direct GC-MS/MS measurements supports internal validity but sample size is limited.

Study Details

PMID:29677345
Participants:33
Impact:Difference between 1st and 2nd eye: 0-mg −0.52±1.16 ng/lens capsule; 60-mg +1.88±2.02 ng/lens capsule; 120-mg +2.09±0.67 ng/lens capsule; 180-mg +3.68±1.86 ng/lens capsule (dose-dependent increase, p<0.05)
Trust score:3/5

postexercise systolic blood pressure and heart rate

1 evidences

In prostate cancer survivors, a single dose of caffeine (~6 mg/kg) increased exercise capacity (faster 400-m walk) and tended to increase grip strength, without changing perceived exertion.

Trust comment: Randomized double-blind placebo-controlled crossover with clear numeric effects on exercise capacity, though modest sample size and single-dose design.

Study Details

PMID:24977700
Participants:30
Impact:Systolic BP and HR significantly higher after caffeine (P=0.006 and P=0.040 respectively)
Trust score:4/5

bronchopulmonary dysplasia (BPD) incidence

1 evidences

In preterm infants at risk of recurrent apnea, early preventive caffeine citrate given within 8 h after birth was associated with larger decreases in IL-6 and IL-8 after therapy compared with later treatment; no significant difference in BPD incidence was demonstrated.

Trust comment: Randomized allocation described but limited reporting and modest sample size in neonatal population; results on cytokines are significant but clinical BPD outcome was not different.

Study Details

PMID:30961342
Participants:56
Impact:No significant difference between groups (P=1.00)
Trust score:3/5

task-switching accuracy

1 evidences

In young adults, a single dose of 97 mg L-theanine combined with 40 mg caffeine improved task-switching accuracy and increased self-reported alertness while reducing tiredness.

Trust comment: Randomized placebo-controlled study with moderate sample, but intervention combined L-theanine and caffeine so caffeine-specific effects are confounded.

Study Details

PMID:21040626
Participants:44
Impact:+ significant improvement (p < 0.01)
Trust score:3/5

self-reported tiredness

1 evidences

In young adults, a single dose of 97 mg L-theanine combined with 40 mg caffeine improved task-switching accuracy and increased self-reported alertness while reducing tiredness.

Trust comment: Randomized placebo-controlled study with moderate sample, but intervention combined L-theanine and caffeine so caffeine-specific effects are confounded.

Study Details

PMID:21040626
Participants:44
Impact:- significant decrease (p < 0.05)
Trust score:3/5

short-term verbal memory (forward digit span)

1 evidences

In a single-blind crossover, breakfast including espresso plus either carbohydrate or protein improved mood, physiological state and short-term verbal memory; authors attribute effects to both croissants and caffeine.

Trust comment: Randomized counterbalanced crossover with reasonable sample, but interventions combined food and coffee so caffeine-specific effects are not isolated.

Study Details

PMID:33640376
Participants:40
Impact:+ improved performance after breakfast
Trust score:3/5

bench press 1RM

1 evidences

In resistance-trained men, a caffeine-containing supplement increased bench-press 1RM but did not affect leg strength, endurance, or Wingate power.

Trust comment: Randomized supplement vs placebo with moderate sample, but single-exercise benefit and lack of broader effects lower confidence.

Study Details

PMID:16937961
Participants:37
Impact:increase
Trust score:3/5

WM‑related brain activation

1 evidences

Acute caffeine in elderly reduced global brain perfusion but enhanced working‑memory related fMRI activation and increased functional connectivity in task networks.

Trust comment: Placebo‑controlled crossover with multimodal MRI and behavioral correlation in a moderate sample of elderly subjects provides credible functional data.

Study Details

PMID:23876323
Participants:24
Impact:increased (enhanced task‑related activation, esp. bilateral striatum and frontal/parietal regions)
Trust score:4/5

Arousal dose–response

1 evidences

Caffeine increased skin conductance (arousal) in children, but dose-response differed between AD/HD and control groups.

Trust comment: Randomized double-blind crossover with matched controls but small sample and outcomes reported with limited quantitative detail.

Study Details

PMID:22266163
Participants:36
Impact:dose-dependent arousal increases in controls but not in AD/HD
Trust score:3/5

alertness (sleep latency, subjective sleepiness, reaction time)

1 evidences

In sleep-deprived healthy men, higher caffeine doses (up to 8.6 mg/kg) increased adrenaline and produced dose-related improvements in alertness measures.

Trust comment: Randomized double-blind with a substantial sample (n=50) and objective/subjective alertness measures; good internal validity.

Study Details

PMID:11151742
Participants:50
Impact:dose-related improvement (higher doses associated with better scores)
Trust score:4/5

durations of ventilation and oxygen therapy

1 evidences

Higher maintenance caffeine dose after loading reduced re-intubation rate within 48 hours and apnea after ventilator weaning in very preterm infants.

Trust comment: Prospective randomized controlled trial with adequate sample (n=162) and clinically relevant outcomes; appears well conducted though full details not shown here.

Study Details

PMID:34753540
Participants:162
Impact:no significant difference reported (P>0.05)
Trust score:4/5

visuospatial organization

1 evidences

At age 11, children randomized to neonatal caffeine therapy showed modest improvements in fine motor and visuomotor/visuospatial skills and no adverse effects on intelligence, attention, or behavior.

Trust comment: Large randomized placebo-controlled trial follow-up (n≈870) with consistent neurodevelopmental assessments and robust results for targeted outcomes.

Study Details

PMID:29643070
Participants:870
Impact:mean difference +1.2 points (95% CI 0.4 to 2.0; P=0.003)
Trust score:5/5

total pain-free rate (5 h or after second dose)

1 evidences

Multicentre randomized trial in adults comparing Indoprocaf (includes caffeine) vs sumatriptan: similar pain-free rates at 2 h, but Indoprocaf showed higher total pain-free rate at 5 h (including re-dosing).

Trust comment: Large multicentre randomized double-blind trial with appropriate endpoints and ITT analysis; high internal validity for clinical efficacy of the combination product.

Study Details

PMID:17627707
Participants:281
Impact:Indoprocaf 79% vs sumatriptan 69% (statistically significant favoring Indoprocaf, p<0.05)
Trust score:4/5

working memory accuracy

1 evidences

In healthy young adults, 200 mg caffeine (alone or with cocoa flavanols) produced little-to-no acute benefits on temporal/spatial attention or working memory, aside from modest faster reaction times on some attention measures.

Trust comment: Well-powered randomized crossover with appropriate tasks and mixed-model analyses; results are largely null with a few modest RT effects.

Study Details

PMID:39607519
Participants:48
Impact:no significant change
Trust score:4/5

visual reaction time

1 evidences

In young adults, combining an energy drink with alcohol reduced some subjective symptoms of intoxication but did not improve objective motor coordination, reaction time, or breath alcohol.

Trust comment: Randomized crossover human study with objective and subjective measures but moderate sample and specificity to alcohol+energy drink context.

Study Details

PMID:16573577
Participants:26
Impact:no significant change
Trust score:3/5

fat mass

1 evidences

Drinking three cups/day of lightly roasted (higher polyphenols and caffeine) or regular coffee for 12 weeks reduced body fat percentage and increased muscle mass in overweight/obese adults; lightly roasted coffee produced a slightly greater fat percentage reduction.

Trust comment: Randomized, controlled crossover in humans with validated measures; small sample (n=38), high dropout and coffee contains multiple bioactives so caffeine-specific attribution is uncertain.

Study Details

PMID:39275165
Participants:38
Impact:LRC vs RC mean difference −0.7 kg (95% CI −1.3 to −0.05); p=0.069 (NS)
Trust score:4/5

Sum of pain intensity differences (SPID)

1 evidences

Paracetamol 1000 mg + caffeine 130 mg relieved migraine pain as well as sumatriptan 50 mg with similar overall tolerability; fatigue was slightly more common with sumatriptan.

Trust comment: Randomized, double-blind, double-dummy cross-over vs active comparator with reasonable sample for a crossover (ITT n=92); moderate external generalizability.

Study Details

PMID:23054063
Participants:92
Impact:Mean SPID 3.2 (PCF) vs 3.2 (SUM); no difference (p=0.88)
Trust score:4/5

Omission errors (vigilance)

1 evidences

A cup of coffee (100 mg caffeine) improved and stabilized reaction time across 120 min regardless of recent sleep quality, but in those with poor sleep it increased commission errors at 90 min and only partially reduced omission errors.

Trust comment: Randomized, counterbalanced trials with a moderate sample (n=69) and repeated objective vigilance measures; design appropriate for tested question.

Study Details

PMID:29866304
Participants:69
Impact:Partially reduced at 90 min in individuals reporting poor sleep quality
Trust score:4/5

pain relief (responder rate)

1 evidences

A combination containing caffeine (AAC) provided faster and greater migraine pain relief and symptom improvement than placebo in both menstruation-associated and non-menstrual migraine.

Trust comment: Large pooled randomized, double-masked trials give robust evidence for the combination product, but caffeine was not tested alone.

Study Details

PMID:10321417
Participants:1220
Impact:significantly greater with AAC vs placebo at 0.5–6 h (P≤0.05)
Trust score:4/5

Estradiol

1 evidences

In an 8-week randomized trial in overweight habitual coffee drinkers, caffeinated and decaffeinated coffee produced some short-term (week 4) changes in sex hormones that were not sustained at week 8.

Trust comment: Randomized controlled trial with biochemical outcomes but small sample (n=42) and transient effects limited to week 4.

Study Details

PMID:23078574
Participants:42
Impact:Men: total estradiol −47.1% and free estradiol −42.8% at week 4 with caffeinated coffee; no consistent change in women
Trust score:3/5

global cerebral blood flow

1 evidences

In preterm infants, caffeine citrate was associated with higher global cerebral blood flow than aminophylline two hours after IV administration.

Trust comment: Randomized neonatal comparison with a clear significant result but small sample and older study methods limit generalizability.

Study Details

PMID:7734901
Participants:33
Impact:caffeine 17.2 vs aminophylline 13.2 ml/100 g/min (difference ≈ +4.0 ml/100 g/min; p=0.01)
Trust score:3/5

salivary α-amylase (sAA) activity

1 evidences

In habitual male caffeine users, single-dose caffeine (200 or 400 mg) did not change salivary alpha-amylase, cortisol, or cardiovascular measures during a non-stressful task.

Trust comment: Randomized, double-blind, placebo-controlled design with adequate sample size (N=45) but limited to young habitual male caffeine users, limiting broader generalizability.

Study Details

PMID:24410993
Participants:45
Impact:no change (no caffeine effect)
Trust score:4/5

subjective arousal/mood (alertness, contentedness, calmness)

1 evidences

Caffeine-associated cues and information about caffeine content modulated physiological and subjective arousal; conditioned and expectancy effects both contributed.

Trust comment: Controlled experimental studies (two experiments) with modest sample sizes and mixed within- and between-subject designs; suitable for conditioning/expectancy effects but not large-scale inference.

Study Details

PMID:11605096
Participants:69
Impact:increased alertness and contentedness; information of caffeine decreased calmness
Trust score:3/5

Performance (total test time)

1 evidences

In trained young adults, a single dose of caffeine before a maximal treadmill test reduced an oxidative stress marker and increased IL-6 after exercise, with no change in performance.

Trust comment: Randomized double‑blind crossover with relevant biomarkers but small sample and some exclusions limit generalizability.

Study Details

PMID:28480382
Participants:24
Impact:no significant change
Trust score:3/5

ventilation

1 evidences

A single 400 mg dose of caffeine before graded CO₂ exposure reduced CO₂ retention and substantially lowered headache ratings compared with placebo.

Trust comment: Randomized double-blind crossover with physiological and symptomatic endpoints (n=23) provides robust within-subject evidence.

Study Details

PMID:40019582
Participants:23
Impact:Caffeine increased ventilation at inspired CO₂ levels between 0% and 6% (significant)
Trust score:4/5

state-anxiety (STAI)

1 evidences

Matcha (contains caffeine and theanine) modestly lowered anxiety and morning salivary stress marker in students, but baseline group differences and modest effects limit certainty.

Trust comment: Randomized double-blind trial but baseline group imbalance and modest sample size reduce confidence in isolating caffeine-specific effects.

Study Details

PMID:30308973
Participants:39
Impact:decrease (significant before practice, p=0.03)
Trust score:3/5

Mean lateral position (distance from centre)

1 evidences

In healthy male drivers, caffeine (2×200 mg) taken before and during night driving reduced lane departures and weaving compared with placebo, improving driving performance.

Trust comment: Randomized, double-blind, placebo-controlled crossover RCT with objective driving measures; moderate sample after excluding 8 dazzle-sensitive participants.

Study Details

PMID:23094031
Participants:40
Impact:-3.45 cm (23.00 → 19.55 cm; caffeine vs placebo; ≈-15%)
Trust score:4/5

Memory accuracy (working & episodic)

1 evidences

In a randomized, double-blind crossover study of healthy young adults, consumption of Red Bull (contains caffeine) improved working and episodic memory accuracy and speed compared with sugar-free and placebo drinks.

Trust comment: Well-controlled crossover design but tests an energy drink (multiple active ingredients) so effects cannot be attributed to caffeine alone.

