L-Carnitine

Also Known As: Carnitine, Carnitor, L-Carnitine

Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine.[1] In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids (fats) for the generation of metabolic energy. It is widely available as a nutritional supplement. Carnitine was originally found as a growth factor for mealworms and labeled vitamin Bt. Carnitine exists in two stereoisomers: Its biologically active form is L-carnitine, whereas its enantiomer, D-carnitine, is biologically inactive.[2]

Carnitine transports long-chain acyl groups from fatty acids into the mitochondrial matrix, so they can be broken down through β-oxidation to acetyl CoA to obtain usable energy via the citric acid cycle. In some organisms, such as fungi, the acetate is used in the glyoxylate cycle for gluconeogenesis and formation of carbohydrates. Fatty acids must be activated before binding to the carnitine molecule to form 'acylcarnitine'. The free fatty acid in the cytosol is attached with a thioester bond to coenzyme A (CoA). This reaction is catalyzed by the enzyme fatty acyl-CoA synthetase and driven to completion by inorganic pyrophosphatase.

In the course of human aging, carnitine concentration in cells diminishes, affecting fatty acid metabolism in various tissues. Particularly adversely affected are bones, which require continuous reconstructive and metabolic functions of osteoblasts for maintenance of bone mass.

There is a close correlation between changes in plasma levels of osteocalcin and osteoblast activity and a reduction in osteocalcin plasma levels is an indicator of reduced osteoblast activity,[7] which appears to underlie osteoporosis in elderly subjects and in postmenopausal women. Administration of a carnitine mixture or propionyl-L-carnitine is capable of increasing serum osteocalcin concentrations of animals thus treated, whereas serum osteocalcin levels tend to decrease with age in control animals.[8]

Antioxidant effects

The carnitines exert a substantial antioxidant action, thereby providing a protective effect against lipid peroxidation of phospholipid membranes and against oxidative stress induced at the myocardial and endothelial cell level.[9]

Potential uses as a pharmaceutical

Heart conditions

Carnitine is primarily used for heart-related conditions. Several clinical trials show that L-carnitine and propionyl-L-carnitine can be used along with conventional treatment for angina to reduce medication needs and improve the ability of those with angina to exercise without chest pain.[10][11] There is little evidence about a positive effect of the use of carnitine after a heart attack. Some studies suggest people taking L-carnitine may be less likely to suffer a subsequent heart attack or experience chest pain and abnormal heart rhythms.[12] However, other studies have not found similar benefits.[13] Further research on this subject is needed.

Kidney disease and dialysis

Because kidneys produce carnitine, kidney disease may lead to the deficiency of carnitine in the body. Thus, carnitine may be prescribed to those with kidney disease.[14]

Effect in male infertility

The use of carnitine showed some promise in a controlled trial in selected cases of male infertility by improving sperm quality.[15] L-Carnitine supplementation has also shown to have beneficial effects in the treatment of varicocele, a major cause of male infertility. [16]

As a weight loss supplement

"Although L-carnitine has been marketed as a weight-loss supplement, there is no scientific evidence to show that it improves weight loss; however, some studies show that oral carnitine reduces fat mass, increases muscle mass, and reduces fatigue. All of these effects may indirectly contribute to weight loss."[17] Furthermore, whereas researchers in the 20th century failed to show that muscle carnitine content could be increased by dietary supplementation, this may have been in part due to inadequate lengths of the supplementation periods.[18] In 2011, researchers using L-carnitine L-tartrate supplementation for six months in a well-controlled study demonstrated not only increased muscle carnitine in subjects without carnitine deficiencies, but also an impact on muscle metabolism and performance; however, measurements of lipid oxidation were not taken in this study, and further research is needed.[19]

Regular supplements of L-carnitine, however, contribute to energy metabolism and improved neurotransmitter function in the brain in elderly patients.[20]

As an antidote in valproic acid poisoning

"[In the treatment of valproate toxicity] L-carnitine supplementation ...is thought to provide benefit, particularly in patients with concomitant hyperammonemia, encephalopathy, and/or hepatotoxicity."[21] Further trials are warranted, as benefit is largely theoretical, rather than proven at this stage.

To improve symptoms in moderate asthmatics

L-carnitine levels are lower in moderate persistent asthmatic children as compared to healthy control children. Asthmatic children who received L-carnitine supplementation for six months showed statistically significant improvement in their 'asthma control testing' and in their pulmonary function tests.

To improve fatigue resulting from ifosfamide cancer chemotherapy

High doses of the chemotherapy agent ifosfamide, due to its potential nephrotoxicity, may cause urinary loss of carnitine. One study suggests, as it is essential for energy production by mitochondria, L-carnitine may have a role in reducing ifosfamide-associated fatigue.[22]

To treat symptoms of hyperthyroidism

L-Carnitine is a peripheral antagonist of thyroid hormone action. It inhibits the entry of triiodo thyronine and thyroxine into the cell nuclei. Through a randomized trial, Benvenga et al. showed that 2–4 g of oral L-carnitine per day could reverse hyperthyroid symptoms even in the most serious form of hyperthyroidism: thyroid storm. They suggest that since hyperthyroidism impoverishes the tissue deposits of carnitine, there is a rationale for using L-carnitine at least in certain clinical settings. Incidentally, the fact that carnitine failed to prevent relapses of hyperthyroidism further supports the concept that carnitine action is in the periphery and not in the thyroid gland.[23]

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