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; adjusted hazard ratio 1.33, 95% CI 1.03-1.73) 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. The same paper fed labelled betaine to mice and showed that swallowed betaine does reach TMAO by way of gut flora, though as a 100-fold poorer precursor than choline, and not at all once the flora were suppressed.

Population

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

Intervention

Fasting plasma choline, betaine and trimethylamine-N-oxide measured; nothing given to the patients. A separate mouse experiment in the same paper gave labelled betaine by gavage

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.