This page shows what was measured, who it was measured in, and what that does not settle.
What Caffeine does in the body
Taken for alertness, and before training or competition for performance
A molecule called adenosine builds up in your brain the longer you are awake, and when it docks onto its receptors you feel tired. Caffeine is shaped enough like adenosine to sit in those receptors without switching them on, so the tiredness signal cannot be delivered. Nothing has been added; a brake has been released. Because the adenosine is still piling up behind the blockade, the tiredness returns when caffeine clears — and if you have been doing this daily, the brain has grown extra receptors to compensate, which is why missing a morning coffee produces a real headache rather than an imagined one.
What happened in people
In 2,006 premature infants it reduced death or neurodevelopmental disability from 46.2% to 40.2% and cerebral palsy from 7.3% to 4.4%
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The recorded finding that sits closest to something a person would notice. Written into the record, not signed off, and it carries no population or interval.
The effect is genuine but not universal: half the cyclists in the habituation study did not improve beyond test variation
Where it acts
Central nervous system, principally striatal and cortical adenosine A1 and A2A receptors; also skeletal muscle, adipose tissue and the renal afferent arteriole
Kind of result
Living longer, or avoiding a major event
Supervision
Not usually supervised: sold as a supplement or food ingredient where recorded. That is a legal category, not a safety judgement.
What the registries record it as
The substance registry classes this as chemical.
FDA substance registry · 3G6A5W338E · read 2026-08-29
The supplement label database classes it as non-nutrient/non-botanical, under the name Caffeine.
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
A limit recorded against this substance. Not signed off as a reviewed claim.
The four opening statements run to 141 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Stand-in result
A stand-in result is a number measured because the real result takes too long.
A picture of it, and where the picture fails
It is like judging a journey by the speedometer rather than by arriving.
Where that stops being true. Speed does predict arrival. Many stand-in results do not predict the real one.
What people get wrong. A stand-in result is often reported as the result itself.
A surrogate endpoint substituted for a clinical endpoint, valid only where the substitution has been shown to hold.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
Confidence interval
A confidence interval is the range the true answer is likely to sit in.
A picture of it, and where the picture fails
It is like a weather forecast giving a range rather than one number.
Where that stops being true. A forecast range covers tomorrow. This one covers what the study could resolve.
What people get wrong. The middle number is read as the answer. A range crossing zero means no change is still possible.
An interval estimate that would contain the true parameter in a stated proportion of repeated studies.
Pathway
A pathway is a chain of steps inside a cell, each one setting off the next.
A picture of it, and where the picture fails
A pathway is like a row of dominoes.
Where that stops being true. Dominoes fall one way. Pathways loop back and can switch themselves off.
What people get wrong. Changing one step is read as changing the outcome. Other steps often absorb it.
An ordered series of molecular interactions producing a defined cellular change.
What happened in people◇Read from sources, not yet reviewed
What was measured, goal by goal
One row for each goal a registered study measured something for. One column for each kind of thing that could be measured.
Registered studies list 40 outcome measures that RNAWiki could read. A registered study says what someone planned to measure. It does not say what they found. 0 of the matched studies tested this substance, and 0 posted a result.
There is no single score. A strong test result and a weak life result are different facts.
Goals down the side, kinds of measurement across the top. Each cell says what kind of thing was registered, not what was found.
Goal
Life outcome
What a body can do
How a person feels
A test result
A step in the body
Harms
How long
Who was studied
Endurance
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
…Waiting for a reviewer1 registered performance measure of this kind.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Pain
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
…Waiting for a reviewer1 registered symptom measure.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Fertility and sexual health
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
∅Nothing in the sources checkedNo registered study lists a performance measure for this goal.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Focus
∅Nothing in the sources checkedNo registered study lists a life outcome for this goal.
…Waiting for a reviewer1 registered performance measure of this kind.
∅Nothing in the sources checkedNo registered study lists a symptom measure for this goal.
∅Nothing in the sources checkedNo registered study lists a test result for this goal.
∅Nothing in the sources checkedNo registered study lists a body-step measure for this goal.
—Not recordedHarms were not a registered measure for this goal.
—Not recordedNo finished study window is recorded.
…Waiting for a reviewerWho was studied is listed further down the page.
Which registered measures put each goal on this table
Endurance
endurance measured on an ergometer bicycle
Pain
pain as measured by visual analog scale
Fertility and sexual health
sexual arousal
Focus
cognitive performance
Sorted by fixed word lists, version v1. A name the rules do not recognise stays unsorted rather than moving to the nearest column.
What each mark on this table means
∅ Nothing in the sources checked
No registered study lists a life outcome for this goal.
… Waiting for a reviewer
1 registered performance measure of this kind.
— Not recorded
Harms were not a registered measure for this goal.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Effect of caffeine ingestion on aerobic endurance, muscle strength, muscle endurance, power, jumping and speed
✓ The study showed what it set out to show
Who was studied
Grgic 2020 umbrella review of 21 meta-analyses of caffeine and exercise
How many people
21
Study design
Umbrella review of 11 systematic reviews containing 21 meta-analyses
Compared against
Not recorded for this study
Kind of result
Measured performance
What was found
Ergogenic across all six domains; GRADE moderate for muscle endurance, muscle strength, anaerobic power and aerobic endurance
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Not all analyses gave a definite direction of effect once the 95% prediction interval was considered, and most individual studies were conducted among young men. Sample size here counts meta-analyses, not participants.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Beverage, tablet, capsule, gum, powder or energy drink; intravenous or oral caffeine citrate as a neonatal prescription drug
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Change in rating of perceived exertion and in exercise performance
✓ The study showed what it set out to show
Who was studied
Doherty 2005 meta-analysis of caffeine and rating of perceived exertion
How many people
21
Study design
Meta-analysis of 21 studies yielding 109 effect sizes
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
RPE during exercise -5.6% (95% CI -4.5 to -6.7), effect size -0.47; performance +11.2% (95% CI 4.6 to 17.8)
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. RPE at exhaustion was completely unchanged (0.01%, 95% CI -1.9 to 2.0), which means caffeine does not raise the subjective ceiling — it delays arrival at it.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Beverage, tablet, capsule, gum, powder or energy drink; intravenous or oral caffeine citrate as a neonatal prescription drug
Interval reported. 95% CI -4
Written into the record, not signed off as a reviewed claim.
40.2% caffeine versus 46.2% placebo, adjusted OR 0.77 (95% CI 0.64 to 0.93), P = 0.008; cerebral palsy 4.4% versus 7.3%, aOR 0.58, P = 0.009
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Caffeine temporarily reduced weight gain, greatest at two weeks (mean difference -23 g, P < 0.001). Rates of death, ultrasonographic brain injury and necrotising enterocolitis did not differ in the short-term analysis.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Beverage, tablet, capsule, gum, powder or energy drink; intravenous or oral caffeine citrate as a neonatal prescription drug
Interval reported. 95% CI 0
Written into the record, not signed off as a reviewed claim.
