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Acetyl-L-Carnitine

 

DESCRIPTION
 

 

Acetyl-L-Carnitine is the acetyl ester of L-carnitine. It occurs naturally in animal products. Chemically, acetyl-L-carnitine is known as beta-acetoxy-gamma-N, N, N-trimethylaminobutyrate and is represented by the following chemical structure:
 

 
 

Acetyl-L-Carnitine
 

 

Acetyl-L-carnitine is also known as acetyl-carnitine, L-acetycarnitine, acetylcarnitine, acetyl levocarnitine, ALC and ALCAR.
 

 

Acetyl-L-carnitine is a delivery form for both L-carnitine and acetyl groups.
 

 
 
 
 
 
 
 

ACTIONS AND PHARMACOLOGY
 

 

ACTIONS
 

 

Supplemental acetyl-L-carnitine may have neuroprotective activity. In addition, it, like L-carnitine, may have cardioprotective activity and may beneficially affect cardiac function. It may enhance sperm motiliy. Acetyl-L-carnitine may also have cytoprotective, antioxidant and anti-apoptotic activity.
 

 

MECHANISM OF ACTION
 

 

Acetyl-L-carnitine is a delivery form for L-carnitine and acetyl groups. The functions of L-carnitine include transport of long-chain fatty acids across the mitochondrial membranes into the mitochondria (wherein their metabolism produces bioenergy) and transport of small-chain and medium-chain fatty acids out of the mitochondria in order to, among other things, maintain normal coenzyme A levels in these organelles. It may also have antioxidant activity.
 

 

The acetyl component of acetyl-L-carnitine provides for the formation of the neurotransmitter acetylcholine. Abnormal acetylcholine metabolism in the brain, leading to acetylcholine deficits in certain brain regions, is thought to be associated with age-related dementias, including Alzheimer's disease.
 

 

Acetyl-L-carnitine has been found to decrease glycation of lens proteins in vitro. It is thought to do so by acetylating certain lens proteins called crystallins. In so doing it protects them from glycation-mediated damage.
 

 

Many biochemical changes occur during the aging process. These include decreased cardiolipin synthesis in the heart and impaired mitochondrial function. Cardiolipin is a key phospholipid necessary for mitochondrial transport processes in the heart. Mitochondria are vital for the production of cellular energy. Experiments in aged rats have shown that acetyl-L-carnitine supplementation leads to improved mitochondrial function and increased cardiolipin production.
 

 

Acetyl-L-carnitine serves as a readily accessible energy pool for use in both activation of respiration and motility in human spermatozoa.
 

 
 
 

PHARMACOKINETICS
 

 

The pharmacokinetics of acetyl-L-carnitine are similar to L-carnitine (see L-carnitine). There is speculation that it is better absorbed than L-carnitine, but this has not yet been established.
 

 
 
 

INDICATIONS AND USAGE
 

 

Acetyl-L-carnitine has recently demonstrated some efficacy as a possible neuroprotective agent and may be indicated for use in strokes, Alzheimer's disease, Down's syndrome and for the management of various neuropathies. It may also have anti-aging properties. Research regarding acetyl-L-carnitine's possible beneficial effect on sperm motility is early-stage but promising.
 

 

RESEARCH SUMMARY
 

 

Several studies have now demonstrated some positive effects of acetyl-L-carnitine supplementation in Alzheimer's patients especially with regard to tasks involving attention and concentration. In a double-blind, parallel design, placebo-controlled pilot study of 30 patients whose mild-to-moderate dementias were believed to be symptoms of Alzheimer's disease, there were significant, positive results as measured by some of the neuropsychological tests used in the study.
 

 

In another early double-blind, placebo-controlled study of 130 patients with clinical diagnoses of Alzheimer's disease, a slower rate of deterioration was observed in 13 of 14 outcome measures at the end of this one-year study. Some of these measures reached statistical significance, including measures of logical intelligence, long-term verbal memory and selective attention.
 

 

More recent studies continue to show beneficial effects in Alzheimer's disease. Younger patients seem to benefit most.
 

 

It has been suggested that cognitive function may be improved in subjects with Alzheimer's disease by acetyl-L-carnitine's hypothesized ability to inhibit apoptosis of cerebral nerve cells.
 

 

Significant improvement in visual memory and attention in Down's syndrome subjects treated with acetyl-L-carnitine has also been reported. These researchers hypothesized that acetyl-L-carnitine's positive actions in both Alzheimer's disease and Down's syndrome result from its direct and indirect cholinomimetic effects.
 

 

There is also preliminary evidence that acetyl-L-carnitine can slow mental decline in the elderly who are not afflicted with dementias.
 

 

Neuroprotective effects of acetyl-L-carnitine have been reported after stroke in both animal models and in humans. Cerebral blood flow reportedly improves in acetyl-L-carnitine treated subjects with cerebrovascular disease.
 

 
 
 
 
 
 
 
 
 

Peripheral nerve function has been improved with the use of acetyl-L-carnitine in experimental diabetes. There is also early clinical evidence that acetyl-L-carnitine may be helpful in various peripheral neuropathies, and it has been suggested that this supplement might be helpful in alleviating the neurotoxicity associated with the nucleoside analogues used in the treatment of AIDS. This latter hypothesis has yet to be tested.
 

