Caffeine
Caffeine is a stimulant that reliably improves alertness and some aspects of exercise performance. Effects and side effects are dose-dependent.
Overview
What is caffeine?
Caffeine is a stimulant found in coffee, tea and many other natural sources. It works mainly by blocking adenosine receptors, and increasing release of stimulating neurotransmitters such as dopamine and norepinephrine. Although it has some side effects, caffeine is commonly consumed through beverages like coffee and tea.
Dosage
A typical dose of caffeine for athletic performance used in studies is around 3–6 mg per kilogram of bodyweight (around 180–360 mg in a 60 kg person).
A cup of coffee provides 50–200 mg caffeine. A cup of green tea provides 20–50 mg caffeine. A cup of black tea provides 20–100 mg caffeine.
Effect graph
Effect heatmap
SupplementDEX Database
29 conditions for , , and rated at least stars. All purchase bands. No minimum star filter.
Database Snapshot
Most caffeine research is concentrated in a handful of conditions.
- Athletic performance accounts for 67 of 197 studies (34%).
- Mental Alertness accounts for 32 of 197 studies (16%).
- Diabetes accounts for 14 of 197 studies (7%).
- Sparse coverage remains for Depression, Gallbladder disease, Hepatitis C.
Safety
Caffeine is generally safe at an intake level of up to 400 mg in non-pregnant adults and 200 mg in pregnant or lactating women.
Special populations
Pregnancy & breastfeeding
Likely safe200 mg in pregnant or lactating women.
Frequently Asked Questions
References
Sources194 references
SupplementDEX uses only high-quality sources to determine supplement effectiveness.
SupplementDEX Database · Athletic performance
66 references1.SupplementDEX Database: Athletic performance — Ergogenic Effects of Combined Caffeine Supplementation and Motivational Music on Anaerobic Performance in Female Handball Players: A Randomized Double-Blind Controlled Trial2025
In 17 female handball players (mean age 16.7), 6 mg/kg caffeine improved countermovement jump, agility, and repeated-sprint performance versus placebo; combined caffeine plus motivational music showed the best overall results.
2.SupplementDEX Database: Athletic performance — Effects of Caffeine Supplementation on Exercise Performance in Volleyball Players: A Systematic Review and Meta-Analysis2025
A 2025 meta-analysis of 11 volleyball crossover studies found caffeine improved attack and serve accuracy (SMD 0.50), single- and repeated-jump performance, handgrip strength, and agility test times.
3.SupplementDEX Database: Athletic performance — Boost or bust? A randomized crossover study on pre-exercise caffeine supplementation for fatigue management in basketball2025
In 14 amateur male basketball players, pre-exercise caffeine 3 mg/kg did not significantly affect countermovement jump, sprint times, heart rate variability, muscle soreness, or perceived fatigue versus placebo after training.
4.SupplementDEX Database: Athletic performance — Effect of caffeine ingestion on time trial performance in cyclists: a systematic review and meta-analysis2024
A meta-analysis of 15 cycling time-trial studies found moderate caffeine doses (4–6 mg/kg) significantly improved completion time (SMD −0.55) and mean power output (SMD 0.44); low doses (1–3 mg/kg) were not significant.
5.SupplementDEX Database: Athletic performance — Effects of Acute Ingestion of Caffeine Capsules on Muscle Strength and Muscle Endurance: A Systematic Review and Meta-Analysis2024
A meta-analysis of 14 studies found acute caffeine capsule ingestion significantly improved upper- and lower-body muscle strength and muscular endurance in men.
6.SupplementDEX Database: Athletic performance — Sex Differences in the Ergogenic Response of Acute Caffeine Intake on Muscular Strength, Power and Endurance Performance in Resistance-Trained Individuals: A Randomized Controlled Trial2024
In 76 resistance-trained adults (38 men, 38 women), 3 mg/kg caffeine increased bench press and back squat velocity and power at 50–90% 1RM and increased repetitions to failure at 65% 1RM similarly in both sexes.
7.SupplementDEX Database: Athletic performance — Supplementation of caffeine and sodium bicarbonate together could not improve performance and performance-related factors in CrossFit participants: a randomized, double-blind, placebo-controlled study2023
In 20 CrossFit participants, caffeine 6 mg/kg, sodium bicarbonate, or their combination did not improve Cindy workout performance versus placebo, though combined caffeine plus bicarbonate reduced perceived exertion.
8.SupplementDEX Database: Athletic performance — Effects of Caffeine Intake on Endurance Running Performance and Time to Exhaustion: A Systematic Review and Meta-Analysis2022
A meta-analysis of 21 running trials (254 participants, caffeine 3–9 mg/kg) found caffeine significantly improved time to exhaustion (g=0.392) and modestly improved time-trial performance (g=−0.101) versus placebo.
9.SupplementDEX Database: Athletic performance — Effects of Multi-Ingredient Pre-Workout Supplement and Caffeine on Bench Press Performance: A Single-Blind Cross-Over Study2022
In 15 resistance-trained men, anhydrous caffeine alone produced greater bench press repetition volume than a multi-ingredient pre-workout supplement containing caffeine, with no differences in perceived exertion or arousal.
10.SupplementDEX Database: Athletic performance — Ergogenic Effects of Caffeine on Ballistic (Throwing) Performance: A Meta-Analytical Review2022
A meta-analysis of 10 studies (151 participants) found caffeine produced a small but significant ergogenic effect on throwing performance (SMD 0.19), especially for throwing velocity at doses ≤3 mg/kg.
11.SupplementDEX Database: Athletic performance — High Dose of Caffeine Mouth Rinse Increases Resistance Training Performance in Men2021
In 14 resistance-trained men, a high-dose (750 mg) caffeine mouth rinse significantly increased bench press repetitions to failure at 60% 1RM and reduced perceived exertion versus placebo; lower doses and 1-RM strength were unaffected.
12.SupplementDEX Database: Athletic performance — Ergogenic Effects of Acute Caffeine Intake on Muscular Endurance and Muscular Strength in Women: A Meta-Analysis2021
A meta-analysis of 8 crossover studies in women found acute caffeine significantly improved muscular endurance (SMD 0.25) and muscular strength (SMD 0.18), with stronger effects on upper-body than lower-body tasks.
13.SupplementDEX Database: Athletic performance — International Society of Sports Nutrition position stand: caffeine and exercise performance2021
The 2021 ISSN position stand concludes caffeine at 3–6 mg/kg acutely enhances endurance, strength, sprinting, jumping, and cognitive performance in many but not all studies, with inter-individual response variation.
14.SupplementDEX Database: Athletic performance — Does Acute Caffeine Supplementation Improve Physical Performance in Female Team-Sport Athletes? Evidence from a Systematic Review and Meta-Analysis2021
A meta-analysis of 18 RCTs in female team-sport athletes found acute caffeine improved team-sport skills (SMD 0.384), countermovement jump (SMD 0.208), total body impacts (SMD 0.488), and handgrip strength (SMD 0.395).
15.SupplementDEX Database: Athletic performance — Acute caffeine supplementation improves jumping, sprinting, and change-of-direction performance in basketball players when ingested in the morning but not evening2021
In 11 adolescent male basketball players, 3 mg/kg caffeine taken in the morning improved vertical jump, sprinting, and change-of-direction performance versus morning placebo, but evening caffeine showed no ergogenic benefit.
16.SupplementDEX Database: Athletic performance — Effects of Caffeine Supplementation on Physical Performance of Soccer Players: Systematic Review and Meta-Analysis2021
A meta-analysis of 16 soccer RCTs found caffeine did not significantly improve aerobic endurance distance, vertical jump, repeated sprints, agility, or perceived exertion versus placebo, though evidence quality was very low.
17.SupplementDEX Database: Athletic performance — CYP1A2 Genotype Modifies the Effects of Caffeine Compared With Placebo on Muscle Strength in Competitive Male Athletes2021
In 97 competitive male cyclists, 4 mg/kg caffeine worsened handgrip strength by 12.8% in CYP1A2 CC genotype carriers versus placebo, while AC/AA genotypes showed no significant caffeine effect on strength or vertical jump.
18.SupplementDEX Database: Athletic performance — Caffeine Mouth Rinse Does Not Improve Time to Exhaustion in Male Trained Cyclists2021
In 10 recreationally trained male cyclists, repeated 85 mg caffeine mouth rinses did not significantly improve cycling time to exhaustion, ratings of perceived exertion, or heart rate versus water placebo.
