TMAO (Trimethylamine-N-oxide)

Trimethylamine-N-oxide (TMAO) is a small organic compound produced when gut bacteria convert dietary choline, phosphatidylcholine and L-carnitine — abundant in red meat, eggs and fish — into trimethylamine (TMA), which is then oxidised to TMAO in the liver by flavin-containing monooxygenases (mainly FMO3). Elevated circulating TMAO has been associated with increased risk of major adverse cardiovascular events, atrial fibrillation and all-cause mortality in multiple large prospective studies, and mechanistic work in mice points to inhibition of reverse cholesterol transport and promotion of foam-cell formation. However, the relationship is complicated by the fact that fish consumption, which is generally cardioprotective, also raises TMAO, and that TMAO levels vary markedly with gut microbiota composition, genetics (FMO3 polymorphisms) and renal clearance — making TMAO a biomarker of exposure and microbial metabolism rather than a straightforward causal risk factor.