Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide

Wang Z, Tang WH, Buffa JA, Fu X, Britt EB, Koeth RA, Levison BS, Fan Y, Wu Y, Hazen SL · European Heart Journal

Higher plasma betaine predicted major adverse cardiac events (1.4-fold, quartile 4 vs 1) but only when trimethylamine-N-oxide was also elevated, and lost significance once TMAO entered the model — the risk tracks the gut-microbial metabolite, not betaine itself.

Population

Stable patients undergoing elective diagnostic coronary angiography, 3-year follow-up

Intervention

Fasting plasma choline, betaine and trimethylamine-N-oxide measured; no supplement given

Comparator

Quartile 4 versus quartile 1

Limitations

Observational, in a referred angiography population; measures circulating concentrations rather than supplement intake; betaine's own contribution is confounded with the TMAO pathway.