What is caffeine's half-life?

In a healthy adult, caffeine's half-life — the time the body needs to eliminate half the dose — averages 4 to 6 hours, with a median around 5 h. It varies a lot with genetics (CYP1A2), smoking (×0.5), pregnancy (×3), oral contraceptives (×2) and certain medications. In newborns it can reach 80 h.

Caffeine's pharmacokinetics are well characterised. Near-complete intestinal absorption within 30-45 minutes, a plasma peak around the 45-minute mark, distribution to all tissues — central nervous system and placenta included — then hepatic metabolism. The main enzyme is CYP1A2 in the liver, responsible for roughly 95 % of clearance. The metabolites paraxanthine, theobromine and theophylline are then excreted by the kidneys.

The CYP1A2 gene is highly polymorphic: a common variant (CYP1A2*1F, rs762551) splits the human population in two. Fast metabolisers (AA genotype) clear caffeine in about 4 h, enjoy the alertness boost without evening interference, and handle 4-5 cups without trouble. Slow metabolisers (AC and CC genotypes) have a half-life of 6-8 h, accumulate caffeine through the day, and often see their sleep disrupted by a coffee after 2 p.m. According to several studies (JAMA 2006, Cornelis et al.), this polymorphism also modulates the cardiovascular risk of heavy intake in slow metabolisers.

Other factors move the needle. Smoking roughly doubles clearance (cigarette smoke induces CYP1A2), so a heavy smoker metabolises caffeine in 2-3 h and often drinks more to compensate; when they quit, the half-life nearly doubles again — a frequent cause of insomnia during nicotine cessation. Pregnancy stretches the half-life to 10-15 h by the third trimester; oral contraceptives double it; certain drugs (fluvoxamine, ciprofloxacin, various SSRIs) lengthen it further. At the opposite end, newborns barely metabolise caffeine at all: a half-life up to 80 h explains the strict 200 mg/day limit during breastfeeding.

Practically, the 'five half-lives' rule gives the decay: after 5 × 5 h = 25 h only about 3 % of the dose remains. For a 130 mg espresso at 8 a.m., you still carry ~65 mg at 1 p.m., ~32 mg at 6 p.m., ~16 mg at 11 p.m. and ~8 mg at 4 a.m. — non-trivial for a slow metaboliser. That is the quantitative backbone of the 'no coffee after 2 p.m.' rule of thumb. This FAQ describes pharmacology; for personal medical questions (medication, pregnancy, liver disease), please see a healthcare professional.

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