Carnitine: Dr. Jekyl or Mr. Hyde?

Author: Dr. Stephen Chaney

It’s both interesting and confusing when one Journal article appears talking about the dangers of a particular supplement and just a couple of weeks later another article appears talking about the benefits of that same supplement – especially when the conclusions of both articles are misrepresented in the media.

But that’s exactly what has just occurred with the supplement L-carnitine. Media reports of the first article trumpeted the headline “Cleveland Clinic study links L-carnitine to increased risk of heart disease”. Media reports of the second article featured the headline “Mayo Clinic review links L-carnitine to multiple health heart benefits”. As you might suspect, neither headline was completely accurate. So let me help you sort out the confusion about L-carnitine and heart health

What is Carnitine?

But first let me give you a little bit of background about L-carnitine. L-Carnitine is an essential part of the transport system that allows fatty acids to enter the mitochondria where they can be oxidized and generate energy. So it is an essential nutrient for any cell that has mitochondria and utilizes fatty acids as an energy source.

L-carnitine is particularly important for muscle cells, and the hardest working muscle cells in our body are those that pump blood through our hearts. So when we think of L-carnitine we should think of heart health first.

But that doesn’t mean that L-carnitine is an essential nutrient. In fact, our bodies generally make all of the L-carnitine that we need. There are some metabolic diseases that can prevent us from making L-carnitine or utilizing L-carnitine efficiently. People with those diseases benefit from L-carnitine supplementation, but those diseases are exceedingly rare.

There is some evidence that supplemental L-carnitine may be of benefit in individuals suffering from congestive heart failure and other diseases characterized by weakened heart muscles. Other than that there is little evidence that supplemental L-carnitine is beneficial for healthy individuals.

Does Carnitine Increase Heart Disease Risk?

Let’s look at the first study (Koeth et al, Nature Medicine, doi:10.1038/nm.3145, April 7, 2013) – the one that purportedly linked L-carnitine to increase risk of heart disease. The authors were trying to gain a better understanding of the well-established link between red meat consumption and cardiovascular disease risk. The classical explanation of this link has been the saturated fat and cholesterol content of the red meat.

However, several recent studies have questioned whether saturated fat and cholesterol actually increase the risk of cardiovascular disease (see last week’s article “Are Saturated Fats Good For You?”)

Since red meat is also high in L-carnitine, the authors hypothesized that it might be the L-carnitine or a metabolite of the L-carnitine that was associated with increased risk of heart disease in people consuming red meat.

The authors honed in on a metabolite of L-carnitine called trimethylamine-N-oxide or TMAO that is produced by bacteria in the intestine and had been previously shown to accelerate atherosclerosis in mice. They developed what they called an L-carnitine challenge. Basically, they gave their subjects an 8 ounce sirloin steak, which contains about 180 mg of L-carnitine, and measured levels of L-carnitine and TMAO in the blood one hour later and the urine 24 hours later. [I’m guessing they didn’t have much trouble finding volunteers for that study.]

When the subjects were omnivores (meaning meat eaters) they found a significant increase in both L-carnitine and TMAO in their blood and urine following the L-carnitine challenge. When they put the same subjects on broad-spectrum antibiotics for a week to wipe out their intestinal bacteria and repeated the L-carnitine challenge, they found an increase in L-carnitine but no increase in TMAO. This simply confirmed that the intestinal bacteria were required for the conversion of L-carnitine to TMAO.

Finally, because previous studies have shown that omnivores and vegetarians have very different populations of intestinal bacteria, they repeated their L-carnitine challenge in a group of vegans and found that consumption of the same 8 ounce sirloin steak by the vegans did not result in any significant increase in TMAO in either their blood or urine.

Armed with this information, the authors measured L-carnitine and TMAO concentrations in the fasting blood of 2595 patients undergoing cardiac evaluation in the Cleveland Clinic. They used an established protocol to assess the three-year risk for major adverse cardiac events in the patients they examined. They observed a significant association between L-carnitine levels and cardiovascular event risks, but only in subjects who also had high blood levels of TMAO.

Now it’s time to compare what the headlines said to what the study actually showed. The headlines said “L-carnitine linked to increased risk of heart disease”. What the study actually showed was that there were two things that were required to increase the risk of heart disease – L-carnitine and a population of intestinal bacteria that converted the L-carnitine to TMAO.

The major source of L-carnitine in the American diet is red meat, and habitual red meat consumption is required to support a population of intestinal bacteria that is capable of converting L-carnitine to TMAO. So the headlines should have read “red meat consumption linked to increased risk of heart disease”. But, of course, that’s old news. It doesn’t sell subscriptions.

Does Carnitine Decrease Heart Disease Risk?

The second study (DiNicolantonio et al, Mayo Clinic Proceedings, dx.doi.org/10.1016/j.mayocp.2013.02.007) was a meta-analysis. It reviewed 13 clinical studies involving 3629 people who had already had heart attacks and were given L-carnitine or a placebo after the heart attack.

In evaluating the results of this study it is useful to remember that a heart attack generally kills some of the heart muscle and weakens some of the surviving heart muscle. When the data from all of the studies was combined the authors reported a 27% reduction in all cause mortality, a 65% reduction in arrhythmias, and a 40% reduction in angina. However, there was no reduction in a second heart attack or the development of heart failure.

So perhaps the headlines describing this study were a little closer to being on target, but they failed to mention that these effects were only seen in people who had already suffered a heart attack and had weakened heart muscles. They also failed to mention that there was no decreased risk of a second heart attack or congestive heart failure.

The Bottom Line:

1)     The first study should be considered preliminary. It needs to be confirmed by other studies. If it is true, it is not ground breaking. It merely gives us a fuller understanding of why red meat consumption may be linked to increased risk of heart disease and gives you yet another reason to minimize red meat consumption.

The study does raise the possibility that use of L-carnitine supplements may increase your risk of heart disease if you eat red meat on a regular basis, and that this same risk may not be associated with L-carnitine supplementation if you are a vegan. But the study did not directly test that hypothesis, and much more research is required before I would give it any weight.

2)     The second study suggests that if you have already had a heart attack, you may want to consult with your physician about whether L-carnitine supplementation might be of benefit. Once again, this study is not ground breaking. We already knew that L-carnitine supplementation was helpful for people with weakened heart muscle. This study merely confirmed that.

Contrary to what the headlines suggested, this study provides no guidance about whether L-carnitine supplementation has any heart health benefits in people without pre-existing heart disease – and the bulk of existing literature suggests that it does not.

3)     Finally, I realize that the major use of L-carnitine in the US market is in sports supplements purported to increase strength and endurance. The literature on that is decidedly mixed, but that’s another subject for another time.

These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure or prevent any disease.