|AHFS/Drugs.com||International Drug Names|
|ATC code||N06BX12 (WHO)|
|Biological half-life||4.2 hours|
|Chemical and physical data|
|3D model (Jmol)||Interactive image|
|(what is this?)|
Acetyl-L-carnitine, ALCAR or ALC, is an acetylated form of L-carnitine. It is naturally produced by the body, although it is often taken as a dietary supplement. Acetylcarnitine is broken down in the blood by plasma esterases to carnitine which is used by the body to transport fatty acids into the mitochondria for breakdown.
Biochemical production and action
Carnitine]] is both a nutrient and made by the body as needed; it serves as a substrate for important reactions in which it accepts and gives up acyl groups. When it accepts one acyl-group, acetyl-L-carnitine is the product; other acylcarnitines include propiony-L-lcarnitine, isovaleryl-L-carnitine, butyryl-L-carnitine, hydroxybutyryl-L-carnitine, hexanoyl-L-carnitine, ortanoyl-L-carnitine, decanoyl-L-carnitine, palmitoyl-L-carnitine, stearoyl-L-carnitine, and acetoacetyl-L-carnitine.
Acetylcarnitine (ALCAR) is the most abundant naturally occurring derivative and is formed in the reaction:
where the acetyl group displaces the hydrogen atom in the central hydroxyl group of carnitine. Coenzyme A (CoA) plays a key role in the Krebs cycle in mitochondria, which is essential for the production of ATP, which powers many reactions in cells; acetyl-CoA is the primary substrate for the Krebs cycle, once it is de-acetylated, it must be re-charged with an acetyl-group in order for the Krebs cycle to keep working.
Most cell types appear to have transporters to import carnitine and export acyl-carnitines, which seems to be a mechanism to dispose of longer-chain moieties; however many cell types can also import ALCAR.
Within cells, carnitine plays a key roles in importing acyl-coA into mitochondria; the acyl-group of the acyl-CoA is transferred to carnitine, and the acyl-carnitine is imported through both mitochondrial membranes before being transferred to a coA molecule, which is then beta oxidized to acetyl-CoA. A separate set of enzymes and transporters also plays a buffering role by eliminating acetyl-CoA from inside mitochondria created by the pyruvate dehydrogenase complex that is in excess of its utilization by the Krebs cycle; carnitine accepts the acetyl moiety and becomes ALCAR, which is then transported out of the mitochondria and into the cytosol, leaving free coA inside the mitochondria ready to accept new import of fatty acid chains. ALCAR in the cytosol can also form a pool of acetyl-groups for coA, should the cell need it.
Excess acetyl-CoA causes more carbohydrates to be used for energy at the expense of fatty acids. This occurs by different mechanisms inside and outside the mitochondria. ALCAR transport decreases acetyl-CoA inside the mitochondria, but increases it outside.
Carnitine and ALCAR supplements carry warnings of a risk that they promote seizures in people with epilepsy, but a 2016 review found no basis for this warning in the literature.
In a small clinical study, when ALCAR was administered intravenously and insulin levels were held steady and a meal low in carnitine but high in carbodydrates was taken by healthy young men, ALCAR appeared to decrease glucose consumption in favor of fat oxidation.
A 2003 Cochrane review sought to determine the safety and efficacy of ALCAR in dementia but the reviewers found only clinical trials studies on Alzheimers disease; the review found that the pharmacology of ALCAR was poorly understood and that based on the lack of efficacy, ALCAR was unlikely to be an important treatment for AD.
As of 2014 ALCAR has been studied in about fourteen clinical trials for various conditions with depressive symptoms; the trials were small (ranging from 20 to 193 subjects) and their design was so different that results cannot be generalized; most studies showed positive results and a lack of adverse effects. The mechanism of action by which ALCAR could treat treat depression is not known.
A 2015 Cochrane review of ALCAR in fragile X syndrome found only two placebo-controlled trials, each of low quality, and concluded that ALCAR is unlikely to improve intellectual functioning or hyperactive behavior in children with this condition.
ALCAR has been studied in hepatic encephalopathy, a complication of cirrhosis involving neuropsychiatric impairment; ALCAR improves blood ammonia levels and generates a modest improvement in psychometric scores but does not resolve the condition — it may play a minor role in managing the condition.
ALCAR has been studied in a randomized placebo-controlled clinical trial in around 400 women underoing chemotherapy to try to prevent peripheral neuropathy, a common side effect of chemo; ALCAR appeared to worsen the condition.
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