19.SupplementDEX Database: Athletic performance — Effects of caffeine supplementation on muscle endurance, maximum strength, and perceived exertion in adults submitted to strength training: a systematic review and meta-analyses2020
A meta-analysis of 19 RCTs found caffeine significantly improved bench-press muscular endurance and maximal strength versus placebo, but effects on leg-press endurance and strength were inconsistent.
20.SupplementDEX Database: Athletic performance — The Effects of Caffeine Ingestion on Measures of Rowing Performance: A Systematic Review and Meta-Analysis2020
A meta-analysis of 7 rowing ergometer studies found acute caffeine improved 2000 m performance by about 4 seconds and increased mean power by 5.7 W versus placebo.
21.SupplementDEX Database: Athletic performance — Caffeine Timing Improves Lower-Body Muscular Performance: A Randomized Trial2020
In 29 resistance-trained adults, caffeine 6 mg/kg taken 1 hour before testing most consistently improved countermovement jump and isometric performance versus 30-minute or 2-hour timing.
22.SupplementDEX Database: Athletic performance — Caffeine Supplementation or Carbohydrate Mouth Rinse Improves Performance2020
In 29 active women, caffeine 6.5 mg/kg or carbohydrate mouth rinse both increased total resistance-training repetitions versus placebo, with no additional benefit from combining them.
23.SupplementDEX Database: Athletic performance — Habitual Caffeine Consumption Does Not Interfere With the Acute Caffeine Supplementation Effects on Strength Endurance and Jumping Performance in Trained Individuals2020
In 36 strength-trained adults stratified by habitual caffeine intake, acute 6 mg/kg caffeine improved countermovement jump and total repetitions regardless of low, moderate, or high daily caffeine consumption.
24.SupplementDEX Database: Athletic performance — Caffeine Supplementation for 4 Days Does Not Induce Tolerance to the Ergogenic Effects Promoted by Acute Intake on Physiological, Metabolic, and Performance Parameters of Cyclists: A Randomized, Double-Blind, Crossover, Placebo-Controlled Study2020
In 14 male cyclists, 4 days of caffeine 6 mg/kg/day did not induce tolerance; acute caffeine still improved 16 km time-trial time and power versus placebo on day 5.
25.SupplementDEX Database: Athletic performance — Effects of CYP1A2 and ADORA2A Genotypes on the Ergogenic Response to Caffeine in Professional Handball Players2020
In 31 professional handball players, 3 mg/kg caffeine improved countermovement jump, sprint velocity, and 9 m throw speed versus placebo; CYP1A2 and ADORA2A genotypes did not modulate most performance outcomes.
26.SupplementDEX Database: Athletic performance — The effect of carbohydrate and caffeine mouth rinsing on kicking performance in competitive Taekwondo athletes during Ramadan2020
In 27 taekwondo athletes during Ramadan, caffeine mouth rinse improved successful kick percentage versus glucose or placebo in early fasting weeks, though Ramadan itself reduced baseline kick success.
27.SupplementDEX Database: Athletic performance — Wake up and smell the coffee: caffeine supplementation and exercise performance—an umbrella review of 21 published meta-analyses2019
An umbrella review of 21 meta-analyses concluded caffeine is ergogenic for aerobic endurance, muscle strength, power, and jumping, with moderate-quality evidence for endurance and strength benefits.
28.SupplementDEX Database: Athletic performance — Establishing a relationship between the effect of caffeine and duration of endurance athletic time trial events: A systematic review and meta-analysis2019
A meta-analysis of 40 endurance time-trial studies (56 comparisons) found caffeine's standardized effect size increased with event duration by 0.15 per 30 minutes, supporting greater benefits in longer events.
29.SupplementDEX Database: Athletic performance — The effects of caffeine ingestion on isokinetic muscular strength: A meta-analysis2019
A meta-analysis of 10 isokinetic strength studies found acute caffeine increased overall isokinetic strength by ~5.3%, with significant knee extensor benefits at 60°/s and 180°/s angular velocities.
30.SupplementDEX Database: Athletic performance — Caffeine Supplementation: Ergogenic in Both High and Low Caffeine Responders2019
In 20 well-trained soccer players, caffeine 6 mg/kg improved time to fatigue and countermovement jump versus placebo in both high and low caffeine responders identified at rest.
31.SupplementDEX Database: Athletic performance — Caffeine mouth rinse has no effects on anaerobic energy yield during a Wingate Test2019
In 10 healthy men, a 300 mg caffeine mouth rinse before a Wingate test did not improve peak power, mean power, fatigue index, or anaerobic energy contribution versus placebo.
32.SupplementDEX Database: Athletic performance — Correction to: The Effect of Acute Caffeine Ingestion on Endurance Performance: A Systematic Review and Meta-Analysis2018
A meta-analysis of 44 endurance time-trial studies found moderate caffeine doses (3–6 mg/kg) improved mean power by ~2.9% and completion time by ~2.3% versus placebo, though individual responses varied.
33.SupplementDEX Database: Athletic performance — The effect of CYP1A2 genotype on the ergogenic properties of caffeine during resistance exercise: a randomized, double-blind, placebo-controlled, crossover study2018
In 30 resistance-trained men, acute caffeine 6 mg/kg increased total reps more in CYP1A2 AA homozygotes than C-allele carriers across bench press, leg press, row, and shoulder press exercises.
34.SupplementDEX Database: Athletic performance — Effects of acute ingestion of caffeine on team sports performance: a systematic review and meta-analysis2018
A meta-analysis of 34 team-sport studies found 3–6 mg/kg caffeine improved single and repeated jumps, sprint speed, agility time, match running distance, and sprint count versus placebo.
35.SupplementDEX Database: Athletic performance — Chronic ingestion of a low dose of caffeine induces tolerance to the performance benefits of caffeine2017
In 18 low-habitual-caffeine adults over 28 days, chronic caffeine 1.5–3 mg/kg/day attenuated the acute ergogenic effect on endurance work versus baseline, suggesting tolerance development.
36.SupplementDEX Database: Athletic performance — Acute effects of caffeine-containing energy drinks on physical performance: a systematic review and meta-analysis2017
A meta-analysis of energy-drink trials found caffeine-containing drinks improved muscle strength/endurance, endurance tests, jumping, and sport-specific actions versus placebo; taurine dose correlated with performance gains.
37.SupplementDEX Database: Athletic performance — Effects of Coffee and Caffeine Anhydrous Intake During Creatine Loading2016
In 54 physically active adults, 5 days of creatine loading with or without caffeine or coffee similarly improved strength and sprint performance versus placebo; caffeine did not block creatine's effects.
38.SupplementDEX Database: Athletic performance — Time of Day and Training Status Both Impact the Efficacy of Caffeine for Short Duration Cycling Performance2016
In 20 male cyclists, caffeine 6 mg/kg improved simulated 3 km time-trial performance in both morning and evening, with trained athletes benefiting more in the morning and untrained more in the evening.
39.SupplementDEX Database: Athletic performance — Combined caffeine and carbohydrate ingestion: effects on nocturnal sleep and exercise performance in athletes2014
In male athlete triathletes/cyclists, late-afternoon caffeine 6 mg/kg with carbohydrate improved 5 km cycling time trial but reduced sleep efficiency, REM sleep, and total sleep time that night.
40.SupplementDEX Database: Athletic performance — The effect of caffeine ingestion on skill maintenance and fatigue in epee fencers2013
In 11 competitive fencers, 3 mg/kg caffeine reduced overall perceived fatigue after fatiguing fencing exercise but did not significantly improve lunge accuracy or Stroop reaction times.
41.SupplementDEX Database: Athletic performance — Caffeine counteracts impairments in task-oriented psychomotor performance induced by chlorpheniramine: a double-blind placebo-controlled crossover study2013
In 16 healthy men, 200 mg caffeine counteracted chlorpheniramine-induced reaction-time impairment and subjective sleepiness, restoring psychomotor performance to near placebo levels.
42.SupplementDEX Database: Athletic performance — Caffeine-containing energy drink improves sprint performance during an international rugby sevens competition2013
In 16 Spanish national women's rugby sevens players, an energy drink with 3 mg/kg caffeine improved running pace and muscle power output during matches versus placebo.
