L-carnitine, an amino acid derivative, is found in nearly all cells of the body. L-carnitine transports long-chain fatty acids across the inner mitochondrial membranes in the mitochondria, where they are processed by beta-oxidation to produce biological energy in the form of adenosine triphosphate or ATP.
It also aids the removal of wastes from the mitochondria. L-carnitine also increases the rate of oxidation of fats in the liver and this suggests that it helps increase the energy level in the body.
L-carnitine is known chemically as (R)-3-carboxy-2-hydroxy-N,N,N-trimethyl-1-propanaminium hydroxide, inner salt; beta-hydroxy-gamma-N,N,N-trimethylaminobutyrate; gamma-amino-beta-hydroxybutyric acid trimethylbetaine; (3-carboxy-2-hydroxypropyl) trimethylammonium hydroxide, inner salt; gamma-trimethyl-beta-hydroxybutyrobetaine, and 3-hydroxy-4-(trimethylammonio) butanoate.
L-carnitine is also known as levocarnitine and was formerly called vitamin BT.
L-carnitine is a quarternary amine and belongs to the same chemical family as choline and is soluble in water.
L-carnitine is represented by the following chemical structure
L-carnitine occurs naturally in animal products. Generally, only very small amounts of it are found in plants, with few exceptions, such as avocado and some fermented soy products, e.g. tempeh.
L-carnitine is a chiral molecule. Its stereoisomer D-carnitine does not have the biological activity of L-carnitine and may even antagonize L-carnitine in its biological roles.
L-carnitine is synthesized in the human body, chiefly in the liver and kidneys, from the essential amino acids L-lysine and L-methionine. Niacin, vitamins B6 and C, and iron are involved in its biosynthesis.
L-carnitine is described as a conditionally essential nutrient. This refers to certain conditions where exogenous L-carnitine may be required, such as in long-term parenteral nutrition, those on valproic acid therapy and possibly for the elderly.
Supplemental L-carnitine may have cardioprotective activity in addition to beneficially affecting cardiac function. It may have a triglyceride-lowering effect in some as well as help to elevate HDL-cholesterol levels. L-carnitine may also have antioxidant properties.
Acetyl-L-carnitine may have neuroprotective activity. It may also aid in the treatment of age-related cholinergic deficits, such as those found in dementia disorder, including Alzheimer's disease.
In summary, L-carnitine is considered to be beneficial as a weight loss aid and because it helps the body to burn fat for energy and it stimulates the body’s metabolism.
L-carnitine also increases the body’s resistance to stress, lowers cholesterol levels, improves heart, liver and kidney functions and increases endurance during physical exercise.
There are at least two major functions of L-carnitine. All tissues except the brain use long-chain fatty acids for bioenergy production. In cardiac and skeletal muscle, a major contribution of bioenergy comes from the beta-oxidation of long-chain fatty acids.
Long-chain fatty acids require L-carnitine to transport them across the inner membranes of the mitochondria, wherein their metabolism produces bioenergy.
Following the delivery of long-chain fatty acids into other mitochondria, L-carnitine, either by itself or esterified to an acyl group, recrosses the mitochondrial membrane to allow for continual use in this shuttle process.
Another function of L-carnitine is to remove short-chain and medium-chain fatty acids from the mitochondria in order to maintain coenzyme A levels in these organelles.
These fatty acids accumulate as a result of normal and abnormal metabolism. This mechanism prevents the build-up in the mitochondria of short-chain and medium-chain fatty acids that may interfere with the bioenergy-producing process vital to the normal function of the cell.
Two types of L-carnitine deficiency states exist: primary systemic carnitine deficiency (SCD) and secondary carnitine deficiency syndromes. SCD is an autosomal recessive disorder characterized by progressive cardiomyopathy, skeletal myopathy, hypoglycemia and hyperammonemia.
SCD appears to be due, in part, to loss of function of the transporter protein called OCT N2, which helps carry L-carnitine into cells. Patients with SCD have low L-carnitine levels in liver and skeletal muscle and variable concentrations of L-carnitine in the serum. Treatment with large doses of L-carnitine either orally or intravenously is sometimes beneficial in this rare genetic disorder.
