Carnitine and Heart Disease Risk

What in the world is carnitine and why are we talking about it on PodMed this week?  I love Wikipedia's definition: "carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine."  Yikes.  So what does this have to do with real life and cardiovascular disease, as described this week in Nature Medicine?  Maybe it's very important as the smoking gun linking red meat consumption and coronary artery occlusion, as well as atherosclerosis elsewhere in the body,or at least that's the speculation.  Here's the evidence, and hang on, because it's a bit convoluted.

The researchers base the current paper on their previous work elucidating a pathway between gut flora, or the microbiota, and utilization of choline and phosphatidylcholine to an intermediate molecule known as TMA, and finally to TMAO via liver enzymes, which is proatherogenic.  They speculated that other dietary substances having the requisite chemical structure might also increase TMAO.  Lo and behold, L-carnitine does have such a structure and is also found in high concentrations in red meat as well as dietary supplements.

Rodents, human omnivores and human vegans were enrolled in the current study. Briefly, all were fed carnitine and both it and TMAO were measured in the blood.  In the human omnivore subjects, after treatment with an antibiotic it was observed that nearly complete suppression of TMAO formation following carnitine challenge occurred, indicating the role of the gut microbiota. A comparison of a long-term vegan's capacity to form TMAO secondary to carnitine challenge with that of a regular red meat eater demonstrated that the vegan essentially lacked to ability to form this compound while the omnivore made plenty.  Work in mice demonstrated that the ability to make TMAO after carnitine feeding is inducible.

In order to evaluate the role of plasma carnitine levels and cardiovascular disease, the authors examined data from almost 2600 human subjects undergoing elective cardiac evaluation.  There were statistically significant relationships between carnitine concentrations and coronary artery disease, peripheral artery disease and overall CVD.  Back to the rodents, mice fed a diet with carnitine demonstrated greater atherosclerosis than those fed a normal diet, yet when their gut flora were manipulated with antibiotics this was not seen.

Wow.  A rather bulky amount of evidence pointing to a relationship between red meat consumption, an intestinal gut flora that is selected by this diet, consequent production of TMAO and an increased risk of atherosclerosis.  As Rick points out in the podcast, more prospective work on this is clearly needed, but at least for now, could be a reason to advise people not to take carnitine supplements and to limit their red meat consumption, something we've been advocating for some time now.

Other topics this week include walking versus running for fitness in a journal we've never previously covered: Arteriosclerosis, Thrombosis and Vascular Biology, PSA screening guidelines of the American College of Physicians in Annals of Internal Medicine, and two we treated together on controlling the childhood obesity problem in Pediatrics and JAMA Pediatrics.  Until next week, y'all live well.

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Carnitine and Heart Disease Risk | jhublogs
April 15, 2013 at 2:51 pm

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Stephen Knows Cancer April 18, 2013 at 9:19 pm

Thanks for sharing the information, because up until reading this I don't think that I had ever heard of carnitine. You know with all the recent talk about these studies on red meat, it has me thinking that I should be trying to eat less. The problem is that there is not much that beats a good juicy steak for dinner....In any case, I can definitely avoid taking carnitine supplements.


Sebastian April 18, 2013 at 9:15 am

Very interesting article. Does this also apply to vegetarians? Is there a difference in carnitine levels between vegans and vegetarians?
Also, could someone perhaps explain the picture? I'm assuming it's a blood vessel with a reduced lumen. Is this correct? Could it be the aorta? Hard to tell I guess..


Elizabeth Tracey April 22, 2013 at 8:49 am

That is of course a blood vessel with partial blockage due to atherosclerosis. Per the question about vegetarians they specifically study them and find that their production of TMAO secondary to carnitine consumption doesn't happen, so clearly it's an inducible reaction.


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