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Carnitine: the claims and why it may not work

Carnitine (also known as L-carnitine) is a substance present in relatively high quantities in meat (the Latin word carnis means meat or muscle). It has received much attention over the past 40 years. As a supplement, or more specifically as a “fat burner”, it has been popular among athletes. Carnitine became especially popular after rumors circulated that it helped the Italian national soccer team to become world champions in 1982. But does carnitine live up to the hype?


Carnitine molecular structure and evidence for use

What are the claims?

The most common claims are that carnitine improves fat metabolism, reduces fat mass, and increases muscle mass. It is generally advertised as a fat burner. In addition, carnitine supplementation is said to increase VO2max and reduce lactate production during strenuous exercise and is also claimed to improve endurance exercise performance by increasing fat oxidation and sparing muscle glycogen. Therefore, carnitine is often used to lose weight, reduce body fat, and improve muscle definition (it is therefore especially popular with body builders). Endurance athletes use carnitine to increase the oxidation of fat and spare muscle glycogen. In the next section, we will look at what carnitine does in the body.


What is carnitine?


Carnitine in the diet and in our body

Carnitine is a substance synthesised in the liver and kidneys. It can also be derived from red meats and to a smaller extent white meat and dairy products in the diet. Production in the body is mostly dependent on the availability of two amino acids: methionine and lysine. Even when dietary sources of carnitine are insufficient, the human body produces enough from methionine and lysine to maintain functional carnitine stores. For this reason, carnitine is not regarded as a vitamin but as a vitamin-like substance. About 98% of the carnitine in the human body is present in skeletal and heart muscle.


Carnotite content in food

The role of carnitine

Carnitine plays an important role in fat metabolism. In the overnight fasted state and during exercise of low to moderate intensity, long chain fatty acids are the main energy source of energy used by most tissues, including skeletal muscle. A critical step in this process of burning fat (oxidising long chain fatty acids), is the transport of fatty acids into the mitochondria (where fatty acids are turned into CO2 and ATP (energy). Carnitine also bind to acetyl groups and prevents the build up of Acetyl-CoA, which is suggested to help with high intensity exercise. We will explore this more in a future blog, but this blog focusses on “fat burning”.


The problem with carnitine

Muscle takes up carnitine against a very large (about 1,000-fold) concentration gradient (plasma carnitine is 40-60 μmol/L and muscle carnitine is 4-5 mmol/L). A transport protein is needed to take up carnitine against this gradient and this transport is the limiting factor. This transport protein is known as the sodium dependent organic cation transporter or OCTN2. Supplementation does not seem to increase muscle carnitine in almost all situations. And if we can't increase carnitine in the muscle with a supplement and we can't get it into the mitochondria, it can not exert its claimed effects.


Carnitine in the muscle


Carnitine as a slimming agent

The belief that carnitine is a slimming agent is based on the assumption that regular oral ingestion of carnitine increases the muscle carnitine concentration. Another assumption is that if carnitine concentration in the muscle increases, fat oxidation also increases, thus leading to a gradual loss of body fat stores. Several carefully conducted studies, however, showed that oral carnitine ingestion (daily ingestion for up to 3 months) does not change the muscle carnitine concentration. Even infusion of carnitine for 5 hours did not increase muscle carnitine concentration. It seems that the reason carnitine was unable to increase muscle carnitine concentration in these studies for 2 reasons:

  1. Poor bioavailability (only 20% for of a 2-6 g dose is absorbed) and

  2. Because the transport of carnitine into the muscle was limited.


Any claims regarding effects of carnitine on fat oxidation or weight loss are, of course, unfounded if carnitine supplementation is unable to increase the carnitine concentration in muscle.


Is there a solution to poor carnitine uptake?

There could be a way around this uptake problem though. In a series of studies, it was observed that it is possible to increase muscle carnitine concentration if carnitine is given when plasma insulin concentrations are elevated. Carnitine is transported into the muscle cell by a OCTN2, and it was demonstrated that with carnitine supplementation in the presence of high insulin concentrations a 15% increase in muscle carnitine can be obtained (1). Follow-up studies demonstrated that the insulin response resulting from carbohydrate feeding can be sufficient to increase the uptake of carnitine into the muscle (2). In this study, 3 g of carnitine was ingested each day followed by four 500 ml (17 fl oz) beverages that each contained 94 g of carbohydrate. It was observed that carnitine retention improved (less carnitine excretion in urine), which suggests increased muscle carnitine. Of course, whether this strategy is practical or meaningful is questionable, especially in a weight-loss situation. If four lots of 94 g of carbohydrate (372 g in total, which is equivalent to 6,000 kJ [1,434 kcal]) has to be ingested to increase muscle carnitine concentration, one might think that weight gain is more likely to result than weight loss! Also, such high carbohydrate intake and insulin concentrations will actually suppress fat oxidation. Nevertheless, the observations are interesting and have been subsequently followed up by a study that showed 12 weeks of daily carnitine and carbohydrate feeding in humans increases skeletal muscle total carnitine content and prevents body mass accrual associated with carbohydrate feeding alone (3). No changes in fat oxidation were reported. It remains to be seen how practical and cost effective this daily supplementation of carnitine with carbohydrates is.