43.SupplementDEX Database: Athletic performance — Acute and chronic caffeine administration increases physical activity in sedentary adults2013
In sedentary adults undergoing repeated exercise sessions, caffeine increased spontaneous physical activity and reduced RPE, with greater activity increases in women; acute caffeine also extended exercise duration after chronic exposure.
44.SupplementDEX Database: Athletic performance — Caffeine and sprinting performance: dose responses and efficacy2012
In 17 well-trained men given caffeine doses from 2 to 10 mg/kg before 10-second sprints, caffeine did not significantly improve peak power, mean power, or time to peak power versus placebo.
45.SupplementDEX Database: Athletic performance — The influence of a CYP1A2 polymorphism on the ergogenic effects of caffeine2012
In 35 trained male cyclists, 6 mg/kg caffeine reduced 40 km time-trial time by 4.9% in CYP1A2 AA homozygotes versus 1.8% in C-allele carriers, suggesting genotype-dependent ergogenic response.
46.SupplementDEX Database: Athletic performance — The effects of different doses of caffeine on endurance cycling time trial performance2011
In 16 well-trained male cyclists, caffeine 3 mg/kg improved time-trial performance by 4.2% versus 2.9% for 6 mg/kg and raised heart rate without changing RPE.
47.SupplementDEX Database: Athletic performance — Caffeine ingestion, affect and perceived exertion during prolonged cycling2011
In 12 endurance-trained men cycling 90 min at 70% VO2max, caffeine 6 mg/kg maintained higher pleasure ratings and lower perceived exertion versus placebo, possibly contributing to ergogenic effects.
50.SupplementDEX Database: Athletic performance — Effect of caffeine ingestion on muscular strength and endurance: a meta-analysis2010
A meta-analysis of 27 MVC strength studies found caffeine increased strength modestly overall (ES 0.19), with larger knee extensor effects (ES 0.37) and greater open-endpoint muscular endurance benefits (~18%).
51.SupplementDEX Database: Athletic performance — Effect of ambient temperature on caffeine ergogenicity during endurance exercise2010
In 11 male cyclists, caffeine 3–6 mg/kg improved simulated 3 km time-trial performance similarly in cool (12°C) and warm (33°C) environments versus placebo.
52.SupplementDEX Database: Athletic performance — Effects of acute supplementation of caffeine on cardiorespiratory responses during endurance running in a hot & humid climate2010
In 9 heat-adapted Malaysian runners, 5 mg/kg caffeine before exercise significantly increased running time to exhaustion in hot, humid conditions without changing heart rate, VO2, or RPE patterns.
53.SupplementDEX Database: Athletic performance — Caffeinated chewing gum increases repeated sprint performance and augments increases in testosterone in competitive cyclists2010
In 9 competitive cyclists, caffeinated gum (240 mg) after repeated sprints reduced performance decline and increased post-exercise testosterone versus placebo, with lower cortisol in caffeine trials.
54.SupplementDEX Database: Athletic performance — Dose response of caffeine on 2000-m rowing performance2010
In 10 competitive male rowers, caffeine doses of 2–6 mg/kg did not significantly improve 2000 m ergometer time-trial performance despite large interindividual variation in plasma caffeine levels.
55.SupplementDEX Database: Athletic performance — The influence of caffeine and carbohydrate coingestion on simulated soccer performance2010
In 15 men during a 90-min soccer simulation, adding caffeine to a carbohydrate-electrolyte drink improved sprint times and countermovement jump versus carbohydrate alone, offsetting fatigue-related declines.
56.SupplementDEX Database: Athletic performance — Effect of caffeine as an ergogenic aid during anaerobic exercise performance in caffeine naïve collegiate football players2009
In 17 caffeine-naïve collegiate football players, 5 mg/kg caffeine before NFL combine-style tests did not significantly improve 40-yard dash, shuttle run, or bench press reps versus placebo.
57.SupplementDEX Database: Athletic performance — Caffeine, cycling performance, and exogenous CHO oxidation: a dose-response study2009
In 9 trained male cyclists fed before exercise, caffeine 1.5 or 3 mg/kg did not significantly improve 7 km time-trial performance or exogenous carbohydrate oxidation versus placebo.
58.SupplementDEX Database: Athletic performance — The effect of a carbohydrate-caffeine sports drink on simulated golf performance2009
In recreational golfers during a simulated round, a carbohydrate-caffeine sports drink improved 5 m and 2 m putting performance and alertness ratings versus flavor-matched placebo.
59.SupplementDEX Database: Athletic performance — Caffeine enhances cognitive function and skill performance during simulated soccer activity2009
In 12 healthy men completing two 90-min soccer simulations, 6 mg/kg caffeine reduced penalty time on a skill test and increased jump height versus placebo, suggesting better skill maintenance during simulated match play.
60.SupplementDEX Database: Athletic performance — The effect of ephedra and caffeine on maximal strength and power in resistance-trained athletes2008
In resistance-trained men, caffeine 300 mg, ephedrine, or their combination increased alertness and mood but did not significantly improve strength, Wingate power, or muscular endurance versus placebo.
61.SupplementDEX Database: Athletic performance — Caffeine has a small effect on 5-km running performance of well-trained and recreational runners2008
In 30 runners (15 well-trained, 15 recreational), 5 mg/kg caffeine before 5 km time trials improved performance by ~1% in both groups versus placebo, a small but statistically significant ergogenic effect.
62.SupplementDEX Database: Athletic performance — Effects of caffeine on prolonged intermittent-sprint ability in team-sport athletes2006
In 10 male team-sport athletes, 6 mg/kg caffeine before intermittent sprint exercise increased total sprint work by 8.5% in the first half and 7.6% in the second half versus placebo.
63.SupplementDEX Database: Athletic performance — Effects of caffeine ingestion on rating of perceived exertion during and after exercise: a meta-analysis2005
A meta-analysis of 21 studies found caffeine reduced rating of perceived exertion during exercise by 5.6% and explained about 29% of variance in performance improvement versus placebo.
64.SupplementDEX Database: Athletic performance — Effects of caffeine ingestion on exercise testing: a meta-analysis2004
A meta-analysis of 40 exercise-testing studies found caffeine improved test outcomes by 12.3% overall (ES 0.41), with the largest benefits in endurance time-to-exhaustion protocols.
65.SupplementDEX Database: Athletic performance — Little effect of caffeine ingestion on repeated sprints in team-sport athletes2001
In 16 team-sport athletes, 6 mg/kg caffeine before repeated 20 m sprints produced at most a negligible mean sprint improvement (~0.1%), suggesting little practical benefit for this task.
66.SupplementDEX Database: Athletic performance — Comparison of caffeine and theophylline ingestion: exercise metabolism and endurance2000
In 8 men, caffeine 6 mg/kg and theophylline 4.5 mg/kg both extended cycling time to exhaustion versus placebo and increased blood glycerol, demonstrating ergogenic effects independent of muscle glycogen.
48.No Effects of Caffeine on Muscle Hypertrophy-Style Resistance Exercise. See external sourceExternal source
No source link49.Ergogenic Effects of Caffeine on Simulated Time-Trial Performance Are Independent of Fitness Level. See external sourceExternal source
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SupplementDEX Database · Migraine
10 references67.SupplementDEX Database: Migraine — Comparison of tolerability and efficacy of a combination of paracetamol + caffeine and sumatriptan in the treatment of migraine attack: a randomized, double-blind, double-dummy, cross-over study2012
In 112 migraine patients (ages 18–62), paracetamol 1000 mg plus caffeine 130 mg was similarly effective and tolerable to sumatriptan 50 mg for acute migraine relief in a double-blind crossover trial.
68.SupplementDEX Database: Migraine — OTC analgesics in headache treatment: open-label phase vs randomized double-blind phase of a large clinical trial2009
Pooled analysis of 1,734 headache patients showed open-label use of usual OTC analgesics produced similar 2-hour pain reduction to blinded acetaminophen/aspirin/caffeine in the randomized trial phase.
69.SupplementDEX Database: Migraine — Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early treatment of migraine: results from the ASSET trial2005
In the ASSET early-treatment migraine trial, acetaminophen 500 mg plus aspirin 500 mg and caffeine 130 mg was significantly more effective than sumatriptan 50 mg for pain relief and associated symptoms when treated at headache onset.