Simulated cycling time-trial completion time stratified by habitual intake
✓ The study showed what it set out to show
Who was studied
Goncalves 2017 — habitual caffeine intake and the acute ergogenic response
How many people
40
Study design
Double-blind randomised crossover, counterbalanced, with a no-supplement control arm
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Caffeine 29.92 min versus placebo 30.81 and control 31.14, P = 0.0002; habitual intake as covariate P = 0.47; between-tertile difference P = 0.75
Repeated elsewhere
Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. Twenty of 40 cyclists improved beyond the test variation, meaning half did not respond meaningfully. All participants were male endurance-trained cyclists.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Beverage, tablet, capsule, gum, powder or energy drink; intravenous or oral caffeine citrate as a neonatal prescription drug
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Self-reported and objectively monitored sleep disturbance
✓ The study showed what it set out to show
Who was studied
Drake 2013 — caffeine 400 mg at 0, 3 and 6 hours before bedtime
How many people
12
Study design
Randomised placebo-controlled crossover with objective home sleep monitoring
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
Significant sleep disturbance at all three timings versus placebo, P < 0.05
Repeated elsewhere
Partially Replicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. A small sample, but the six-hour finding is the empirical basis of the standard sleep-hygiene recommendation and had not previously been tested directly in the home environment.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Beverage, tablet, capsule, gum, powder or energy drink; intravenous or oral caffeine citrate as a neonatal prescription drug
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 5 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
■Living longer, or avoiding a major eventEvidence recorded. Death, a heart attack, a stroke, a hospital stay.1 registered measure of this kind. No reviewed result.
■What a body can do day to dayEvidence recorded. Walking, dressing, breathing, recovering.2 registered measures of this kind.
■Measured performanceEvidence recorded. How much was lifted, how far was run, how fast.2 registered measures of this kind.
■Symptoms and quality of lifeEvidence recorded. Pain, tiredness, mood, sleep, as the person rated it.2 registered measures of this kind.
■A number that stands in for healthEvidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.4 registered measures of this kind.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
■AnimalsEvidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.Stored records in Yeast, C. elegans (roundworm), Drosophila (fruit fly), Mouse, Rat. A result in animals says what to test next. It does not say what happens in people.
■Cells in a dishEvidence recorded. Cells or chemistry on a bench, far from a whole body.Stored mechanism abstracts describe steps measured in cells or tissue.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
Caffeine
What a person takes: Beverage, tablet, capsule, gum, powder or energy drink; intravenous or oral caffeine citrate as a neonatal prescription drug.
The measurement behind this step
Sold in the United States as a dietary supplement under DSHEA when in supplement form, and regulated as a food additive in beverages. Absorption is near-complete and rapid by any oral route, and caffeine gum is absorbed buccally and faster still. The problematic format is bulk anhydrous powder, where a teaspoon can contain a dose several times what a person would ever consume as coffee and domestic scales cannot weigh accurately at the required precision. Pre-workout formulas are the most adulterated supplement category, and a performance effect from one of them is not necessarily a caffeine effect.
Getting in
Absorbed almost completely, and in the brain within an hour
Caffeine is small, fat-soluble and absorbed essentially in full. It crosses into the brain freely, which is why the effect arrives fast and does not depend on any transporter.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Oral bioavailability approaches 100% with peak plasma concentration typically 30 to 60 minutes after ingestion. Caffeine crosses the blood-brain barrier by passive diffusion and is not a substrate for efflux pumps at relevant concentrations, so brain concentration tracks plasma closely — an unusual property that removes most of the pharmacokinetic uncertainty that clouds other supplements in this file.
It occupies the tiredness receptor without switching it on
Adenosine builds up while you are awake and, when it docks, tells the brain to slow down. Caffeine fits the same dock and blocks it. Nothing is added; a signal is silenced.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
Caffeine is a competitive, non-selective antagonist at adenosine A1 and A2A receptors with low-micromolar affinity, which is the range achieved by ordinary consumption. A2A antagonism in the striatum, where A2A forms heteromers with dopamine D2 receptors, accounts for most of the psychostimulant effect. Phosphodiesterase inhibition and ryanodine receptor sensitisation require concentrations far above human exposure and are not the operative mechanism.
The clearest measured consequence during exercise is not more force. It is that a given effort registers as less hard, so more work gets done before the same subjective ceiling is reached.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Doherty and Smith measured a 5.6% reduction in rating of perceived exertion during constant-load exercise with no change at all in RPE at exhaustion, and an 11.2% improvement in performance, with the RPE reduction accounting for about 29% of the performance variance. The endpoint moves because the perceptual cost of the work falls, not because the ceiling rises.
CYP1A2 clears it, at very different speeds in different people
One liver enzyme does most of the work of breaking caffeine down, and how fast it runs varies several-fold between people, which is why identical cups produce opposite experiences.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
CYP1A2 performs the initial N3-demethylation to paraxanthine, which accounts for roughly 80% of caffeine clearance. Half-life in a healthy adult is around five hours but is roughly doubled by oral contraceptives and in pregnancy, roughly halved by smoking, and modified by the rs762551 polymorphism that defines the *1A and *1F alleles. Cornelis found opposite directions of coffee-associated myocardial infarction risk in slow and rapid metabolisers, with a gene-by-coffee interaction of P = .04.
Daily use builds more receptors, and stopping exposes them
Under a permanent blockade the brain adds more adenosine receptors. When the caffeine clears, all of them receive the accumulated signal at once, which is a genuine headache rather than a psychological one.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Chronic caffeine exposure upregulates adenosine receptor density, which is the physical substrate of tolerance and of withdrawal. Juliano and Griffiths validated ten withdrawal symptoms, with headache incidence of 50%, functional impairment in 13%, onset at 12 to 24 hours, peak at 20 to 51 hours and duration of 2 to 9 days, from doses as low as 100 mg per day. Notably, Goncalves found the ergogenic response was unaffected by habitual intake — tolerance for alertness does not simply transfer to tolerance for performance.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What it would be like to take◇Read from sources, not yet reviewed
Felt, measured, or meaningful
Three different things that get called the same word. Registered studies measured all three, and mixing them is how a blood test becomes a health claim.
Felt
Things a person could notice without a test.
tinnitus handicap inventory
pain as measured by visual analog scale
Measured
Things only a test, a scale or a device shows.
endurance measured on an ergometer bicycle
dextromethorphan urinary molar
systolic and diastolic blood pressure
heart rate
plasma auc of day 1 and day 8
Meaningful
Things that change how a life goes, not only a number.
survival
cognitive performance
A registered study says what someone planned to measure. It does not say what they found. A number moving is not the same as a life going better. The two are shown apart here.
