The gene that decides most of it
One liver enzyme, CYP1A2, metabolizes about 95% of your caffeine, and the gene that builds it comes in fast and slow versions. Roughly half of populations carry the slow variant — for them, the standard '5-hour half-life' advice systematically understates nighttime residue. The split is why two people can drink the same 4 PM coffee and one sleeps like a stone while the other stares at the ceiling.
Consumer genetics reports include this variant, but you can also infer yours behaviorally: if a single afternoon cup reliably reaches your night, assume slow. The calculator's presets let you run both scenarios and see the spread.
Smoking speeds it up; pregnancy slows it way down
Smoking induces CYP1A2, roughly doubling clearance — one reason heavy smokers can drink evening espresso with apparent impunity, and why quitting often comes with a surprise: the same coffee suddenly keeps them up, because the enzyme's induction fades within days to weeks.
Pregnancy is the mirror image. Elimination slows progressively; by the third trimester half-life can reach 15+ hours, and caffeine crosses the placenta while the fetus metabolizes it poorly. That's the reasoning behind the 200 mg/day pregnancy cap combined with a strict early cutoff.
Medications and interactions worth knowing
Estrogen-containing oral contraceptives can roughly double half-life. Certain antibiotics (notably some quinolones), the antidepressant fluvoxamine, and some heart-rhythm medications inhibit CYP1A2 as well. None of this means caffeine is forbidden — it means your effective dose is bigger than the label says, so budget accordingly: fewer total milligrams and an earlier cutoff both compensate.
The tracker's half-life setting exists for exactly this: log your real drinks, set the preset that matches your situation, and the bedtime countdown reflects your physiology rather than the population average.
Put it to work: cutoff calculator · daily tracker · 110-drink database