Study Details

PMID:28168925
Participants:24
Impact:Significant improvement vs sugar-free and placebo (medium effect size)
Trust score:3/5

Mesenteric tissue oxygen saturation (mesenteric rSO2)

1 evidences

In 87 very low‑birthweight preterm infants, initiating caffeine in the first 24 hours was associated with lower mesenteric tissue oxygen saturation and a higher incidence of necrotizing enterocolitis compared with starting at 72 hours.

Trust comment: Prospective randomized trial in a relevant neonatal population with objective NIRS and clinical outcomes, though single-center and modest size.

Study Details

PMID:33878772
Participants:87
Impact:Lower mesenteric rSO2 in first 72 hours with early (≤24 h) caffeine treatment (statistically significant)
Trust score:4/5

Palpitations frequency

1 evidences

In this randomized crossover PK/safety study, consuming anagrelide with a standardized breakfast including two cups of coffee (caffeine) delayed tmax and was associated with larger early heart-rate increases and a numerically higher frequency of palpitations versus fasted dosing.

Trust comment: Phase I randomized crossover with detailed PK and ECG measures; sample size typical for PK study but not large for safety events.

Study Details

PMID:23184666
Participants:34
Impact:Higher in fed+caffeine state: 35% (12/34) vs 17% (6/35) (trend, p=0.09)
Trust score:4/5

cognitive impairment

1 evidences

Randomized comparison of caffeine versus aminophylline for apnea of prematurity showed trends toward lower risks of cognitive, motor, and language impairments with caffeine but differences were not statistically significant.

Trust comment: Randomized trial with 240 infants and objective neurodevelopmental assessment, but reported differences were not statistically significant.

Study Details

PMID:29286928
Participants:240
Impact:risk reduced (RR 0.16; ~83% lower) but not statistically significant (CI 0.02–1.36)
Trust score:4/5

pain intensity reduction and overall efficacy

1 evidences

Post-hoc subgroup analysis found the ASA+paracetamol+caffeine combination provided faster and greater pain relief than placebo in patients with severe headache.

Trust comment: Randomized trial subgroup analysis shows efficacy but is post-hoc and uses a multi-ingredient product so caffeine-specific attribution is limited.

Study Details

PMID:21908446
Participants:179
Impact:superior to placebo across secondary endpoints (significant)
Trust score:3/5

standard deviation of lateral position (SDLP)

1 evidences

A 250-ml Red Bull (80 mg caffeine) consumed during a short break improved driving stability and reduced sleepiness for about 2 hours compared with placebo or no break.

Trust comment: Well-controlled double-blind crossover simulator study with objective and subjective endpoints, moderate sample (n=21) and some simulator limitations.

Study Details

PMID:21063868
Participants:21
Impact:decrease (hour 3: −2.3 cm; hour 4: −3.1 cm vs placebo)
Trust score:4/5

Coffee consumption after deprivation

1 evidences

Across three experiments, caffeine-related attentional biases were observed, but deprivation increased coffee consumption and subjective drowsiness without altering attentional bias.

Trust comment: Multiple experiments (between- and within-subject) showing consistent behavioural outcomes; sample sizes per experiment were modest.

Study Details

PMID:16170233
Participants:28
Impact:Increased consumption when participants were caffeine-deprived
Trust score:3/5

skin blood flow response

1 evidences

In 28 participants (14 habituated, 14 non-habituated), 5 mg/kg caffeine increased end-exercise esophageal temperature and attenuated skin blood flow responses in caffeine-habituated individuals but had no effect in non-habituated participants or on sweating.

Trust comment: Randomized, double-blind, crossover with clear habituation stratification and physiological measures; sample size adequate for mechanistic outcomes.

Study Details

PMID:34435513
Participants:28
Impact:HAB: attenuated % max skin blood flow with caffeine; NHAB: no change
Trust score:5/5

resting energy expenditure (REE), physical activity EE, total EE

1 evidences

In 30 healthy physically active males, 5 mg/kg/day caffeine over 4 days did not change resting or activity-related energy expenditure but reduced total sleep time.

Trust comment: Well-controlled double-blind crossover with objective measures (accelerometry, calorimetry); moderate sample size and clear outcomes.

Study Details

PMID:23368828
Participants:30
Impact:no significant change
Trust score:4/5

microstate class A occurrence (in SZ)

1 evidences

In early-phase psychosis patients (vs controls), acute caffeine shifted EEG microstate dynamics: it reduced class D and increased classes A and B parameters in patients but had little effect in controls.

Trust comment: Randomized, double-blind within-subject EEG study with objective measures, but small sample and some reporting inconsistencies limit generalizability.

Study Details

PMID:35257622
Participants:25
Impact:increased with caffeine (4.83 vs 3.28 occurrences/s, caffeine vs placebo)
Trust score:3/5

psychomotor speed (DSST)

1 evidences

Caffeine counteracted some alcohol-induced slowing on psychomotor speed and partially reduced alcohol-related errors on specific tasks.

Trust comment: Randomized, double-blind, placebo-controlled design with a moderate sample (n=64); task-based outcomes are straightforward.

Study Details

PMID:12404692
Participants:64
Impact:caffeine increased speed and antagonized alcohol-induced slowing
Trust score:4/5

colon cancer risk (men, high coffee intake)

1 evidences

Case-control analysis found associations between coffee (methylxanthine) intake and colon cancer risk in men that varied by intake level and tumor location.

Trust comment: Large population-based case-control study (cases+controls=4,403) but observational design and potential confounding reduce causal certainty.

Study Details

PMID:10188719
Participants:4403
Impact:- inverse association reported (OR 0.81, 95% CI 0.58–1.12)
Trust score:3/5

oxygen deficit

2 evidences

Caffeine increased time to exhaustion and oxygen deficit in a supramaximal anaerobic test and raised metabolic markers.

Trust comment: Randomized double-blind trial with physiological measures but small sample (24) and mixed drug comparisons.

Study Details

PMID:11474345
Participants:24
Impact:increased
Trust score:4/5

In elite male endurance athletes, 4.5 mg·kg-1 caffeine increased endurance performance and several physiological markers during incremental running to exhaustion.

Trust comment: Randomized double-blind placebo-controlled crossover in elite athletes with objective physiological measures; small, all-male elite sample limits generalizability.

Study Details

PMID:34033621
Participants:23
Impact:+6.4 mL·kg⁻¹ (63.1 → 69.5 mL·kg⁻¹)
Trust score:4/5

surgical performance (total score)

1 evidences

In novices, low-dose caffeine worsened simulator surgical performance and increased tremor; seniors showed mainly tremor changes without dexterity loss.

Trust comment: Self-controlled simulator study with repeated exposures and modest sample sizes (novices n=15, seniors n=11); internal control is strength but ecological validity limited.

Study Details

PMID:36782058
Participants:26
Impact:decreased in novices after 2.5 mg/kg caffeine
Trust score:3/5

bench press movement velocity and power

1 evidences

A moderate dose of caffeine (3 mg/kg) acutely improved bench-press velocity/power, muscle endurance, vertical jump height, and Wingate power in resistance-trained men, with no clear genotype differences.

Trust comment: Randomized double-blind crossover, registered trial in trained men (n=22); robust within-subject design though moderate sample size.

Study Details

PMID:32295624
Participants:22
Impact:increased across loads (significant main effect)
Trust score:4/5

healing time (HT)

1 evidences

Topical caffeine combined with interferon shortened healing time of recurrent herpetic lesions more than either agent alone; caffeine alone shortened healing time in many patients but had little effect on lesion spread.

Trust comment: One-center randomized placebo-controlled clinical trial with clear group sizes (115 total) though methodological details and modern replication are limited.

Study Details

PMID:8578993
Participants:115
Impact:shortened (75% of caffeine-alone patients ≥4 days shorter; mixture produced universal shortening)
Trust score:3/5

anxiety symptoms

1 evidences

In a crossover RCT of postmenopausal women with OAB, 400 mg/day caffeine for 7 days produced a small reduction in anxiety; depression, insomnia, and perceived stress showed no change.

Trust comment: Randomized double-blind crossover with 56 completers supports internal validity, but short 7-day exposures limit long-term conclusions.

Study Details

PMID:35363563
Participants:56
Impact:small decrease during 400 mg/day caffeine over 7 days (statistically reported as decreased)
Trust score:4/5

Pathway-level changes

1 evidences

In a three-arm randomized crossover trial (n=21), different coffee intake patterns produced distinct urinary metabolomic changes implicating pathways (e.g., phenylalanine/tyrosine, energy metabolism, steroid and arginine biosynthesis), suggesting coffee (which contains caffeine) alters metabolic profiles.

Trust comment: Randomized crossover metabolomics in 21 volunteers; robust metabolite identification but effects are indirect measures of caffeine specifically (coffee is a complex mixture).

Study Details

PMID:33300301
Participants:21
Impact:associations with steroid hormone biosynthesis and arginine metabolism (qualitative metabolomic shifts)
Trust score:3/5

grams of urine loss

1 evidences

Self-monitoring (including advice on caffeine) reduced urine loss and improved quality of life; participants also reduced caffeine intake.

Trust comment: Large randomized clinical trial (n=224) with clear primary outcomes, though caffeine change was part of a multi-component intervention.

Study Details

PMID:17366526
Participants:224
Impact:-13.3 g (self-monitoring vs wait list, adjusted)
Trust score:4/5

laboratory energy intake (breakfast)

1 evidences

In a double-blind crossover trial of 50 adults, 1 mg/kg caffeine transiently reduced laboratory breakfast intake by about 10% but did not change appetite ratings or free-living intake.

Trust comment: Double-blind randomized crossover design with complete reporting (n=50) supports moderate-high confidence; effects were small and transient.

Study Details

PMID:30033159
Participants:50
Impact:-~10% (650.4 kcal at 1 mg/kg vs 721.2 kcal at 0 mg/kg)
Trust score:4/5

Days to discharge after randomization

1 evidences

Extending caffeine citrate in moderately preterm infants did not shorten hospital stay or time to physiological maturity but led to earlier resolution of apnea.

Trust comment: Large multicenter randomized clinical trial (n=827) with prespecified outcomes and stopping for futility, high-quality evidence.

Study Details

PMID:40294395
Participants:827
Impact:no difference (median 18.0 vs 16.5 days; adjusted median difference 0 days; 95% CI -1.7 to 1.7)
Trust score:5/5

macular vessel density

1 evidences

A single 200 mg oral caffeine dose acutely reduced macular blood flow and vessel density measured by OCT-A at 1 hour.

Trust comment: Randomized allocation with objective OCT-A imaging and moderate sample size (n=52); acute study limits long-term inference.

Study Details

PMID:29401177
Participants:52
Impact:decrease (significant, P<0.05)
Trust score:4/5

psychomotor speed

1 evidences

Single-blind randomized study found small improvements in basic attention and psychomotor speed after matcha products; no significant mood changes.

Trust comment: Randomized, placebo-controlled single-blind study with small sample (n=23) and modest effects, moderate quality.

Study Details

PMID:28784536
Participants:23
Impact:improved (small, significant)
Trust score:3/5

axial diffusivity

1 evidences

In very preterm infants, caffeine was linked to microstructural changes in white matter but not to changes in brain volumes.

Trust comment: Randomized trial with MRI outcomes supports moderate-high trust, though some diffusion data were only available in a subset (n=28).

Study Details

PMID:21031585
Participants:70
Impact:decrease (improved white matter microstructure)
Trust score:4/5

Wingate peak and mean power

1 evidences

In resistance-trained men, a caffeine-containing supplement increased bench-press 1RM but did not affect leg strength, endurance, or Wingate power.

Trust comment: Randomized supplement vs placebo with moderate sample, but single-exercise benefit and lack of broader effects lower confidence.

Study Details

PMID:16937961
Participants:37
Impact:no change
Trust score:3/5

1RM leg extension

1 evidences

A multi-ingredient caffeine supplement did not change strength or cycling time-to-exhaustion in untrained men.

Trust comment: Double-blind placebo crossover but small sample and supplement contained other ingredients (not caffeine-only), limiting causal attribution to caffeine.

Study Details

PMID:19834348
Participants:21
Impact:no change
Trust score:3/5

ADORA2A genotype effect on TMH

1 evidences

Caffeine modestly increased tear volume; genetic variants in ADORA2A and CYP1A2 influenced the size of the increase.

Trust comment: Well-powered double-masked placebo crossover with objective measurement and genotyping, though effect size was small and of limited clinical significance.

Study Details

PMID:22336631
Participants:78
Impact:heterozygous +0.07 mm; minor homozygous +0.08 mm (greater increase)
Trust score:4/5

cerebellar hemorrhage (term MRI, earlier finding)

1 evidences

Follow-up of very preterm infants (randomized to high vs standard loading caffeine dose) found no clear differences in cognitive, language, motor, or socioemotional outcomes at age five, despite higher early cerebellar hemorrhage in the high-dose group.

Trust comment: Randomized double-blind trial with long-term follow-up but pilot-sized sample, attrition, and limited power reduce confidence in detecting small effects.

Study Details

PMID:35145209
Participants:46
Impact:higher in high-dose (36% vs 10%)
Trust score:3/5

Fatigue (adverse event)

1 evidences

Paracetamol 1000 mg + caffeine 130 mg relieved migraine pain as well as sumatriptan 50 mg with similar overall tolerability; fatigue was slightly more common with sumatriptan.

Trust comment: Randomized, double-blind, double-dummy cross-over vs active comparator with reasonable sample for a crossover (ITT n=92); moderate external generalizability.