Felt, but not shown to help. A person notices a change. No study showed it leads anywhere good.
Measured, but not felt. A number moves. The person notices nothing. Both can be true.
Measured, but not shown to matter. A number moves in the good direction. Nobody showed that lives went better.
Matters, but takes years. The result that counts may take longer than anyone would keep watching.
Names that fit none of the three (31)
forearm blood flow
fat after 16 weeks treatment using a hologic qdr 4500 dexa
adverse events at end of each cohort
hematology/chemistry/urinalysis at end of each cohort
physical examination at end of each cohort
vital signs and electrocardiogram at end of each cohort
cocaine use
fat oxidation
visual analog scale subjective rating of drug effects
pk variables
pharmacokinetic parameters
methacholine pc20
sexual arousal
total beverage consumed
anti dac hyp neutralizing antibodies ecl ada assay
cmax of faldaprevir
c24hr of faldaprevir
cmax of deleobuvir
c6hr of deleobuvir
auc 0 6hr of deleobuvir
These are harms, study-process measures, or names the rules did not recognise. They are shown rather than dropped.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
Roughly most adults on earth, mostly as coffee and tea. Also athletes taking measured doses before competition, shift workers, students, and — under prescription and by a completely different route — premature infants with apnea.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What the label states about particular groups
On people who are pregnant, the label states: “In studies performed in adult animals, caffeine (as caffeine base) administered to pregnant mice as sustained release pellets at 50 mg/kg (less than the maximum recommended intravenous loading dose for infants on a mg/m 2 basis), during the period of organogenesis, caused a low incidence of cleft palate and exencephaly in the fetuses.”
US prescribing information · baf9f88a-776a-44e7-82cc-8f0ca419572f · read 2026-08-30
Where the result stopped carrying
The two-decade sports-nutrition practice of pre-competition caffeine abstinence, which a controlled crossover found unnecessary
The pre-1990s belief that phosphodiesterase inhibition was the mechanism, which requires concentrations no human reaches
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment.
On this record: The clearest measured consequence during exercise is not more force. It is that a given effort registers as less hard, so more work gets done before the same subjective ceiling is reached.
The change is too small to feel
A real change can still sit below what a person notices.
On this record: The effect is genuine but not universal: half the cyclists in the habituation study did not improve beyond test variation
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
The product may not be what it says
Contents of a sold product are not always what the label states.
On this record: This is sold as a supplement, so no agency checked what is in a given tub before it was sold.
Other reasons RNAWiki checked and found nothing for (7)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Varies by country
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Beverage, tablet, capsule, gum, powder or energy drink; intravenous or oral caffeine citrate as a neonatal prescription drug
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Not usually supervised: sold as a supplement or food ingredient where recorded. That is a legal category, not a safety judgement.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
The identity record classes it as a supplement ingredient; no medicines register records an approval.
No source is stored against this line.
What is in the pack
Sold in the United States as a dietary supplement under DSHEA when in supplement form, and regulated as a food additive in beverages. Absorption is near-complete and rapid by any oral route, and caffeine gum is absorbed buccally and faster still.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold. The rest of the recorded wording: The problematic format is bulk anhydrous powder, where a teaspoon can contain a dose several times what a person would ever consume as coffee and domestic scales cannot weigh accurately at the required precision. Pre-workout formulas are the most adulterated supplement category, and a performance effect from one of them is not necessarily a caffeine effect.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
Anxiety, tremor, palpitations, gastro-oesophageal reflux and diuresis at higher intakes. Sleep disruption is measurable from a moderate dose taken six hours before bed. Withdrawal is a validated syndrome: 50% headache incidence, 13% clinically significant impairment, onset 12 to 24 hours, duration 2 to 9 days, from habits as small as 100 mg per day. Clearance is roughly halved in smokers and roughly doubled by oral contraceptives and in pregnancy. Caffeine markedly raises exposure to and is raised by CYP1A2 interactions including fluvoxamine and ciprofloxacin. In slow CYP1A2 metabolisers a case-control study found higher myocardial infarction odds at four or more cups daily, which is observational and inconsistently replicated. Acute overdose from concentrated powder is the one genuinely lethal presentation.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
These are reports people sent to a regulator. They do not show the medicine caused the reaction.
Nobody counted how many people took the medicine and reported nothing.
The same event can be reported more than once, and many reports are incomplete.
News coverage, lawsuits and new warnings change how often people report.
A count is not a rate and not a risk.
Caffeine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1286 reaction mentions were counted. One report can name several reactions.
The recorded terms (10)
pain — 164 reaction mentions
toxicity to various agents — 158 reaction mentions
headache — 153 reaction mentions
hypotension — 151 reaction mentions
drug hypersensitivity — 138 reaction mentions
constipation — 119 reaction mentions
fall — 114 reaction mentions
cognitive disorder — 99 reaction mentions
depressed level of consciousness — 98 reaction mentions
balance disorder — 92 reaction mentions
open-targets-adr · recorded 2026-06-24 · a recorded source, not a stored snapshot
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Beverage, tablet, capsule, gum, powder or energy drink; intravenous or oral caffeine citrate as a neonatal prescription drug
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
Absorption is near-complete and rapid by any oral route, and caffeine gum is absorbed buccally and faster still.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold. The rest of the recorded wording: The problematic format is bulk anhydrous powder, where a teaspoon can contain a dose several times what a person would ever consume as coffee and domestic scales cannot weigh accurately at the required precision. Pre-workout formulas are the most adulterated supplement category, and a performance effect from one of them is not necessarily a caffeine effect.
No source is stored against this line.
What is recorded as being sold
551 products list this as an active ingredient in the United States drug directory. 95 of them contain it and nothing else.
FDA National Drug Code directory · 72090-007 · read 2026-08-29
They are sold as capsule, capsule, coated, capsule, liquid filled, chewable gel, cream and gel, taken extracorporeal, intramuscular, intravenous and oral.
FDA National Drug Code directory · 72090-007 · read 2026-08-29
The regulator's established pharmacologic class for it is central nervous system stimulant [epc], central nervous system stimulation [pe] and methylxanthine [epc].
FDA National Drug Code directory · 72090-007 · read 2026-08-29
487 published labels name it as an active ingredient. 66 of them describe this substance alone, which is where its own label text on this page comes from.
US prescribing information · 7f0f8b3c-c226-4a3a-af46-a708f345e4f5 · read 2026-08-29
Those labels are classed as human otc drug and human prescription drug.
US prescribing information · 7f0f8b3c-c226-4a3a-af46-a708f345e4f5 · read 2026-08-29
8345 marketed supplement labels list this ingredient, classed as non-nutrient/non-botanical and other combinations.
