April 7th, 2013
Researchers Find New Pathway Linking Heart Disease To Carnitine
Larry Husten, PHD
A new line of preliminary research has turned up a novel pathway linking atherosclerosis to red meat and a common supplement contained in energy drinks. If the research is upheld, the findings may have important implications for dietary recommendations and our understanding of atherosclerosis. The research also provides another quite surprising example of the previously unsuspected health effects of bacteria in the intestine.
Published online in Nature Medicine, the new studies suggest a possible major role in atherosclerosis for carnitine, which is commonly added to energy drinks and is found naturally in high concentrations in red meat. The new theory combines several lines of evidence from studies in both animals and humans.
Led by Stanley Hazen, researchers at the Cleveland Clinic and elsewhere found that digestive tract bacteria metabolize carnitine into trimethylamine-N-oxide (TMAO), which has previously been linked to atherosclerosis in mice, though the exact mechanism is still unknown. The researchers found that these bacteria were able to flourish and produce large amounts of TMAO, only in an environment of a carnitine-rich diet. For instance, after taking carnitine supplements or eating a steak rich in carnitine, vegetarians produced far less TMAO than omnivores.
In an additional line of evidence, based on an analysis of blood samples from a group of patients evaluated for cardiovascular risk, carnitine levels were significantly associated with the risk of cardiovascular disease, but the association was significant only in subjects who also had high TMAO levels.
Studies in mice suggest a possible direct connection between carnitine, bacteria, TMAO, and atherosclerosis. When mice were given carnitine supplements they had the expected increases in bacteria. This resulted in increased production of TMAO, and, eventually, atherosclerosis. However, the atherosclerosis was suppressed when the mice were given antibiotics to prevent bacterial growth in the gut.
“The bacteria living in our digestive tracts are dictated by our long-term dietary patterns,” said Hazen in a Cleveland Clinic press release. “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 authors noted that although the consumption of red meat has been linked to the risk of cardiovascular disease, previous targets of suspicion — dietary cholesterol and saturated fat — have not been able to fully explain the link. According to Hazen, the current research suggests a new possible candidate.
Hazen told the New York Times that although he is not a vegetarian and that he still likes red meat, he has dramatically reduced his own consumption of red meat as a result of his research.
“Carnitine is not an essential nutrient; our body naturally produces all we need,” said Hazen. “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.”
Hazen is particularly concerned about the potential effect of carnitine supplements. He told the Cleveland Plain Dealer that “the amount of carnitine in many energy drinks is equivalent to a porterhouse steak, or more. Especially if you’re talking about kids who are being targeted with all this advertising, drinking these drinks is like eating steaks every day and they’re getting it in a can and don’t even realize it.”
Interesting study – the implication is that we might screen people in the future to let them know if red meat might increase the risk of heart disease – but we would have a lot to learn before we would even consider such an approach. I wrote a piece for the public on this article – I said, in part:
“First, the study, while important and potentially groundbreaking, needs replication. In the end it is a rather small study of people – and a small number of mice – and is supportive of the theory that red meat may cause heart disease because of actions of the intestinal bacteria. Before we start measuring the gut microflora to determine if you can safely eat meat, we have a lot more work to do.”
If you are interested in reading more, it is at:
http://www.forbes.com/sites/harlankrumholz/2013/04/08/is-your-gut-bacteria-increasing-your-risk-of-heart-disease-3-things-to-know/
And for all we know, TMAO may just be a marker. What is the TMAO converted to in our bodies, and could that molecule be the actual culprit? And if suppressing gut bacteria is one answer to ASCVD prevention, what is the data on ASCVD in patients who take antibiotics daily, such as some COPD’ers,etc.?