Study Details

PMID:23054063
Participants:92
Impact:Fatigue more frequent with SUM 15.1% vs PCF 5.5% (p=0.026)
Trust score:4/5

reintubation rate within 48 h

1 evidences

In preterm infants (≤32 weeks) on mechanical ventilation, an extra 5 mg/kg maintenance dose of caffeine 1 hour before weaning reduced reintubation and apnea episodes and lowered intraventricular hemorrhage incidence, with improved blood gas (higher pH, lower PaCO2) at 2 hours.

Trust comment: Prospective randomized controlled trial with sizeable sample (338) and statistically significant clinical outcomes, though full trial details (blinding, allocation concealment) not in excerpt.

Study Details

PMID:33476534
Participants:338
Impact:decreased (observation vs routine; P = 0.034)
Trust score:4/5

postoperative pain intensity (SPID 0–3h)

1 evidences

Single-dose combinations containing caffeine (with paracetamol and opium) provided superior analgesia to placebo and were non-inferior to tramadol after third-molar extraction, with faster onset and greater analgesic effect at 1 hour for the stronger formulation and acceptable safety.

Trust comment: Well-conducted randomized double-blind multicenter trial, but caffeine was studied only as part of a combination product so isolated caffeine effects cannot be determined.

Study Details

PMID:20080382
Participants:228
Impact:improved vs placebo (p<0.005); non-inferior to tramadol
Trust score:3/5

death or survival with disability at 5 years

1 evidences

At 5-year follow-up of a large neonatal RCT, early caffeine therapy for apnea of prematurity did not significantly change the combined outcome of death or survival with disability compared with placebo (no lasting significant benefit on survival without disability).

Trust comment: Large multicenter randomized placebo-controlled trial with high follow-up rate and clinically important long-term outcomes.

Study Details

PMID:22253394
Participants:1640
Impact:no significant difference (21.1% vs 24.8%; adjusted OR 0.82; P = 0.09)
Trust score:5/5

recovery sleep duration

1 evidences

After 26 h wakefulness, caffeine did not worsen recovery or next-night sleep compared with placebo.

Trust comment: Randomized placebo-controlled trial in 32 subjects; clear methods but modest sample size limits generalizability.

Study Details

PMID:38790126
Participants:32
Impact:no significant change with caffeine vs placebo
Trust score:4/5

subjective sleep quality (Groningen Sleep Quality Scale)

1 evidences

After 26 h wakefulness, caffeine did not worsen recovery or next-night sleep compared with placebo.

Trust comment: Randomized placebo-controlled trial in 32 subjects; clear methods but modest sample size limits generalizability.

Study Details

PMID:38790126
Participants:32
Impact:no significant decline with caffeine (decline seen with modafinil)
Trust score:4/5

plasma IL-6

1 evidences

Caffeine (6 mg/kg) before a 15-km run increased plasma IL-10 and IL-6 responses after exercise versus placebo, but did not affect cytokines in blood mononuclear cells.

Trust comment: Randomized double-blind trial with direct cytokine measurements but small sample size (n=28).

Study Details

PMID:26132827
Participants:28
Impact:greater postexercise increase with caffeine vs placebo
Trust score:4/5

state-dependent expression of preference

1 evidences

Caffeine-conditioned increases in drink pleasantness were expressed only when subjects were tested in the same caffeine-deprivation state as during conditioning.

Trust comment: Double-blind behavioral study with clear effects but modest sample size and subjective outcomes.

Study Details

PMID:10907674
Participants:44
Impact:preference expressed only when training and test deprivation states matched
Trust score:3/5

cognitive development (MDI/PDI)

1 evidences

Stopping coffee in iron-deficient Guatemalan toddlers increased night and total sleep but did not change cognitive test scores.

Trust comment: Randomized assignment with masked testers in 132 toddlers and repeated sleep assessments; reasonable quality.

Study Details

PMID:10088991
Participants:132
Impact:no significant change
Trust score:4/5

insomnia / dry mouth / heartburn (adverse effects)

1 evidences

A 6-month randomized trial of an herbal ephedra/caffeine product produced greater weight loss than placebo and increased some GI and sleep-related side effects.

Trust comment: Large randomized double-blind trial with 6-month follow-up, but intervention combines ephedra and caffeine so effects are not due to caffeine alone.

Study Details

PMID:12032741
Participants:167
Impact:increased (dry mouth P<0.01; heartburn P<0.05; insomnia P<0.01)
Trust score:4/5

blood pressure and heart rate

1 evidences

In habitual male caffeine users, single-dose caffeine (200 or 400 mg) did not change salivary alpha-amylase, cortisol, or cardiovascular measures during a non-stressful task.

Trust comment: Randomized, double-blind, placebo-controlled design with adequate sample size (N=45) but limited to young habitual male caffeine users, limiting broader generalizability.

Study Details

PMID:24410993
Participants:45
Impact:no main effect of caffeine on SBP/DBP/HR
Trust score:4/5

startle eyeblink reflex

1 evidences

Caffeine-associated cues and information about caffeine content modulated physiological and subjective arousal; conditioned and expectancy effects both contributed.

Trust comment: Controlled experimental studies (two experiments) with modest sample sizes and mixed within- and between-subject designs; suitable for conditioning/expectancy effects but not large-scale inference.

Study Details

PMID:11605096
Participants:69
Impact:conditioned increase (observed in follow-up experiment)
Trust score:3/5

Perceived alertness

1 evidences

A single 300 mg oral caffeine dose acutely increased inner-retinal electrophysiological responses at high/medium contrast and increased subjective alertness in young adults.

Trust comment: Double-masked, placebo-controlled within-subject crossover (n=24) with objective electrophysiology and clear statistical reporting; sample limited to young adults.

Study Details

PMID:39230997
Participants:24
Impact:increased (mean change +1.29 on 1–10 scale vs placebo)
Trust score:4/5

IL-6 (inflammatory cytokine)

1 evidences

In trained young adults, a single dose of caffeine before a maximal treadmill test reduced an oxidative stress marker and increased IL-6 after exercise, with no change in performance.

Trust comment: Randomized double‑blind crossover with relevant biomarkers but small sample and some exclusions limit generalizability.

Study Details

PMID:28480382
Participants:24
Impact:+50% (post‑exercise mean 2.1 vs 1.4 pg/mL)
Trust score:3/5

end-tidal CO₂ (PetCO₂)

1 evidences

A single 400 mg dose of caffeine before graded CO₂ exposure reduced CO₂ retention and substantially lowered headache ratings compared with placebo.

Trust comment: Randomized double-blind crossover with physiological and symptomatic endpoints (n=23) provides robust within-subject evidence.

Study Details

PMID:40019582
Participants:23
Impact:Caffeine lowered end-tidal CO₂ during exposures (significant decrease vs placebo)
Trust score:4/5

global adverse events (gastrointestinal)

1 evidences

Among ~296 migraine patients, the ergotamine+100 mg caffeine combination was less effective and had more gastrointestinal adverse effects than calcium carbasalate+metoclopramide.

Trust comment: Large randomized double-blind multicenter trial; robust design though caffeine was tested as part of a combination therapy.

Study Details

PMID:9885327
Participants:296
Impact:EC 21% vs CM 7% (GI events higher with EC, p=0.001)
Trust score:4/5

Standard deviation of lateral position (weaving, SDLP)

1 evidences

In healthy male drivers, caffeine (2×200 mg) taken before and during night driving reduced lane departures and weaving compared with placebo, improving driving performance.

Trust comment: Randomized, double-blind, placebo-controlled crossover RCT with objective driving measures; moderate sample after excluding 8 dazzle-sensitive participants.

Study Details

PMID:23094031
Participants:40
Impact:-3.82 cm (28.56 → 24.74 cm; caffeine vs placebo; ≈-13%)
Trust score:4/5

Necrotizing enterocolitis (NEC) incidence

1 evidences

In 87 very low‑birthweight preterm infants, initiating caffeine in the first 24 hours was associated with lower mesenteric tissue oxygen saturation and a higher incidence of necrotizing enterocolitis compared with starting at 72 hours.

Trust comment: Prospective randomized trial in a relevant neonatal population with objective NIRS and clinical outcomes, though single-center and modest size.

Study Details

PMID:33878772
Participants:87
Impact:Higher with caffeine started ≤24 h: 20% vs 9% (difference +11 percentage points)
Trust score:4/5

Heart rate increase (fed+caffeine vs fasted)

1 evidences

In this randomized crossover PK/safety study, consuming anagrelide with a standardized breakfast including two cups of coffee (caffeine) delayed tmax and was associated with larger early heart-rate increases and a numerically higher frequency of palpitations versus fasted dosing.

Trust comment: Phase I randomized crossover with detailed PK and ECG measures; sample size typical for PK study but not large for safety events.

Study Details

PMID:23184666
Participants:34
Impact:Greater early HR rise at 1 h: +12.2 vs +5.1 beats/min (fed+caffeine vs fasted; p<0.001)
Trust score:4/5

time to 50% pain relief

1 evidences

Post-hoc subgroup analysis found the ASA+paracetamol+caffeine combination provided faster and greater pain relief than placebo in patients with severe headache.

Trust comment: Randomized trial subgroup analysis shows efficacy but is post-hoc and uses a multi-ingredient product so caffeine-specific attribution is limited.

Study Details

PMID:21908446
Participants:179
Impact:shorter with combination vs placebo (p=0.0008)
Trust score:3/5

blood pressure and pulse

1 evidences

A multi-ingredient product (including caffeine and ephedrine) produced modest additional weight loss (~1.5 kg) and greater reductions in BMI and waist circumference versus placebo over 12 weeks; no BP or pulse increases were observed.

Trust comment: Large randomized placebo-controlled trial but attribution to caffeine is limited because the active product contained ephedrine and other ingredients and actual caffeine dose was lower than intended.

Study Details

PMID:15356670
Participants:102
Impact:no change
Trust score:3/5

Inappropriate line crossings (ILC)

1 evidences

In healthy male drivers, caffeine (2×200 mg) taken before and during night driving reduced lane departures and weaving compared with placebo, improving driving performance.

Trust comment: Randomized, double-blind, placebo-controlled crossover RCT with objective driving measures; moderate sample after excluding 8 dazzle-sensitive participants.

Study Details

PMID:23094031
Participants:40
Impact:-52.6% (26.42 → 12.51 ILC; caffeine vs placebo)
Trust score:4/5

Anagrelide tmax (with food+caffeine)

1 evidences

In this randomized crossover PK/safety study, consuming anagrelide with a standardized breakfast including two cups of coffee (caffeine) delayed tmax and was associated with larger early heart-rate increases and a numerically higher frequency of palpitations versus fasted dosing.

Trust comment: Phase I randomized crossover with detailed PK and ECG measures; sample size typical for PK study but not large for safety events.

Study Details

PMID:23184666
Participants:34
Impact:Delayed from median 1.5 h (fasted) to 4.0 h (fed with coffee) for anagrelide and metabolite (p<0.05)
Trust score:4/5

24-h ambulatory blood pressure level

1 evidences

Regular consumption of black tea (3 cups/day) reduced nighttime blood-pressure variability by about 10% compared with a flavonoid-free caffeine-matched control; effect appears independent of caffeine.

Trust comment: Large (n=111), randomized, double-blind, 6-month trial with appropriate control (caffeine-matched), supporting robustness of findings.

Study Details

PMID:23553154
Participants:111
Impact:no major change reported (effect on variation independent of mean BP and HR)
Trust score:5/5

ad libitum meal energy intake

1 evidences

In overweight/obese adults, a higher-dose coffee (6 mg/kg caffeine) reduced energy intake at the next meal and over the day versus lower-dose or water; appetite ratings were unchanged.

Trust comment: Small randomized crossover trial with within-subject comparisons; reasonable design but modest sample size.

Study Details

PMID:23671022
Participants:33
Impact:decrease (Coffee 6 vs Coffee 3; p=0.03)
Trust score:4/5

total day energy intake

1 evidences

In overweight/obese adults, a higher-dose coffee (6 mg/kg caffeine) reduced energy intake at the next meal and over the day versus lower-dose or water; appetite ratings were unchanged.

Trust comment: Small randomized crossover trial with within-subject comparisons; reasonable design but modest sample size.

Study Details

PMID:23671022
Participants:33
Impact:decrease (Coffee 6 vs water and Coffee 3; p=0.04 and p=0.008 respectively)
Trust score:4/5

appetite feelings

1 evidences

In overweight/obese adults, a higher-dose coffee (6 mg/kg caffeine) reduced energy intake at the next meal and over the day versus lower-dose or water; appetite ratings were unchanged.

Trust comment: Small randomized crossover trial with within-subject comparisons; reasonable design but modest sample size.

Study Details

PMID:23671022
Participants:33
Impact:no change
Trust score:4/5

pain-free at 2 hours

1 evidences

Across multiple attacks, the indomethacin+prochlorperazine+caffeine combination produced a higher percentage of pain-free attacks at 2 hours than sumatriptan and better sustained pain-free responses.

Trust comment: Multicenter randomized crossover RCT with clinically relevant endpoints and adequate sample completing protocol.

Study Details

PMID:12940804
Participants:88
Impact:+15 percentage points (49% vs 34%; p<.01)
Trust score:5/5

headache relief at 2 hours

1 evidences

Across multiple attacks, the indomethacin+prochlorperazine+caffeine combination produced a higher percentage of pain-free attacks at 2 hours than sumatriptan and better sustained pain-free responses.