70.SupplementDEX Database: Migraine — Efficacy of diclofenac sodium softgel 100 mg with or without caffeine 100 mg in migraine without aura: a randomized, double-blind, crossover study2004
In a phase II crossover migraine trial, diclofenac softgel 100 mg plus caffeine 100 mg provided significantly more 60-minute headache relief (41% vs 14%) and less rescue medication use than placebo or diclofenac alone.
71.SupplementDEX Database: Migraine — Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial2003
In 88 compliant migraine patients treating 4 attacks, rectal indomethacin/prochlorperazine/caffeine achieved pain-free status in 49% at 2 hours versus 34% for sumatriptan, with better nausea relief and sustained pain-free response.
72.SupplementDEX Database: Migraine — Treatment of severe, disabling migraine attacks in an over-the-counter population of migraine sufferers: results from three randomized, placebo-controlled studies of the combination of acetaminophen, aspirin, and caffeine1999
In pooled post-hoc analysis of 172 severe migraine patients from three RCTs, acetaminophen/aspirin/caffeine significantly improved pain, disability, photophobia, and phonophobia from 1–6 hours versus placebo.
73.SupplementDEX Database: Migraine — Treatment of menstruation-associated migraine with the nonprescription combination of acetaminophen, aspirin, and caffeine: results from three randomized, placebo-controlled studies1999
In 185 women with menstruation-associated migraine from three RCTs, acetaminophen/aspirin/caffeine significantly improved pain and associated symptoms similarly to non-menstrual migraine attacks versus placebo.
74.SupplementDEX Database: Migraine — Comparative efficacy and safety of calcium carbasalate plus metoclopramide versus ergotamine tartrate plus caffeine in the treatment of acute migraine attacks1999
In 296 migraine patients treating 2 attacks, calcium carbasalate plus metoclopramide achieved 54% vs 36% headache relief at 2 hours versus ergotamine plus caffeine, with significantly fewer GI adverse events.
75.SupplementDEX Database: Migraine — Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain: three double-blind, randomized, placebo-controlled trials1998
In three placebo-controlled migraine RCTs (1,220 efficacy-evaluable patients), acetaminophen/aspirin/caffeine reduced pain to mild/none in 59% at 2 hours and rendered 51% pain-free at 6 hours versus 24% and 24% on placebo.
76.SupplementDEX Database: Migraine — A randomized, double-blind comparison of sumatriptan and Cafergot in the acute treatment of migraine. The Multinational Oral Sumatriptan and Cafergot Comparative Study Group1991
In 580 European migraine patients, oral sumatriptan 100 mg reduced headache to mild/none in 66% at 2 hours versus 48% for Cafergot (ergotamine 2 mg plus caffeine 200 mg), with faster relief but more headache recurrence on sumatriptan.
SupplementDEX Database · Asthma
1 reference77.SupplementDEX Database: Asthma — Caffeine for asthma2010
A Cochrane review of 7 crossover trials (75 adults with asthma) found caffeine, even below 5 mg/kg, modestly improved FEV1 for up to 4 hours; people should avoid caffeine for at least 4 hours before lung function testing.
78.SupplementDEX Database: Cognitive performance — A review of caffeine’s effects on cognitive, physical and occupational performance2016
A review concluded caffeine at ~3–4 mg/kg enhances alertness, reaction time, and physical performance in occupational and athletic settings, with benefits for vigilance and team-sport actions at moderate doses.
SupplementDEX Database · Diabetes
14 references79.SupplementDEX Database: Diabetes — Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over trial2024
In 16 adults with type 1 diabetes on insulin degludec, pre-exercise caffeine 250 mg plus 10 g glucose reduced exercise-related hypoglycemia risk by 86% versus aspartame control without causing hyperglycemia.
80.SupplementDEX Database: Diabetes — Assessment of Caffeine Consumption and Maternal Cardiometabolic Pregnancy Complications2021
In 2,583 pregnant women, second-trimester caffeinated beverage intake 1–100 mg/day was associated with lower gestational diabetes risk and better glucose and lipid profiles; no links to preeclampsia or gestational hypertension were found.
81.SupplementDEX Database: Diabetes — Long-term effects of coffee and caffeine intake on the risk of pre-diabetes and type 2 diabetes: Findings from a population with low coffee consumption2018
In 1,878–2,139 Iranian adults followed ~5.8 years, coffee drinkers had lower incidence of pre-diabetes (HR 0.73) and type 2 diabetes (HR 0.66) versus non-drinkers after adjustment.
82.SupplementDEX Database: Diabetes — Caffeinated and decaffeinated coffee consumption and risk of type 2 diabetes: a systematic review and a dose-response meta-analysis2014
A dose-response meta-analysis of 28 prospective studies found each additional cup of coffee associated with lower type 2 diabetes risk for both caffeinated (RR 0.91 per cup) and decaffeinated coffee (RR 0.94).
83.SupplementDEX Database: Diabetes — Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies2013
A meta-analysis of prospective studies (up to 1,096,647 participants) found highest coffee intake associated with 29–30% lower type 2 diabetes incidence; each 2 cups/day reduced risk by 12% (caffeinated) to 14% (caffeine).
84.SupplementDEX Database: Diabetes — Coffee and tea consumption and risk of type 2 diabetes2009
In 40,011 Dutch adults over ~10 years, drinking 4.1–6.0 cups coffee/day or >5 cups tea/day was inversely associated with type 2 diabetes versus lower intake, independent of caffeine-related mediators tested.
85.SupplementDEX Database: Diabetes — Does long-term coffee intake reduce type 2 diabetes mellitus risk?2009
A review of 14 of 18 cohort studies concluded moderate-to-high coffee/caffeine intake (≥4 cups or ≥400 mg/day) associates with lower type 2 diabetes risk, though causality and decaffeinated effects need more trial evidence.
86.SupplementDEX Database: Diabetes — Acute caffeine ingestion and glucose tolerance in women with or without gestational diabetes mellitus2009
In 19 women with and without gestational diabetes, acute caffeine 3 mg/kg impaired insulin sensitivity and glucose tolerance in GDM patients but not in controls during an oral glucose tolerance test.
87.SupplementDEX Database: Diabetes — The relationship between green tea and total caffeine intake and risk for self-reported type 2 diabetes among Japanese adults2006
In 17,413 Japanese adults aged 40–65 followed 5 years, ≥6 cups/day green tea (OR 0.67) and ≥3 cups/day coffee (OR 0.58) were inversely associated with self-reported type 2 diabetes; black or oolong tea were not.
88.SupplementDEX Database: Diabetes — Influence of caffeine on frequency of hypoglycemia detected by continuous interstitial glucose monitoring system in patients with long-standing type 1 diabetes2005
In 19 women with long-standing type 1 diabetes monitored 4 weeks, caffeine reduced nocturnal hypoglycemia duration and shifted episodes from moderate to mild versus placebo without changing overall glycemic control.
89.SupplementDEX Database: Diabetes — Caffeine ingestion is associated with reductions in glucose uptake independent of obesity and type 2 diabetes before and after exercise training2005
In lean, obese, and type 2 diabetic men, acute caffeine 5 mg/kg reduced insulin-mediated glucose uptake during clamp testing; chronic exercise training did not remove this insulin-desensitizing effect.
90.SupplementDEX Database: Diabetes — Coffee consumption and risk for type 2 diabetes mellitus2004
In 126,270 U.S. men and women followed up to 18 years, higher coffee intake was inversely associated with type 2 diabetes incidence in a dose-response pattern for regular and decaffeinated coffee.
91.SupplementDEX Database: Diabetes — Caffeine ingestion before an oral glucose tolerance test impairs blood glucose management in men with type 2 diabetes2004
In 12 obese men with type 2 diabetes, caffeine 5 mg/kg before oral glucose loading raised post-load glucose and insulin despite higher proinsulin and C-peptide, indicating impaired glucose management.
92.SupplementDEX Database: Diabetes — Influence of caffeine on the frequency and perception of hypoglycemia in free-living patients with type 1 diabetes2000
In 34 type 1 diabetes patients over 3 months, caffeine 200 mg/day increased symptomatic hypoglycemia episodes and symptom intensity versus placebo without worsening HbA1c or causing severe hypoglycemia.
SupplementDEX Database · Memory
3 references93.SupplementDEX Database: Memory — Caffeine, extraversion and working memory2013
In 128 adults, 65 mg caffeine benefited working memory serial recall and reaction time more in extraverts than introverts, while caffeine alone sped encoding of new information regardless of extraversion.
