TMAO and Vegetarian Diets: Seeds of Discontent Over Recent Headlines

Give a man a fish and he will tweet over and over that it raises trimethylamine-N-oxide (TMAO). Indeed, studies indicate that eating some species of fish may acutely raise TMAO levels. As studies exist relating dietary patterns of fish consumption and favorable cardiovascular outcomes, the hundreds of studies indicating that elevated TMAO levels relate to poor health outcomes are swept aside. Fishy business indeed that conflicts with data since 2011 when researchers from the Cleveland Clinic demonstrated that meat eaters had high levels of TMAO. In those investigations, TMAO was not elevated in vegans who were asked to eat a meat meal for the purposes of the study.

The clinical importance of the rise in TMAO after the consumption of some species of fish requires further study and at least one animal model indicates potential harm. The oddest twist in our understanding of the potential role of TMAO in human health is the possibility that consuming vegetables may raise TMAO. Where did this notion come from? Indeed, an earlier study indicated that higher adherence to a diet high in fruits and vegetables and lower in meat (Mediterranean diet) was associated with lower levels of TMAO.

I am unaware of any discussion of the possibility that vegetable diets raise TMAO until the publication on November 6, 2018 of an online summary of a basic science study. The headline read: “Eat your vegetables (and fish): Another reason why they may promote heart health. Fish and gut bacteria-produced compound both protect hypertensive rats from heart disease”. In this summary, linked to the original research paper from Warsaw, Poland, it was reported “Elevated levels of trimethylamine N-oxide (TMAO) — a compound linked with the consumption of fish, seafood and a primarily vegetarian diet — may reduce hypertension-related heart disease symptoms”. Suddenly other online sites were posting similar headlines. What does the actual research study linked to Science Daily indicate? The attack on vegetables appears to relate to the following introductory passage “On the other hand, several-fold higher TMAO plasma levels were observed in humans after ingestion of fish and vegetarian diet than after ingestion of red meat and eggs (4). Therefore, it seems that fish-rich and vegetarian diet, which is beneficial or at least neutral for cardiovascular risk, is associated with a significantly higher plasma TMAO than red-meat and eggs-rich diets which are considered to increase the cardiovascular risk.” Indeed, the actual research study from Warsaw, Poland was an evaluation of rats fed water with or without TMAO. A diet containing vegetables was not studied.

Tracking down reference 4 listed above in the paper from Poland, the apparent smoking gun for inciting headlines linking vegetables to levels of TMAO, was the next order of business. This search identified a small study of subjects in the EPIC study. They were used to test a hypothesis whether biomarker, like TMAO and others, could be used in epidemiology studies, as correlates of meat and fish intake. One biomarker for chicken, four for meat, and two for dietary fish consumption (including TMAO) were identified as having a potential role in future population studies of diet. Indeed, the study did not test if vegetable intake or vegetarian diets were related to blood levels of TMAO. Am I missing something or is this a shocking abuse of headlines?

In a scientific study of dietary sources of TMAO in man, glaringly missing from the recent round of research and media headlines, fruits, vegetables and cereals had no measurable effects on levels measured. The potential role of TMAO as a marker or even a causative factor in atherosclerotic arterial disease has been appreciated for less than a decade and much more needs to be learned. For now, we can rest easy that fruits and vegetables, and vegetarian diets, are not raising TMAO levels. Incorrect headlines should not be used by those eating meat and egg yolks to ignore the concern that the production of TMAO from dietary factors does relate to the risk vascular disease.