A new Cleveland Clinic research study has found that a compound abundant in red meat - that is also a supplement to energy drinks - promotes atherosclerosis. It also found that a diet high in carnitine promotes the growth of bacteria that metabolize carnitine, which produces artery-clogging trimethylamine-N-oxide (TMAO) - a metabolite the researchers previously linked in a 2011 study to the promotion of atherosclerosis in humans.
By examining the cardiac effects of a carnitine-enhanced diet in normal mice compared to mice with suppressed levels of gut microbes researchers also discovered that TMAO alters cholesterol metabolism at multiple levels, which explains how it enhances atherosclerosis.
Carnitine And TMAO
The research study published in Nature Medicine - also discovered that increased carnitine levels in patients predicted increased risks for cardiovascular disease and major cardiac events like heart attack, stroke and death, but only in subjects with concurrently high TMAO levels.
The study tested the carnitine and TMAO levels of omnivores, vegans and vegetarians, and examined the clinical data of 2,595 patients undergoing elective cardiac evaluations. They learned that vegans and vegetarians - even after consuming a large amount of carnitine - did not produce significant levels of the microbe product TMAO, whereas omnivores consuming the same amount of carnitine did. Baseline TMAO levels were also significantly lower among vegans and vegetarians than omnivores.
Leading the research team was Stanley Hazen, M.D., Ph.D., Vice Chair of Translational Research for the Lerner Research Institute and section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at Cleveland Clinic, and Robert Koeth, a medical student at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University.
Meat Eaters More Susceptible To Forming TMAO
"The bacteria living in our digestive tracts are dictated by our long-term dietary patterns," Hazen said. "A diet high in carnitine actually shifts our gut microbe composition to those that like carnitine, making meat eaters even more susceptible to forming TMAO and its artery-clogging effects. Meanwhile, vegans and vegetarians have a significantly reduced capacity to synthesize TMAO from carnitine, which may explain the cardiovascular health benefits of these diets."
Prior research has shown that a diet with frequent red meat consumption is associated with increased cardiovascular disease risk, but that the cholesterol and saturated fat content in red meat does not appear to be enough to explain the increased cardiovascular risks. This discrepancy has been attributed to genetic differences, a high salt diet that is often associated with red meat consumption, and even possibly the cooking process, among other explanations. But Hazen says this new research suggests a new connection between red meat and cardiovascular disease.
"This process is different in everyone, depending on the gut microbe metabolism of the individual," he says. "Carnitine metabolism suggests a new way to help explain why a diet rich in red meat promotes atherosclerosis."
While carnitine is naturally occurring in red meats - including beef, venison, lamb, mutton, duck, and pork - it's also a dietary supplement available in pill form and a common ingredient in energy drinks. With this new research in mind, Hazen cautions that more research needs to be done to examine the safety of chronic carnitine supplementation.
"Carnitine is not an essential nutrient; our body naturally produces all we need," Hazen said. "We need to examine the safety of chronically consuming carnitine supplements as we've shown that, under some conditions, it can foster the growth of bacteria that produce TMAO and potentially clog arteries."
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