Review articleSupplementation of l-carnitine in athletes: does it make sense?☆
Introduction
Dietary supplements to improve performance are familiar to many athletes. Manufacturers more or less aggressively claim that the substances improve the performance of athletes (i.e., act as ergogenic aids) and/or speed up their recovery from exercise. Most of these claims are purely speculative and based on assumptions about how the dietary supplement influences metabolism. The substance l-carnitine has been particularly popular as a potential ergogenic aid because of its role in the conversion of fat into energy.1, 2 For a scheme, the reader is referred to Figure 1.
l-carnitine was first discovered in muscle extracts by two Russian scientists3 who named the substance for the Latin word carnis (flesh or meat). Its chemical structure was established in 1927, and in 1935 a pioneer article about l-carnitine was published,4 which triggered numerous studies on the physiological functions of the chemical. In 1959 Fritz showed that carnitine increases long-chain fatty oxidation in liver and heart.5 Another name for l-carnitine was vitamin B T (T = tenebrio) because the larva of black beetle Tenebrio molitor (Tenebrionidae, Coleoptera) requires l-carnitine as a growth factor in addition to folic acid and other known B vitamins. Considering the chemical structure, the choline-like metabolite l-carnitine (3-hydroxy-4-N,N,N-trimethylaminobutyrate, L-3-hydroxy-4-N-trimethylaminobutyric acid or γ-trimethylamino-β-hydroxybutyric acid) is a quaternary amine. In phrenic nerve diaphragm preparations, its effect, namely induction of tetanic fade, can be reduced by addition of choline.6
The function that has been investigated most thoroughly scientifically is the carnitine-dependent transport of fatty acids through the inner mitochondrial membrane. Other established functions of l-carnitine are the preservation of membrane integrity, the stabilization of a physiologic coenzyme A (CoA) acetyl-CoA (coASH) ratio in mitochondria, and the reduction of lactate production.7, 8 In vitro investigations have strongly supported the notion that l-carnitine is able to inhibit apoptosis (programmed cell death)9, 10, 11 (Figure 2).
The intracellular homeostasis of carnitine is controlled by different membrane transporters. The organic cation transporters (OCTNs), in particular OCTN2, physiologically the most important, operate on intestinal absorption and renal reabsorption of l-carnitine and play a major role in tissue distribution and variations in transport rates. Inborn or acquired defects on this carnitine transport mechanism lead to primary or secondary carnitine deficiency. The OCTN2 mRNA content of cells is reduced with aging12 and by oxygen radicals.13 OCTN2 is directly inhibited by several agents and substances known to induce systemic carnitine deficiency.
Secondary carnitine deficiency is often seen in patients on regular hemodialysis,14 with metabolic disorders, and in pregnancy.15
l-carnitine, widely available over the counter, is also favored among athletes. Rumors that l-carnitine supplementation helped the Italian national soccer team to win the world championship in 1982 contributed immensely to its popularity. The most important claim relates to the role of carnitine in fat metabolism. l-carnitine is often advertized to improve fat metabolism, reduce fat mass, and increase muscle mass. In other words, the substance is portrayed as a “fat burner.” Therefore, carnitine is often recommended for conditions in which weight loss is indicated. Endurance athletes use carnitine to increase the oxidation of fat during exercise and spare muscle glycogen. This review critically examines whether the claims associated with l-carnitine are justified.
Section snippets
Endogenous synthesis and regulation of carnitine body pools
Carnitine is synthesized in mammals from the essential amino acids lysine and methionine.16, 17 Availability of the intermediate trimethyl lysine limits carnitine biosynthesis, and most of the trimethyl lysine body stores are located in skeletal muscle protein. As a consequence, skeletal muscle protein turnover is considered to be the rate-limiting step in carnitine biosynthesis.18 The last step, the hydroxylation of butyrobetaine to carnitine, is limited to liver, kidney, and brain; other
Carnitine in the human body
Skeletal muscles are the main reservoir of l-carnitine in the body and possess an l-carnitine concentration at least 50 to 200 times higher than in blood plasma, where average concentrations are between 41 (females) and 50 (males) μM/L.20 Considering diet, red meat and dairy products represent the major sources. Even with a diet largely lacking carnitine, healthy humans are able to synthesize enough of it. Therefore, l-carnitine is not regarded as a vitamin, but as a vitamin-like substance.
Role of carnitine in fat metabolism
l-carnitine plays an important role in fat metabolism. In the overnight-fasted state, during the resting state, and during exercise of low to moderate intensity, long-chain fatty acids represent up to 80% of the energy sources. The best described function of l-carnitine is in its role as a cofactor of carnitine, acyltransferases transporting long-chain fatty acids across the mitochondrial inner membrane.21 In the absence of l-carnitine, the inner mitochondrial membrane would be impermeable to
Buffering the mitochondrial coenzyme A pool
In some metabolic conditions, e.g., exercise, ischemia, fasting or acute stress, increased PDH activity and fatty acid supply from activated lipolysis may exceed the rate of acetyl-CoA oxidation, which leads to an accumulation of acetyl-CoA and of short-chain acyl-CoA esters, which are mainly degradation products of branched-chain amino acids. The acetyl-CoA/CoASH ratio is an important regulating factor of the oxidation of pyruvate, α-ketoglutarate, and fatty acids. All of them depend on the
Carnitine as a weight loss agent
The rationale for carnitine supplementation as a weight-loss agent is based on the assumption that regular oral ingestion of the substance increases its intracellular concentration. This would trigger increased fat oxidation and gradual reduction of the body's fat reserves. Several studies have shown that oral carnitine ingestion (up to 6 g/d for 14 d) does not change muscle carnitine concentration in healthy non-obese humans and does not promote weight loss.32, 33 This is not in keeping with
Exercise
Carnitine is critical for normal skeletal muscle bioenergetics for at least three reactions. First, l-carnitine is required for long-chain fatty acid oxidation; second, it assists in removing accumulated acyl groups from the mitochondria; and third, it plays an important role in detoxification. Muscles require optimum performance of these metabolic processes during peak exercise. Theoretically, carnitine availability may be the limiting factor for fatty acid oxidation or the removal of
Immune system
Acute bouts of prolonged, strenuous exercise are often associated with immune suppression and an increased risk of infection.71 Although high-performance athletes cannot be described as clinically immune deficient, there is evidence that several parameters of the immune system are suppressed after prolonged periods of intense physical exercise. These are decreases in neutrophil function, serum and salivary immunoglobulin concentrations, natural killer cell activity, secretory immunoglobulin A
Safety aspects of l-carnitine
It is not easy to make a clear distinction or classification for a substance, which, on one hand, is synthesized endogenously and, on the other, has to be taken with food. l-carnitine belongs to a group of substances that is sold over the counter as a nutritional supplement but is also a prescribed drug. Because the investigations refer to a heterogeneous population of humans, large individual variations have to be taken into account. An LD for carnitine in rats was determined as 8.9 to 9.1
Conclusions and directions for further work
On a theoretical basis, the benefits of carnitine supplementation for skeletal muscle during exercise in athletes have been documented in more than 300 subjects participating in placebo-controlled studies. However, interindividual differences in response to supplementation should be taken into account when carnitine is applied as an ergogenic aid and for weight control. In addition, l-carnitine may attenuate side effects of high-intensity training by reducing the magnitude of exercise-induced
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This study was supported by the Bürgermeisterfonds der Stadt Wien.