L-Carnitine (Vitamin Bt)
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.
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 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. L-Carnitine is made in the body from the amino acids lysine and methionine. It increases the use of fat as an energy source by transporting fatty acids into the mitochondria, where they are ‘burned’ to release energy for body functions. The L-carnitine form may cause adverse side effects however. It is available in several different forms including propionyl-L-carnitine and acetyl-L-carnitine. Propionyl-L-carnitine, through its enhancement of metabolism has been proven to prevent ischemia-induced heart dysfunction, and acetyl-L-carnitine has been suggested to delay the progression of Alzheimer’s disease. L-carnitine is found naturally in avocados, breast milk, dairy products, red meats (namely lamb and beef), and tempeh (fermented soybean product). A deficiency of L-Carnitine can cause muscle fatigue, cramps, or low blood-sugar levels.
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 transfers long-chain fatty acids, such as triglycerides into mitochondria (a cell's energy powerhouse), where they may be oxidized to produce energy. L-carnitine is a very popular supplement that promotes growth and development. It is also used for fat-burning, increasing energy, and improving resistance to muscle fatigue. As a speculated muscle disease, liver disease, and kidney disease fighter, L-carnitine has also been shown to help build muscle and treat some forms of cardiovascular disease. It is also great in dieting, as it reduces feelings of hunger and weakness - helping curb your appetite.