Red meat and heart disease: L-carnitine linked to increased risk

08-Apr-2013 - Last updated on 09-Apr-2013 at 13:00 GMT

Meat eaters produce gut bacteria to metabolise carnitine, while vegans produce much less

High intakes of red meat repeatedly have been linked to heart disease, but new research suggests that along with saturated fat and certain preservatives, l-carnitine is another red meat constituent that may contribute to cardiovascular risk.

In a study published in Nature Medicine, researchers from Cleveland Clinic found specific bacteria in the gut that metabolise l-carnitine into trimethylamine-N-oxide (TMAO), a substance that has been linked to hardening of the arteries. In addition, they found that diets high in carnitine promoted the growth of the bacteria that metabolise it, thereby compounding the effect.

"The bacteria living in our digestive tracts are dictated by our long-term dietary patterns,” said lead researcher Dr Stanley Hazen. “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."

The association between consumption of red meat and heart disease is well-established, but the researchers said the increased risk could not entirely be accounted for by red meat’s saturated fat and cholesterol content.

They examined carnitine levels in 2,595 heart patients, and found high levels were associated with increased risk of heart disease, heart attack and stroke – but only when TMAO levels were also high. TMAO levels in vegetarian and vegan participants were significantly lower than in omnivores, and they did not produce significant levels of TMAO even after consuming a large amount of carnitine.

In omnivores, however, carnitine consumption promoted TMAO production.

The researchers suggested that better understanding of the role of gut microbiota in heart disease risk could help in the development of new ways to reduce risk.

Carnitine supplement risk?

Carnitine is also taken as a weight loss supplement and is added to some energy drinks. Hazen warned that supplement and energy drink makers may need to exercise caution with the ingredient in light of these findings.

"Carnitine is not an essential nutrient; our body naturally produces all we need," he 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."

The American Meat Institute (AMI) Foundation's chief scientist Dr Betsy Booren issued a statement in response to the study, in which she said that linking carnitine in red meat to heart disease was an oversimplification of a complex disease.

"It is important to keep in mind that there are many other studies done on L-carnitine that do not show any adverse health effects at a variety of doses," she wrote, adding that the US government's National Institute of Health has a fact sheet on L-carnitine that "shows it is safe and essential."

Source: Nature Medicine

Published online ahead of print doi:10.1038/nm.3145

“Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis”

Authors: Robert A Koeth, Zeneng Wang,, Bruce S Levison, Jennifer A Buffa, Elin Org, Brendan T Sheehy, Earl B Britt, Xiaoming Fu, Yuping Wu, Lin Li, Jonathan D Smith, Joseph A DiDonato, Jun Chen, Hongzhe Li, Gary D Wu, James D Lewis, Manya Warrier, J Mark Brown, Ronald M Krauss,W H Wilson Tang, Frederic D Bushman, Aldons J Lusis & Stanley L Hazen

2 comments

Flora?

Posted by Michael Avenoso, 12 April 2013 - 15:55 GMT

Has there been any research to isolate the specific bacteria involved in metabolizing carnitine?

If vegetarians have low TMAO levels when they do eat carnitine, suggesting they lose the bacteria over time (perhaps due to removing their food source), maybe these particular bugs are not part of the essential gut flora.

One solution could be targeting the bacteria that creates the atherogenic chemical.

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Carnitine and choline

Posted by chris aylmer, 12 April 2013 - 01:15 GMT

Average human consumption of carnitine for omnivores is in the range 60-180mg, compared with only 10-12mg for vegans(USDA). It is likely that the level of carnitine, even in a human diet high in red meat, is likely to be much lower relatively than the 1.3% by weight in the mouse chow used in the animal experiments. However, the use of supplements may give cause for concern. A popular supplement is acetyl-l-carnitine, at around 500mg per day. Therefore this and other similar carnitine supplements could indeed markedly increase overall carnitine intake and blood levels in humans. One pill could treble the high end daily intake in omnivores and increase vegan intake by 50 times.

Dr Hazen's earlier work showed similar effects on mouse atherosclerosis of high choline and phosphatidyl choline diets(also metabolized to TMAO), but again, the mice were fed on diets containing around 1.0% choline (much higher than the approx 0.05 to 0.1% likely in a balanced human diet)or they were force-fed with egg yolk, very high in phosphatidyl choline. Human diets very high in eggs, liver and other organ meats would be very high in choline and so could also be a cause for concern.
One added point: Attempting to reduce the formation of TMAO by enzyme inhibition would presumably cause build up of Trimethylamine(TMA)causing the syndrome trimethylaminuria, characterised by an unpleasant fishy odour in the breath and sweat. Knocking out gut flora would cause even worse problems. If this research is to be believed, what options are there apart from cutting down on carnitine and/or choline to prevent heart disease?