94.SupplementDEX Database: Memory — Caffeine enhances working memory for extraverts2010
In 59 participants in a double-blind crossover study, 200 mg caffeine enhanced working memory performance specifically in extraverted individuals, consistent with dopamine-related mechanisms.
95.SupplementDEX Database: Memory — Caffeine's effects on true and false memory2009
In a DRM false-memory paradigm, 200 mg caffeine increased recall of both studied words and critical lures versus placebo, intensifying semantic associations rather than selectively improving accurate memory.
SupplementDEX Database · Mental Alertness
32 references96.SupplementDEX Database: Mental Alertness — Daily Caffeine Intake and the Effect of Caffeine on Pilots' Performance After Extended Wakefulness2023
In 30 aeromedically fit subjects after ~17 h awake, a single 300 mg caffeine dose at midnight significantly preserved psychomotor vigilance and tracking performance overnight versus placebo, regardless of daytime caffeine habits.
97.SupplementDEX Database: Mental Alertness — Effects of acute caffeine consumption following sleep loss on cognitive, physical, occupational and driving performance: A systematic review and meta-analysis2019
A meta-analysis of 45 sleep-loss studies found acute caffeine improved attention, executive function, reaction time, information processing, driving control, and occupational performance versus placebo.
98.SupplementDEX Database: Mental Alertness — Using coffee to compensate for poor sleep: Impact on vigilance and implications for workplace performance2018
In 69 adults after poor sleep, coffee improved and stabilized reaction time on a vigilance task, but increased commission errors in poor sleepers, suggesting faster responding without better inhibitory control.
99.SupplementDEX Database: Mental Alertness — The combination of short rest and energy drink consumption as fatigue countermeasures during a prolonged drive of professional truck drivers2014
In professional truck drivers during 150-min simulated drives, an energy drink with 160 mg caffeine before driving and a 10-min rest at 100 min improved lane control and reduced fatigue versus placebo.
100.SupplementDEX Database: Mental Alertness — Sleep restriction and serving accuracy in performance tennis players, and effects of caffeine2013
In performance tennis players after 5 h sleep restriction, caffeine 80 mg did not restore serve accuracy versus placebo; sleep loss impaired serving, and caffeine provided no significant benefit.
101.SupplementDEX Database: Mental Alertness — Caffeine can decrease subjective energy depending on the vehicle with which it is consumed and when it is measured2013
In 90-min testing sessions, caffeine 80 mg in water increased tiredness and hostility later in the day versus water alone, while caffeine in yoghurt transiently increased subjective energy without consistent mood benefits.
102.SupplementDEX Database: Mental Alertness — Faster but not smarter: effects of caffeine and caffeine withdrawal on alertness and performance2013
In 212 medium-high caffeine consumers, withdrawal caused afternoon sleepiness and poorer reaction time; acute caffeine improved physical reaction times in both groups but did not enhance mental alertness in non-low consumers.
103.SupplementDEX Database: Mental Alertness — Combined caffeine and bright light reduces dangerous driving in sleep-deprived healthy volunteers: a pilot cross-over randomised controlled trial2013
In 12 sleep-deprived healthy men (ages 20–50), caffeine 200 mg plus bright light at 1 a.m. significantly reduced lane drifting during simulated nighttime driving at 6 a.m. versus caffeine or light alone.
104.SupplementDEX Database: Mental Alertness — Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task2012
In 27 adults over a 2-hour SART vigilance task, caffeine 50 mg plus theanine 100 mg reduced error rates over time versus placebo; caffeine alone lowered tonic alpha power, but neither alone improved all attention measures.
105.SupplementDEX Database: Mental Alertness — A cognitive and neurophysiological test of change from an individual's baseline2011
In 16 healthy adults, alcohol, caffeine, diphenhydramine, and sleep deprivation were distinguished using combined cognitive performance and EEG sub-scores, with caffeine affecting alertness-related measures in a double-blind crossover design.
106.SupplementDEX Database: Mental Alertness — Effect of caffeine and taurine on simulated laparoscopy performed following sleep deprivation2011
In 18 surgical novices after sleep deprivation, caffeine 150 mg (± taurine) restored laparoscopic simulator speed and economy to rested levels and improved reaction time, though error counts remained elevated versus rested baseline.
107.SupplementDEX Database: Mental Alertness — Expectation of having consumed caffeine can improve performance and mood2011
In 88 participants, expecting caffeine improved attention and psychomotor speed even with placebo; actual caffeine also improved mood and reward responsivity, without a synergistic expectation-by-drug interaction.
108.SupplementDEX Database: Mental Alertness — Glucose and caffeine effects on sustained attention: an exploratory fMRI study2010
In 40 young adults undergoing fMRI during sustained attention, combined caffeine 75 mg and glucose 75 g increased efficiency of visual attention networks versus placebo, though caffeine alone reduced tonic alpha-band activity.
109.SupplementDEX Database: Mental Alertness — Effects of 2 adenosine antagonists, quercetin and caffeine, on vigilance and mood2010
In 57 adults, caffeine 200 mg improved vigilance reaction time and self-rated vigor versus placebo; quercetin 2000 mg did not enhance performance or mood, supporting caffeine but not quercetin as a stimulant at these doses.
110.SupplementDEX Database: Mental Alertness — Acute caffeine consumption enhances the executive control of visual attention in habitual consumers2010
In 36 high-caffeine consumers, 400 mg caffeine improved executive control of visual attention on the Attention Network Test versus lower doses and placebo, while 100–200 mg doses were less effective in this population.
111.SupplementDEX Database: Mental Alertness — Caffeine for the prevention of injuries and errors in shift workers2010
A Cochrane review of 13 trials found caffeine reduced errors and improved cognitive performance in shift workers and sleep-disordered schedules, though evidence quality was moderate and injury outcomes were not measured.
112.SupplementDEX Database: Mental Alertness — Effects of caffeine and glucose, alone and combined, on cognitive performance2010
In healthy volunteers, combined caffeine 75 mg and glucose 75 g improved sustained attention and verbal memory consolidation versus either alone; caffeine alone improved reaction time but not all memory measures.
113.SupplementDEX Database: Mental Alertness — L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness2010
In 29 adults, combined L-theanine 97 mg and caffeine 40 mg improved task-switching accuracy versus placebo; caffeine or theanine alone did not significantly change subjective alertness or intersensory attention.
114.SupplementDEX Database: Mental Alertness — The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness2010
In 44 young adults, L-theanine 97 mg plus caffeine 40 mg significantly improved task-switching accuracy and self-reported alertness while reducing tiredness versus placebo over 70–120 minutes.
115.SupplementDEX Database: Mental Alertness — Sustaining executive functions during sleep deprivation: A comparison of caffeine, dextroamphetamine, and modafinil2009
After 44 h awake in 16 healthy adults, caffeine 600 mg and modafinil 400 mg improved tower-task and WCST performance versus placebo; dextroamphetamine 20 mg also helped, with modality-specific differences across executive tests.
116.SupplementDEX Database: Mental Alertness — The effects of L-theanine, caffeine and their combination on cognition and mood2008
In a crossover study, caffeine 150 mg improved digit vigilance and RVIP accuracy and reduced mental fatigue; combined with L-theanine 250 mg it further improved reaction time and memory, though L-theanine alone increased headache ratings.
117.SupplementDEX Database: Mental Alertness — Effects of caffeine on alertness as measured by infrared reflectance oculography2008
In 12 low-caffeine users, 200 mg caffeine reduced drowsiness on Johns Drowsiness Scale and improved vigilance reaction times for up to 3–4 hours versus placebo in rested participants.
118.SupplementDEX Database: Mental Alertness — Comparing the benefits of caffeine, naps and placebo on verbal, motor and perceptual memory2008
In healthy adults, caffeine enhanced physical reaction times in medium-high and non-low consumers but did not improve mental alertness in non-low consumers; withdrawal worsened afternoon sleepiness and reaction time before dosing.
119.SupplementDEX Database: Mental Alertness — Effects of dextroamphetamine, caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness2008
After 44 h awake in 53 adults, caffeine 600 mg, modafinil 400 mg, and dextroamphetamine 20 mg all restored psychomotor vigilance versus placebo; caffeine had the shortest duration and most side effects among stimulants tested.
