Life Extension Magazine

Life Extension Magazine August 2013

Report

Rebuttal to Attack Against Carnitine

By By William Faloon, Steven V. Joyal, MD, Luke Huber, ND, MBA, Blake Gossard, and Richard A. Stein, MD, PHD

Life Extension Conducts Survey of Members Using Carnitine Supplementation

As part of a thorough evaluation of this issue, Life Extension’s Health Advisors spoke to a representative sample of 115 members who supplement with carnitine and inquired as to their experience with the compound. Not surprisingly, not one member reported having a cardiovascular event such as a heart attack or stroke after initiation of carnitine supplementation.

Summary Examination of the Media-Hyped Carnitine Article Exposes Several Problems

Despite the media attention given to the negative carnitine study published in Nature Medicine, caution must be used when applying the results to cardiovascular risk. Life Extension has carefully examined this study and identified the following factors with this study that are summarized below.

  1. Limited research on TMAO and associated effects on human health prevents causal interpretation at this time . A search of the peer-reviewed literature using terms “TMAO” and “atherosclerosis” yields only 4 results, with the first suggestion of a potential association in 2011.48 Correlation is not causation, and in fact, TMAO is found in relatively large quantities in fish, a food that is linked to a markedly reduced risk of cardiovascular events. In contrast, components of red meat such as saturated fat raise LDL cholesterol, and a search of the peer-reviewed literature using the terms “LDL,” “cholesterol,” and “atherosclerosis” returns over 10,500 results.
  2. Only 10 human subjects examined in carnitine supplementation substudy. The researchers used only 10 subjects in their small substudy of carnitine supplementation and TMAO levels.2 This is a very small data set with which to make such sweeping conclusions. Since so few humans were directly examined in this context, the validity and applicability of the scientists’ findings are questionable at best.
  3. Published, peer-reviewed research demonstrates L-carnitine prevents the progression of atherosclerotic lesions.
    Published, peer-reviewed research demonstrates L-carnitine prevents the progression of atherosclerotic lesions.  
    The recent negative study published in Nature Medicine focused upon the metabolic conversion of L-carnitine to TMAO by gut bacteria and the differences in the gut microbiome between red meat eaters and vegetarians.2 In fact, many studies show that L-carnitine has a variety of beneficial effects upon cardiovascular function, including prevention of the progression of atherosclerotic lesions. For example, one study reported that in the context of hypercholesterolemia, L-carnitine supplementation “completely prevented the progression of atherosclerotic lesions induced by hypercholesterolemia in both aorta and coronaries.”49 In another study, supplementation with propionyl-L-carnitine (PLC), a derivative of carnitine used as a drug in Europe for treatment of atherosclerosis, “induced a marked lowering of plasma triglycerides, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) triglycerides…” while plasma cholesterol was slightly and transiently reduced. In addition, PLC treatment “…exhibited a reduction of plaque thickness and extent…and a reduction of the number of both proliferating macrophage- and smooth muscle cell-derived foam cells.”41 Foam cells are precursors to atherosclerotic lesions.
  4. Published, peer-reviewed evidence shows L-carnitine effectively treats peripheral artery disease caused by atherosclerosis. Intermittent claudication (IC) is a painful, atherosclerotic syndrome that is known to be caused by peripheral artery disease.50 A 2013 systematic review of 40 articles on IC found that L-carnitine demonstrates a benefit in functional performance with carnitine supplementation. The authors suggest routine supplementation with carnitine “may therefore be a useful adjunct therapy for management of intermittent claudication.”51
  5. Heavy red meat consumption is a known, well-validated risk factor for atherosclerosis in contrast to plant-based diets. In the recent study, L-carnitine alone did not raise TMAO levels—the increases in TMAO were observed when L-carnitine was exposed to the bacterial gut microbiome of red meat eaters in comparison with vegetarians’ gut microbiome.2 Extrapolation of these preliminary test results involving the gut microbiome in heavy red meat eaters is not representative of health conscious individuals who typically limit red meat consumption given the known adverse health effects associated with a diet rich in red meat.
  6. Heart-healthy salmon is associated with high TMAO levels. Consistency of association is critical in order to draw conclusions from study data across the published literature. The fact that heart-healthy fish consumption is associated with an increase in TMAO levels is challenging to reconcile with the idea that TMAO necessarily causes atherosclerosis. For example, one research team reported that consumption of salmon, a food known for cardiovascular health benefits, led to an increase in TMAO levels in human test subjects.52 In another study, it was also observed that TMAO levels increased in individuals consuming large amounts of seafood products.53
  7. Carnitine decreases LDL and VLDL cholesterol, established risk factors for cardiovascular disease. Unlike TMAO, LDL, and VLDL cholesterol blood levels are widely recognized risk factors for cardiovascular disease. Carnitine supplementation has been shown to reduce both LDL and VLDL cholesterol levels.54
  8. The gut microbiome of red meat eaters is different from vegetarians.
    The gut microbiome of red meat eaters is different from vegetarians.  
    In this study vegans had almost no increase in TMAO levels.2 It was suggested that this was due to a different gut microbiota that develops in vegetarians compared to omnivores.
  9. Probiotic supplementation may modulate gut microbiota and suppress formation of TMAO. Not all gut bacteria strongly generate TMAO. On the contrary, certain strains of commensal bacteria have been shown to manipulate the gut microbiome in a manner favorable to human health. Specifically, members of the Lactobacilli species were inversely associated with TMAO in the human subjects examined.2 Also, Lactobacilli spp. have been shown to increase the ratio of genus Bacteroidetes to genus Firmicutes in the human intestine following oral administration; this is important because many species of the Firmicutes genus were shown to produce TMAO (though the associations were not consistent across all species of Firmicutes tested).2,55 In addition, the current study showed that antibiotics, by suppressing intestinal bacterial colonization, virtually abolished TMAO formation.2 While antibiotic prophylaxis is not an ideal method for reducing TMAO formation since it also eliminates beneficial intestinal bacteria, evidence suggests that certain members of the probiotic species Bifidobacterium and Lactobacilli may generate antibiotic-like metabolic byproducts called short-chain fatty acids that modify the intestinal microbiota in a favorable way.56

Summary

In the wake of a single negative study, deceptive media headlines have generated concern that supplemental forms of L-carnitine may be detrimental to heart health. This notion flies in the face of numerous published, peer-reviewed studies showing L-carnitine promotes cardiovascular health in a variety of ways. The media’s effort to generate outrageous headlines has undermined decades of scientific research on the heart-health benefits of carnitine.

Carnitine is a vital nutrient for health. The discovery of carnitine’s ability to maximize cellular fuel efficiency and minimize the impact of normal cellular metabolism on delicate cellular machinery has led to a revolution in the way scientists think about some of the most troubling age-related conditions. Supplementing with carnitine can help preserve cell energy levels, enhance heart muscle strength, reduce the impact of obesity and diabetes, and protect heart attack victims from dying.

If you have any questions on the scientific content of this article, please call a Life Extension® Health Advisor at 1-866-864-3027.