A study published in the April 25 issue of the New England Journal of Medicine (NEJM) reveals a finding that certain gut bacteria turn dietary phosphatidylcholine into the artery-clogging compound trimethylamine N-oxide (TMAO).
This study — from Stanley Hazen and colleagues — follows up on work they did in 2011 study showing that TMAO was associated with cardiovascular disease. Suppression of intestinal microflora that metabolized phosphatidylcholine to yield TMAO in mice inhibited atherosclerosis, the accumulation of plaque on blood vessel walls. In the 2012 study, Hazen and colleagues had 40 healthy adults eat two hard-boiled eggs (which have high amounts of phosphatidylcholine). The level of TMAO in their blood rose. After a week of receiving antibiotics, however, and again eating two hard-boiled eggs, their TMAO levels stayed the same, showing that the bacteria killed off by the antibiotics were needed for TMAO production. The researchers also measured TMAO levels in 4,007 heart patients. After accounting for factors like age and previous cardiovascular events, they found that high TMAO levels predicted heart attack risk more accurately than triglyceride or cholesterol levels: those in the top 25 percent for TMAO levels had 2.5 times the risk of getting a heart attack or stroke than those in the lower three quartiles.
There are some caveats to the new finding. The importance of TMAO levels to predict heart disease, especially with no other risk factors, is still debatable. Gordon Tomaselli, former head of the American Heart Association, believes that only 10 percent of those whose only indicator of heart disease is TMAO are at risk of a heart event since there are many other factors, such as genetic predisposition and triglyeride levels that contribute to disease. And dietary phosphatidylcholine is present in a wide range of high-nutrient foods, and avoiding it may not be necessary or beneficial, according to the researchers of the NEJM study.
But the finding is important: it means, in theory, that tests can be developed to identify and reduce levels of gut bacteria whose metabolism leads to TMAO. If someone does not have this type of bacteria, their cardiovascular disease risk (also depending on other factors) may be low, even if they eat foods with high amounts of phosphatidylcholine. But bacteria will eventually become resistant to antibiotics, so developing new drugs that lessen or stop the ability of the bacteria to create TMAO — rather than compounds that kill off the bacteria themselves — may be the better approach here.