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Research Newsletter-Spring/Summer 2013

Does Carnitine Cause Heart Disease?

Balz Frei, Ph.D.

You may have heard or read about carnitine—found in red meat or taken as a supplement—as a possible risk factor for heart disease. Many of you may be taking dietary supplements containing carnitine, often in combination with lipoic acid. This combination, as well as carnitine taken alone, is believed to increase fat burning and improve energy metabolism, especially in older adults.

According to the new study, a metabolite of carnitine called trimethylamine oxide (TMAO) is formed by gut bacteria (intestinal microbiota) and absorbed into the body. High plasma levels of carnitine in humans were found to be associated with an increased risk of cardiovascular disease, including heart attack and stroke. Furthermore, in mice TMAO enhanced cholesterol absorption and altered cholesterol metabolism in the liver and in monocyte-macrophages (inflammatory white blood cells), thereby promoting atherosclerosis (the underlying cause of cardiovascular disease).

My immediate reaction to the study is that it is intriguing and novel but far from definitive. I certainly wouldn’t draw any conclusions at this point with respect to heart disease risk in humans. The possible culprit, TMAO, comes also from many other sources besides carnitine, such as choline, choline phospholipids, acetyl choline, and even fish, which we know lowers cardio-vascular risk. In fact, a 1999 study found that eating 8 oz. of marine fish, such as cod, haddock, halibut, or herring, elevated urinary levels of TMAO and its precursor, trimethylamine, by about 35 times, whereas 8 oz. of beef, pork, or other meats did not. Moreover, while carnitine levels were associated with an increased risk of cardiovascular disease in the study, TMAO itself was not. Only after some statistical manipulations did the authors find an association between increased heart disease risk and increased levels of carnitine and TMAO combined.

It is possible that carnitine and TMAO levels in humans are only markers of meat intake rather than causative agents in heart disease. Just because carnitine levels are associated with increased heart disease risk in humans does not mean carnitine (or TMAO) causes heart disease; correlation is not necessarily causation. Much more work needs to be done to establish causality in humans. To call carnitine a culprit in heart disease (as the press labeled it) is premature. The main culprit in red meat is saturated fat, and I don’t think carnitine or TMAO will get even close to saturated fat in terms of causing atherosclerosis and increasing cardiovascular risk in humans. Relative risk is important, and we know the major coronary risk factors in humans.

There is a large body of work accumulated over decades showing that acetyl-L-carnitine and lipoic acid are safe to use at appropriate doses. Acetyl-L-carnitine alone has been given clinically at very high doses (as much as 8 grams per day) with no observed side effects, including those suggested by this study. We know from rodent studies that acetyl-L-carnitine improves mito-chondrial function, lowers lipid levels (which would lower cardiovascular risk), and improves muscle function and cognition. Carnitine has health benefits, and its “benefit-to-risk” ratio needs to be taken into account. This new study is the only one suggesting that carnitine is associated with atherosclerosis. I believe that, on balance, current evidence favors the use of carnitine supplements. However, we must prudently and continually reassess our recommendations based on new scientific information.

For now, I continue to take my combined lipoic acid and carnitine supplement and will also continue to monitor my heart disease risk—which is very low due to a highly favorable lipid profile (low total and LDL cholesterol, high HDL cholesterol, low triglycerides), normal blood pressure, normal blood glucose, healthy body weight and waist circumference, and low inflammation (plasma CRP levels). In addition, I exercise regularly and avoid red meat.

Last updated May 2013