The Carnitine Dilemma

The role of nutritional supplements in sports performance and health is in constant flux, and the story of L-carnitine is a prime example. L-carnitine was discovered as an extract from meat by a Latvian biochemist in the early 1900s.¹ The biochemical role of L-carnitine in long-chain fatty acid oxidation was described in the late 1950s.¹ Supplementation to improve fat burning soon followed. However, only in recent times have we truly begun to realize its role in our health and metabolism.

L-carnitine helps shuttle long-chain fatty acids into cellular mitochondria such that they can be burned to produce ATP. It basically acts as a “furnace tender,” shoveling the coal in and taking the soot out. It is important to realize that the soot removal is also critical to proper functioning of the mitochondrial “furnace.” The “soot” is acetyl-coenzyme A (CoA). When acetyl-CoA builds up, it shuts down the metabolism of glucose. L-carnitine removes the acetyl group from acetyl-CoA. By renewing coenzyme A availability, carnitine helps glucose metabolism drive forward during intense exercise.

Improved Recovery From Exercise

L-carnitine has been shown to improve recovery from exercise.² It is thought that since L-carnitine controls entry of fats into the mitochondria, that supplementation could help burn fat more efficiently. Unfortunately, this hasn’t been unanimously supported by the scientific literature. L-carnitine’s ability to improve glucose control and heart function has been investigated extensively. By acting in its role of “soot” removal, L-carnitine supplementation has demonstrated improvements in glucose metabolism and insulin sensitivity.³ This could potentially reduce the risk of complications from diabetes and the metabolic syndrome.

Furthermore, since heart muscle utilizes fats for energy, L-carnitine supplementation has been studied to protect the heart from acute heart attacks and its late complications. The results from these studies are both beneficial and detrimental, as the picture is more complex than just adding the benefits of L-carnitine to the system. Our bodies have the ability to metabolize and convert the ingredients of foods and supplements into other biologically active compounds. Buildup of compounds like long-chain fatty acid acylcarnitines can result metabolic dysfunction, insulin resistance and pro-inflammatory effects.¹

Our Complex Metabolism

As you can tell from the multitude of supplements on the market, our physiology and metabolism are extremely complex. The interplay between the foods we eat, the hormones we produce and the enzymes in our mitochondria that burn fat is further complicated by the symbiotic relationship that we have with bacteria in our bodies. Our gastrointestinal (GI) tracts are teaming with so many species of bacteria that have unique metabolic processes, that bacteriologists are ostensibly overwhelmed. When some bacteria are exposed to the foods we eat, they also “eat” some of those foods. When bacteria eat, they “poop” too. In other words, they produce metabolites that end up back in our GI tracts. Those metabolites can then be absorbed and enter our circulation.

Our understanding of all of these bacterial metabolites and their effects on our health is infantile. We know that some short-chain fatty acids produced by bacteria from soluble fiber can be beneficial to our bodies. On the other hand, metabolites like trimethylamines (TMAs) may be detrimental when processed by our livers to artery-hardening trimethylamine oxides (TMAO). This is where the L-carnitine dilemma comes into play.

Red Meat and Gut Bacteria

As scientists have largely disproven the role of saturated fats and cholesterol in the formation of heart disease, they have looked to see if other components of meat contribute to atherosclerosis (hardening of the arteries). Everything from salt content, heterocyclic amines from cooking meat, carnitine and phosphatidylcholine have been studied to find a link between these meat-specific compounds and heart disease.

Recent studies suggest a complex link between eating meat, its L-carnitine and choline content, carnivore-specific gut bacteria and atherosclerotic heart disease. The research demonstrates that gut bacteria specifically found in those who eat meat can convert L-carnitine and choline into TMA.^4,5 Your body absorbs the TMA and converts it to TMAO in your liver. TMAO then enters circulation and impairs your body’s ability to remove cholesterol from your artery walls. This leads to inflammatory plaques that cause arterial wall damage and eventual narrowing of the arteries. Furthermore, TMAO appears to worsen insulin sensitivity.

Improving Carnitine Function

With so many bacterial species in our guts, it is hard to imagine that we should be killing them all with antibiotics to rid ourselves of the TMA-producing species. Another option would be to support the healthy species like Lactobacillus paracasei with probiotic supplements.⁶ Further, we should focus on improving bacterial health with “prebiotics.” Prebiotics are foods rich in soluble fibers and glutamine that fuel healthy bacterial growth in the colon. High-fiber diets keep you regular AND prevent heart disease.