Those labels carry all other, nutrient and structure/function claims. A claim of that kind is written by the manufacturer and is not assessed by any regulator, so its presence says nothing about whether it is true.
Recorded price in US: 0.0848 USD per one unit as the pricing file counts it — a tablet, capsule, patch or single item, for the one priced product, as of 2026-08-26, paid by retail pharmacies buying the product, as surveyed by the Centers for Medicare & Medicaid Services. It is not a list price, an insurance price, or what anyone pays at a counter..
Recorded source · 2026-08-26 · read 2026-08-28
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
Watching one thing carefully can tell you whether it moved. It cannot tell you what moved it.
This is sold without a prescription, so a person can sensibly watch one thing and see whether it moves.
Pick one goal. One goal only. Two at once cannot be told apart afterwards.
Pick one thing to watch. Registered studies measured things like: endurance measured on an ergometer bicycle; dextromethorphan urinary molar; systolic and diastolic blood pressure.
Measure before you start. Take the same measurement several times first. One reading is not a starting point.
Know the swing. Write down how much it moves on its own across a normal week.
Change one thing. Change nothing else at the same time, including training and sleep.
Give it the study length. No finished study window is recorded, so no length is suggested here.
Track whether you took it. Missed days are the most common reason a home test shows nothing.
Read the trend. Look at the line across weeks. A single reading tells you almost nothing.
What not to measure
Anything that swings more day to day than the change you are looking for.
A wearable estimate of sleep stages, which is an estimate and not a measurement.
Weight on one morning, which mostly records water.
A feeling you did not write down before starting, such as: tinnitus handicap inventory.
When to stop
Stop if something new and unpleasant starts, and ask a pharmacist or doctor.
Stop if you cannot keep everything else steady, because the result will not mean anything.
Stop at the end of the window you set, and read the trend then.
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki does not work out an amount for anyone.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That the daily lift a habitual user feels is a drug effect on a neutral baseline rather than partly withdrawal reversal
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a consumer CYP1A2 genotype result can tell an individual how much coffee is cardiovascularly safe
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That the neonatal cerebral palsy result says anything about caffeine in adults, which it does not
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That an ergogenic effect measured almost entirely in young men generalises unchanged to everyone
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of Caffeine are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
Twenty-one meta-analyses, six exercise domains, all ergogenic
In plain words
Researchers reviewed every published meta-analysis of caffeine and exercise. Caffeine improved endurance, strength, muscular endurance, power, jumping and speed. This is not a marginal result.
What was measured
Pooled effect of caffeine across aerobic endurance, muscle strength, muscle endurance, power, jumping and speed
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Grgic and colleagues conducted an umbrella review across twelve databases, identifying eleven reviews containing 21 separate meta-analyses, all of moderate or high methodological quality by AMSTAR 2. Caffeine was ergogenic for aerobic endurance, muscle strength, muscle endurance, power, jumping performance and exercise speed. Using GRADE, the quality of evidence for muscle endurance, muscle strength, anaerobic power and aerobic endurance was moderate, coming from moderate-to-high quality systematic reviews; for the other outcomes the underlying evidence was low or very low. Two caveats are stated by the authors and belong here: not all analyses gave a definite direction of effect once the 95% prediction interval was considered, and most individual studies were conducted among young men. This is the strongest performance evidence base for any substance on this site, and it still carries a generalisability limit that the marketing does not mention.
Written into the record, not signed off as a reviewed claim
It makes hard work feel easier, and that explains part of why it works
In plain words
Across 21 studies caffeine made a given workload feel about six percent easier, and performance improved eleven percent. The two are linked.
What was measured
Percentage change in rating of perceived exertion during constant-load exercise and in exercise performance
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Doherty and Smith pooled 21 studies yielding 109 effect sizes for ratings of perceived exertion. Against placebo, caffeine reduced RPE during constant-load exercise by 5.6% (95% CI -4.5% to -6.7%), an effect size of -0.47 (95% CI -0.35 to -0.59). Crucially, RPE at the point of exhaustion did not differ at all (0.01% change, 95% CI -1.9 to 2.0) — people stopped at the same subjective ceiling, they just reached more work before hitting it. Exercise performance improved by 11.2% (95% CI 4.6 to 17.8%), and regression showed that the reduction in RPE during exercise accounted for approximately 29% of the variance in performance improvement. This is a rare case of a supplement having a partly identified mechanism of action at the behavioural level, not just the molecular one.
Written into the record, not signed off as a reviewed claim
CAP: 2,006 premature infants, less lung disease and less cerebral palsy
In plain words
In the largest randomised trial ever run on caffeine, very premature babies given it needed less oxygen support and, at eighteen months, were less likely to have died or developed a disability.
What was measured
Bronchopulmonary dysplasia at 36 weeks postmenstrual age, and death or neurodevelopmental disability at 18 to 21 months
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The Caffeine for Apnea of Prematurity trial randomised 2,006 infants with birth weights of 500 to 1,250 g within the first ten days of life to caffeine or placebo until therapy for apnea was no longer needed. At 36 weeks postmenstrual age, 350 of 963 caffeine infants (36%) still required supplemental oxygen against 447 of 954 placebo infants (47%), adjusted odds ratio 0.63 (95% CI 0.52 to 0.76, P < 0.001), and positive airway pressure was discontinued a week earlier. Caffeine temporarily reduced weight gain, greatest at two weeks (mean difference -23 g, 95% CI -32 to -13, P < 0.001). At 18 to 21 months corrected age, the composite of death, cerebral palsy, cognitive delay, deafness or blindness occurred in 377 of 937 caffeine infants (40.2%) against 431 of 932 (46.2%) on placebo, adjusted odds ratio 0.77 (95% CI 0.64 to 0.93, P = 0.008). Cerebral palsy fell from 7.3% to 4.4% (aOR 0.58, 95% CI 0.39 to 0.87, P = 0.009) and cognitive delay from 38.3% to 33.8% (aOR 0.81, 95% CI 0.66 to 0.99, P = 0.04). Caffeine citrate holds an FDA approval for this indication under NDA 020793.
Written into the record, not signed off as a reviewed claim
Half of habitual users get a withdrawal headache, from doses as low as 100 mg a day
In plain words
Caffeine withdrawal is a real, validated syndrome with ten confirmed symptoms. Half of people get a headache, and it can be triggered by a daily habit as small as one cup.
