New Cardiovascular Risk Factor, Again: Gut Bugs, L-Carnitine, and TMAO

Trimethylamine-N-oxide production in the gut is associated with adverse cardiovascular events.

In May 2013, we reported the discovery of a proatherogenic molecule, trimethylamine-N-oxide (TMAO; JW Gen Med May 14 2013). People with the highest blood levels of TMAO, compared with those with the lowest levels, had 2.5-fold higher risk for cardiovascular disease. TMAO is produced when certain gut bacteria metabolize lecithin.

In a new study, researchers found that gut bacteria also produce TMAO when metabolizing L-carnitine, a compound that is abundant in red meat. Meat-eaters produced more TMAO after meals containing a measured amount of L-carnitine than vegans did; meat-eaters also harbored more of the types of bacteria that metabolize L-carnitine into TMAO. Studies in mice confirmed that diets rich in L-carnitine increased the number of gut bacteria that metabolize L-carnitine into TMAO and were associated with atherosclerosis in the mice.

Plasma L-carnitine levels in human subjects who underwent cardiac evaluation predicted adverse cardiovascular events during the months following evaluation, after adjustment for risk factors. And, as in the lecithin study, when gut bacteria in mice were eradicated by antibacterials, diets rich in L-carnitine did not lead to higher TMAO production or to atherosclerosis.

CITATION(S):

Koeth RA et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013 May; 19:576. 

Bäckhed F. Meat-metabolizing bacteria in atherosclerosis. Nat Med 2013 May; 19:533.