Trust comment: Multicenter randomized crossover RCT with clinically relevant endpoints and adequate sample completing protocol.

Study Details

PMID:12940804
Participants:88
Impact:no significant difference (71% vs 65%)
Trust score:5/5

sustained pain-free response

1 evidences

Across multiple attacks, the indomethacin+prochlorperazine+caffeine combination produced a higher percentage of pain-free attacks at 2 hours than sumatriptan and better sustained pain-free responses.

Trust comment: Multicenter randomized crossover RCT with clinically relevant endpoints and adequate sample completing protocol.

Study Details

PMID:12940804
Participants:88
Impact:increase (combination superior; higher sustained pain-free and fewer relapses/no rescue within 48 h)
Trust score:5/5

ambulatory blood pressure

1 evidences

A single 500 mg caffeine dose in habitual coffee drinkers raised ambulatory blood pressure by ~4/3 mmHg, lowered heart rate by ~2 bpm, and increased urinary free epinephrine by ~32%, amplifying stress-related cardiovascular responses.

Trust comment: Within-subject double-blind design with ambulatory measures and moderate sample size; findings plausible though single high dose may limit real-world generalizability.

Study Details

PMID:12140349
Participants:47
Impact:increase (≈+4/ +3 mmHg systolic/diastolic)
Trust score:4/5

urinary free epinephrine excretion

1 evidences

A single 500 mg caffeine dose in habitual coffee drinkers raised ambulatory blood pressure by ~4/3 mmHg, lowered heart rate by ~2 bpm, and increased urinary free epinephrine by ~32%, amplifying stress-related cardiovascular responses.

Trust comment: Within-subject double-blind design with ambulatory measures and moderate sample size; findings plausible though single high dose may limit real-world generalizability.

Study Details

PMID:12140349
Participants:47
Impact:increase (≈+32%)
Trust score:4/5

reticulocyte count

1 evidences

In preterm infants treated for apnoea, caffeine did not differ from theophylline in erythropoietin levels by week 7; reticulocyte counts were higher with caffeine.

Trust comment: Randomized clinical study in humans (n=50) with clear measurements but some within-group vs between-group nuance limits interpretation.

Study Details

PMID:9625339
Participants:50
Impact:+higher with caffeine vs theophylline (P<0.05)
Trust score:3/5

serum erythropoietin (EP) level

1 evidences

In preterm infants treated for apnoea, caffeine did not differ from theophylline in erythropoietin levels by week 7; reticulocyte counts were higher with caffeine.

Trust comment: Randomized clinical study in humans (n=50) with clear measurements but some within-group vs between-group nuance limits interpretation.

Study Details

PMID:9625339
Participants:50
Impact:caffeine: increase vs baseline; theophylline: decrease vs baseline; between-groups at week 7: no significant difference
Trust score:3/5

haemoglobin/haematocrit

1 evidences

In preterm infants treated for apnoea, caffeine did not differ from theophylline in erythropoietin levels by week 7; reticulocyte counts were higher with caffeine.

Trust comment: Randomized clinical study in humans (n=50) with clear measurements but some within-group vs between-group nuance limits interpretation.

Study Details

PMID:9625339
Participants:50
Impact:similar falls in both groups (no between-group difference)
Trust score:3/5

need for intubation by 12 hours

1 evidences

In this pilot RCT of extremely preterm infants, early intravenous caffeine (≤2 h age) improved blood pressure and systemic blood flow measures but did not change need for intubation by 12 h.

Trust comment: Pilot randomized trial in very preterm infants (n=21) with physiological outcome improvements but small sample and pilot design limit definitive conclusions.

Study Details

PMID:25607226
Participants:21
Impact:no significant difference (p=0.08)
Trust score:3/5

blood pressure and systemic blood flow (SVC flow, right ventricular output)

1 evidences

In this pilot RCT of extremely preterm infants, early intravenous caffeine (≤2 h age) improved blood pressure and systemic blood flow measures but did not change need for intubation by 12 h.

Trust comment: Pilot randomized trial in very preterm infants (n=21) with physiological outcome improvements but small sample and pilot design limit definitive conclusions.

Study Details

PMID:25607226
Participants:21
Impact:improved with early caffeine (BP p=0.03; SVC flow p=0.04; RVO p=0.03)
Trust score:3/5

cerebral oxygenation

1 evidences

In this pilot RCT of extremely preterm infants, early intravenous caffeine (≤2 h age) improved blood pressure and systemic blood flow measures but did not change need for intubation by 12 h.

Trust comment: Pilot randomized trial in very preterm infants (n=21) with physiological outcome improvements but small sample and pilot design limit definitive conclusions.

Study Details

PMID:25607226
Participants:21
Impact:transient decrease 1 hour after caffeine administration
Trust score:3/5

gut-secreted PGDPs (GLP-1, GLP-2, oxyntomodulin, glicentin)

1 evidences

In a 33-subject crossover trial, coffee with caffeine altered postprandial gut- and pancreas-derived proglucagon peptides compared with water.

Trust comment: Randomized crossover RCT with validated assays and n=33 gives moderate-high confidence though effects are short-term and assay-focused.

Study Details

PMID:35114286
Participants:33
Impact:postprandial increase with high-dose coffee (vs water)
Trust score:4/5

pancreas-secreted PGDPs (glucagon, MPGF)

1 evidences

In a 33-subject crossover trial, coffee with caffeine altered postprandial gut- and pancreas-derived proglucagon peptides compared with water.

Trust comment: Randomized crossover RCT with validated assays and n=33 gives moderate-high confidence though effects are short-term and assay-focused.

Study Details

PMID:35114286
Participants:33
Impact:postprandial decrease with low- and high-dose coffee (vs water)
Trust score:4/5

daytime sleepiness

1 evidences

In 27 participants across three groups, slow-release caffeine reduced daytime sleepiness after an eastbound 7-time-zone flight but tended to affect sleep quality.

Trust comment: Double-blind randomized placebo-controlled study with objective sleep measures; group sizes small (n=9 per arm) but design is robust.

Study Details

PMID:12959951
Participants:27
Impact:reduced with slow-release caffeine (objective measures) vs placebo
Trust score:4/5

vigilant attention (error rate)

1 evidences

In healthy adults, 50 mg caffeine reduced errors on a 2-hour sustained attention task and reduced alpha-band EEG activity (especially in the first hour); theanine also reduced errors but did not change alpha activity.

Trust comment: Well-controlled double-blind randomized crossover with EEG and a moderate sample (n=27); results plausible and directly measured.

Study Details

PMID:22326943
Participants:27
Impact:error rates significantly reduced with caffeine vs placebo (reduced time-on-task increase)
Trust score:4/5

alpha-band oscillatory activity (8-14 Hz)

1 evidences

In healthy adults, 50 mg caffeine reduced errors on a 2-hour sustained attention task and reduced alpha-band EEG activity (especially in the first hour); theanine also reduced errors but did not change alpha activity.

Trust comment: Well-controlled double-blind randomized crossover with EEG and a moderate sample (n=27); results plausible and directly measured.

Study Details

PMID:22326943
Participants:27
Impact:reduced with caffeine, particularly in first hour
Trust score:4/5

combined caffeine+theanine effect

1 evidences

In healthy adults, 50 mg caffeine reduced errors on a 2-hour sustained attention task and reduced alpha-band EEG activity (especially in the first hour); theanine also reduced errors but did not change alpha activity.

Trust comment: Well-controlled double-blind randomized crossover with EEG and a moderate sample (n=27); results plausible and directly measured.

Study Details

PMID:22326943
Participants:27
Impact:no additional benefit over individual compounds at studied doses
Trust score:4/5

combined functional impairment (academic, motor, behavior)

1 evidences

Follow-up of a neonatal RCT found no significant difference in combined functional impairment at age 11, but neonatal caffeine therapy was associated with lower rates of motor impairment versus placebo.

Trust comment: Large multicenter randomized placebo-controlled trial with long-term follow-up and adequate sample for primary outcomes, high reliability.

Study Details

PMID:28437520
Participants:920
Impact:no significant difference (31.7% caffeine vs 37.6% placebo; P=0.07)
Trust score:5/5

motor impairment

1 evidences

Follow-up of a neonatal RCT found no significant difference in combined functional impairment at age 11, but neonatal caffeine therapy was associated with lower rates of motor impairment versus placebo.

Trust comment: Large multicenter randomized placebo-controlled trial with long-term follow-up and adequate sample for primary outcomes, high reliability.

Study Details

PMID:28437520
Participants:920
Impact:reduced with neonatal caffeine (19.7% vs 27.5%; absolute −7.8 percentage points; adjusted OR 0.66, P=0.009)
Trust score:5/5

academic performance and behavior problems

1 evidences

Follow-up of a neonatal RCT found no significant difference in combined functional impairment at age 11, but neonatal caffeine therapy was associated with lower rates of motor impairment versus placebo.

Trust comment: Large multicenter randomized placebo-controlled trial with long-term follow-up and adequate sample for primary outcomes, high reliability.

Study Details

PMID:28437520
Participants:920
Impact:no significant difference between groups
Trust score:5/5

circulating adenosine concentration

1 evidences

In human endotoxemia, circulating adenosine rose; pretreatment with intravenous caffeine (4 mg/kg) did not alter the inflammatory cytokine response or markers of (subclinical) organ injury compared with placebo.

Trust comment: Controlled human experimental endotoxemia with randomized caffeine/placebo and detailed measures, but modest sample size (n=30).

Study Details

PMID:21211004
Participants:30
Impact:increased during endotoxemia (caffeine group mean increase ~+53% ±47%)
Trust score:4/5

inflammatory cytokines (TNF-α, IL-6, IL-10, IL1RA)

1 evidences

In human endotoxemia, circulating adenosine rose; pretreatment with intravenous caffeine (4 mg/kg) did not alter the inflammatory cytokine response or markers of (subclinical) organ injury compared with placebo.

Trust comment: Controlled human experimental endotoxemia with randomized caffeine/placebo and detailed measures, but modest sample size (n=30).

Study Details

PMID:21211004
Participants:30
Impact:no significant change with caffeine vs placebo
Trust score:4/5

organ injury markers (ICAM/VCAM, urinary GSTs)

1 evidences

In human endotoxemia, circulating adenosine rose; pretreatment with intravenous caffeine (4 mg/kg) did not alter the inflammatory cytokine response or markers of (subclinical) organ injury compared with placebo.

Trust comment: Controlled human experimental endotoxemia with randomized caffeine/placebo and detailed measures, but modest sample size (n=30).

Study Details

PMID:21211004
Participants:30
Impact:no significant difference with caffeine vs placebo
Trust score:4/5

endurance time (cycling)

1 evidences

In adults ≥70 years, a single 6 mg/kg dose of caffeine increased cycling endurance time versus placebo; other measures showed no consistent benefit.

Trust comment: Randomized double-blind crossover in a relevant elderly cohort (n=30); modest size but appropriate design for acute effects.

Study Details

PMID:16081625
Participants:30
Impact:increased (median from 7.5 to 10.3 min; P=0.02)
Trust score:4/5

reaction and movement times, postural stability, walking speed, strength

1 evidences

In adults ≥70 years, a single 6 mg/kg dose of caffeine increased cycling endurance time versus placebo; other measures showed no consistent benefit.

Trust comment: Randomized double-blind crossover in a relevant elderly cohort (n=30); modest size but appropriate design for acute effects.

Study Details

PMID:16081625
Participants:30
Impact:no consistent significant changes reported
Trust score:4/5

perceived effort during cycling

1 evidences

In adults ≥70 years, a single 6 mg/kg dose of caffeine increased cycling endurance time versus placebo; other measures showed no consistent benefit.

Trust comment: Randomized double-blind crossover in a relevant elderly cohort (n=30); modest size but appropriate design for acute effects.

Study Details

PMID:16081625
Participants:30
Impact:no significant consistent change reported
Trust score:4/5

maximal oxygen uptake (V˙O2max)

1 evidences

In elite male endurance athletes, 4.5 mg·kg-1 caffeine increased endurance performance and several physiological markers during incremental running to exhaustion.

Trust comment: Randomized double-blind placebo-controlled crossover in elite athletes with objective physiological measures; small, all-male elite sample limits generalizability.

Study Details

PMID:34033621
Participants:23
Impact:+0.9 mL·kg⁻¹·min⁻¹ (75.8 → 76.7 mL·kg⁻¹·min⁻¹)
Trust score:4/5

cerebral blood flow decrease (%CBF↓)

1 evidences

In healthy volunteers, caffeine induced a marked decrease in cerebral blood flow measured by ASL, but measured magnitude differed by vendor/sequence affecting multicenter reproducibility.

Trust comment: Well-controlled repeated-measures imaging in healthy volunteers focusing on technical reproducibility; clinically informative but primarily methodological.

Study Details

PMID:25588906
Participants:22
Impact:−23.9% (3D spiral, GE) vs −19.2% (2D EPI, Philips); difference ≈4.7 percentage points (p=0.02)
Trust score:3/5

sustained vigilant attention (PVT performance)

1 evidences

In sleep-deprived young men, 200 mg caffeine attenuated performance impairments and EEG changes (frontal theta gradient) observed with prolonged waking, especially in caffeine-sensitive individuals.

Trust comment: Double-blind crossover with sensitivity stratification and EEG measures, but relatively small, all-male sample and subgroup analyses reduce robustness.