What was measured
Incidence, onset, peak and duration of validated caffeine withdrawal symptoms after abstinence
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Juliano and Griffiths reviewed 57 experimental and 9 survey studies. Of 49 candidate symptom categories, ten met validity criteria: headache, fatigue, decreased energy or activeness, decreased alertness, drowsiness, decreased contentedness, depressed mood, difficulty concentrating, irritability, and feeling foggy or not clearheaded. Flu-like symptoms, nausea or vomiting and muscle pain or stiffness were judged likely valid. In experimental studies the incidence of headache was 50% and of clinically significant distress or functional impairment 13%. Onset was typically 12 to 24 hours after abstinence, peak intensity at 20 to 51 hours, duration 2 to 9 days. Incidence and severity rose with daily dose, and abstinence from doses as low as 100 mg per day produced symptoms. The authors specifically reviewed and rejected expectancy as a prime determinant, and concluded that avoidance of withdrawal plays a central role in habitual consumption. The audit point is not that caffeine does not work — it plainly does — but that a habitual user's morning baseline is not a neutral one, and the daily subjective lift is partly the repair of a deficit the habit itself produced.
Written into the record, not signed off as a reviewed claim
The habituation myth: heavy coffee drinkers get the same performance benefit
In plain words
For years athletes were told to abstain from caffeine before competition so it would work better. A controlled study across low, moderate and heavy habitual users found their daily intake made no difference to the benefit.
What was measured
Simulated cycling time-trial completion time by habitual caffeine intake tertile
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Goncalves and colleagues ran a double-blind, crossover, counterbalanced study in 40 male endurance-trained cyclists, stratified into tertiles by habitual daily caffeine intake: low (58 +/- 29 mg/day), moderate (143 +/- 25) and high (351 +/- 139). Each completed three simulated cycling time trials after caffeine 6 mg/kg, placebo, or no supplement. Time-trial performance improved significantly with caffeine — 29.92 +/- 2.18 minutes against 30.81 +/- 2.67 for placebo and 31.14 +/- 2.71 for control (P = 0.0002). Analysis of covariance found no influence of habitual caffeine intake on the response (P = 0.47), performance did not differ across tertiles (P = 0.75), and there was no correlation between habitual intake and the absolute caffeine-minus-control change (P = 0.524). Individual analysis showed eight, seven and five responders in the low, moderate and high tertiles respectively, with no significant difference between them by Fisher's exact test. The withdrawal-abstinence protocols that dominated sports nutrition advice for two decades were, on this evidence, unnecessary — and worth noting for what it also shows: the tolerance that develops for alertness does not straightforwardly transfer to the ergogenic effect.
Written into the record, not signed off as a reviewed claim
CYP1A2 genotype: opposite heart-attack associations in slow and fast metabolisers
In plain words
In a large case-control study, people who break caffeine down slowly had a higher risk of heart attack with heavy coffee intake. People who break it down quickly did not.
What was measured
That a CYP1A2 genotype result can tell an individual how much coffee is safe for their heart
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Cornelis and colleagues genotyped 2,014 cases with a first acute nonfatal myocardial infarction and 2,014 matched population controls in Costa Rica between 1994 and 2004. Among carriers of the slow CYP1A2*1F allele — 55% of cases and 54% of controls — the multivariate odds ratios for nonfatal MI at less than one, one, two to three, and four or more cups of coffee daily were 1.00, 0.99 (0.69 to 1.44), 1.36 (1.01 to 1.83) and 1.64 (1.14 to 2.34). Among rapid *1A/*1A metabolisers the corresponding odds ratios were 1.00, 0.75 (0.51 to 1.12), 0.78 (0.56 to 1.09) and 0.99 (0.66 to 1.48), with a gene-by-coffee interaction of P = .04. This is the most-cited evidence that individual caffeine responses are genetically stratified, and it must be read for what it is: a single-population observational case-control study with a modest interaction p-value, not a randomised result. Subsequent attempts to replicate the CYP1A2 interaction for cardiovascular outcomes have been inconsistent, and consumer genetic tests that report a caffeine sensitivity result on this basis are extrapolating well past what one case-control study supports.
Written into the record, not signed off as a reviewed claim
Four hundred milligrams six hours before bed measurably wrecks sleep
In plain words
A controlled study gave people a moderate caffeine dose at bedtime, three hours before, and six hours before. All three disrupted sleep, including the one taken six hours ahead.
What was measured
Self-reported and objectively monitored sleep disturbance after 400 mg caffeine at 0, 3 and 6 hours before bedtime
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Drake and colleagues compared a fixed 400 mg caffeine dose administered at 0, 3 and 6 hours before habitual bedtime against placebo, with self-reported sleep and objective monitoring by a validated portable sleep monitor in the home. All three timings produced significant sleep disturbance relative to placebo (P < 0.05 for all). The authors concluded that the magnitude of reduction in total sleep time means caffeine taken six hours before bed has important disruptive effects, and that this provides the empirical basis for the standard sleep hygiene recommendation to stop caffeine at least six hours before bedtime. The result matters mechanistically and not just practically: caffeine works by blocking the adenosine signal that sleep exists to clear, so using it late costs the very recovery it is compensating for.
This order is fixed in code and does not count clicks or time on the page.
What is not here
4 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
Caffeine is the best-evidenced performance substance in this file and one of the best-evidenced in existence — ergogenic across six distinct exercise domains in 21 meta-analyses, and a licensed neonatal drug that cut death or neurodevelopmental disability from 46.2% to 40.2% — with the honest caveat that half of habitual users get a withdrawal headache on stopping, so part of the daily lift is the reversal of a deficit the habit created.
Recorded evidence blocks (16)
Q1
What did Caffeine's largest trial (80452 people) and its longest (25 years) measure?
80452 people in Caffeine's largest registered study, 25 years in its longest registered window, measuring combined rate of mortality and neurodevelopmental disability in survivors at a corrected age of 18 months. ClinicalTrials.gov · 2026-09-01
150 na, 84 phase1, 26 phase2, 24 phase3, 24 phase4, 11 early phase1, 7 na or unstated; NCT00162383; 2020-12; no ageing endpoint recorded. Last human test completed 2026, NCT07604519.
Interpretation These counts include studies where Caffeine was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
na
150
phase1
84
phase2
26
phase3
24
phase4
24
early phase1
11
2 more recorded rows
na or unstated
7
Last recorded human testNCT07604519
2026-06-30
recorded 2026-09-01 · last checked 2026-09-04
Q2
From yeast to human: where has Caffeine shown lifespan?