 

There is some evidence in animal work that acetyl-L-carnitine might have anti-aging effects. Mitochondrial function and ambulatory activity were assessed in a study of old rats fed acetyl-L-carnitine. Ambulatory activity was significantly increased in the old rats, and an examination of liver cells in the treated animals showed a significant reversal of age-associated decline of mitochondrial membrane potential. Cardiolipin, which declines with age, was significantly restored.
 

 

Finally, acetyl-L-carnitine has been reported to increase sperm motility in vitro, and in one human trial, 4 grams daily of this substance given to 20 oligoasthenospermic men, produced increased progressive sperm motility which was associated with a greater number of pregnancies.
 

 
 
 

CONTRAINDICATIONS,PRECAUTIONS, ADVERSE REACTIONS
 

 

CONTRAINDICATIONS
 

 

None Known.
 

 

PRECAUTIONS
 

 

Because of lack of long-term safety studies, acetyl-L-carnitine is not advised for pregnant women or nursing mothers. Those with seizure disorders should only use acetyl-L-carnitine under medical advisement and supervision.
 

 
 
 

ADVERSE REACTIONS
 

 

Mild gastrointestinal symptoms may occur in those taking acetyl-L-carnitine supplements. These include nausea, vomiting, abdominal cramps and diarrhea.

Increased agitation has been reported in some with Alzheimer's disease when taking oral acetyl-L-carnitine. In those with seizure disorders, an increase in seizure frequency and/or severity has been reported in some taking this substance. The incidence of this in this population is low.
 

 
 
 
 
 
 
 
 
 
 
 
 
 

INTERACTIONS
 

 

Therapy with the nucleoside analogues didanosine (ddI), zalcitabine (ddC) and stavudine (d4T) may lead to decreased acetyl-L-carnitine levels.
 

 

Therapy with valproic acid and the pivalic acid-containing antibiotics may lead to secondary L-carnitine deficiencies (see L-carnitine).
 

 
 
 

OVERDOSAGE
 

 

There are no reports of overdosage.
 

 
 
 

DOSAGE AND ADMINISTRATION
 

 

Typical doses of supplemental acetyl-L-carnitine are 500 milligrams to 2 grams daily in divided doses.
 

 
 
 

LITERATURE
 

 

Brooks JO 3d, Yesavage JA, Carta A, Bravi D. Acetyl-L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled trial using the trilinear approach. Int Psychogeriatr. 1998; 10:193-203.
 

 

Chuang WW, Lin WW, Lamb DJ, Lipshultz LI. Effect of acetylcarnitine on sperm motility. J Urol. 2000; 163(4 Suppl):Abstract1324.
 

 

Famularo G, Morreti S, Marcellini S, et al. Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. AIDS. 1997; 11:185-190.
 

 

Gorini A, D'Angelo A, Villa RF. Action of L-acetylcarnitine on different cerebral mitochondrial populations from cerebral cortex. Neurochem Res. 1998; 23:1485-1491.
 

 

Hagen TM, Ingersoll RT, Wehr CM, et al. Acetyl-L-carnitine fed to old rats partially restores mitochondrial function and ambulatory activity. Proc Natl Acad Sci USA. 1998; 95:9562-9566.
 

 

Hagen TM, Wehr CM, Ames BN. Mitochondrial decay in aging. Reversal through supplementation of acetyl-L-carnitine and N-tert-butyl-alpha-phenyl-nitrone. Ann NY Acad Sci. 1998; 854,214-223.
 

 

Lolic MM, Fiskum G, Rosenthal RE. Neuroprotective effects of acetyl-L-carnitine after stroke in rats. Ann Emerg Med. 1997; 29:758-765.
 

 

Moncada ML, Vicari E, Cimino C, et al. Effect of acetylcarnitine treatment in oligoasthenospermic patients. Acta Eur Fertil. 1992: 23:221-224.
 

 

Onofrj M, Fulgente T, Melchiadona D, et al. L- acetylcarnitine as a new therapeutic approach for peripheral neuropathies with pain. Int J Clin Pharmacol Res. 1995; 15:9-15.
 

 

Pettegrew JW, Klunke WE, Panchalingam K. Clinical and biochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging. 1995; 16:1-4.
 

 

Piovesan P, Quatrini G, Pacifici L, et al. Acetyl-L-carnitine restores choline acetyltransferase activity in the hippocampus of rats with partial unilateral fimbria-fornix transection. Int J Dev Neurosci. 1995; 13:13-19.
 

 

Salvioli G, Neri M. L-acetylcarnitine treatment of mental decline in the elderly. Drugs Exp Clin Res. 1994; 20:169-176.
 

 

Sano M, Bell K, Cote L, et al. Double-blind parallel pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Arch Neurol. 1992; 49:1137-1141.
 

 

Thal LJ, Carta A, Clarke WR, et al. A one year multicenter placebo-controlled study of acetyl-L-carnitine in patients with Alzheimer's disease. Neurology. 1996; 47:705-711.
 

 

White HL, Scates PW. Acetyl-L-carnitine as a precursor of acetylcholine. Neurochem Res. 1990; 15:597-601.
 

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Vitamins.com

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Smartbomb.com

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