Study Details

PMID:17035531
Participants:22
Impact:caffeine counteracted sleep-deprivation–induced PVT impairment in caffeine-sensitive men (improved vs placebo)
Trust score:3/5

frontal theta power gradient

1 evidences

In sleep-deprived young men, 200 mg caffeine attenuated performance impairments and EEG changes (frontal theta gradient) observed with prolonged waking, especially in caffeine-sensitive individuals.

Trust comment: Double-blind crossover with sensitivity stratification and EEG measures, but relatively small, all-male sample and subgroup analyses reduce robustness.

Study Details

PMID:17035531
Participants:22
Impact:caffeine attenuated the frontal > posterior theta power increase induced by sleep deprivation in sensitive subjects
Trust score:3/5

sleep slow oscillation distribution

1 evidences

In sleep-deprived young men, 200 mg caffeine attenuated performance impairments and EEG changes (frontal theta gradient) observed with prolonged waking, especially in caffeine-sensitive individuals.

Trust comment: Double-blind crossover with sensitivity stratification and EEG measures, but relatively small, all-male sample and subgroup analyses reduce robustness.

Study Details

PMID:17035531
Participants:22
Impact:sleep deprivation effects differed by sensitivity and were mirrored/modified by caffeine
Trust score:3/5

analgesic efficacy of fixed combination (ASA+paracetamol+caffeine)

1 evidences

In a large randomized double-blind trial, the fixed combination acetylsalicylic acid+paracetamol+caffeine showed superior efficacy for treated headaches compared with formulations lacking caffeine, single agents, and placebo.

Trust comment: Large (n=1734), randomized double-blind trial with clear superiority reported for the caffeine-containing combination.

Study Details

PMID:18823361
Participants:1734
Impact:significantly superior to combination without caffeine, single agents, and placebo (p<0.05)
Trust score:5/5

Yo-Yo IR1 total distance

1 evidences

In adolescent male athletes, 6 mg/kg caffeine increased endurance performance (Yo-Yo IR1 distance) and VO2max in ACE II and DI genotype carriers but not in DD carriers; heart rate and perceived exertion also rose in I-allele carriers.

Trust comment: Randomized, double-blind crossover in 75 adolescents with genotyping and reported p-values; moderate sample and genotype subgroup sizes (II n=13) limit subgroup precision.

Study Details

PMID:38896643
Participants:75
Impact:ACE DI: 914→1200 m (+≈286 m, p=0.001); ACE II: 871→1031 m (+≈160 m, p=0.03); no significant change in DD
Trust score:4/5

heart rate and RPE at exhaustion

1 evidences

In adolescent male athletes, 6 mg/kg caffeine increased endurance performance (Yo-Yo IR1 distance) and VO2max in ACE II and DI genotype carriers but not in DD carriers; heart rate and perceived exertion also rose in I-allele carriers.

Trust comment: Randomized, double-blind crossover in 75 adolescents with genotyping and reported p-values; moderate sample and genotype subgroup sizes (II n=13) limit subgroup precision.

Study Details

PMID:38896643
Participants:75
Impact:HR increased in DI (+~5 bpm) and II (+~4 bpm) vs placebo (p≤0.02); RPE increased in II (17→20, p=0.03)
Trust score:4/5

systolic/diastolic blood pressure response

1 evidences

In borderline hypertensive men, a dietary dose of caffeine (3.3 mg/kg) combined with a psychomotor stressor produced larger blood pressure increases than in normotensive controls.

Trust comment: Double-blind crossover with both borderline hypertensive and control groups (n=24 each); clear acute BP increases reported but modest sample size.

Study Details

PMID:8788536
Participants:48
Impact:Borderline hypertensives: combined caffeine+task +15/+11 mmHg vs controls +10/+6 mmHg (exaggerated BP response)
Trust score:4/5

self-reported drowsiness

1 evidences

In a small randomized double-blind trial using caffeine as the active comparator, both placebo and caffeine reduced self-reported drowsiness and increased prefrontal blood flow; subjects with L/L 5-HTTLPR genotype showed larger placebo responses.

Trust comment: Randomized double-blind with objective NIRS measures but small sample (n=42) and limited genotype subgroups, so findings are exploratory.

Study Details

PMID:29441949
Participants:42
Impact:improved after caffeine and also after placebo (placebo improvement similar to caffeine)
Trust score:3/5

prefrontal blood flow (NIRS)

1 evidences

In a small randomized double-blind trial using caffeine as the active comparator, both placebo and caffeine reduced self-reported drowsiness and increased prefrontal blood flow; subjects with L/L 5-HTTLPR genotype showed larger placebo responses.

Trust comment: Randomized double-blind with objective NIRS measures but small sample (n=42) and limited genotype subgroups, so findings are exploratory.

Study Details

PMID:29441949
Participants:42
Impact:increased after placebo and caffeine; greater placebo-related increase in L/L genotype (statistically significant)
Trust score:3/5

time to complete time-trial

1 evidences

5 mg/kg caffeine improved ~30-min cycling time-trial performance and modestly altered physiological responses in trained male cyclists.

Trust comment: Randomized double-blind placebo-controlled crossover in trained cyclists (n=40) with clear physiological and performance measures.

Study Details

PMID:33170731
Participants:40
Impact:−1.1 min (29.7 vs 30.8 min; ≈−3.6%)
Trust score:4/5

mean heart rate during submaximal exercise

1 evidences

5 mg/kg caffeine improved ~30-min cycling time-trial performance and modestly altered physiological responses in trained male cyclists.

Trust comment: Randomized double-blind placebo-controlled crossover in trained cyclists (n=40) with clear physiological and performance measures.

Study Details

PMID:33170731
Participants:40
Impact:−2.9 beats·min⁻¹
Trust score:4/5

pain-free walking distance

1 evidences

Single-dose caffeine (6 mg/kg) increased pain-free and maximal walking distances, strength and endurance but worsened balance in patients with intermittent claudication.

Trust comment: Randomized double-blind placebo-controlled crossover with a substantial sample (n=88) and clinically relevant functional outcomes.

Study Details

PMID:20629111
Participants:88
Impact:+20.0% (95% CI 3.7 to 38.8)
Trust score:4/5

maximal walking distance

1 evidences

Single-dose caffeine (6 mg/kg) increased pain-free and maximal walking distances, strength and endurance but worsened balance in patients with intermittent claudication.

Trust comment: Randomized double-blind placebo-controlled crossover with a substantial sample (n=88) and clinically relevant functional outcomes.

Study Details

PMID:20629111
Participants:88
Impact:+26.6% (95% CI 12.1 to 43.0)
Trust score:4/5

postural stability (eyes open)

1 evidences

Single-dose caffeine (6 mg/kg) increased pain-free and maximal walking distances, strength and endurance but worsened balance in patients with intermittent claudication.

Trust comment: Randomized double-blind placebo-controlled crossover with a substantial sample (n=88) and clinically relevant functional outcomes.

Study Details

PMID:20629111
Participants:88
Impact:−22.1% (95% CI 11.7 to 33.4)
Trust score:4/5

spike jump height (SJ)

1 evidences

In 90 male adolescent athletes, acute caffeine (6 mg/kg) improved several performance measures (strength, jump height, sit-ups, and Yo-Yo endurance) versus placebo; these ergogenic effects were independent of ADORA2A and CYP1A2 genotypes.

Trust comment: Large (n=90) double-blind, randomized crossover in athletes; robust design supports findings though limited to adolescent male athletes.

Study Details

PMID:36385314
Participants:90
Impact:+1.6 cm (54.7 vs 53.1 cm)
Trust score:4/5

sit-ups (number)

1 evidences

In 90 male adolescent athletes, acute caffeine (6 mg/kg) improved several performance measures (strength, jump height, sit-ups, and Yo-Yo endurance) versus placebo; these ergogenic effects were independent of ADORA2A and CYP1A2 genotypes.

Trust comment: Large (n=90) double-blind, randomized crossover in athletes; robust design supports findings though limited to adolescent male athletes.

Study Details

PMID:36385314
Participants:90
Impact:+2 reps (37 vs 35)
Trust score:4/5

Yo-Yo IR1 distance

1 evidences

In 90 male adolescent athletes, acute caffeine (6 mg/kg) improved several performance measures (strength, jump height, sit-ups, and Yo-Yo endurance) versus placebo; these ergogenic effects were independent of ADORA2A and CYP1A2 genotypes.

Trust comment: Large (n=90) double-blind, randomized crossover in athletes; robust design supports findings though limited to adolescent male athletes.

Study Details

PMID:36385314
Participants:90
Impact:+95.6 m (991.6 vs 896.0 m)
Trust score:4/5

Sprint peak/total power

1 evidences

In 54 active men, creatine loading with or without added caffeine (or coffee) did not provide additional improvements in strength or sprint performance compared with placebo over 5 days.

Trust comment: Randomized controlled design with moderate sample and objective performance measures but short (5-day) supplementation period.

Study Details

PMID:26439785
Participants:54
Impact:no significant effect of caffeine or coffee vs placebo
Trust score:4/5

Pain relief (TOTPAR)

1 evidences

In a randomized double-blind crossover trial in ~93 completers, paracetamol 1000 mg plus caffeine 130 mg provided more pain relief than placebo and had similar tolerability to placebo and naproxen over 4 hours.

Trust comment: Well-designed multicentre randomized double-blind crossover with adequate completed sample size, though industry sponsorship noted.

Study Details

PMID:18815727
Participants:93
Impact:increased (PCF mean 8.5 vs PLA 4.8; PCF > placebo, P < 0.05)
Trust score:4/5

Pain intensity reduction (SPID)

1 evidences

In a randomized double-blind crossover trial in ~93 completers, paracetamol 1000 mg plus caffeine 130 mg provided more pain relief than placebo and had similar tolerability to placebo and naproxen over 4 hours.

Trust comment: Well-designed multicentre randomized double-blind crossover with adequate completed sample size, though industry sponsorship noted.

Study Details

PMID:18815727
Participants:93
Impact:increased (PCF mean 4.0 vs PLA 2.1; PCF > placebo, P < 0.05)
Trust score:4/5

Adverse events (4-h post-dose)

1 evidences

In a randomized double-blind crossover trial in ~93 completers, paracetamol 1000 mg plus caffeine 130 mg provided more pain relief than placebo and had similar tolerability to placebo and naproxen over 4 hours.

Trust comment: Well-designed multicentre randomized double-blind crossover with adequate completed sample size, though industry sponsorship noted.

Study Details

PMID:18815727
Participants:93
Impact:no higher rate vs placebo (36.6% PCF vs 36.6% PLA)
Trust score:4/5

Salivary gastrin

1 evidences

In 40 habitual coffee consumers in a randomized crossover design, single servings of coffee (160 mg caffeine) increased salivary alpha-amylase and transiently increased salivary gastrin and blood pressure, but did not change salivary cortisol or self-reported GI symptoms.

Trust comment: Randomized double-blind crossover with objective biochemical measures, though modest sample and short-term assessments.

Study Details

PMID:26979712
Participants:40
Impact:temporarily increased after coffee (time effect, P < 0.001)
Trust score:4/5

Self-reported GI symptoms

1 evidences

In 40 habitual coffee consumers in a randomized crossover design, single servings of coffee (160 mg caffeine) increased salivary alpha-amylase and transiently increased salivary gastrin and blood pressure, but did not change salivary cortisol or self-reported GI symptoms.

Trust comment: Randomized double-blind crossover with objective biochemical measures, though modest sample and short-term assessments.

Study Details

PMID:26979712
Participants:40
Impact:no change
Trust score:4/5

Insulin sensitivity index

1 evidences

In 27 pregnant women (19 controls, 8 with GDM) in a randomized crossover trial, acute caffeine (3 mg/kg) impaired insulin sensitivity and raised glucose and C-peptide AUCs in women with gestational diabetes but not in controls.

Trust comment: Double-blind randomized crossover design but small subgroup sizes, limiting generalizability.

Study Details

PMID:19497149
Participants:27
Impact:decreased by 18% in GDM group after caffeine (P < 0.05)
Trust score:3/5

Time to first bowel movement

1 evidences

In a double-blind RCT after elective laparoscopic colectomy (58 analyzed), oral caffeine (100 mg TID) was safe and led to a significantly earlier first bowel movement (by ~18 hours) compared with placebo; other recovery endpoints were not significantly different.

Trust comment: Prospective double-blind randomized clinical trial with clinically meaningful endpoint but moderate sample and some exclusions.

Study Details

PMID:33900493
Participants:58
Impact:earlier by ~18 hours in caffeine group (P = 0.012)
Trust score:4/5

Time to first flatus / diet tolerance / length of stay

1 evidences

In a double-blind RCT after elective laparoscopic colectomy (58 analyzed), oral caffeine (100 mg TID) was safe and led to a significantly earlier first bowel movement (by ~18 hours) compared with placebo; other recovery endpoints were not significantly different.

Trust comment: Prospective double-blind randomized clinical trial with clinically meaningful endpoint but moderate sample and some exclusions.

Study Details

PMID:33900493
Participants:58
Impact:no significant difference
Trust score:4/5

cognitive function (composite measures)

1 evidences

In partially sleep-deprived healthy volunteers an acute energy shot improved multiple composite cognitive measures and self-rated alertness for up to 6 hours compared with placebo.

Trust comment: Randomized double-blind crossover with large N (94) and validated cognitive tests, but the active composition of the energy shot (explicit caffeine content) is not specified in the provided text, so attribution to caffeine is indirect.

