Routes of
administration Oral, intravenous Legal status US: OTC Formula C7H15NO3 | ATC code A16AA01 (WHO) (L form) Bioavailability <10% Molar mass 161.199 g/mol | |
AHFS/Drugs.com Micromedex Detailed Consumer Information Pregnancy
category US: B (No risk in non-human studies) | ||
Carnitine (β-hydroxy-γ-N-trimethylaminobutyric acid, 3-hydroxy-4-N,N,N- trimethylaminobutyrate) is a quaternary ammonium compound involved in metabolism in most mammals, plants and some bacteria. Carnitine may exist in two isomers, labeled -carnitine and -carnitine, as they are optically active. At room temperature, pure carnitine is a white powder, and a water-soluble zwitterion with low toxicity. Carnitine only exists in animals as the -enantiomer, and -carnitine is toxic because it inhibits the activity of -carnitine. Carnitine was discovered in 1905 as a result of its high concentration in muscle tissue. It was originally labeled vitamin BT; however, because carnitine is synthesized in the human body, it is no longer considered a vitamin. Carnitine is involved in the oxidation of fatty acids, and involved in systemic primary carnitine deficiency. It has been studied for preventing and treating other conditions, and is used as a purported performance enhancing drug.
Contents
How acetyl l carnitine helps treat neuropathy
Biosynthesis and metabolism
Many eukaryotes have the ability to synthesize carnitine, including humans. Humans synthesize carnitine from the substrate TML (6-N-trimethyllysine), which is in turn derived from the methylation of the amino acid lysine. TML is then hydroxylated into hydroxytrimethyllysine (HTML) by trimethyllysine dioxygenase, requiring the presence of ascorbic acid. HTML is then cleaved by HTML aldose, yielding 4-trimethylaminobutyraldehyde (TMABA) and glycine. TMABA is then dehydrogenated into gamma-butyrobetaine, in an NAD+-dependent reaction, catalyzed by TMABA dehydrogenase. Gamma-butyrobetaine is then hydroxylated by gamma butyrobetaine hydroxylase into L-carnitine, requiring iron in the form of Fe2+.
Carnitine is involved in transporting fatty acids across the mitochondrial membrane, by forming a long chain acetylcarnitine ester and being transported by carnitine palmitoyltransferase I and carnitine palmitoyltransferase II. Carnitine also plays a role in stabilizing Acetyl-CoA and coenzyme A levels through the ability to receive or give an acetyl group.
Deficiency
Carnitine deficiency caused by a genetic defect in carnitine transport occurs in roughly 1 in 50,000 in the US. Systemic primary carnitine deficiency (SPDC) is characterized by various cardiological, metabolic and musculoskeletal symptoms that vary widely in age of onset and presentation. Prognosis is generally good with carnitine supplementation.
Secondary carnitine deficiency may occur due to conditions such as malnutrition, poor absorption or access to only vegetables.
Supplementation
Some research has been carried out on carnitine supplementation in athletes, given its role in fatty acid metabolism; however, individual responses varied significantly in the 300 people involved in one study. Carnitine has been studied in various cardiometabolic conditions, with a bit of evidence pointing towards efficacy as an adjunct in heart disease and diabetes. However, there are insufficient trials to determine its efficacy. Carnitine has no effect on preventing mortality associated with cardiovascular conditions. Carnitine has no effect on serum lipids, except a possible lowering of LDL Carnitine has no effect on most parameters in end stage kidney disease, however it possibly has an effect on c-reactive protein. The effects on mortality and disease outcome are unknown.
Atherosclerosis
An important interaction between diet and the intestinal microbiome brings into play additional metabolic factors that aggravate atherosclerosis beyond dietary cholesterol. This may help to explain some benefits of the Mediterranean diet. Hazen’s group from the Cleveland Clinic reported that carnitine from animal flesh (four times as much in red meat as in fish or chicken), as well as phosphatidylcholine from egg yolk, are converted by intestinal bacteria to trimethylamine (the compound that causes uremic breath to smell fishy). Trimethylamine is oxidized in the liver to trimethylamine N-oxide (TMAO), which causes atherosclerosis in animal models. Patients in the top quartile of TMAO had a 2.5-fold increase in the 3-year risk of stroke, death, or myocardial infarction.
A key issue is that vegans who consumed L-carnitine did not produce TMAO because they did not have the intestinal bacteria that produce TMA from carnitine.
History
Levocarnitine was approved by the U.S. Food and Drug Administration as a new molecular entity under the brand name Carnitor on December 27, 1985.