An US randomized crossover study showed that chronic dietary red meat increases systemic trimethylamine N-oxide (TMAO) levels through enhanced dietary precursors, increased microbial trimethylamine (TMA)/TMAO production from carnitine, but not choline, and reduced renal TMAO excretion. Discontinuation of dietary red meat reduces plasma TMAO within 4 weeks. There were 113 healthy volunteers enrolled in the randomized 2-arm (high- or low-saturated fat) crossover design study. Within each arm, three 4-week isocaloric diets (with washout period between each) were evaluated (all meals prepared in metabolic kitchen with 25% calories from protein). Chronic red meat, but not white meat or non-meat ingestion, increased plasma and urine TMAO (each >two-fold; P < 0.0001). Red meat ingestion also significantly reduced fractional renal excretion of TMAO (P < 0.05), but conversely, increased fractional renal excretion of carnitine, and two alternative gut microbiota-generated metabolites of carnitine. Oral isotope challenge revealed red meat or white meat (vs. non-meat) increased TMA and TMAO production from carnitine (P < 0.05 each) but not choline. Dietary-saturated fat had no effect on TMAO or its metabolites. The findings have potential clinical relevance and suggest that a diet rich in red meat may increase mortality and cardiovascular diseases (CVD) given the growing body of evidence suggesting a mechanistic link between elevated circulating TMAO levels and both CVD and mortality risks. Source: https://academic.oup.com/eurheartj/
