Previous studies that have tied red meat consumption to increased cardiovascular risk have shown while some of the raised risk is due to the fat and cholesterol in red meat, these culprits aren't enough to explain all of it.
Researchers have pointed to other factors, such as genetic differences, a diet high in salt, which is often linked to red meat consumption, and even the way the meat is cooked.
But this latest study, led by Stanley Hazen of the Cleveland Clinic in Ohio, and published online in Nature Medicine this week, offers a new link between red meat and heart risk.
Hazen is section head of Preventive Cardiology & Rehabilitation in the Miller Family Heart and Vascular Institute at the Cleveland Clinic.
In 2011, the researchers reported a study where they linked TMAO to the promotion of atherosclerosis (where arteries get clogged up by cholesterol and other fatty compounds) in humans.
In this latest study, Hazen and colleagues discovered human gut bacteria turn L-carnitine into TMAO.
They also found that a diet high in L-carnitine encourages the growth of the bacteria that metabolize it, thereby boosting the production of even more artery-clogging TMAO.
Hazen, who is also Vice Chair of Translational Research for the Lerner Research Institute at the Cleveland Clinic, says in a statement:
"The bacteria living in our digestive tracts are dictated by our long-term dietary patterns."
"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," he adds.
The researchers also found that the gut of vegans and vegetarians is significantly less able to make TMAO from carnitine, which may explain the cardiovascular health benefits of their diets.
Study of Mice and Humans Reveal Carnitine and TMAO as CulpritsFor their research, Hazen and colleagues studied mice and humans.
In mouse experiments, they found that a diet consistently high in L-carnitine eventually changed the gut microbe balance in the mice, resulting in "markedly enhanced synthesis" of TMAO and increased atherosclerosis. But this did not happen in mice whose gut microbes were suppressed.
In a further mouse experiment, the researchers found that TMAO and L-carnitine may accelerate atherosclerosis by interfering with the body's ability to transport cholesterol out of cells.
In human subjects the researchers carried out various investigations.
For example, they looked at the clinical data of 2,595 patients who underwent heart checks and found that raised levels of L-carnitine were tied to higher risk for cardiovascular disease, heart attack, stroke and death, but only in those patients who also had higher levels of TMAO.
They also found that specific gut bacteria were linked to levels of TMAO and type of diet, and that omnivores (people whose diet includes meat) had higher levels of TMAO than did vegans and vegetarians.
Plus, they were surprised to find that even after consuming large amounts of L-carnitine, the guts of vegans and vegetarians did not produce significant amounts of TMAO. This was in sharp contrast to omnivores, who after consuming a large amount of L-carnitine did produce significant levels of TMAO in their gut.
Carnitine Not An Essential NutrientHazen says the process of converting L-carnitine into TMAO is different in different people, depending on the microbe metabolism of their gut.
"Carnitine metabolism suggests a new way to help explain why a diet rich in red meat promotes atherosclerosis," he adds, also noting that:
"Carnitine is not an essential nutrient; our body naturally produces all we need."
But he cautions that more studies need to be done before any recommendations can be made about the safety of carnitine, which while naturally occurring in red meats, such as beef, venison, lamb, mutton, pork, and duck, is also available in pill form and commonly found in energy drinks.
"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," he urges.
Grants from the National Institutes of Health helped finance the study.
In 2012, researchers from the Harvard School of Public Health reporting in Archives of Internal Medicine said people who switched even just some of their regular red meat consumption to another healthier source of protein such as fish, poultry, legumes, nuts, low fat dairy and whole grains, could reduce their risk of premature death.
Written by Catharine Paddock PhD