Caffeine and CYP1A2
How a common CYP1A2 variant relates to caffeine clearance, what the coffee and heart attack study actually found, and how strong the evidence is.
The short answer
CYP1A2 is the liver enzyme that clears most caffeine. People with two copies of the A version at rs762551 are usually classed as faster metabolizers; carriers of a C are classed as slower. In one large case-control study, coffee was linked to higher heart attack risk only in the slower group. The evidence is real but moderate, and your habits change caffeine clearance as much as your genes do.
The study everyone cites
In 2006, researchers in Costa Rica compared 2,014 people who had survived a first heart attack with matched controls. Among slower metabolizers, drinking two to three cups of coffee a day was associated with higher odds of a nonfatal heart attack (odds ratio 1.36), rising to 1.64 at four or more cups. Faster metabolizers showed no such increase. The effect was strongest in people under 59, where slow metabolizers drinking four or more cups had an odds ratio of 2.33.1
This was an observational study in one population, so it shows an association and stops short of proof. It is still one of the clearer examples of a gene changing what a food does to you.
| Your result at rs762551 | Usual label |
|---|---|
| AA | Faster caffeine metabolizer |
| AC | Slower metabolizer |
| CC | Slower metabolizer |
Things that matter as much as the gene
CYP1A2 activity responds to how you live. Smoking speeds it up; pregnancy and some oral contraceptives slow it down, and a number of medicines compete for the same enzyme. The FDA notes wide variation in how sensitive people are to caffeine and how fast they eliminate it, and cites 400 mg a day, about two to three 12-ounce cups of coffee, as an amount not generally associated with negative effects in healthy adults.2
What GenomEats suggests for slower metabolizers
- Keep coffee to one or two cups a day and drink it earlier.
- Count all sources: energy drinks, pre-workout powders, strong tea and some pain relievers.
- If caffeine gives you palpitations or wrecks your sleep, believe your body over any gene report.
Sources
- Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006;295(10):1135–1141. pubmed.ncbi.nlm.nih.gov
- US Food and Drug Administration. Spilling the beans: how much caffeine is too much? www.fda.gov
This page is educational and does not diagnose or treat any condition. Talk to a qualified clinician before making medical decisions based on a genetic result.