It remains to be seen how practical and cost effective daily supplementation of carnitine with carbohydrate is

Carnitine and endurance exercise

The belief that carnitine is an ergogenic aid for endurance exercise is based on assumptions similar to the weight-loss assumptions:

  1. Carnitine concentration in muscle becomes too low to allow the transport of carnitine into the mitochondria to function at a high velocity

  2. Oral ingestion of carnitine increases the total carnitine concentration in muscle

  3. Any increase in muscle carnitine increases the oxidation rate of plasma FAs and intramuscular triacylglycerols during exercise

  4. Any increase in fatty acids will reduce muscle glycogen breakdown and postponing fatigue.


As previously mentioned, early studies using direct measurements in muscle after 14 days on 4 to 6 g of carnitine per day failed to show increases in the muscle carnitine concentration (4, 5). Several other studies confirmed that carnitine supplementation on its own does not increase fat oxidation and reduce glycogen breakdown and does not improve performance during prolonged cycling and running exercise.


Interestingly, a placebo-controlled study (6) has shown that substantial elevations (~20%) of muscle carnitine content do occur in humans following prolonged daily supplementation with carnitine tartrate when carbohydrate is ingested at the same time. Importantly, this study also showed that this results in muscle glycogen sparing during low-intensity exercise (consistent with an increase in fat oxidation) and lower lactate accumulation during high-intensity exercise. Furthermore, these changes were associated with an 11% improvement in a 30-min work output exercise performance trial (6).


Carnitine for fat burning

Conclusion

So, in conclusion, although carnitine has an important function in the muscle and it is attractive to speculate that it can increase fat burning, it has proven very difficult to increase carnitine concentrations in muscle. Even high doses have not resulted in improved carnitine concentrations in muscle and no change in function. The only way to increase carnitine in muscle is very prolonged carnitine supplementation in conjunction with a very high carbohydrate load or any other feeding that produces high insulin levels. Whether this is a practical strategy is questionable.


Reference

  1. Stephens FB, Constantin-Teodosiu D, Laithwaite D, Simpson EJ, Greenhaff PL. An acute increase in skeletal muscle carnitine content alters fuel metabolism in resting human skeletal muscle. J Clin Endocrinol Metab. 2006 Dec;91(12):5013-8. doi: 10.1210/jc.2006-1584. Epub 2006 Sep 19. PMID: 16984983.

  2. Stephens FB, Evans CE, Constantin-Teodosiu D, Greenhaff PL. Carbohydrate ingestion augments L-carnitine retention in humans. J Appl Physiol (1985). 2007 Mar;102(3):1065-70. doi: 10.1152/japplphysiol.01011.2006. Epub 2006 Nov 30. PMID: 17138832.

  3. Stephens FB, Wall BT, Marimuthu K, Shannon CE, Constantin-Teodosiu D, Macdonald IA, Greenhaff PL. Skeletal muscle carnitine loading increases energy expenditure, modulates fuel metabolism gene networks and prevents body fat accumulation in humans. J Physiol. 2013 Sep 15;591(18):4655-66. doi: 10.1113/jphysiol.2013.255364. Epub 2013 Jul 1. PMID: 23818692; PMCID: PMC3784205.

  4. Barnett C, Costill DL, Vukovich MD, Cole KJ, Goodpaster BH, Trappe SW, Fink WJ. Effect of L-carnitine supplementation on muscle and blood carnitine content and lactate accumulation during high-intensity sprint cycling. Int J Sport Nutr. 1994 Sep;4(3):280-8. doi: 10.1123/ijsn.4.3.280. PMID: 7987362.

  5. Vukovich MD, Costill DL, Fink WJ. Carnitine supplementation: effect on muscle carnitine and glycogen content during exercise. Med Sci Sports Exerc. 1994 Sep;26(9):1122-9. PMID: 7808246.

  6. Wall BT, Stephens FB, Constantin-Teodosiu D, Marimuthu K, Macdonald IA, Greenhaff PL. Chronic oral ingestion of L-carnitine and carbohydrate increases muscle carnitine content and alters muscle fuel metabolism during exercise in humans. J Physiol. 2011 Feb 15;589(Pt 4):963-73. doi: 10.1113/jphysiol.2010.201343. Epub 2011 Jan 4. PMID: 21224234; PMCID: PMC3060373.

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