Study Details

PMID:23587521
Participants:94
Impact:+improved (small–medium effect); benefits on 4 measures remained at 6h
Trust score:3/5

caffeine Cmax (pharmacokinetics)

1 evidences

In healthy adults, coadministration of lisdexamfetamine did not materially change caffeine pharmacokinetics (no meaningful CYP1A2 interaction) after single doses.

Trust comment: Well-conducted randomized crossover pharmacokinetic study with serial sampling and standard bioequivalence analysis, though single-dose only.

Study Details

PMID:25862215
Participants:30
Impact:geometric LS mean ratio 0.977 (≈ −2.3% change)
Trust score:5/5

caffeine AUC0–∞ (pharmacokinetics)

1 evidences

In healthy adults, coadministration of lisdexamfetamine did not materially change caffeine pharmacokinetics (no meaningful CYP1A2 interaction) after single doses.

Trust comment: Well-conducted randomized crossover pharmacokinetic study with serial sampling and standard bioequivalence analysis, though single-dose only.

Study Details

PMID:25862215
Participants:30
Impact:geometric LS mean ratio 1.009 (≈ +0.9% change)
Trust score:5/5

middle cerebral artery blood velocity

1 evidences

In patients recovering from middle cerebral artery stroke and controls, 250 mg caffeine caused a significant reduction in cerebral blood flow and middle cerebral artery velocity versus placebo.

Trust comment: Randomized, double-blind, crossover with direct xenon clearance flow measures in a clinical population provides reliable evidence though sample modest (n=29 total).

Study Details

PMID:15082437
Participants:29
Impact:significant decrease after 250 mg caffeine vs placebo
Trust score:4/5

Emotion perception (correct hits)

1 evidences

Two-week daily matcha (contains caffeine) preserved attention after mild stress in young adults.

Trust comment: Randomized placebo-controlled trial in 42 participants; multi-constituent intervention (matcha) so caffeine-specific attribution limited.

Study Details

PMID:33744591
Participants:42
Impact:Increased correct hits
Trust score:4/5

Rest percent defect

1 evidences

In patients undergoing adenosine myocardial perfusion imaging, supplemental coffee (raising plasma caffeine) did not change measures of perfusion defect or reversibility.

Trust comment: Prospective study with objective plasma caffeine measurement and clinical imaging endpoints, though moderate sample size (n=30).

Study Details

PMID:22302182
Participants:30
Impact:No significant change reported
Trust score:4/5

negative mood (anxiety/sadness)

1 evidences

In habitual coffee-drinking middle-aged women, caffeine (50–100 mg) reduced negative mood scores (notably anxiety/sadness); combining aspirin and caffeine did not increase positive mood or show clear abuse potential.

Trust comment: Randomized double-blind design with adequate sample (n=96) in habitual coffee drinkers; outcomes focused on mood scales.

Study Details

PMID:11486635
Participants:96
Impact:decreased with caffeine
Trust score:4/5

drowsiness

1 evidences

Intravenous caffeine as an opioid adjuvant modestly reduced pain scores and improved drowsiness in advanced cancer patients, but clinical significance was limited.

Trust comment: Double-blind RCT but very small sample; statistically significant but modest effects with uncertain clinical importance.

Study Details

PMID:23498965
Participants:38
Impact:statistically improved after first infusion in caffeine group (magnitude not specified)
Trust score:3/5

CAP score (hepatic steatosis)

1 evidences

Six months of 200 mg/day caffeine (alone) in T2D patients with NAFLD did not change hepatic steatosis, fibrosis, enzymes, inflammatory markers or glycemia vs placebo; caffeine reduced total cholesterol by ~20.7 mg/dL.

Trust comment: Randomized double-blind placebo-controlled trial with appropriate endpoints; limited by modest sample size, dropouts (84 completers) and single 200 mg/day dose.

Study Details

PMID:33838673
Participants:84
Impact:no significant change vs placebo
Trust score:4/5

task completion speed

1 evidences

After prolonged wakefulness in 54 adults, 600 mg caffeine improved performance on the Tower of Hanoi (fewer moves) compared with other groups, with no effect on completion speed.

Trust comment: Randomized, double‑blind stimulant comparison using validated cognitive tasks; single high caffeine dose limits dose‑response insights.

Study Details

PMID:19238808
Participants:54
Impact:no change (caffeine vs others/placebo)
Trust score:4/5

patient satisfaction

1 evidences

After outpatient general surgery, analgesia was similar between the codeine+acetaminophen+caffeine regimen and acetaminophen+ibuprofen, but the codeine+caffeine group had more side effects and lower satisfaction.

Trust comment: Double-blind randomized trial with high completion (95%); results are credible though effects reflect a combination product rather than caffeine alone.

Study Details

PMID:18308218
Participants:139
Impact:Tylenol No.3 64% vs AcIBU 83% (−19 percentage points).
Trust score:4/5

total abdominal fat area

1 evidences

In moderately obese adults, 12-week intake of glucosyl hesperidin combined with caffeine (especially 50–75 mg caffeine) reduced abdominal fat (mainly subcutaneous), and the highest caffeine dose group showed reductions in body weight and BMI versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with adequate sample size and objective CT-based fat measures, but caffeine was combined with another active ingredient so effects are combinatorial.

Study Details

PMID:26786000
Participants:75
Impact:GH+Caf50: −8.4 ± 21.9 cm² (p<0.05 vs placebo); GH+Caf75: −17.0 ± 31.4 cm² (p<0.01 vs placebo).
Trust score:4/5

body composition

1 evidences

In 33 obese women followed 16 months, supplementation including 100 mg caffeine did not affect weight-regain or body composition vs controls.

Trust comment: Randomized 16-month trial but small sample (n=33) and combined supplements make isolating caffeine effects difficult.

Study Details

PMID:9426382
Participants:33
Impact:no significant difference between groups at 16 months
Trust score:3/5

hypoglycemia warning symptom intensity

1 evidences

In adults with type 1 diabetes, 200 mg caffeine increased the weekly frequency of symptomatic hypoglycemia and intensified warning symptoms, caused a modest systolic BP rise in women, and slightly improved simple reaction time.

Trust comment: Randomized, placebo-controlled, double-blind crossover (n=34) with objective monitoring and symptom scoring; sample size moderate and outcomes clinically relevant.

Study Details

PMID:10857934
Participants:34
Impact:increased total symptom score (29 vs 26; P<0.05)
Trust score:4/5

skeletal muscle mass (percentage)

1 evidences

Drinking three cups/day of lightly roasted (higher polyphenols and caffeine) or regular coffee for 12 weeks reduced body fat percentage and increased muscle mass in overweight/obese adults; lightly roasted coffee produced a slightly greater fat percentage reduction.

Trust comment: Randomized, controlled crossover in humans with validated measures; small sample (n=38), high dropout and coffee contains multiple bioactives so caffeine-specific attribution is uncertain.

Study Details

PMID:39275165
Participants:38
Impact:modest increase at end of both interventions (significant vs baseline); between-coffee difference non-significant (between-coffee mean diff +0.3 kg; p=0.213)
Trust score:4/5

smoking cessation rate

1 evidences

Randomized double-blind trial testing ephedrine plus caffeine vs placebo for smoking cessation: no difference in 1-year quit rates; combination reduced short-term (first 12 weeks) postcessation weight gain but not weight at 1 year.

Trust comment: Large double-blind RCT (n=225) with 1-year follow-up; effect cannot be attributed to caffeine alone because it was given combined with ephedrine.

Study Details

PMID:8988071
Participants:225
Impact:17% (ephedrine+caffeine) vs 16% (placebo) at 1 year; no significant difference
Trust score:4/5

lymphocyte count

1 evidences

Caffeine given before simulated match increased white blood cell counts and augmented some muscle-injury enzyme responses to exercise, suggesting more muscle/endothelial stress.

Trust comment: Placebo-controlled double-blind protocol in 22 athletes; moderate-quality sport-specific study but limited sample size.

Study Details

PMID:17473001
Participants:22
Impact:+38% after exercise; additional ≈+35% when combined with caffeine (synergistic increase)
Trust score:3/5

Sleep drive during deprivation

1 evidences

During 40.5 h sleep deprivation, caffeine reduced sleep drive compared with placebo but did not improve sleep-related recovery measures; other stimulants had differing effects.

Trust comment: Well-powered randomized double-blind pharmacologic comparison in humans (n=76), though specific numeric sleep metrics for caffeine are not reported here.

Study Details

PMID:12887139
Participants:76
Impact:Caffeine (300 mg/70 kg) decreased sleep drive during sleep deprivation (compared with placebo)
Trust score:4/5

Endocrine responses

1 evidences

During 40.5 h sleep deprivation, caffeine reduced sleep drive compared with placebo but did not improve sleep-related recovery measures; other stimulants had differing effects.

Trust comment: Well-powered randomized double-blind pharmacologic comparison in humans (n=76), though specific numeric sleep metrics for caffeine are not reported here.

Study Details

PMID:12887139
Participants:76
Impact:Tyrosine stimulated prolactin; caffeine effects on endocrine measures not emphasized
Trust score:4/5

withdrawals due to adverse effects

1 evidences

An 8-week randomized trial of an herbal mix (includes 240 mg/day caffeine) produced greater short-term weight and fat loss but more withdrawals and side effects.

Trust comment: Randomized, double-blind, placebo-controlled RCT but small, short-term and multi-ingredient so effects cannot be attributed solely to caffeine.

Study Details

PMID:11319627
Participants:48
Impact:23% (8/35) active vs 0% (0/32) placebo
Trust score:4/5

Quadriceps cross-sectional area (CSA)

1 evidences

In resistance-trained men taking a multi-ingredient supplement containing extended‑release caffeine (~129 mg) for 12 weeks, ultrasound measures of muscle size increased and lower-body fat decreased versus placebo; blood markers remained within normal ranges.

Trust comment: Randomized placebo-controlled 12‑week trial but multi-ingredient product prevents isolating caffeine's independent effect.

Study Details

PMID:27293386
Participants:21
Impact:increased (TRT > PLA at weeks 8,10,12)
Trust score:3/5

Aerobic performance (Yo‑Yo IR1)

1 evidences

In 100 adolescent athletes, 6 mg/kg caffeine taken 1 hour before testing improved muscular endurance and aerobic performance compared with placebo, independent of CYP1A2 genotype.

Trust comment: Large sample of adolescent athletes with within‑subject placebo comparison; design details limited in excerpt but findings are plausible and directly reported.

Study Details

PMID:32538495
Participants:100
Impact:increased (improved vs placebo)
Trust score:4/5

working memory (N-back)

1 evidences

Acute ingestion of various energy drinks (contain caffeine plus blends) produced group-specific increases in blood pressure, heart rate, cortisol, and mixed effects on anxiety and working memory.

Trust comment: Moderate-sized acute study (n=80) but tested commercial energy drinks with multiple active ingredients, so effects cannot be attributed to caffeine alone.

Study Details

PMID:27312565
Participants:80
Impact:percent improvement in group A
Trust score:3/5

total cholesterol

2 evidences

Six months of 200 mg/day caffeine (alone) in T2D patients with NAFLD did not change hepatic steatosis, fibrosis, enzymes, inflammatory markers or glycemia vs placebo; caffeine reduced total cholesterol by ~20.7 mg/dL.

Trust comment: Randomized double-blind placebo-controlled trial with appropriate endpoints; limited by modest sample size, dropouts (84 completers) and single 200 mg/day dose.

Study Details

PMID:33838673
Participants:84
Impact:decreased −20.66 mg/dL vs placebo (p=0.04)
Trust score:4/5

Ten-week daily caffeine+EGCG drink with/without exercise was associated with improved muscle mass and lower total cholesterol in overweight/obese women.

Trust comment: Randomized placebo-controlled design but supplement combined with EGCG and exercise confounds attribution to caffeine alone; modest sample (n=27).

Study Details

PMID:20962916
Participants:27
Impact:significant decrease in active-supplementing groups (exact % not reported)
Trust score:3/5

cumulative opioid consumption (POD 0–3)

1 evidences

Intraoperative IV caffeine citrate 200 mg did not reduce early postoperative opioid use; after adjustment caffeine was associated with increased opioid consumption and otherwise no differences in pain or neuropsychological outcomes.

Trust comment: Randomized, double-blind single-center trial with 60 analyzed patients; robust design though single-center and adjusted post-hoc analyses influenced primary interpretation.

Study Details

PMID:33939649
Participants:60
Impact:median 77 mg (caffeine) vs 51 mg (placebo); adjusted analysis associated with increased opioid use +87 mg (95% CI 26–148; p=0.005)
Trust score:4/5

performance

1 evidences

In a 54.5 h total sleep deprivation trial with 50 adults, a single 600 mg caffeine dose maintained performance and alertness relative to placebo, comparable to effective modafinil doses.

Trust comment: Well‑controlled sleep‑deprivation trial with placebo and active comparators; caffeine arm small (n≈10) but design is robust.

Study Details

PMID:11862356
Participants:50
Impact:maintained/improved versus placebo (caffeine 600 mg)
Trust score:4/5

musculoskeletal discomfort

1 evidences

A 7-day multi-ingredient supplement (including vitamin D) reduced pain severity and musculoskeletal discomfort vs baseline and performed similarly or better than acetaminophen in this small crossover trial.

Trust comment: Randomized double-blind crossover RCT with thorough outcome measures but small sample size limits generalizability; caffeine was one of multiple active ingredients.

