By Steve Blechman

BREAKING NEWS!

Two new studies published on Monday in the Journal of Clinical Investigation (Dec. 10, 2018) and the European Heart Journal (Dec. 10, 2018) showed that red meat and carnitine supplements may increase the risk for heart disease! The study in the European Heart Journal involved 113 healthy men and women to determine the effect of consuming red meat and white meat (such as chicken or turkey) on TMAO levels. All the subjects were on the diet for a month. After a month, TMAO levels for red meat eaters tripled compared to those consuming white meat or non-meat protein sources. Nutrition experts recommend reducing intake of red meat in the diet because it is high in saturated fat, which promotes coronary artery disease. A Cleveland Clinic study led by Stanley Hazen found that carnitine, a popular athletic supplement and component of red meat, may also trigger heart disease. Bacteria in the gut break down carnitine to trimethylamine N-oxide (TMAO), which can promote arterial disease by increasing cholesterol deposits in the arteries and inflammation. High TMAO in the blood can cause abnormal blood clots and is a good predictor of heart attack and stroke. This raises the question: does l-carnitine cause heart problems?

Thirty-five years ago, in 1983, I was the first to introduce and bring l-carnitine to America from Japan as a supplement during my 27 years as Head of Product Development at Twinlab (1974-2001.) Today l-carnitine is an extremely popular supplement. I have ceased taking L-carnitine as a dietary supplement for many years because of the lack research supporting L-carnitine for weight loss, fat loss, exercise performance and of course the concern of TMAO and its involvement in cardiovascular disease risk. L-carnitine is an important chemical found in mitochondria – the cells’ energy centers – where it helps break down long-chain fatty acids and promotes oxygen consumption. Despite its role in energy production, the question remains about l carnitine heart health and whether it truly benefits the cardiovascular system. A study published in the International Journal of Sports Nutrition and Exercise Metabolism showed that L-carnitine supplementation combined with aerobic training does not promote weight loss. A most recent study published in the Scandinavian Journal of Medicine & Science in Sports in 2018 found that increasing muscle carnitine during 24 weeks of HIIT (high-intensity interval training) did not enhance muscle metabolic adaptations or performance gains beyond those with HIIT alone. An Iranian meta-analysis (combination of many studies) showed that supplementing L-carnitine had no effect on physical performance.

In the most recent study from the Journal of Clinical Investigation, it was acknowledged that l-carnitine has been shown to accelerate atherosclerosis in mice by the formation of TMAO in the GI tract. What’s most concerning in the recent Journal of Clinical Investigation study that l-carnitine supplementation, even among vegan/vegetarians, has an effect on gut microbiota and can increase TMAO. It is clear from this study that chronic l-carnitine supplementation stimulates TMAO concentrations in humans

Research has shown that red meat has raised the risk of heart disease and colon cancer. From a recent report on NBC News in a report by Maggie Fox: “Hazen’s team showed gut bacteria convert an amino acid called carnitine into TMAO. When they gave carnitine supplements to meat eaters, their gut bacteria quickly started making TMAO. At first the bodies of vegetarians and vegans did not produce much TMAO even when they took supplements, but after a few weeks they did, Hazen’s team reported in the Journal of Clinical Investigation.”

In Medical Express December 10, 2018 they reported, “The findings suggest that measuring and targeting TMAO levels—something doctors can do with a simple blood test—may be a promising new strategy for individualizing diets and helping to prevent heart disease. The study was funded largely by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health.” It was published December 10, 2018 in the European Heart Journal.

“This study shows for the first time what a dramatic effect changing your diet has on levels of TMAO, which is increasingly linked to heart disease,” said Stanley L. Hazen, M.D., Ph.D., senior author of the study and section head of Preventive Cardiology & Rehabilitation at the Cleveland Clinic. “It suggests that you can lower your heart disease risk by lowering TMAO.”

Unfortunately, supplementation with l-carnitine has been shown to have no influence on fat loss when consumed alone. L-carnitine functions by transporting fatty acids into the mitochondrion, where they are burned for energy. Even though L-carnitine’s central role is enhancing fatty acid oxidation, L-carnitine has been shown to have no influence on fat burning or fat loss when consumed alone. In fact, a study in the American Journal of Clinical Nutrition, 2016, showed that when L-carnitine is consumed with whey protein, whey protein inhibited the uptake of L-carnitine. The combined use of whey protein to increase L-carnitine levels for fat loss is ineffective and therefore, not recommended. As recently as March 2018, it was reported in the International Journal of Sports Nutrition and Exercise Metabolism that, “it is likely that the lack of efficacy in many studies is due to its low bioavailability and failure to increase muscle L-carnitine stores.”

In conclusion, the researchers in The Journal of Clinical Investigation say that, “These studies also indicate that daily consumption of L-carnitine, even while maintaining a vegan/vegetarian diet, can induce the gut microbiota-dependent γBB→TMA transformation, resulting in heightened formation of the atherogenic and prothrombotic metabolite TMAO. This raises concerns about l carnitine and heart health, as increased TMAO levels can pose risks. Finally, our studies provide important insights for efforts aimed at development of therapeutic interventions designed to inhibit dietary L-carnitine conversion into TMAO in humans.”

References:

l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. SL.Hazen et al Published December 10, 2018 J Clin Invest 2018. https://doi.org/10.1172/JCI94601

Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women, European Heart Journal, SL Hazen et al; https://doi.org/10.1093/eurheartj/ehy799

Evidence-Based Supplements for the Enhancement of Athletic Performance. P Peeling, MJ Binnie, et al. International Journal of Sport Nutrition and Exercise Metabolism, 28; 2. 3/2018 (28) 178-187.

L-carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women. Villani RG, Gannon J, et al. Int. J Sport Nutr Exerc Metab, 2000; 10, 199-207.

Koeth RA, Wang Z, Levison BS, Hazen, SL et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013;19(5):576-85.;

Intestinal Microbial Metabolism of Phosphatidylcholine and Cardiovascular Risk. SL Hazen et al. New England Journal of Medicine, 368: 1575-1584 https://www.nejm.org/doi/full/10.1056/NEJMoa1109400

Zhu W, et al. Gut microbial metabolite TMAO enhances platelet hyperreactivity and thrombosis risk. Cell 2016;165(1):111-124.

Janeiro, M.H., Ramírez, M.J., Milagro, F.I., Martínez, J.A., & Solas, M. (2018). Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target. Nutrients 10(10), 1398. doi:10.3390/nu10101398

Study links frequent red meat consumption to high levels of chemical associated with heart disease, Medical Express, December 11, 2018, NIH/National Heart, Lung and Blood Institute https://medicalxpress.com/news/2018-12-links-frequent-red-meat-consumption.html

Protein ingestion acutely inhibits insulin-stimulated muscle carnitine uptake in healthy young men. Shannon CE, Nixon AV, et al. Am J Clin Nutr 2016.

Increasing skeletal muscle carnitine availability does not alter the adaptations to high-intensity interval training. Christopher E. Shannon, et al. Scand J Med Sci Sports 2018;28: 107-115.

Study explains how red meat raises heart disease risk. Eating meat also altered kidney function, the researchers found. Maggie Fox, NBC News, December 10, 2018 https://www.nbcnews.com/health/health-news/study-explains-how-red-meat-raises-heart-disease-risk-n946241