120.SupplementDEX Database: Mental Alertness — L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance2008
In 27 adults, combined L-theanine 100 mg and caffeine 50 mg reduced tonic alpha power and improved target detection in a cued attention task versus placebo, suggesting enhanced tonic visual attention deployment.
121.SupplementDEX Database: Mental Alertness — Influence of caffeine ingestion on perceived mood states, concentration, and arousal levels during a 75-min university lecture2007
In 10 university students, caffeine before a 75-min lecture significantly increased self-reported alertness, concentration, energy, and anxiety versus placebo.
122.SupplementDEX Database: Mental Alertness — Cognitive and physiological effects of an "energy drink": an evaluation of the whole drink and of glucose, caffeine and herbal flavouring fractions2004
In 20 healthy volunteers, a whole energy drink and its caffeine-plus-glucose components improved secondary memory and attention speed versus placebo, suggesting synergy beyond caffeine alone.
123.SupplementDEX Database: Mental Alertness — An evaluation of a caffeinated taurine drink on mood, memory and information processing in healthy volunteers without caffeine abstinence2001
In 42 adults with minimal caffeine deprivation, an 80-mg caffeinated taurine drink improved attention and verbal reasoning versus sugar-free and sugar-containing placebos.
124.SupplementDEX Database: Mental Alertness — Effect of caffeine on simulator flight performance in sleep-deprived military pilot students2000
In sleep-deprived military pilot students during simulated flight after 37 h awake, 200 mg caffeine did not significantly improve flight performance versus placebo, though caffeine subjects rated performance optimistically.
125.SupplementDEX Database: Mental Alertness — Effect of three caffeine doses on plasma catecholamines and alertness during prolonged wakefulness2000
In 50 sleep-deprived adults, caffeine doses up to 8.6 mg/kg improved alertness (sleep latency, sleepiness, reaction time) and raised adrenaline for 1–4 h versus placebo in a dose-related pattern.
126.SupplementDEX Database: Mental Alertness — The effects of a low dose of caffeine on cognitive performance1998
In 8 men, 60 mg caffeine from tea or hot water significantly sped reaction time on CANTAB tests within minutes of consumption, detectable on pattern recognition, delayed match-to-sample, and visual search tasks.
127.SupplementDEX Database: Mental Alertness — The effects of black tea and other beverages on aspects of cognition and psychomotor performance1998
In 19 healthy adults, tea (with ~100 mg caffeine) throughout the day prevented the usual afternoon decline in alertness and largely maintained cognitive performance versus caffeine-matched placebo over ~90 min testing periods.
SupplementDEX Database · Obesity
8 references128.SupplementDEX Database: Obesity — Eight weeks of supplementation with a multi-ingredient weight loss product enhances body composition, reduces hip and waist girth, and increases energy levels in overweight men and women2013
In 45 overweight adults over 8 weeks, METABO multi-ingredient supplement (including caffeine and raspberry ketone) plus diet/exercise reduced body weight, fat mass, and waist/hip girth more than placebo, with no adverse safety signals.
129.SupplementDEX Database: Obesity — Effect of green tea catechins with or without caffeine on anthropometric measures: a systematic review and meta-analysis2010
A meta-analysis of 15 RCTs (1,243 adults) found green tea catechins with caffeine reduced BMI, body weight, and waist circumference versus caffeine alone, but catechins without caffeine showed no anthropometric benefit.
130.SupplementDEX Database: Obesity — A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity2009
A systematic review of herbal obesity treatments concluded ephedra/caffeine combinations and several other herbals show weight-loss efficacy in trials, though ephedra-caffeine products carry stimulant side-effect concerns.
131.SupplementDEX Database: Obesity — Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial2002
In 167 obese adults over 6 months, herbal ephedra/caffeine (90/192 mg/day ephedrine alkaloids/caffeine) produced greater weight and fat loss than placebo (−5.3 vs −2.6 kg) with no significant blood pressure increase.
132.SupplementDEX Database: Obesity — Randomised comparison of diets for maintaining obese subjects' weight after major weight loss: ad lib, low fat, high carbohydrate diet v fixed energy intake1997
In obese adults after major weight loss, ad lib low-fat high-carbohydrate diet with ephedrine/caffeine maintained weight better over 1 year than fixed-energy intake (5.4 kg less regain), regardless of initial loss rate.
133.SupplementDEX Database: Obesity — Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity. A double-blind multi-centre trial in general practice1994
In 103 obese patients over 15 weeks, ephedrine/caffeine 20/200 mg three times daily lost 8.3 kg versus 6.9 kg on dexfenfluramine, with more CNS side effects but similar weight loss in BMI ≥30 subgroup.
134.SupplementDEX Database: Obesity — The acute and chronic effects of ephedrine/caffeine mixtures on energy expenditure and glucose metabolism in humans1993
In obese patients followed 24 weeks after a prior trial, continuing ephedrine/caffeine 20/200 mg three times daily yielded an additional 1.1 kg weight loss with minor, transient side effects and no withdrawal problems.
135.SupplementDEX Database: Obesity — The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial1992
In 141 obese adults on a 4.2 MJ/day diet for 24 weeks, ephedrine/caffeine 20/200 mg three times daily produced 16.6 kg mean weight loss versus 13.2 kg on placebo; ephedrine or caffeine alone were ineffective.
SupplementDEX Database · Pain
5 references136.SupplementDEX Database: Pain — Caffeine as an analgesic adjuvant for acute pain in adults2014
A Cochrane review of 20 studies (7,238 participants) found adding ≥100 mg caffeine to analgesics increased patients achieving ≥50% pain relief, with NNT ~14; evidence supports caffeine as an analgesic adjuvant for acute pain.
137.SupplementDEX Database: Pain — [Treating pain after dental surgery: a randomised, controlled, double-blind trial to assess a new formulation of paracetamol, opium powder and caffeine versus tramadol or placebo]2010
In postoperative dental pain, paracetamol plus opium powder and caffeine formulations were non-inferior to tramadol 100 mg and provided faster analgesia, with the 50 mg opium strength showing strongest early pain relief.
138.SupplementDEX Database: Pain — A risk-benefit assessment of paracetamol (acetaminophen) combined with caffeine2010
A risk-benefit review concluded paracetamol 1000 mg plus caffeine 130 mg improves acute analgesic efficacy versus paracetamol alone without evidence of increased hepatotoxicity at therapeutic doses.
139.SupplementDEX Database: Pain — The onset of action and the analgesic efficacy of Saridon (a propyphenazone/paracetamol/caffeine combination) in comparison with paracetamol, ibuprofen, aspirin and placebo (pooled statistical analysis)2002
A pooled analysis of 500 dental pain patients across eight studies found propyphenazone/paracetamol/caffeine (Saridon) provided faster and stronger analgesia than paracetamol, ibuprofen, aspirin, or placebo over 4 hours.
140.SupplementDEX Database: Pain — Analgesic efficacy of ibuprofen alone and in combination with codeine or caffeine in post-surgical pain: a meta-analysis1998
A meta-analysis of ibuprofen analgesic trials found ibuprofen effective for post-surgical pain with dose-response up to 400 mg; codeine 60 mg added ~8% extra relief, while caffeine's adjuvant effect was inconsistent across studies.
SupplementDEX Database · Atrial fibrillation
1 reference141.SupplementDEX Database: Atrial fibrillation — Peri-operative oral caffeine does not prevent postoperative atrial fibrillation after heart valve surgery with cardiopulmonary bypass: A randomised controlled clinical trial2018
In 110 heart valve surgery patients, peri-operative oral caffeine 400 mg every 8 hours for 2 days did not prevent postoperative atrial fibrillation (33% vs 29%) and increased nausea/vomiting versus placebo.
142.SupplementDEX Database: Attention deficit hyperactivity disorder (ADHD) — Objectively measured hyperactivity--II. Caffeine and amphetamine effects1985
In 15 hyperactive children, amphetamine 1.6–5 mg twice daily and 300–600 mg/day caffeine reduced commission errors and parent-rated symptoms in high-scorers, though high-dose caffeine caused side effects.
143.SupplementDEX Database: Attention deficit hyperactivity disorder (ADHD) — The acute effects of caffeine on evoked response, vigilance, and activity level in hyperkinetic children1979
In 17 hyperkinetic children given placebo, low, or high caffeine doses, evoked-response changes were significant but behavioral vigilance and activity measures showed only non-significant dose-related trends.
