A recent study investigating the link between dietary phosphatidylcholine (lecithin) and the production of trimethylamine-N-oxide (TMAO), “a proatherosclerotic metabolite,” has concluded that “the production of TMAO from dietary phosphatidylcholine is dependent on metabolism by the intestinal microbiota.” W.H. Wilson Tang, et al., “Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk,” The New England Journal of Medicine, April 2013. During the first phase of the study, researchers administered a dietary phosphatidylcholine challenge (two hard-boiled eggs and 250 mg of deuterium [d9]-labeled phosphatidylcholine) to 40 healthy adults, then analyzed participants’ plasma and urinary TMAO levels as well as their plasma choline and betaine levels. The study’s authors also performed the same analyses after six participants took a week-long course of antibiotics to suppress their gut microbiota and after the effects of the antibiotics had worn off.

According to the study, the researchers not only observed “time-dependent increases in levels of both TMAO and its d9 isotopologue, as well as other choline metabolites,” following the dietary phosphatidylcholine challenge, but found that “plasma levels of TMAO were markedly suppressed after the administration of antibiotics and then reappeared after withdrawal of antibiotics.” In addition, the second part of the study examined “the relationship between fasting levels of TMAO and incident major adverse cardiovascular events” during three years of follow-up in 4,007 adults undergoing elective coronary angiography. The results evidently revealed that, even in low-risk cohorts, “fasting plasma TMAO levels predict the risk of incident major adverse cardiovascular events independently of traditional cardiovascular risk factors and the presence or extent of coronary artery disease.”

“Our findings suggest that pathways that are dependent on the intestinal microbiota may contribute to the pathophysiology of atherosclerotic coronary artery disease and suggest potential therapeutic targets,” concluded the study’s authors. “The ability of oral broad-spectrum antibiotics to temporarily suppress the production of TMAO is a direct demonstration that intestinal microorganisms play an obligatory role in the production of TMAO from phosphatidylcholine in humans.” Additional details about a similar study on the role of intestinal bacterial in producing TMAO from carnitine appear in Issue 479 of this Update. See NEJM Editorial, April 25, 2013.