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:
Chemical Structure
Acetyl-L-Carnitine
Acetyl-L-carnitine is also known as acetyl-carnitine, L-acetycarnitine, acetylcarnitine, acetyl levocarnitine, N-acetyl-L-carnitine, ALC and ALCAR.
Acetyl-L-carnitine is a delivery form for both L-carnitine and acetyl groups.
Actions & 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 motility. 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 is 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 & 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. One group of researchers suggested that acetyl-L-carnitine might be useful in the treatment of HIV lipoatrophy, although evidence for this is presently lacking.
Overdosage
There are no reports of overdosage.
Dosage
Typical doses of supplemental acetyl-L-carnitine are 500 milligrams to 2 grams daily in divided doses.
Literature
Aliev G, Liu J, Shenk JC, et al. Neuronal mitochondrial amelioration by feeding acetyl-L-carnitine and lipoic acid to aged rats. J Cell Mol Med. Epub: 2008 Mar 28.Brooks JO 3rd, Yesavage JA, Carta A, et al. 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.Chiechio S, Copani A, Gereau RW 4th, et al. Acetyl-L-carnitine in neuropathic pain: experimental data. CNS Drugs. 2007;21 Suppl 1:31-80;discussion 45-60.Chiechio S, Copani A, Nicoletti F, et al. L-acetylcarnitine: a proposed therapeutic agent for painful peripheral neuropathies. Curr Neuropharmacol. 2006;4(3):233-237.Chuang WW, Lin WW, Lamb DJ, et al. Effect of acetylcarnitine on sperm motility. J Urol. 2000; 163(4 Suppl):Abstract1324.Day L, Shikuma C, Gerschenson M. Acetyl-L-carnitine for the treatment of HIV lipoatrophy. Ann NY Acad Sci. 2004;1033:139-146.De Grandis D. Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review. CNS Drugs. 2007;21 Suppl 1:39-43; discussion 45-60.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, Liu J, Lykkesfeldt J, et al. Feeding acetyl-L-carnitine and lipoic acid to old rats significantly improves metabolic function while decreasing oxidative stress. Proc Natl Acad Sci U S A. 2002;99(4):1870-1875.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.Hudson S, Tabet N. Acetyl-L-carnitine for dementia. Cochrane Database Syst Rev. 2003;(2):CD003158.Lolic MM, Fiskum G, Rosenthal RE. Neuroprotective effects of acetyl-L-carnitine after stroke in rats. Ann Emerg Med. 1997;29:758-765.Milgram NW, Araujo JA, Hagen TM, et al. Acetyl-L-carnitine and alpha-lipoic acid supplementation of aged beagle dogs improves learning in two landmark discrimination tests. FASEB J. 2007;21(13):3756-3762.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.Pettegrew JW, Levine J, McClure RJ. Acetyl-L-carnitine physical-chemical, metabolic, and therapeutic properties: relevance for its mode of action in Alzheimer's disease and geriatric depression. Mol Psychiatry. 2000;5(6):616-632.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.Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci. 2004;1033:30-41.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.Sima AA. Acetyl-L-carnitine in diabetic polyneuropathy: experimental and clinical data. CNS Drugs. 2007;21 Suppl 1:13-23; discussion 45-60.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.Youle M. Acetyl-L-carnitine in HIV-associated antiretroviral toxic neuropathy. CNS Drugs. 2007;21 Suppl 1:25-30; discussion 45-46.Zhou X, Liu F, Zhai S. Effect of L-carnitine and/or L-acetyl-carnitine in nutrition treatment for male infertility: a systematic review. Asia Pac J Clin Nutr. 2007;16 Suppl 1:383-390.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.
Recently, there has been some further work with lipoic acid, in combination with acetyl-L-carnitine, related to aging. In one study, feeding acetyl-L-carnitine and alpha-lipoic acid to old rats was said to significantly improve metabolic function while decreasing oxidative stress. In another study, this same combination was reported to maintain myocardial function in aging rats. Beagle dogs between 7.6 and 8.8 years of age that were administered a twice-daily supplement of these agents over a two-month period reportedly made fewer errors in two learning tests, compared with controls. The researchers concluded that they believe long-term supplementation could slow cognitive decline in these animals. Whether these findings might have clinical relevance is unknown.
One group of researchers hypothesized that acetyl-L-carnitine might be useful in the treatment of HIV lipoatrophy, a syndrome that features both fat accumulation and wasting, sometimes accompanied by metabolic derangement of glucose and lipids. The researchers proposed a pilot study to test this hypothesis. As yet, there are no results to support or refute the idea.
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
Known hypersensitivity to an acetyl-L-carnitine-containing product.
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).