144.SupplementDEX Database: Attention deficit hyperactivity disorder (ADHD) — Methylphenidate vs dextroamphetamine vs caffeine in minimal brain dysfunction: controlled comparison by placebo washout design with Bayes' analysis1978
In 29 children with minimal brain dysfunction, methylphenidate and dextroamphetamine were significantly better than placebo and caffeine on six ratings; only 1 of 26 drug responders did best on caffeine.
145.SupplementDEX Database: Attention deficit hyperactivity disorder (ADHD) — Caffeine versus methylphenidate and d-amphetamine in minimal brain dysfunction: a double-blind comparison1975
In a double-blind crossover trial, methylphenidate and d-amphetamine significantly improved minimal brain dysfunction symptoms versus placebo and were significantly superior to pure caffeine.
146.SupplementDEX Database: Attention deficit hyperactivity disorder (ADHD) — Methylphenidate and caffeine in the treatment of children with minimal brain dysfunction1975
In 8 boys with minimal brain dysfunction, 20 mg/day methylphenidate controlled impulsivity and hyperactivity better than 160 mg/day caffeine, which was superior to decaffeinated coffee and placebo.
147.SupplementDEX Database: Attention deficit hyperactivity disorder (ADHD) — Caffeine as a substitute for Schedule II stimulants in hyperkinetic children1973
An early report exploring caffeine as a substitute for Schedule II stimulants in hyperkinetic children; available abstract text provides no outcome data beyond the title.
Age-related cognitive decline
1 reference148.Meta-Analysis on the Effects of Caffeine on Neurodegenerative Cognitive Decline. See external sourceExternal source
No source link
SupplementDEX Database · Dementia
3 references149.SupplementDEX Database: Dementia — Relationships Between Caffeine Intake and Risk for Probable Dementia or Global Cognitive Impairment: The Women's Health Initiative Memory Study2016
In 6,467 postmenopausal women followed up to 10 years, caffeine intake above the median (~261 mg/day) was associated with 26% lower hazard of probable dementia and cognitive impairment versus lower intake.
150.SupplementDEX Database: Dementia — Caffeine intake and dementia: systematic review and meta-analysis2010
A systematic review and meta-analysis of 11 cohort/case-control studies found caffeine/coffee associated with reduced dementia risk (summary RR 0.84), though heterogeneity and methodological differences limit certainty.
151.SupplementDEX Database: Dementia — Caffeine as a protective factor in dementia and Alzheimer's disease2010
A narrative review concluded moderate coffee consumption (3–5 cups/day) may lower dementia and Alzheimer's risk, possibly via caffeine, antioxidants, and improved insulin sensitivity, but more prospective data are needed.
153.SupplementDEX Database: Delayed onset muscle soreness — The Effect of Caffeine Ingestion on Delayed Onset Muscle Soreness2013
In 9 low-caffeine-consuming men, caffeine before eccentric bicep curls increased final-set repetitions and attenuated DOMS on days 2–3 versus placebo.
152.Effect of caffeine on delayed-onset muscle soreness: a meta-analysis of RCT. See external sourceExternal source
No source link154.EFFECT OF CAFFEINE ON THE AMOUNT OF PERCEIVED PAIN, JOINT RANGE OF MOTION AND EDEMA AFTER DELAYED MUSCLE SORENESS. See external sourceExternal source
No source link
SupplementDEX Database · Depression
2 references155.SupplementDEX Database: Depression — Caffeine is negatively associated with depression in patients aged 20 and older2022
In 3,263 U.S. adults (ages 20+), higher caffeine intake correlated with lower depression scores on PHQ-9, but the association disappeared above ~90 mg/day in curve-fitting analysis.
156.SupplementDEX Database: Depression — Coffee and caffeine consumption and depression: A meta-analysis of observational studies2016
A meta-analysis of 11 observational studies (330,677 participants) found coffee and caffeine intake associated with lower depression risk (pooled RR 0.76 for coffee, 0.72 for caffeine).
SupplementDEX Database · Gallbladder disease
2 references157.SupplementDEX Database: Gallbladder disease — Relation of coffee, green tea, and caffeine intake to gallstone disease in middle-aged Japanese men2003
In 7,637 Japanese men, coffee and high caffeine intake (≥300 mg/day) were associated with higher odds of known gallstone disease (OR 2.2), while green tea showed no consistent association with gallstones.
158.SupplementDEX Database: Gallbladder disease — Association of coffee consumption with gallbladder disease2000
In 13,938 U.S. adults, total ultrasound gallbladder disease prevalence was unrelated to coffee intake, though women who drank more coffee had lower prevalence of previously diagnosed gallbladder disease.
SupplementDEX Database · Hepatitis C
2 references159.SupplementDEX Database: Hepatitis C — Impact of caffeine in hepatitis C virus infection: a systematic review and meta-analysis2017
A meta-analysis in hepatitis C patients found regular caffeine consumption associated with lower odds of advanced liver fibrosis (OR 0.48) and a non-significant trend toward less moderate-to-severe inflammation (OR 0.61).
160.SupplementDEX Database: Hepatitis C — Association of caffeine intake and histological features of chronic hepatitis C2011
In 238 treatment-naïve chronic hepatitis C patients, caffeine intake >408 mg/day (about 3+ cups) was associated with lower histologic activity grade (OR 0.19 for moderate/severe activity) but not fibrosis stage.
SupplementDEX Database · Hypnic headache
2 references161.SupplementDEX Database: Hypnic headache — Hypnic headache: A review of 348 cases published from 1988 to 20182019
A review of 348 published hypnic headache cases (1988–2018) found caffeine provided the best acute relief and, with lithium and indomethacin, effective prophylaxis in most patients, though RCT evidence is lacking.
162.SupplementDEX Database: Hypnic headache — Hypnic headache: clinical course and treatment2012
A clinical review of hypnic headache recommends caffeine as first-line acute and prophylactic therapy (e.g., strong coffee at night), with lithium as second-line if caffeine is ineffective or poorly tolerated.
SupplementDEX Database · Hypotension
3 references163.SupplementDEX Database: Hypotension — The effects of caffeine in adults with neurogenic orthostatic hypotension: a systematic review2021
A systematic review of 5 small crossover studies in neurogenic orthostatic hypotension found caffeine ± ergotamine may improve symptoms and seated blood pressure, but evidence quality was low and effects were inconsistent.
164.SupplementDEX Database: Hypotension — The effect of caffeine on postprandial blood pressure in the frail elderly1991
In 20 frail elderly adults (mean age 84), 100 mg caffeine before a glucose drink attenuated postprandial sitting systolic blood pressure drop and prevented symptomatic postprandial hypotension in 4 subjects versus placebo.
165.SupplementDEX Database: Hypotension — Hemodynamic and humoral effects of caffeine in autonomic failure. Therapeutic implications for postprandial hypotension1985
In 12 patients with autonomic failure, caffeine 250 mg raised blood pressure and markedly attenuated post-meal hypotension; 7 days of caffeine kept postprandial pressures higher than placebo in 5 patients.
166.SupplementDEX Database: Intermittent claudication — Randomized double-blind placebo-controlled crossover study of caffeine in patients with intermittent claudication2010
In 88 patients with intermittent claudication, single-dose caffeine 6 mg/kg increased pain-free walking distance by 20% and maximal walking distance by 27% versus placebo, but worsened postural stability.
SupplementDEX Database · Liver disease
5 references167.SupplementDEX Database: Liver disease — Protective Effect of Caffeine and Chlorogenic Acids of Coffee in Liver Disease2024
A review concluded moderate coffee/caffeine intake correlates with lower risk and slower progression of chronic liver diseases including NASH, cirrhosis, and hepatocellular carcinoma via anti-fibrotic and anti-inflammatory mechanisms.
168.SupplementDEX Database: Liver disease — Caffeine in liver diseases: Pharmacology and toxicology2022
A pharmacology review summarized preclinical and clinical evidence that caffeine, mainly as an adenosine receptor antagonist, may help prevent and treat various liver diseases when consumed in moderate coffee amounts.
169.SupplementDEX Database: Liver disease — Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: Biochemical and histological study2017
In rats with thioacetamide-induced liver injury, co-treatment with caffeine reduced oxidative stress, inflammation, and fibrosis markers and restored histology, suggesting anti-fibrogenic and anti-inflammatory hepatic effects.