20 recorded entries; human; also "Caffeine 300 MG", "Caffeine (200 mg)", "C2 (200mg of caffeine; 1/2 L of water)"
Show the evidence
human
NCT00733993
Caffeine 150 MG
NCT00733993
Caffeine 300 MG
NCT00741468
Caffeine (200 mg)
NCT01435837
C2 (200mg of caffeine; 1/2 L of water)
NCT01435837
C3(200mg of caffeine; 1 L of water)
NCT01435837
C1 (200mg of caffeine, no water)
14 more recorded rows
humanNCT01875159
Caffeine citrate 6 mg/kg/day
humanNCT02056743
Caffeine 200mg
humanNCT02109783
Caffeine 2mg
humanNCT02109783
Caffeine 4 mg
humanNCT02135965
100mg of Caffeine
humanNCT02135965
200mg of Caffeine
humanNCT02135965
Albuterol 2mg & Caffeine 100mg
humanNCT02135965
Albuterol 2mg and Caffeine 200mg
humanNCT02135965
Albuterol 4mg and Caffeine 100mg
humanNCT02135965
Albuterol 4mg and Caffeine 200mg
humanNCT02438072
Caffeine (50 mg, N06BC01)
humanNCT02510911
Caffeine (100 mg)
humanNCT02577770
200mg caffeine
humanNCT02577770
400mg caffeine
recorded 2026-09-01 · last checked 2026-09-04
Q5
Did Caffeine move PhenoAge, and by how much?
PhenoAge: "Notably, these correlations were more pronounced among participants with lower caffeine intake (KDM-BA: 0.80 [0.41-1.19]; PhenoAge: 0.80 [0.30-1.30])." Europe PMC · epigenetic clock search · 2025-08-06
1 recorded sentence; 2025; biomarker
Show the evidence
PhenoAgePMID 40773913
2025; "Notably, these correlations were more pronounced among participants with lower caffeine intake (KDM-BA: 0.80 [0.41-1.19]; PhenoAge: 0.80 [0.30-1.30])."
recorded 2025-08-06 · last checked 2026-09-04
Q6
More Caffeine was worse in human: at what point?
U-shaped in human: "However, there was a U-shaped association between caffeine intake and all-cause mortality (inflection point: 277 mg)." Europe PMC · dose-response search · 2026-08-01
6 recorded sentences naming Caffeine; U-shaped, dose-response
Show the evidence
U-shaped
PMID 41505074
"However, there was a U-shaped association between caffeine intake and all-cause mortality (inflection point: 277 mg)."
PMID 39563256
"Association between dietary caffeine and muscle mass was found to be W-shaped in males and U-shaped in young females, wherein mediation effect of hs-CRP was not discovered."
dose-response
PMID 42588110
"Higher caffeine intake was associated with progressively increasing odds of short sleep duration (<6 h/day), indicating a clear dose-response relationship (<i>p</i>-overall < 0.001; <i>p</i>-nonlinear < 0.001)."
PMID 42033594
"Meta-regression of dose-response effects showed a significant association between caffeine dose and tachycardia (slope = 0.31, p < 0.001), headache (slope = 0.23, p < 0.001), abdominal discomfort (slope = 0.29, p < 0.001), vigor/activeness (slope = 0.18, p < 0.001), increased urine output (slope = 0.28, p < 0.001), and anxiety (slope = 0.37, p < 0.001)."
PMID 39740191
"Nevertheless, our findings lay the groundwork for future investigations into the dose-response relationship between caffeine intake and endometriosis."
PMID 39563256
"Restricted cubic spline analysis was conducted to investigate dose-response effect of dietary caffeine on muscle mass."
recorded 2026-08-01 · last checked 2026-09-04
Q7
Could one person measure Caffeine's effect on endurance measured on an ergometer bicycle?
Endurance measured on an ergometer bicycle: measured in Caffeine's trials.
Interpretation endurance measured on an ergometer bicycle is the recorded endpoint.
Show the evidence
biomarkers
endurance measured on an ergometer bicycle; 2026-09-01
forearm blood flow; 2026-09-01
dextromethorphan urinary molar; 2026-09-01
fat after 16 weeks treatment using a hologic qdr 4500 dexa; 2026-09-01
adverse events at end of each cohort; 2026-09-01
hematology/chemistry/urinalysis at end of each cohort; 2026-09-01
14 more recorded rows
biomarkers
physical examination at end of each cohort; 2026-09-01
biomarkers
vital signs and electrocardiogram at end of each cohort; 2026-09-01
biomarkers
survival; 2026-09-01
biomarkers
cocaine use; 2026-09-01
biomarkers
fat oxidation; 2026-09-01
biomarkers
tinnitus handicap inventory; 2026-09-01
biomarkers
visual analog scale subjective rating of drug effects; 2026-09-01
biomarkers
systolic and diastolic blood pressure; 2026-09-01
biomarkers
heart rate; 2026-09-01
biomarkers
plasma auc of day 1 and day 8; 2026-09-01
biomarkers
pain as measured by visual analog scale; 2026-09-01
biomarkers
pk variables; 2026-09-01
biomarkers
pharmacokinetic parameters; 2026-09-01
biomarkers
methacholine pc20; 2026-09-01
half life
2026-09-04; halfLife; 2026-08-01
human trials at or under30
159
smallest human trial
0; NCT00809627; NA; the smallest recorded human enrolment at or below 30; the registry states no direction of its result; WITHDRAWN
Q8
Which of adverse events at end of each cohort, anti dac hyp neutralizing antibodies ecl ada assay and auc 0 6hr of deleobuvir did Caffeine's trials measure?
adverse events at end of each cohort, anti dac hyp neutralizing antibodies ecl ada assay and auc 0 6hr of deleobuvir lead 40 outcome terms across Caffeine's trials. ClinicalTrials.gov · 2026-09-01
fat after 16 weeks treatment using a hologic qdr 4500 dexa, adverse events at end of each cohort, hematology/chemistry/urinalysis at end of each cohort, physical examination at end of each cohort, vital signs and electrocardiogram at end of each cohort and survival follow.
Show the evidence
endurance measured on an ergometer bicycle
1
forearm blood flow
1
dextromethorphan urinary molar
1
fat after 16 weeks treatment using a hologic qdr 4500 dexa
1
adverse events at end of each cohort
1
hematology/chemistry/urinalysis at end of each cohort
1
14 more recorded rows
physical examination at end of each cohort
1
vital signs and electrocardiogram at end of each cohort
1
survival
1
cocaine use
1
fat oxidation
1
tinnitus handicap inventory
1
visual analog scale subjective rating of drug effects
1
systolic and diastolic blood pressure
1
heart rate
1
plasma auc of day 1 and day 8
1
pain as measured by visual analog scale
1
pk variables
1
pharmacokinetic parameters
1
methacholine pc20
1
recorded 2026-09-01 · last checked 2026-09-04
Q9
Which of Caffeine's 38 ongoing trials reports first?
