Editors' ChoiceCardiovascular Disease

I’ll Take a Steak, with Antibiotic on the Side…

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Science Translational Medicine  01 May 2013:
Vol. 5, Issue 183, pp. 183ec75
DOI: 10.1126/scitranslmed.3006372

Eating a diet high in red meat has been linked to an increased risk of cardiovascular disease (CVD), presumably because of an increase in cholesterol and saturated fats. A recent study suggests that the increased CVD risk may be mediated by l-carnitine, an abundant nutrient in red meat, which is metabolized by gut bacteria to trimethylamine-N-oxide (TMAO). TMAO, in turn, leads to accumulation of cholesterol in the arteries, promoting the deposition of atherosclerotic plaques that lead to heart disease.

In this study of a large cohort of patients, the authors report that l-carnitine is associated with increased cardiovascular events, but only in those subjects with high concentrations of TMAO. Vegans and vegetarians in the cohort, who had a decreased incidence of CVD, had lower concentrations of TMAO as compared with that of patients who ate red meat regularly. In a clinical study in healthy volunteers, production of TMAO from dietary l-carnitine (after eating a steak) was higher in omnivores than in vegans and vegetarians but could be completely inhibited after treatment with antibiotics. Further supporting a role of gut bacteria in TMAO production, the authors report that germ-free mice were unable to produce TMAO after eating l-carnitine. However, after microbial colonization, these mice acquired the capacity to metabolize l-carnitine to TMAO. In addition, chronic supplementation of mice with l-carnitine resulted in increased atherosclerosis in the aorta, whereas cotreatment of these mice with antibiotics completely prevented this effect.

Although the exact mechanism by which TMAO promotes atherosclerotic plaque formation is not clear, it seems to inhibit the clearance of cholesterol, leading to increased accumulation of cholesterol in the arterial walls.

Recognizing l-carnitine and the gut bacteria that metabolize it as the missing links connecting consumption of red meat with increased CVD risk has important implications for public health and may lead to new interventions to help prevent CVD. In addition, this study raises concerns about the long-term safety of l-carnitine, which is an over-the-counter dietary supplement in widespread use.

R. A. Koeth et al., Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med., published online 7 April 2013 (10.1038/nm.3145). [Abstract]

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