Gut bacteria in the colon turn choline, L-carnitine and betaine into trimethylamine, and the liver then oxidizes it to TMAO.Choline, L-carnitine, and betaine reach the colon, where specific gut bacteria metabolize them into trimethylamine (TMA). TMA enters the liver via the portal vein, where FMO (flavin-containing monooxygenase) oxidizes it to TMAO, which then enters systemic circulation. The choline path is Wang 2011; L-carnitine is Koeth 2013.
2 · Association is strong, causality not
Cohort studies link high TMAO to cardiovascular events, but no has shown that lowering TMAO reduces or death.Multiple prospective cohorts link high TMAO to cardiovascular events (Tang 2013 etc.). But association is not causation: TMAO may simply be a marker of declining kidney function or gut barrier damage, not a causal molecule. No has yet shown that lowering TMAO reduces or death.
3 · The fish paradox
Eating fish raises blood TMAO, yet fish eaters have lower cardiovascular risk, which challenges the idea that TMAO itself is atherogenic.Fish itself is rich in TMAO; eating fish raises blood TMAO, yet fish eaters have lower cardiovascular risk. This directly challenges the simple narrative that TMAO itself is atherogenic — food source and overall dietary pattern matter far more than a single molecule.
4 · What to do in practice
For healthy people 1-2 eggs a day is safe, and overall diet quality, kidney function and gut health matter more than the single molecule TMAO.For healthy people, 1-2 eggs daily is safe and nutrient-dense; those with or diabetes can limit to 3-4 yolks per week. No need to fear TMAO — dietary pattern > single food > single molecule. Focus on overall diet quality, kidney function, and gut health, not a molecule whose causal chain remains incomplete.