Subjective response to alcohol and other common substances utilizing mood questionnaires in adult drinkers; Blood flow change in back of eye before and after caffeine; latest 2050-12
Show the evidence
Trial
NCT00961792
"Chicago Social Drinking Project"; n 800; "Subjective response to alcohol and other common substances utilizing mood questionnaires in adult drinkers"; 2027-10
NCT03675412
"Caffeine Consumption in Glaucoma Patients and Healthy Subjects"; n 80; "Blood flow change in back of eye before and after caffeine"; 2027-06-30
NCT04570085
"Effect of CAFfeine on Cognition in Alzheimer's Disease"; n 248; "Changes in NTB scores"; 2027-12
NCT05055830
"Opportunistic PK/PD Trial in Critically Ill Children (OPTIC)"; n 2000; "Clearance (CL) or apparent oral clearance (CL/F) as measured by PK sampling"; 2028-10-30
NCT05088759
"Randomized Controlled Trial of Alert-Based Computerized Decision Support for Optimizing Low-Density Lipoprotein Management"; n 400; "frequency of prescription of appropriate LDL-lowering therapy"; 2026-06-30
NCT05325502
"Does Caffeine Facilitate Human Reward Learning Behaviors?"; n 36; "The accuracy (% of correct answers) in implicit learning through different probabilities of monetary reward feedback"; 2026-12-31
14 further recorded trials
NCT05761756
"Oxygen Toxicity: Mechanisms in Humans"; n 62; "Hypercapnic ventilatory response"; 2026-08-31
NCT06026163
"Caffeine as an Adjuvant Therapy for Late Preterm Infants With Respiratory Distress"; n 134; "Duration of respiratory support"; 2028-01-01
NCT06327152
"Caffeine Use in the Management of Preterm Infants"; n 80; "Time to full feeds"; 2026-12-31
NCT06401083
"The Effect of an Additional Pre-extubational Loading Dose of Caffeine-citrate"; n 226; "Rate of extubation failure"; 2028-12
NCT06448780
"Dose Optimization of Caffeine for HIE"; n 16; "Apparent Caffeine Clearance"; 2028-07
NCT06632990
"A Study Evaluating the Potential of BMS-984923 to Alter the Systemic Exposure of Three Orally Administered Probe Substrates"; n 36; "Area under the curve for the first and last 96 hours of dosing (AUC96h) as determined by PK modeling"; 2025-10-15
NCT06704711
"Caffeine Mouth Rinse on Salivary Immunoglobulin A, Lactoferrin and A-Amylase Levels"; n 30; "Salivary antimicrobial proteins (Salivary a-amylase, lactoferrin and Ig-A)"; 2024-12-30
NCT06763172
"Effects of Caffeine on Reinforcement Learning in Healthy Adults Using PET/MRI"; n 12; "Dopamine D2/D3 receptor availability"; 2026-12-31
NCT06855108
"Caffeine for Hypoxic Ischemic Encephalopathy"; n 830; "Composite outcome, defined by the occurrence of any of the following:"; 2030-07
NCT06935214
"The Repeatability of the Effect of Caffeine Supplementation on Submaximal Physiological Responses and Cycling Time Trial Performance"; n 12; "Blood lactate concentration"; 2025-12-31
NCT06972108
"CAffeine Use in Prolonged Oxygen Use in meConium aspIration Syndrome in Neonatal Outcomes (CAPUCINO)"; n 20; "24 hours oxygenation- 48-72 hours"; 2028-12-31
NCT06972849
"Caffeine Citrate to Improve Neonatal Outcomes."; n 3900; "Number of participants who progress by at least one level higher on the PLATIPUS Ordinal Outcome Scale"; 2050-12
NCT07022496
"Assessment of Oral Caffeine Intake in Changing the Severity of Acute Migraine Attack Using VAS Score Among Patients Attending Headache and Neurology Outpatients Clinic of Ainshams University Hospitals"; n 120; "To reduce the severity of migraine attack"; 2025-08
NCT07193264
"Impact of Chronic and Acute Caffeine Intake on the Hematopoietic System"; n 100; "Mobilization of hematopoietic stem and progenitor cells"; 2028-06
recorded 2026-09-01 · last checked 2026-09-04
Q10
Which running trial of Caffeine could settle function?
NCT07742150 measures Physical Performance Capacity (total distance in running, metres), reading out 2029-03-31.
1 open trial; n 120; "Placebo Effect in Field-Based Physical Performance"
Show the evidence
TrialNCT07742150
"Placebo Effect in Field-Based Physical Performance"; n 120; "Physical Performance Capacity (total distance in running, metres)"; 2029-03-31
Q11
Which 144 trials of Caffeine posted no result?
Posted no result
144 of 144 completed trials
Registrations
NCT00377975, NCT00205166, NCT00130026, NCT00487227, NCT00137098 and NCT00184912, and 138 more
Completion dates
oldest 2004-11; newest 2024-07-01
Show the evidence
Trial
NCT00377975
2004-11
NCT00205166
2004-12
NCT00130026
2005-10
NCT00487227
2005-11
NCT00137098
2006-01
NCT00184912
2006-01
14 further recorded trials
NCT00310323
2006-02
NCT00611416
2006-02
NCT00117520
2006-03
NCT00268554
2006-07
NCT00430170
2007-04
NCT00950898
2007-06
NCT02048215
2007-11
NCT00781586
2008-04-21
NCT01288547
2008-07
NCT00437632
2008-08-22
NCT00790114
2008-09
NCT00628316
2008-12
NCT00824057
2009-03
NCT00851175
2009-09
Q12
At the median, Caffeine's trials enrolled 30 people — anything larger?
Median enrolment
30
Largest enrolment
80452
Registered trials counted
316
Q13
What do 1286 spontaneous reports say about Caffeine — and not say?
These are reports people sent to a regulator. They do not show the medicine caused the reaction. Nobody counted how many people took the medicine and reported nothing. The same event can be reported more than once, and many reports are incomplete. News coverage, lawsuits and new warnings change how often people report. A count is not a rate and not a risk.
Caffeine appears in spontaneous reports to regulators. Across the 10 most-reported reaction terms, 1286 reaction mentions were counted: pain 164; toxicity to various agents 158; headache 153; hypotension 151. open-targets-adr · CHEMBL113 · 2026-06-24
Show the evidence
pain
164
toxicity to various agents
158
headache
153
hypotension
151
drug hypersensitivity
138
constipation
119
4 more recorded rows
fall
114
cognitive disorder
99
depressed level of consciousness
98
balance disorder
92
recorded 2026-06-24 · last checked 2026-09-04
Q14
Caffeine and CYP1A2: shared by which compounds?
