Chronic Red Meat Consumption Associated With Increased TMAO Concentrations TMAO: Associated With Increased Risk of Atherosclerosis and CVD

A recent study published in the European Heart Journal showed that chronic red meat consumption is associated with increased serum and urine concentrations of trimethylamine N-oxide (TMAO), a metabolite associated with increased risk of atherosclerosis and cardiovascular disease (CVD), when compared to white meat and non-meat sources of protein.

Different protein regimens with washout periods

This randomized-controlled crossover dietary intervention study enrolled 113 individuals into two arms (high- and low- saturated fat). Within each arm, individuals had 4 weeks of diet with protein from red meat, 4 weeks of diet with protein from white meat, and 4 weeks of diet with protein from non-meat sources, with washout periods between every 4 weeks. The meals were isocaloric with 25% calories from protein. It was found that chronic red meat consumption was associated with more than two-fold increase in the plasma and urine concentrations of TMAO. It was also found that red meat was associated with decreased fractional renal excretion of TMAO but increased fractional renal excretion of carnitine and two gut-microbiota generated metabolites of carnitine (gamma-butyrobetaine, and crotonobetaine).

TMAO has been proven to be associated with increased CVD risk in a dose-dependent manner in previous studies. Also, TMAO was found to be associated with increased platelet responsiveness, thereby promoting thrombus formation. Similarly, red meat was known to be associated with increased CVD risk. In the PREDIMED trial, the Mediterranean diet (with less content of red meat) was associated with a 30% reduction in CVD risk. Moreover, urine TMAO levels were decreased in individuals following the Mediterranean diet in a study comparing omnivores to vegetarians or vegans.

Possible explanations

The authors suggested some explanations to the increased TMAO levels with red meat such as increased dietary trimethylamine precursors, increased production of TMAO from carnitine by bacteria, and decreased fractional renal excretion of TMAO. It was also found that abstaining from consuming red meat for 4 weeks was sufficient to decrease TMAO levels to their baseline. The authors stated, “To our knowledge, the present studies are the first to directly explore the relationship of dietary protein source to plasma TMAO levels with defined isocaloric randomized diets, and the time needed to reduce TMAO levels with dietary changes.” They added, “They thus reveal that beyond quantity, the quality of diet composition (with respect to the protein source, but not saturated fat content) impacts overall TMAO metabolism and excretion.”