Is it possible to improve carnitine function without having to consume L-carnitine and expose it to GI production of TMAO? Indeed, recent research suggests that we can through supplementation with betaine.⁷ Betaine acts as a methyl-group donor and can improve body composition. In human studies, low betaine levels have been correlated with the metabolic syndrome and lipid disorders. Through a series of enzymatic steps, betaine can donate its methyl group to produce trimethyl-lysine, a precursor to production of L-carnitine. Supplementation with betaine can increase muscle L-carnitine levels by 1.4-fold.⁷

As far as we know, betaine isn’t converted by our bacteria into any bad metabolites. The moral of this story is that our knowledge of how supplements affect our health and metabolism is constantly in flux and getting increasingly more complex. This only reinforces your need to keep reading Muscular Development for further updates on your treasured supplements in Supplement Performance!

[Here’s some fun with biochemistry and linguistics. Betaine supplementation improves metabolism by enhancing carnitine function in muscle. Beta-alanine supplementation improves production of carnosine in muscle. Confused yet?]

Dr. Victor Prisk is a board certified orthopaedic surgeon and IFBB professional bodybuilder in Pittsburgh, PA. Dr. Prisk is an active member of the GNC Medical Advisory Board and creator of the “G.A.I.N. Plan.” He is an NCAA All-American gymnast, champion swing dancer and NPC Welterweight National Champion.

References:

1. Dambrova M, Liepinsh E. Risks and Benefits of Carnitine Supplementation in Diabetes. Exp Clin Endocrinol Diabetes 2014;Oct 24. [Epub, ahead of print]

2. Huang A, Owen K. Role of supplementary L-carnitine in exercise and exercise recovery. Med Sport Sci 2012;59: 135-142.

3. Vidal-Casariego A, et al. Metabolic effects of L-carnitine on type 2 diabetes mellitus: systematic review and meta-analysis. Exp Clin Endocrinol Diabetes 2013;Apr;121(4):234-8.

4. Koeth RA, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013; May;19(5):576-85.

5. Wang Z, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011;Apr 7;472(7341):57-63.

6. Martin FP, et al. Probiotic modulation of symbiotic gut microbial-host metabolic interactions in a humanized microbiome mouse model. Mol Syst Biol 2008;4:157.

7. Pekkinen J, et al. Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach. Mol Nutr Food Res 2013;Nov;57(11):1959-68.

Whey Protein and Carnitine Don’t Mix

By Michael J. Rudolph, Ph.D.

Carnitine functions by shuttling fatty acids into the mitochondrion, where they are burned for energy. Despite the central role that carnitine has in fatty acid oxidation, supplementation with carnitine has been shown to have no influence on fat burning or fat loss, when consumed alone.¹ Conversely, a more recent investigation by Wall et al.² demonstrated a way to increase muscle carnitine levels, which actually increased fatty acid oxidation and fat loss. In the study, researchers gave the subjects carnitine while simultaneously administering insulin and glucose. This treatment generated a significant increase in carnitine levels, which stimulated fat oxidation during high-intensity, submaximal exercise. These results suggest that cellular uptake of carnitine is enhanced when taken together with a glucose-rich meal, which stimulates insulin secretion and drives carnitine into the muscle cell.

Since increasing muscle carnitine content represents an appealing intervention for type 2 diabetes and obesity, another study by Shannon et al.³ investigated whether whey protein combined with carbohydrate intake could reduce the overall requirement for carbohydrate to stimulate insulin-mediated carnitine uptake into muscle tissue, as whey protein is rich in leucine, which potently stimulates insulin secretion. Furthermore, the ability of whey protein to promote fat loss and increase lean body mass also makes it a better choice than carbohydrates for this task, especially with type 2 diabetics and the obese population. In spite of this, the results of this study surprisingly showed that whey protein ingestion with a lower amount of carbohydrate completely prevented carnitine uptake instead of increasing it, despite a comparable rise of insulin levels to the group ingesting carbohydrate alone. As a result, the combined use of whey protein and carbohydrate to increase carnitine levels for fat loss is likely insufficient and therefore not recommended.

References:

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

2. Wall BT, Stephens FB, et al. Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. J Physiol 2011;589, 963-973.

3. Shannon CE, Nixon AV, et al. Protein ingestion acutely inhibits insulin-stimulated muscle carnitine uptake in healthy young men. Am J Clin Nutr 2016;103, 276-282.

For most of Michael Rudolph’s career he has been engrossed in the exercise world as either an athlete (he played college football at Hofstra University), personal trainer or as a research scientist (he earned a B.Sc. in Exercise Science at Hofstra University and a Ph.D. in Biochemistry and Molecular Biology from Stony Brook University). After earning his Ph.D., Michael investigated the molecular biology of exercise as a fellow at Harvard Medical School and Columbia University for over eight years. That research contributed seminally to understanding the function of the incredibly important cellular energy sensor AMPK— leading to numerous publications in peer-reviewed journals including the journal Nature. Michael is currently a scientist working at the New York Structural Biology Center doing contract work for the Department of Defense on a project involving national security.

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