CYP1A2 appear in Caffeine's recorded interaction sentences, 1 in all. openfda-label+europepmc · 2026-08-30
Interpretation pharmacokinetics
Show the evidence
CYP1A2pharmacokinetics
Metabolism Hepatic cytochrome P450 1A2 (CYP1A2) is involved in caffeine biotransformation.
recorded 2026-08-30 · last checked 2026-09-04
Q15
Was Caffeine studied with exercise?
exercise is named in Caffeine's label sentences: "Subgroup analyses demonstrated similar ergogenic effects in both trained and highly trained individuals consuming moderate caffeine doses. <b>Conclusions:</b> This is the first meta-analysis specifically focused on aerobic time-trial performance to suggest that pre-exercise ingestion of low…" openfda-label+europepmc · 2026-08-30
1 recorded statement; exercise
Show the evidence
exercise
Subgroup analyses demonstrated similar ergogenic effects in both trained and highly trained individuals consuming moderate caffeine doses. <b>Conclusions:</b> This is the first meta-analysis specifically focused on aerobic time-trial performance to suggest that pre-exercise ingestion of low caffeine doses (1.3-3 mg·kg<sup>-1</sup>) may enhance endurance performance by reducing time-trial…
recorded 2026-08-30 · last checked 2026-09-04
Q16
What is recorded about Caffeine and AMPK?
"Caffeine intake positively correlated with the percentage of circulating EPCs in SLE patients; moreover, caffeine in vitro treatment was able to improve EPC survival and vitality through the inhibition of apoptosis and the promotion of autophagy via A2AR/SIRT3/AMPK pathway." — where Caffeine and AMPK appear together. Europe PMC · pathway abstract search · 2025-09-10
"Caffeine intake positively correlated with the percentage of circulating EPCs in SLE patients; moreover, caffeine in vitro treatment was able to improve EPC survival and vitality through the inhibition of apoptosis and the promotion of autophagy via A2AR/SIRT3/AMPK pathway."
sirtuinPMID 39380132
"Caffeine intake positively correlated with the percentage of circulating EPCs in SLE patients; moreover, caffeine in vitro treatment was able to improve EPC survival and vitality through the inhibition of apoptosis and the promotion of autophagy via A2AR/SIRT3/AMPK pathway."
autophagyPMID 39380132
"Caffeine intake positively correlated with the percentage of circulating EPCs in SLE patients; moreover, caffeine in vitro treatment was able to improve EPC survival and vitality through the inhibition of apoptosis and the promotion of autophagy via A2AR/SIRT3/AMPK pathway."
mTORPMID 40584586
"We have previously suggested that caffeine modulates cell cycle progression and lifespan by inhibiting the Target of Rapamycin Complex 1 (TORC1)."
AMPKPMID 40584586
"Our findings show that caffeine accelerates mitotic division and is beneficial for CLS through AMPK."
NAD+PMID 40931339
"Wobbler mice received caffeine supplementation (60 mg/kg/day) via drinking water, and key parameters, including muscle strength, NAD metabolism, oxidative stress, and motor neuron morphology, were assessed at critical disease stages."
4 more recorded rows
IGF-1PMID 40366911
"Similarly, Epigallocatechin-3-gallate activates AKT signaling, caffeine reduces transforming growth factor-β2 (TGF-β2) and raises IGF-1, and Carthamus tinctorius enhances VEGF and KGF while suppressing TGF-β1."
mTORPMID 36988546
"Therefore, in the present study, we found that curcumin can exert a similar anti-fatigue effect to caffeine and may act by regulating energy metabolism through modulating the expression of the proteins in the PI3K/Akt/AMPK/mTOR pathway."
AMPKPMID 36988546
"Therefore, in the present study, we found that curcumin can exert a similar anti-fatigue effect to caffeine and may act by regulating energy metabolism through modulating the expression of the proteins in the PI3K/Akt/AMPK/mTOR pathway."
mTOR
"Caffeine enhanced phagocytosis rates while inhibiting fluid-phase pinocytosis in KAX3 cells, implicating mTORC2 as a target."
IGF-1
PMID 37279709
"This study aimed to determine the kinetics of IGF-1, testosterone, and cortisol concentrations during prolonged wakefulness under caffeine or placebo intake in 37 healthy participants, and to analyze whether the responses are dependent on COMT rs4680 or ADORA2A rs5751876 SNPs."
PMID 37279709
"Acute caffeine intake exerted a COMT genotype-dependent reducing effect on IGF-1 kinetic response (104 ± 26, 107 ± 27, and 106 ± 26 vs. 100 ± 25 ng/mL for A/A genotype, at 25, 35, and 37 h of wakefulness vs. 1 h; p < 0.05 condition X time X SNP), plus on resting levels after overnight recovery (102 ± 5 vs. 113 ± 6 ng/mL) (p < 0.05, condition X SNP)."
autophagy
PMID 35012409
"Caffeine decreased cell proliferation, and induced autophagy flux via inhibition of MTOR signaling in these cells."
PMID 35012409
"Genetic deletion of the key autophagy gene <i>Atg5</i>, and the <i>Sqstm1</i>/<i>p62</i> gene encoding a receptor protein, showed that the anti-proliferative effect by caffeine was dependent upon autophagy."
sirtuinPMID 38745725
"Caffeine inhibited acetylated Mapt through sirtuin 2 (SITR2), promoted Mapt nuclear translocation, and improved mitochondrial dysfunction, which was subsequently weakened by the SIRT2 inhibitor, AK-7."
NAD+PMID 35730144
"We assessed whether NR with or without caffeine, which increases nicotinamide mononucleotide transferase subtype 2 (NMNAT2), an essential enzyme in NAD production, modulates bioenergetic functions in LOAD."
sirtuinPMID 30555576
"Using a combination of RNAi and chemical treatment, we demonstrate that caffeine activates autophagy through a series of sequential events, starting from the inhibition of its primary cellular target adenosine A2a receptor (A2AR) to an increase in the protein level of Sirtuin 3 (SIRT3) and to the activation of 5' adenosine monophosphate-activated protein kinase (AMPK)."
recorded 2025-09-10 · last checked 2026-09-04
Where it is registeredIdentifiers, relations and other names
Caffeine component of anoquan, Caffeine component of cafergot, Caffeine component of darvon compound, Caffeine component of dhc plus, Caffeine component of esgic, Caffeine component of excedrin, Caffeine component of femcet, Caffeine component of fioricet, Caffeine component of fiorinal, Caffeine component of invagesic, Caffeine component of invagesic forte, Caffeine component of lanorinal
ChEMBL ATC CC BY-SA · ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · Open Targets 26.06 — CC0 · derived from this page's own recorded fields; no external licence · mixed register set; per-register licences in docs/specs/corpus-20k-sources.md · openFDA / DailyMed — US Government work
✗ required summary fields resolved: 5 required field(s) not terminal: Why people use it, Best-supported result, Most important common problem, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 12 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
✓ no raw internal fields: enforced by the copy-contract test over the rendered page
This is a record of evidence. It is not medical advice, and it does not say this substance suits you. Nothing here says any substance on RNAWiki is appropriate for a child.