Caffeine and NAT2
Caffeine is the standard probe drug for NAT2 phenotyping: the ratio of its acetylated metabolites in urine reveals acetylator status. Genotype and phenotype agree in most people.
Why does NAT2 matter for Caffeine?
Caffeine is the standard probe drug for NAT2 phenotyping: the ratio of its acetylated metabolites in urine reveals acetylator status. Genotype and phenotype agree in most people. NAT2 inactivates drugs by acetylation. Its common haplotypes split people into rapid, intermediate and slow acetylators, and the split is strongly population-dependent: about half of Europeans and South Asians are slow acetylators, against roughly one in ten East Asians. Slow acetylators clear isoniazid, hydralazine, sulfasalazine, dapsone and procainamide more slowly and are more prone to their toxicities, from isoniazid liver injury to hydralazine-induced lupus.
What does CPIC recommend for each NAT2 phenotype on Caffeine?
The guidance below is the CPIC recommendation for prescribers, reproduced for reference. It is written for a clinician who knows the whole picture — never start, stop or change a medicine on the basis of this page.
| Phenotype | CPIC-based guidance |
|---|---|
| Rapid Acetylator | Normal caffeine metabolism. Less likely to experience prolonged stimulant effects. |
| Intermediate Acetylator | Moderate caffeine sensitivity. Standard intake generally well-tolerated. |
| Slow Acetylator | Slower caffeine metabolism may lead to prolonged stimulant effects, sleep disruption, and anxiety with moderate intake. Consider limiting caffeine consumption, especially in the afternoon/evening. |
Which NAT2 alleles decide the phenotype?
The phenotype is read from the two NAT2 star alleles a person carries. The full allele table, with the defining variants and their population frequencies, is on the NAT2 gene page.
NAT2 haplotypes are inferred from a panel of seven coding SNPs; consumer chips usually carry the four that define the common slow alleles (rs1801279, rs1801280, rs1799930, rs1799931). Phase — which variants sit on the same chromosome — is not observed directly, so the diplotype is a statistical inference.
Other drugs affected by NAT2
- Isoniazid — Anti-tuberculosis
- Hydralazine — Antihypertensive (vasodilator)
- Sulfasalazine — Anti-inflammatory (DMARD)
- Procainamide — Antiarrhythmic
- Dapsone — Anti-infective / Anti-inflammatory
Upload your raw DNA file and see your metaboliser status → · Ask G2: “Does my NAT2 genotype affect Caffeine?”
Genetic associations describe risk across populations, not a diagnosis for any one person. Most variants shift risk modestly and act alongside lifestyle, environment and other genes. Consumer DNA chips do not read every position and can be wrong at any single one. For general education only; talk to a clinician or genetic counsellor before acting on anything here, and never change a prescribed medicine without your prescriber.