171.SupplementDEX Database: Liver disease — Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-β2014
In rats, caffeine co-administration during thioacetamide exposure blocked TGF-β elevation and reduced fibrosis, collagen, and inflammatory markers, preventing experimental cirrhosis over 8 weeks.
170.Association between caffeine consumption and nonalcoholic fatty liver disease: a systemic review and meta-analysis. See external sourceExternal source
No source link
SupplementDEX Database · Multiple sclerosis (MS)
4 references172.SupplementDEX Database: Multiple sclerosis (MS) — Coffee consumption and risk of multiple sclerosis: A systematic review and meta-analysis2025
A meta-analysis of 10 observational studies (19,430 participants) found coffee consumption associated with lower multiple sclerosis risk (OR 0.66 before symptom onset, 0.58 around onset), though heterogeneity was high.
173.SupplementDEX Database: Multiple sclerosis (MS) — The Effects of Coffee/Caffeine in Patients with Multiple Sclerosis; A Systematic Review2024
A systematic review of 8 studies in MS patients found no consistent link between coffee/caffeine and disability, but reported associations with better cognitive outcomes; evidence remains limited and heterogeneous.
174.SupplementDEX Database: Multiple sclerosis (MS) — Potential efficacy of caffeine ingestion on balance and mobility in patients with multiple sclerosis: Preliminary evidence from a single-arm pilot clinical trial2024
In 30 persons with MS taking 200 mg/day caffeine for 12 weeks, objective balance (Berg Balance Scale) and mobility (Timed Up and Go) improved significantly versus run-in, though self-reported walking disability did not change.
175.SupplementDEX Database: Multiple sclerosis (MS) — Preliminary evidence that caffeine improves attention in multiple sclerosis2022
In MS patients after caffeine abstention, acute caffeine selectively reduced the attentional blink on an RSVP task versus decaffeinated control, suggesting improved attention under high demand without broad cognitive gains.
SupplementDEX Database · Narcolepsy
2 references176.SupplementDEX Database: Narcolepsy — The effects of caffeine on drowsiness in patients with narcolepsy: a double-blind randomized controlled pilot study2020
In 16 narcolepsy patients over 1 week, 200 mg/day caffeine significantly reduced long eye closures and improved Karolinska Sleepiness Scale alertness versus placebo, without changing reaction time or Stanford Sleepiness Scale scores.
177.Self-Medication with Caffeine for 31 Years: A Case of Undiagnosed Childhood Narcolepsy Type II. See external sourceExternal source
No source link
SupplementDEX Database · Nonmelanoma skin cancer
2 references178.SupplementDEX Database: Nonmelanoma skin cancer — Coffee consumption and risk of nonmelanoma skin cancer: a dose-response meta-analysis2016
A dose-response meta-analysis found higher coffee intake associated with lower nonmelanoma skin cancer risk, with summary RRs of 0.96 (1 cup/day) down to 0.81 (>3 cups/day), especially for basal cell carcinoma.
179.SupplementDEX Database: Nonmelanoma skin cancer — Daily coffee consumption and prevalence of nonmelanoma skin cancer in Caucasian women2007
In 93,676 Women's Health Initiative participants, daily caffeinated coffee consumption showed a dose-related association with lower self-reported nonmelanoma skin cancer prevalence in Caucasian women, up to ~30% reduction at ≥6 cups/day.
SupplementDEX Database · Postoperative ileus
3 references180.SupplementDEX Database: Postoperative ileus — Caffeine intake enhances bowel recovery after colorectal surgery: a meta-analysis of randomized and non-randomized studies2024
A meta-analysis of 8 studies (610 colorectal surgery patients) found postoperative caffeine intake shortened time to first bowel movement and solid food tolerance versus non-caffeinated drinks, suggesting benefit for ileus prevention.
181.SupplementDEX Database: Postoperative ileus — The effect of coffee/caffeine on postoperative ileus following elective colorectal surgery: a meta-analysis of randomized controlled trials2022
A meta-analysis of 4 RCTs (312 colorectal surgery patients) found postoperative coffee or caffeine reduced time to first bowel movement by ~10 hours and shortened hospital stay by ~1 day versus control.
182.SupplementDEX Database: Postoperative ileus — Does caffeine enhance bowel recovery after elective colorectal resection? A prospective double-blinded randomized clinical trial2021
In 70 laparoscopic colectomy patients (ages 19–79), oral caffeine 100 mg three times daily after surgery shortened time to first bowel movement by 18 hours versus placebo without adverse events.
SupplementDEX Database · Postoperative pain
2 references183.SupplementDEX Database: Postoperative pain — Single dose oral ibuprofen plus caffeine for acute postoperative pain in adults2015
A Cochrane review of 5 studies (1,501 adults) found single-dose ibuprofen 200 mg plus caffeine 100 mg significantly increased postoperative pain relief versus placebo, with NNT ~2.1 for ≥50% pain relief.
184.SupplementDEX Database: Postoperative pain — Effect of caffeine on ibuprofen analgesia in postoperative oral surgery pain1991
In 298 postoperative dental pain patients, ibuprofen 50–200 mg plus caffeine 100 mg was 2.4–2.8 times more potent than ibuprofen alone, with faster onset and longer duration of analgesia.
SupplementDEX Database · Pre-eclampsia
2 references186.SupplementDEX Database: Pre-eclampsia — Maternal caffeine intake, blood pressure, and the risk of hypertensive complications during pregnancy. The Generation R Study2011
In 7,890 pregnant women (Generation R), caffeine intake was associated with slightly higher first- and third-trimester systolic blood pressure, but 2–3.9 units/day caffeine linked to lower pre-eclampsia odds (OR 0.63) versus <2 units/day.
185.Caffeine Consumption and Incidence of Hypertension in Pregnancy. See external sourceExternal source
No source link
SupplementDEX Database · Stroke
4 references187.SupplementDEX Database: Stroke — Coffee Consumption and Stroke Risk: A Meta-analysis of Epidemiologic Studies2012
A meta-analysis of 9 cohort studies found highest vs lowest coffee intake was associated with 17% lower stroke risk (RR 0.83); benefit was seen at 4+ cups/day and for ischemic stroke and women.
188.SupplementDEX Database: Stroke — Coffee and acute ischemic stroke onset: the Stroke Onset Study2010
In a case-crossover study of 390 people after acute ischemic stroke, coffee in the prior hour doubled stroke risk (RR 2.0), mainly among infrequent drinkers; tea and cola showed no similar effect.
189.SupplementDEX Database: Stroke — Caffeine reduces cerebral blood flow in patients recovering from an ischaemic stroke2004
In 19 stroke patients and 10 controls, a double-blind crossover trial found 250 mg caffeine significantly reduced cerebral blood flow and middle cerebral artery velocity vs placebo after 48-hour abstinence.
190.SupplementDEX Database: Stroke — Ethanol plus caffeine (caffeinol) for treatment of ischemic stroke: preclinical experience2003
In rat models of transient MCA occlusion, low-dose ethanol plus caffeine (caffeinol) reduced infarct volume 70–80% and improved behavior; chronic pretreatment eliminated benefit and pairing with hypothermia enhanced effect.
SupplementDEX Database · Tinnitus
4 references191.SupplementDEX Database: Tinnitus — The effect of caffeine on tinnitus: Randomized triple-blind placebo-controlled clinical trial2021
An RCT of 80 chronic tinnitus patients found 300 mg caffeine did not significantly change tinnitus psychoacoustic measures or discomfort vs placebo, though mood scores shifted after caffeine.
192.SupplementDEX Database: Tinnitus — Tinnitus features according to caffeine consumption2021
A case-control study of 282 tinnitus patients and 140 controls found high caffeine intake was not linked to tinnitus features; lower-caffeine tinnitus patients reported slightly higher distress on VAS.
193.SupplementDEX Database: Tinnitus — Does Caffeine Intake Increase the Incidence of Tinnitus? A Systematic Review2020
A systematic review of 4 studies concluded evidence on caffeine and new tinnitus is inconclusive; two population studies reported inverse associations while preexisting tinnitus outcomes varied by dose.
194.SupplementDEX Database: Tinnitus — A prospective study of caffeine intake and risk of incident tinnitus2014
In 65,085 women followed 18 years, higher caffeine intake was inversely associated with incident tinnitus (HR 0.79 for ≥600 mg/day vs <150 mg/day); 5,289 new cases occurred.