It has long been known that a high intake of red meat increases the risk of coronary artery disease, presumably due to its saturated fat. But a recent study by researchers from the Cleveland Clinic and other institutions made headlines when it pointed to a “previously unknown” culprit in red meat, one most people haven’t heard of—a nutrient called L-carnitine. Further raising eyebrows is the fact that L-carnitine is in many dietary supplements marketed for healthy aging, weight loss, exercise and even heart health, as well as in some energy drinks.
Carnitine and intestinal bacteria
The potential problem isn’t carnitine per se, but rather what happens to it when it interacts with bacteria in the colon (large intestine), called the colonic microflora. As we’ve been reporting, these intestinal microbes are the focus of intense scientific research for the countless ways they affect human health.
The study, published in Nature Medicine, presented an elaborate series of experiments, mostly in mice fed chow supplemented with L-carnitine but also in a small number of humans who were fed steak plus an L-carnitine supplement.
It found that intestinal microbes break down L-carnitine into a compound called trimethylamine (TMA), which is absorbed into the bloodstream and can then be converted in the liver to a substance called trimethylamine-N-oxide (TMAO). Research has linked TMAO to increased formation of arterial plaque (atherosclerosis), and the new study confirmed this in mice.
When the mice and human subjects were given antibiotics for a week—which killed off many of the intestinal microbes—and then consumed carnitine, there was almost no TMAO in blood or urine, confirming the role of the microflora. And, interestingly, when vegetarians were told to consume carnitine from meat or supplements, they produced far less TMAO than omnivores did, apparently because their microflora was different as a result of their customary diet. It’s theorized that a diet high in carnitine may alter the composition of the microflora in favor of organisms that like carnitine.
The researchers also looked at 2,600 people undergoing cardiac evaluation and found that those who had high blood levels of L-carnitine and TMAO were at increased risk for cardiovascular disease, independent of traditional cardiac risk factors such as blood pressure and cholesterol levels.
Carnitine in meat, seafood and eggs
While this study is fascinating basic research, it is still very preliminary and its practical implications are unclear. So it was surprising how much media attention it received.
We already know that it’s best to limit red meat. But how much carnitine do you need to consume before it’s a problem? The amounts used in the study, especially for the mice, were quite large. Are other sources of carnitine also a problem? What about fish? Saltwalter fish and crustaceans actually contain TMAO, so when you eat them your blood level rises. Yet fish is clearly associated with reduced coronary risk.
Then there are eggs. Egg yolk is one of the richest sources of choline, which is structurally similar to carnitine. That has always been considered a nutritional plus. But in an even more recent study, in the New England Journal of Medicine, the same research group from the Cleveland Clinic looked at 40 healthy people and found that choline from eggs and supplements also interacts with intestinal microbes to form TMAO.
Keep in mind that choline is a vitamin-like compound that plays key roles in the body. And it is found in many other healthful foods—salmon, sardines, broccoli, milk and beans—along with meat and poultry.
Carnitine: good and bad for the heart?
A week after the Cleveland Clinic study on carnitine appeared, an analysis in Mayo Clinic Proceedings looked at 13 clinical trials testing supplemental L-carnitine in people who had a prior heart attack. It concluded that the supplements reduce the risk of angina, serious arrhythmias and premature death. And it noted carnitine’s “excellent safety profile.”
It’s known that heart muscle contains high levels of carnitine, that carnitine levels are depleted during a heart attack, and that carnitine deficiency can cause heart enlargement and rhythm abnormalities. In our 2009 article on carnitine supplements, we concluded that the evidence of cardiovascular benefits is promising, though not conclusive. We saw no research indicating cardiovascular risk even from high doses.
How could carnitine be both good and bad for heart health? The proposed mechanisms (the negative one involving atherosclerosis, the positive one the heart muscle itself) are very different. Also, the studies involved different populations. Finally, the supplements may be digested and absorbed somewhat differently than carnitine in meat.
Bottom line: Coronary artery disease is multifactorial, involving many competing and/or overlapping biochemical mechanisms, plus genetic and environmental factors. The new research highlights the complex roles intestinal microbes play, but it doesn’t change the basics of a healthy diet. It shouldn’t scare you off eggs, for instance, though if it makes you eat less red meat, that’s a good thing. As for carnitine supplements, we can’t recommend them unless large, long studies establish their benefits and safety.
Published September 06, 2013