Study Details

PMID:32575480
Participants:27
Impact:Total musculoskeletal discomfort score decreased by ~34% with Pain Bloc-R after 7 days.
Trust score:4/5

body weight and BMI

1 evidences

In moderately obese adults, 12-week intake of glucosyl hesperidin combined with caffeine (especially 50–75 mg caffeine) reduced abdominal fat (mainly subcutaneous), and the highest caffeine dose group showed reductions in body weight and BMI versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with adequate sample size and objective CT-based fat measures, but caffeine was combined with another active ingredient so effects are combinatorial.

Study Details

PMID:26786000
Participants:75
Impact:GH+Caf75 showed greater weight/BMI decreases (e.g., body weight −1.43 ± 2.0 kg at week 8; BMI −0.56 ± 0.74 kg/m² at week 8 vs baseline, with significant differences vs placebo at some timepoints).
Trust score:4/5

subjective experience

1 evidences

In undergraduates, 5 mg/kg caffeine increased systolic blood pressure and altered heart rate/HRV measures and subjective experience 40 minutes after ingestion; expectancies contributed to subjective effects but not objective measures.

Trust comment: Well-powered double-blind placebo-controlled design (n=107) with objective and subjective endpoints and control for expectancies, supporting credible differentiation of pharmacologic vs expectancy effects.

Study Details

PMID:25481367
Participants:107
Impact:increased subjective effects; also influenced by response expectancies (placebo component)
Trust score:4/5

systolic blood pressure (women)

1 evidences

In adults with type 1 diabetes, 200 mg caffeine increased the weekly frequency of symptomatic hypoglycemia and intensified warning symptoms, caused a modest systolic BP rise in women, and slightly improved simple reaction time.

Trust comment: Randomized, placebo-controlled, double-blind crossover (n=34) with objective monitoring and symptom scoring; sample size moderate and outcomes clinically relevant.

Study Details

PMID:10857934
Participants:34
Impact:modest increase (115 vs 110 mmHg; P<0.01)
Trust score:4/5

analgesia (acetaminophen efficacy)

1 evidences

Adding 130 mg caffeine to 1000 mg acetaminophen sped absorption and produced stronger, longer pain relief than acetaminophen alone.

Trust comment: Double-blind, placebo-controlled, 4-way crossover with objective pain measures supports internal validity though sample moderate (n=24).

Study Details

PMID:17442681
Participants:24
Impact:combination > acetaminophen alone (significant reduction in pain-related potentials from 30 min, effect sustained up to 3 h)
Trust score:4/5

Growth hormone (post-exercise)

1 evidences

In 30 resistance-trained men, 6 mg/kg caffeine before exercise raised growth hormone and testosterone post-exercise in ADORA2A rs5751876 TT homozygotes.

Trust comment: Randomized double-blind crossover with genotyping (n=30) showing genotype-dependent hormonal responses; moderate sample size.

Study Details

PMID:38931158
Participants:30
Impact:Increased post-RE with caffeine in TT genotype (significant)
Trust score:4/5

cutaneous microcirculation

1 evidences

Double-blind randomized placebo-controlled trial of a topical multi-ingredient anti-cellulite product (includes caffeine) in 46 healthy women showed improvement in skin macrorelief (reduced 'orange peel') and increased cutaneous microcirculation versus placebo.

Trust comment: Randomized, placebo-controlled design; multi-ingredient topical formulation prevents attributing effects to caffeine alone and limits mechanistic conclusions.

Study Details

PMID:11479653
Participants:46
Impact:significant increase vs placebo
Trust score:3/5

skin tonicity

1 evidences

Randomized double-blind placebo-controlled trial of a multi-ingredient topical slimming product (contains caffeine) in 78 women found significant reductions in body circumferences (abdomen, hips/buttocks, waist) from 4 weeks and improvements in cellulite and skin tonicity over 12 weeks.

Trust comment: Placebo-controlled clinical study with moderate sample (n=78); multi-ingredient product prevents attribution of effects specifically to caffeine.

Study Details

PMID:21564138
Participants:78
Impact:improved (significant from 8 weeks)
Trust score:3/5

Pain relief (TOTPAR2)

1 evidences

A single dose of a two-tablet analgesic containing acetaminophen, aspirin, and caffeine relieved migraine pain faster and more effectively than ibuprofen or placebo.

Trust comment: Large multicenter double-blind randomized placebo-controlled trial with clear endpoints and large sample size.

Study Details

PMID:16618262
Participants:1555
Impact:AAC mean TOTPAR2 2.7 vs IB 2.4 and placebo 2.0 (AAC > IB, P < .03)
Trust score:5/5

Pain-free response / pain intensity reduction

1 evidences

A single dose of a two-tablet analgesic containing acetaminophen, aspirin, and caffeine relieved migraine pain faster and more effectively than ibuprofen or placebo.

Trust comment: Large multicenter double-blind randomized placebo-controlled trial with clear endpoints and large sample size.

Study Details

PMID:16618262
Participants:1555
Impact:AAC superior to ibuprofen for pain intensity reduction and pain-free outcomes (statistically significant)
Trust score:5/5

Decisional cognitive performance (go/no-go reaction time)

1 evidences

A multivitamin–mineral product with guarana improved decision-making speed for about 30–90 min and maintained parasympathetic HRV measures during the first hour compared with caffeine alone or placebo.

Trust comment: Randomized, double-blind within-subject design with moderate sample (n=56); caffeine dose equivalent was included for direct comparison.

Study Details

PMID:25558905
Participants:56
Impact:Improved after guarana complex from 30 to 90 min; maximal difference vs caffeine ~8.5% faster RT at 60 min (p < 0.05)
Trust score:4/5

positive mood

1 evidences

In habitual coffee-drinking middle-aged women, caffeine (50–100 mg) reduced negative mood scores (notably anxiety/sadness); combining aspirin and caffeine did not increase positive mood or show clear abuse potential.

Trust comment: Randomized double-blind design with adequate sample (n=96) in habitual coffee drinkers; outcomes focused on mood scales.

Study Details

PMID:11486635
Participants:96
Impact:no increase with aspirin+caffeine combination
Trust score:4/5

postoperative atrial fibrillation incidence

1 evidences

Peri-operative oral caffeine did not reduce post-op atrial fibrillation and increased postoperative nausea/vomiting.

Trust comment: Randomized controlled trial with adequate design though stopped early for futility; results are direct and clearly reported.

Study Details

PMID:29702502
Participants:110
Impact:33% (caffeine) vs 29% (placebo); P=0.67 (no significant difference)
Trust score:4/5

Muscle thickness (MT)

1 evidences

In resistance-trained men taking a multi-ingredient supplement containing extended‑release caffeine (~129 mg) for 12 weeks, ultrasound measures of muscle size increased and lower-body fat decreased versus placebo; blood markers remained within normal ranges.

Trust comment: Randomized placebo-controlled 12‑week trial but multi-ingredient product prevents isolating caffeine's independent effect.

Study Details

PMID:27293386
Participants:21
Impact:increased (TRT > PLA)
Trust score:3/5

postdural puncture headache incidence

1 evidences

Oral paracetamol+caffeine given prophylactically (75 or 125 mg caffeine repeated) did not reduce rates of postdural puncture headache compared with placebo.

Trust comment: Randomized, placebo-controlled, blinded trial with adequate sample size (n=210); results show no effect of the paracetamol-caffeine regimens on PDPH.

Study Details

PMID:15721731
Participants:210
Impact:no significant difference (placebo 15.7% vs 75 mg caffeine 14.28% vs 125 mg caffeine 14.28%)
Trust score:4/5

psychomotor vigilance (PVT)

1 evidences

ADORA2A genotype influenced caffeine effects after sleep deprivation: caffeine improved vigilance and reduced recovery-sleep SWA in non-HT4 carriers but was ineffective in HT4 carriers.

Trust comment: Genotype-stratified, placebo-controlled experimental study with crossover drug challenge in a defined sample (n=45 tested); findings robust for gene–drug interaction but subgroup sizes moderate.

Study Details

PMID:21950736
Participants:45
Impact:caffeine improved PVT in non-HT4 allele carriers but not in HT4 carriers
Trust score:4/5

postoperative pain and neuropsychological outcomes

1 evidences

Intraoperative IV caffeine citrate 200 mg did not reduce early postoperative opioid use; after adjustment caffeine was associated with increased opioid consumption and otherwise no differences in pain or neuropsychological outcomes.

Trust comment: Randomized, double-blind single-center trial with 60 analyzed patients; robust design though single-center and adjusted post-hoc analyses influenced primary interpretation.

Study Details

PMID:33939649
Participants:60
Impact:no significant differences between groups
Trust score:4/5

subjective intoxication

1 evidences

In 24 adults, an 80 mg‑caffeine energy drink increased self-rated alertness and reduced depression scores; combining it with alcohol did not alter blood alcohol or subjective intoxication versus alcohol alone.

Trust comment: Double‑blind, placebo‑controlled crossover is strong methodology, though sample size is modest (n=24).

Study Details

PMID:25163441
Participants:24
Impact:increased with alcohol and alcohol+energy drink (no difference between these two)
Trust score:4/5

clinically meaningful improvement (MCII) rate

1 evidences

A 7-day multi-ingredient supplement (including vitamin D) reduced pain severity and musculoskeletal discomfort vs baseline and performed similarly or better than acetaminophen in this small crossover trial.

Trust comment: Randomized double-blind crossover RCT with thorough outcome measures but small sample size limits generalizability; caffeine was one of multiple active ingredients.

Study Details

PMID:32575480
Participants:27
Impact:32% on Pain Bloc-R vs 16% acetaminophen vs 5% placebo achieved MCII in overall pain severity.
Trust score:4/5

propranolol effect on thermogenesis

1 evidences

A bioactive combination including caffeine increased resting metabolic rate (thermogenesis) in men, and propranolol (beta-blocker) reduced about half of that thermogenic response.

Trust comment: Randomized double-blind crossover study with objective metabolic measures, but caffeine was part of a multi-ingredient mix so attribution to caffeine alone is indirect.

Study Details

PMID:19497591
Participants:22
Impact:Propranolol (5–10 mg) blunted the thermogenic response by ~50%.
Trust score:3/5

muscle mass

1 evidences

Ten-week daily caffeine+EGCG drink with/without exercise was associated with improved muscle mass and lower total cholesterol in overweight/obese women.

Trust comment: Randomized placebo-controlled design but supplement combined with EGCG and exercise confounds attribution to caffeine alone; modest sample (n=27).

Study Details

PMID:20962916
Participants:27
Impact:significant time × treatment increase (exact % not reported)
Trust score:3/5

peak oxygen consumption (VO2)

1 evidences

Ten-week daily caffeine+EGCG drink with/without exercise was associated with improved muscle mass and lower total cholesterol in overweight/obese women.

Trust comment: Randomized placebo-controlled design but supplement combined with EGCG and exercise confounds attribution to caffeine alone; modest sample (n=27).

Study Details

PMID:20962916
Participants:27
Impact:improvement with exercise (time × training interaction; no exact % reported)
Trust score:3/5

self-reported fatigue/sleepiness

1 evidences

In 68 SEAL trainees after 72 h sleep deprivation and stress, 200–300 mg caffeine improved vigilance, reaction time, learning, and reduced fatigue/sleepiness vs placebo.

Trust comment: Randomized allocation in a realistic stress model with measurable cognitive outcomes, moderate sample size (n=68).

Study Details

PMID:12424548
Participants:68
Impact:decrease (improved alertness; greatest at 1 h, persisted to 8 h)
Trust score:4/5

frequency of symptomatic hypoglycemia

1 evidences

In adults with type 1 diabetes, 200 mg caffeine increased the weekly frequency of symptomatic hypoglycemia and intensified warning symptoms, caused a modest systolic BP rise in women, and slightly improved simple reaction time.

Trust comment: Randomized, placebo-controlled, double-blind crossover (n=34) with objective monitoring and symptom scoring; sample size moderate and outcomes clinically relevant.

Study Details

PMID:10857934
Participants:34
Impact:increased (1.3 vs 0.9 episodes/week; P<0.03)
Trust score:4/5

acetaminophen absorption (early AUC)

1 evidences

Adding 130 mg caffeine to 1000 mg acetaminophen sped absorption and produced stronger, longer pain relief than acetaminophen alone.

Trust comment: Double-blind, placebo-controlled, 4-way crossover with objective pain measures supports internal validity though sample moderate (n=24).

Study Details

PMID:17442681
Participants:24
Impact:accelerated (increased early AUC with caffeine)
Trust score:4/5

Testosterone (post-exercise)

1 evidences

In 30 resistance-trained men, 6 mg/kg caffeine before exercise raised growth hormone and testosterone post-exercise in ADORA2A rs5751876 TT homozygotes.

Trust comment: Randomized double-blind crossover with genotyping (n=30) showing genotype-dependent hormonal responses; moderate sample size.

Study Details

PMID:38931158
Participants:30
Impact:Increased post-RE with caffeine in TT genotype (significant)
Trust score:4/5

withdrawal symptoms/craving

1 evidences

Randomized double-blind trial testing ephedrine plus caffeine vs placebo for smoking cessation: no difference in 1-year quit rates; combination reduced short-term (first 12 weeks) postcessation weight gain but not weight at 1 year.

Trust comment: Large double-blind RCT (n=225) with 1-year follow-up; effect cannot be attributed to caffeine alone because it was given combined with ephedrine.