Secondary L-carnitine deficiency disorders include a large number of entities. Some of these are genetic defects of metabolism such as methylmalonic aciduria, cytochrome C oxidase deficiency, fatty acyl-coenzyme A dehydrogenase deficiency, including long-chain and medium-chain deficiency, isovaleric acidemia, glutaric aciduria and propionic acidemia.
The mechanism of L-carnitine deficiency in these disorders is unclear. Some hypothesize that an accumulation of short-chain and medium-chain fatty acyl CoA molecules occurs in the mitochondria because insufficient L-carnitine is available to expel them.
This accumulation would disturb the bioenergy-producing processes of the mitochondria. Symptoms of secondary muscle L-carnitine deficiency, not surprisingly, include muscle weakness and fatigue.
Secondary L-carnitine deficiency may also be found secondary to other conditions such as chronic renal failure treated by hemodialysis, cirrhosis with cachexia, chronic severe myopathies, myxedema, hypopituitarism, adrenal insufficiency, hyperammonemia associated with valproic acid therapy, valproate-induced Reye's syndrome, advanced AIDS and pregnancy.
It may also be seen in those with HIV who are being treated with the nucleoside analogues didanosine (ddI), zalcitabine (ddC) and stavudine (d4T). In addition, it may occur in premature infants receiving parenteral nutrition. There is some preliminary evidence that secondary L-carnitine deficiency may also be associated with aging.
L-carnitine may possess antioxidant properties. A disturbance in long-chain fatty acid oxidation in mitochondria and/or the accumulation of small-chain and medium-chain fatty acyl CoA molecules in the mitochondria might be expected to increase oxidative stress.
There is some evidence that proprionyl-L-carnitine, a delivery form of L-carnitine, might protect the ischemic heart from reperfusion injury via an antioxidant effect.
The strongest evidence for the use of supplemental L-carnitine may be in the management of cardiac ischemia and peripheral arterial disease. It may also more generally be indicated for cardioprotection. It lowers triglyceride levels and increases levels of HDL-cholesterol in some.
It is used with some benefit in those with primary and secondary carnitine deficiency syndromes. There is less evidence to support arguments that carnitine is indicated in liver, kidney and immune disorders or in diabetes and Alzheimer's disease.
Favorable results have been reported for many years with regard to the use of L-carnitine in the treatment of various forms of cardiovascular disease. The walking capacity of patients with intermittent claudication was significantly improved in one double-blind, cross-over study of patients receiving oral L-carnitine. The data in this study suggests that L-carnitine enhances pyruvate utilization and oxidative phosphorylation efficiency in the skeletal muscle of the ischemic leg.
In a more recent, multicenter study, propionyl-L-carnitine was compared with placebo in the treatment of those with peripheral arterial disease of the legs. The study of 162 patients receiving propionyl-L-carnitine and 166 patients receiving placebo continued for one year. Walking ability and quality of life were evaluated at regular intervals.
Those initially presenting with the most severe disability (able to walk no more than 250 meters) exhibited significant improvement, increasing walking distance by 98 meters compared with 54 meters in the placebo group. Those able to walk more than 250 meters at baseline also improved, versus placebo, but not at a level of statistical significance.
An indirect role for supplemental L-carnitine in some forms of liver disease is suggested, because hepatic disease impairs the last stage of L-carnitine synthesis resulting in L-carnitine deficiencies in heart and skeletal muscle. Preliminary work suggests that L-carnitine can reduce fat deposits in some fatty livers. Research is ongoing.
The kidney is also an important locus of carnitine synthesis. Chronic kidney disease may eventually be an indication for L-carnitine supplementation, but more research is needed to demonstrate this. There is some evidence that dialysis patients can benefit from L-carnitine supplementation since dialysis removes the low-molecular-weight L-carnitine.
There is no evidence that L-carnitine will prevent diabetes, although abnormal carnitine metabolism is associated with diabetes. Ongoing research may demonstrate some benefit from L-carnitine supplementation. Animal model work in diabetes has shown improved myocardial function with administration of parenteral L-carnitine.
L-carnitine effects on immunity are suggested, as well, from animal model work. Reductions in circulating cytokines and tumor necrosis factor have been observed.
Choline supplementation may lead to increased L-carnitine retention. Vitamin C deficiency may lead to secondary L-carnitine deficiency.