Caffeine
Caffeine blocks adenosine A1 and A2A receptors. Adenosine builds up during waking hours and drives sleep pressure, so caffeine masks fatigue rather than removing it. How long that lasts depends on a half-life that varies more than fourfold between people, mostly because of differences in the liver enzyme CYP1A2.
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What It Does
CYP1A2 handles about 95% of caffeine metabolism, mainly to paraxanthine. A typical half-life is 3-6 hours, but the range is wide (Nehlig 2018). Smoking induces CYP1A2 and shortens it substantially. Oral contraceptives roughly double it, late pregnancy can more than triple it, and fluvoxamine, a strong CYP1A2 inhibitor, prolongs it dramatically. Liver disease slows clearance.
For exercise, 3-6 mg/kg about 60 minutes beforehand improves performance, most consistently in endurance events and to a smaller degree in strength and power (Guest 2021). Genotype may change that. In 101 male athletes, 4 mg/kg improved 10 km cycling time by 6.8% in those homozygous for the fast-metabolizer CYP1A2 allele and worsened it by 13.7% in the small group of slow-metabolizer homozygotes (Guest 2018). In an earlier case-control study, heavy coffee drinking was associated with higher heart attack risk only in slow metabolizers (Cornelis 2006). Both are single studies; genotype testing is not yet a practical guide for most people.
Sleep effects outlast the alertness. 400 mg taken six hours before bed still measurably disrupted sleep (Drake 2013), and many people underestimate how much a mid-afternoon coffee costs them.
Tolerance develops as adenosine receptors upregulate, and much of the lift a habitual user feels from the morning coffee is reversal of overnight withdrawal. Withdrawal is well characterized: headache in about half of people, plus fatigue, low mood, and poor concentration, starting 12-24 hours after the last dose, peaking at one to two days, and lasting up to nine days. It occurs in people using as little as 100 mg a day (Juliano 2004). Tapering over a week or two avoids most of it.
Forms and Bioavailability
Absorption ratings are broad tiers. Head-to-head human trials rarely support a finer ranking among well-absorbed forms.
| Form | Active content | Absorption | Typical dose | Cost | Labels |
|---|---|---|---|---|---|
| Caffeine Anhydrousanhydrous caffeine, pure caffeine | 100% | HighEssentially complete oral absorption, peak plasma levels in 30-120 minutes. Cleared mainly by hepatic CYP1A2 with a half-life of about 5 hours that varies widely. | 100-200 mg per dose; ergogenic dosing 3-6 mg/kg | Low | 82 |
| Caffeine Citratecitrated caffeine | 50% | HighDissociates in solution to caffeine and citric acid; pharmacokinetics are those of caffeine. | Prescription neonatal dosing; 2 mg caffeine citrate equals 1 mg caffeine | Moderate | 0 |
| Dicaffeine MalateInfinergy | 74.3% | HighTwo caffeine molecules bound ionically to malic acid; dissociates to caffeine in the gut. Claims of smoother onset or fewer GI effects rest on limited, manufacturer-linked data. | 100-300 mg compound | Moderate | 0 |
Labels column: number of labels named as caffeine products that list this form. A product can list more than one form, and some labels do not state a form at all.
Caffeine anhydrous is caffeine with the water of crystallization removed; it is the same molecule as in coffee and tea. Caffeine citrate is half caffeine by weight and is mainly used in neonatal apnea; labels may list compound weight. Dicaffeine malate is about 74% caffeine and is marketed as smoother and longer lasting, a claim without human pharmacokinetic data behind it. Coffee, tea, and tablets differ in dose precision and in what comes along with the caffeine, not in how caffeine works.
Typical Dosing
Upper limit: FDA: up to 400 mg per day is not generally associated with adverse effects in healthy adults.
Performance studies use 3-6 mg/kg about 60 minutes before exercise. Sensitivity varies widely with CYP1A2 activity, pregnancy, oral contraceptives, and smoking.
Food sources: coffee, tea, cola, energy drinks, dark chocolate.
What to Look For
Find the milligrams of caffeine per serving. Pre-workout and "energy" products often stack several sources (guarana, green tea extract, yerba mate, kola nut) and some list only a proprietary blend, so the true total is unknowable. Avoid those.
FDA considers up to 400 mg a day unlikely to cause harm in healthy adults; pregnancy guidance is 200 mg. A 200 mg tablet is a predictable dose, which is the real advantage of pills over coffee, whose content varies several-fold by brew.
Never buy bulk pure caffeine powder. A teaspoon can hold about 3,200 mg, and it has killed people who misjudged a dose with a kitchen spoon. Red flags also include stacking with other stimulants such as synephrine or yohimbine.
Caffeine Anhydrous
Plain caffeine in a tablet. Precise dosing is its only advantage over coffee, and before competition that advantage is real.
What to look for: 100-200 mg tablets. Dose by body weight; 3 mg/kg is a reasonable starting point for exercise.
Find on iHerb Affiliate linkDicaffeine Malate
Sold as gentler and longer lasting. No human data back either claim.
What to look for: Caffeine content per serving, which is about three-quarters of the compound weight.
Find on iHerb Affiliate linkProducts on Titrate
2,771 of the 214,745 labels in the NIH Dietary Supplement Label Database list caffeine as an active ingredient (1,876 on market). 175 are sold as caffeine products by name.
Top on-market labels, ranked by label completeness and simplicity:
Caffeine does not have its own search category yet. Each product above links to its full label in the NIH database.
Related Tools
References
US Food and Drug Administration. Spilling the Beans: How Much Caffeine is Too Much?.
Juliano LM, Griffiths RR. A critical review of caffeine withdrawal: empirical validation of symptoms and signs, incidence, severity, and associated features. Psychopharmacology (Berl). 2004;176(1):1-29.
Cornelis MC, et al. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006;295(10):1135-1141.
Drake C, et al. Caffeine effects on sleep taken 0, 3, or 6 hours before going to bed. J Clin Sleep Med. 2013;9(11):1195-1200.
Nehlig A. Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption. Pharmacol Rev. 2018;70(2):384-411.
Guest N, et al. Caffeine, CYP1A2 Genotype, and Endurance Performance in Athletes. Med Sci Sports Exerc. 2018;50(8):1570-1578.
Guest NS, et al. International society of sports nutrition position stand: caffeine and exercise performance. J Int Soc Sports Nutr. 2021;18(1):1.
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