Study Details

PMID:8988071
Participants:225
Impact:no difference between groups
Trust score:4/5

skin macrorelief (orange-peel appearance)

1 evidences

Double-blind randomized placebo-controlled trial of a topical multi-ingredient anti-cellulite product (includes caffeine) in 46 healthy women showed improvement in skin macrorelief (reduced 'orange peel') and increased cutaneous microcirculation versus placebo.

Trust comment: Randomized, placebo-controlled design; multi-ingredient topical formulation prevents attributing effects to caffeine alone and limits mechanistic conclusions.

Study Details

PMID:11479653
Participants:46
Impact:significant improvement vs placebo (decrease in orange-peel effect)
Trust score:3/5

orange-peel/cellulite appearance

1 evidences

Randomized double-blind placebo-controlled trial of a multi-ingredient topical slimming product (contains caffeine) in 78 women found significant reductions in body circumferences (abdomen, hips/buttocks, waist) from 4 weeks and improvements in cellulite and skin tonicity over 12 weeks.

Trust comment: Placebo-controlled clinical study with moderate sample (n=78); multi-ingredient product prevents attribution of effects specifically to caffeine.

Study Details

PMID:21564138
Participants:78
Impact:significant decrease from 4 weeks
Trust score:3/5

packed cell volume / platelets

1 evidences

Caffeine given before simulated match increased white blood cell counts and augmented some muscle-injury enzyme responses to exercise, suggesting more muscle/endothelial stress.

Trust comment: Placebo-controlled double-blind protocol in 22 athletes; moderate-quality sport-specific study but limited sample size.

Study Details

PMID:17473001
Participants:22
Impact:PCV increase with exercise was enhanced by caffeine; caffeine promoted thrombocytosis
Trust score:3/5

Parasympathetic modulation (RMSSD and HF)

1 evidences

A multivitamin–mineral product with guarana improved decision-making speed for about 30–90 min and maintained parasympathetic HRV measures during the first hour compared with caffeine alone or placebo.

Trust comment: Randomized, double-blind within-subject design with moderate sample (n=56); caffeine dose equivalent was included for direct comparison.

Study Details

PMID:25558905
Participants:56
Impact:Stability in RMSSD/HF during first hour with guarana complex vs decreases with caffeine and placebo (end-experiment decreases: Pl −18.5%, C −16.8%, Ac −15.9%)
Trust score:4/5

postoperative nausea and vomiting

1 evidences

Peri-operative oral caffeine did not reduce post-op atrial fibrillation and increased postoperative nausea/vomiting.

Trust comment: Randomized controlled trial with adequate design though stopped early for futility; results are direct and clearly reported.

Study Details

PMID:29702502
Participants:110
Impact:27% (caffeine) vs 7% (placebo); P=0.005 (increased)
Trust score:4/5

Lower-body fat mass / % fat

1 evidences

In resistance-trained men taking a multi-ingredient supplement containing extended‑release caffeine (~129 mg) for 12 weeks, ultrasound measures of muscle size increased and lower-body fat decreased versus placebo; blood markers remained within normal ranges.

Trust comment: Randomized placebo-controlled 12‑week trial but multi-ingredient product prevents isolating caffeine's independent effect.

Study Details

PMID:27293386
Participants:21
Impact:decreased (TRT < PLA)
Trust score:3/5

sleep disturbance / tachycardia / hypertension (caffeine side effects)

1 evidences

Oral paracetamol+caffeine given prophylactically (75 or 125 mg caffeine repeated) did not reduce rates of postdural puncture headache compared with placebo.

Trust comment: Randomized, placebo-controlled, blinded trial with adequate sample size (n=210); results show no effect of the paracetamol-caffeine regimens on PDPH.

Study Details

PMID:15721731
Participants:210
Impact:no increase observed in caffeine groups
Trust score:4/5

slow-wave activity (SWA) rebound

1 evidences

ADORA2A genotype influenced caffeine effects after sleep deprivation: caffeine improved vigilance and reduced recovery-sleep SWA in non-HT4 carriers but was ineffective in HT4 carriers.

Trust comment: Genotype-stratified, placebo-controlled experimental study with crossover drug challenge in a defined sample (n=45 tested); findings robust for gene–drug interaction but subgroup sizes moderate.

Study Details

PMID:21950736
Participants:45
Impact:caffeine reduced SWA rebound of recovery sleep in non-HT4 carriers but not in HT4 carriers
Trust score:4/5

depression‑dejection (mood)

1 evidences

In 24 adults, an 80 mg‑caffeine energy drink increased self-rated alertness and reduced depression scores; combining it with alcohol did not alter blood alcohol or subjective intoxication versus alcohol alone.

Trust comment: Double‑blind, placebo‑controlled crossover is strong methodology, though sample size is modest (n=24).

Study Details

PMID:25163441
Participants:24
Impact:decreased (energy drink alone)
Trust score:4/5

Tower of Hanoi performance (executive function)

1 evidences

After prolonged wakefulness in 54 adults, 600 mg caffeine improved performance on the Tower of Hanoi (fewer moves) compared with other groups, with no effect on completion speed.

Trust comment: Randomized, double‑blind stimulant comparison using validated cognitive tasks; single high caffeine dose limits dose‑response insights.

Study Details

PMID:19238808
Participants:54
Impact:improved (fewer moves with caffeine 600 mg)
Trust score:4/5

side effects incidence

1 evidences

After outpatient general surgery, analgesia was similar between the codeine+acetaminophen+caffeine regimen and acetaminophen+ibuprofen, but the codeine+caffeine group had more side effects and lower satisfaction.

Trust comment: Double-blind randomized trial with high completion (95%); results are credible though effects reflect a combination product rather than caffeine alone.

Study Details

PMID:18308218
Participants:139
Impact:Tylenol No.3 (codeine+acetaminophen+caffeine) 57% vs AcIBU 41% (+16 percentage points).
Trust score:4/5

weight regain at 16 months

1 evidences

In 33 obese women followed 16 months, supplementation including 100 mg caffeine did not affect weight-regain or body composition vs controls.

Trust comment: Randomized 16-month trial but small sample (n=33) and combined supplements make isolating caffeine effects difficult.

Study Details

PMID:9426382
Participants:33
Impact:no significant difference between supplemented and control groups (average regain 66.1% ± 81.2% of initial loss)
Trust score:3/5

cerebral blood flow

1 evidences

In patients recovering from middle cerebral artery stroke and controls, 250 mg caffeine caused a significant reduction in cerebral blood flow and middle cerebral artery velocity versus placebo.

Trust comment: Randomized, double-blind, crossover with direct xenon clearance flow measures in a clinical population provides reliable evidence though sample modest (n=29 total).

Study Details

PMID:15082437
Participants:29
Impact:significant decrease after 250 mg caffeine vs placebo
Trust score:4/5

Attentional function (Stroop reaction time)

1 evidences

Two-week daily matcha (contains caffeine) preserved attention after mild stress in young adults.

Trust comment: Randomized placebo-controlled trial in 42 participants; multi-constituent intervention (matcha) so caffeine-specific attribution limited.

Study Details

PMID:33744591
Participants:42
Impact:Decreased reaction time (improved attention) vs placebo
Trust score:4/5

Resting GH and testosterone (cross-sectional)

1 evidences

In 30 resistance-trained men, 6 mg/kg caffeine before exercise raised growth hormone and testosterone post-exercise in ADORA2A rs5751876 TT homozygotes.

Trust comment: Randomized double-blind crossover with genotyping (n=30) showing genotype-dependent hormonal responses; moderate sample size.

Study Details

PMID:38931158
Participants:30
Impact:Higher in TT homozygotes vs C-allele carriers
Trust score:4/5

postcessation weight gain (short-term)

1 evidences

Randomized double-blind trial testing ephedrine plus caffeine vs placebo for smoking cessation: no difference in 1-year quit rates; combination reduced short-term (first 12 weeks) postcessation weight gain but not weight at 1 year.

Trust comment: Large double-blind RCT (n=225) with 1-year follow-up; effect cannot be attributed to caffeine alone because it was given combined with ephedrine.

Study Details

PMID:8988071
Participants:225
Impact:reduced during first 12 weeks (significant) but similar to placebo at 1 year
Trust score:4/5

body circumference (abdomen/hips/waist)

1 evidences

Randomized double-blind placebo-controlled trial of a multi-ingredient topical slimming product (contains caffeine) in 78 women found significant reductions in body circumferences (abdomen, hips/buttocks, waist) from 4 weeks and improvements in cellulite and skin tonicity over 12 weeks.

Trust comment: Placebo-controlled clinical study with moderate sample (n=78); multi-ingredient product prevents attribution of effects specifically to caffeine.

Study Details

PMID:21564138
Participants:78
Impact:significant reductions (visible from 4 weeks; improved further by 12 weeks)
Trust score:3/5

muscle injury markers (AST, LDH, ALT)

1 evidences

Caffeine given before simulated match increased white blood cell counts and augmented some muscle-injury enzyme responses to exercise, suggesting more muscle/endothelial stress.

Trust comment: Placebo-controlled double-blind protocol in 22 athletes; moderate-quality sport-specific study but limited sample size.

Study Details

PMID:17473001
Participants:22
Impact:exercise increased AST and LDH; ALT increased in both groups with a synergistic enhancement when combined with caffeine
Trust score:3/5

Stress percent defect / percent defect reversibility

1 evidences

In patients undergoing adenosine myocardial perfusion imaging, supplemental coffee (raising plasma caffeine) did not change measures of perfusion defect or reversibility.

Trust comment: Prospective study with objective plasma caffeine measurement and clinical imaging endpoints, though moderate sample size (n=30).

Study Details

PMID:22302182
Participants:30
Impact:No significant change despite large increases in plasma caffeine (no relationship between caffeine concentration and defect measures)
Trust score:4/5

pain intensity reduction

1 evidences

Intravenous caffeine as an opioid adjuvant modestly reduced pain scores and improved drowsiness in advanced cancer patients, but clinical significance was limited.

Trust comment: Double-blind RCT but very small sample; statistically significant but modest effects with uncertain clinical importance.

Study Details

PMID:23498965
Participants:38
Impact:mean reduction 0.833 (caffeine) vs 0.350 (placebo) after second infusion
Trust score:3/5

Muscular endurance

1 evidences

In 100 adolescent athletes, 6 mg/kg caffeine taken 1 hour before testing improved muscular endurance and aerobic performance compared with placebo, independent of CYP1A2 genotype.

Trust comment: Large sample of adolescent athletes with within‑subject placebo comparison; design details limited in excerpt but findings are plausible and directly reported.

Study Details

PMID:32538495
Participants:100
Impact:increased (improved vs placebo)
Trust score:4/5

circulating BHB concentration

1 evidences

A pre-workout drink containing BHB salts, ~100 mg caffeine and amino acids increased blood ketones and improved time-to-exhaustion by ~8–10% versus water.

Trust comment: Randomized crossover but small sample (n=24) and caffeine was co-administered with ketone salts and amino acids, so caffeine-specific effects are unclear.

Study Details

PMID:32330107
Participants:24
Impact:rapid increase (e.g., KN 154→732 μM; KA 848→1,973 μM)
Trust score:3/5

STAI anxiety score

1 evidences

Acute ingestion of various energy drinks (contain caffeine plus blends) produced group-specific increases in blood pressure, heart rate, cortisol, and mixed effects on anxiety and working memory.

Trust comment: Moderate-sized acute study (n=80) but tested commercial energy drinks with multiple active ingredients, so effects cannot be attributed to caffeine alone.

Study Details

PMID:27312565
Participants:80
Impact:decreased in group C
Trust score:3/5

LSM (liver stiffness / fibrosis)

1 evidences

Six months of 200 mg/day caffeine (alone) in T2D patients with NAFLD did not change hepatic steatosis, fibrosis, enzymes, inflammatory markers or glycemia vs placebo; caffeine reduced total cholesterol by ~20.7 mg/dL.

Trust comment: Randomized double-blind placebo-controlled trial with appropriate endpoints; limited by modest sample size, dropouts (84 completers) and single 200 mg/day dose.

Study Details

PMID:33838673
Participants:84
Impact:no significant change vs placebo
Trust score:4/5

subcutaneous fat area

1 evidences

In moderately obese adults, 12-week intake of glucosyl hesperidin combined with caffeine (especially 50–75 mg caffeine) reduced abdominal fat (mainly subcutaneous), and the highest caffeine dose group showed reductions in body weight and BMI versus placebo.

Trust comment: Randomized double-blind placebo-controlled trial with adequate sample size and objective CT-based fat measures, but caffeine was combined with another active ingredient so effects are combinatorial.

Study Details

PMID:26786000
Participants:75
Impact:GH+Caf50: −9.3 ± 17.1 cm² (p<0.01 vs placebo); GH+Caf75: −12.4 ± 18.7 cm² (p<0.01 vs placebo).
Trust score:4/5

headache pain intensity (VAS) at 2 hours

1 evidences

Large clinical trial showed the fixed triple combination including caffeine produced ~38–45 mm greater pain reduction on a 100-mm VAS at 2 hours compared with baseline in treated headache episodes.

Trust comment: Large randomized double-blind phase supports efficacy of combination containing caffeine, though comparisons include multi-ingredient formulations.

Study Details

PMID:19472437
Participants:1734
Impact:~37.7–44.7 mm reduction vs baseline depending on group (triple combo with caffeine ~43–44.7 mm)
Trust score:4/5