Acetyl L-Carnitine


Clinical Studies
References


Acetyl-L-Carnitine occurs naturally in the body within the inner membrane of mitochondria. It is structurally related to acetylcholine, a neurotransmitter. Acetyl-L-Carnitine is used for Alzheimer's disease, age-related memory deficits, senile depression, Down syndrome, alcoholism-related cognitive deficits and cerebro-vascular insufficiency after stroke as it increases cerebral blood flow. It is also used for peripheral neuropathies, diabetic neuropathy, neuropathy due to anti-viral drugs used in the treatment of AIDS, facial paralysis, male infertility and Peyronie's disease, as an increase in sperm motility is seen in vitro when acetyl-L-Carnitine or L-Carnitine is added to the sample.


Published Clinical Studies
Acetyl L-Carnitine
   


Acetyl-L-carnitine supplementation restores decreased tissue carnitine levels and impaired lipid metabolisms in aged rats.

Tanaka Y, Sasaki R, Fukui F, Waki H, Kawabata T, Okazaki M, Hasegawa K, Ando S.

The aim of this study was to evaluate the effect of long-term carnitine supplementation on age-related changes in tissue carnitine levels and in lipid metabolism. The total carnitine levels in heart, skeletal muscle, cerebral cortex and hippocampus were about 20 % less in aged rats than in young rats. On the contrary, serum carnitine levels were not affected by aging. Young and aged rats were given acetyl-L-carnitine (ALCAR, 100 mg/kg BW/day) for 3 months and sacrificed at ages of 6 and 22 months. This treatment significantly increased the tissue carnitine levels in aged rats, but had little effect on the tissue carnitine levels in young rats. Serum triacylglycerol, cholesterol and phospholipid levels were higher in aged rats than in young rats. Lipoprotein analyses revealed that triacylglycerol levels in very low density lipoprotein (VLDL), and cholesterol levels in low density lipoprotein (LDL) and in high density lipoprotein (HDL) were all significantly higher in aged rats than in young rats. Supplementation of ALCAR decreased all lipoprotein fractions and consequently the levels of triacylglycerol and cholesterol. The reduction in serum cholesterol contents in aged rats when treated with ALCAR was mainly due to a decrease of cholesteryl esters than to a decrease of free cholesterol. Another remarkable effect of ALCAR was that it decreased the cholesterol content and cholesterol/phospholipid ratio in the brain tissues of aged rats. These results indicate that chronic ALCAR supplementation reverses the age-associated changes in lipid metabolism.

PMID: 14703509 [PubMed - as supplied by publisher]

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Brain-specific" nutrients: a memory cure?

McDaniel MA, Maier SF, Einstein GO.

Department of Psychology, University of New Mexico, Albuquerque, New Mexico 87131, USA. mcdaniel@umn.edu

OBJECTIVE: We review the experimental evaluations of several widely marketed nonprescription compounds claimed to be memory enhancers and treatments for age-related memory decline. We generally limit our review to double-blind placebo-controlled studies. The compounds examined are phosphatidylserine (PS), phosphatidylcholine (PC), citicoline, piracetam, vinpocetine, acetyl-L-carnitine (ALC), and antioxidants (particularly vitamin E). RESULTS: In animals, PS has been shown to attenuate many neuronal effects of aging, and to restore normal memory on a variety of tasks. Preliminary findings with humans, though, are limited. For older adults with probable Alzheimer's disease, a single study failed to demonstrate positive effects of PS on memory performance. For older adults with moderate cognitive impairment, PS has produced consistently modest increases in recall of word lists. Positive effects have not been as consistently reported for other memory tests. There is one report of consistent benefits across a number of memory tests for a subset of normal adults who performed more poorly than their peers at baseline. The choline compounds PC and citicoline are thought to promote synthesis and transmission of neurotransmitters important to memory. PC has not proven effective for improving memory in patients with probable Alzheimer's disease. The issue remains open for older adults without serious degenerative neural disease. Research on citicoline is practically nonexistent, but one study reported a robust improvement in story recall for a small sample of normally aging older adults who scored lower than their peers in baseline testing. Animal studies suggest that piracetam may improve neuronal efficiency, facilitate activity in neurotransmitter systems, and combat the age-related decrease in receptors on the neuronal membrane. However, for patients with probable Alzheimer's disease, as well as for adults with age-associated memory impairment, there is no clear-cut support for a mnemonic benefit of piracetam. Vinpocetine increases blood circulation and metabolism in the brain. Animal studies have shown that vinpocetine can reduce the loss of neurons due to decreased blood flow. In three studies of older adults with memory problems associated with poor brain circulation or dementia-related disease, vinpocetine produced significantly more improvement than a placebo in performance on global cognitive tests reflecting attention, concentration, and memory. Effects on episodic memory per se have been tested minimally, if at all. ALC participates in cellular energy production, a process especially important in neurons, and in removal of toxic accumulation of fatty acids. Animal studies show that ALC reverses the age-related decline in the number of neuron membrane receptors. Studies of patients with probable Alzheimer's disease have reported nominal advantages over a range of memory tests for ALC-treated patients relative to placebo groups. Significant differences have been reported rarely, however. Whether ALC would have mnemonic benefits for aging adults without brain disease is untested as far as we know. Antioxidants help neutralize tissue-damaging free radicals, which become more prevalent as organisms age. It is hypothesized that increasing antioxidant levels in the organism might retard or reverse the damaging effects of free radicals on neurons. Thus far, however, studies have found that vitamin E does not significantly slow down memory decline for Alzheimer's patients and does not produce significant memory benefits among early Parkinson's patients. Neither did a combination of vitamins E and C significantly improve college students' performance on several cognitive tasks. CONCLUSIONS: In sum, for most of the "brain-specific" nutrients we review, some mildly suggestive effects have been found in preliminary controlled studies using standard psychometric memory assessments or more general tests designed to reveal cognitive impairment. We suggest that future evaluations of the possible memory benefits of these supplements might fruitfully focus on memory processes rather than on memory tests per se.

PMID: 14624946 [PubMed - in process]

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[Neural and molecular mechanisms of fatigue and recovery from fatigue]

Watanabe Y.

Department of Physiology, Osaka City University Graduate School of Medicine, 1-4-3, Asahi-cho, Abeno-ku, Osaka, 545-8585 Japan.

Fatigue is an indispensable biosignal for maintaining life. However, the neural/molecular mechanisms of fatigue are still unclear. Here, the recent progress in this field is introduced, mostly through our project research under the control of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japanese Government. The sensing mechanisms of fatigue in the brain might be related to the orbitofrontal-dorsoprefrontal-cingulate triangle circuits. We hypothesized the neural circuits for fatigue sensation through our PET study on chronic fatigue patients and healthy volunteers. The serotonergic system might be involved in the sensation in the prefrontal cortex, although the hyperserotonin hypothesis might be wrong. The fatigue sensation is somehow related to hypofunction of the glutamatergic system through reduced uptake of acetyl-carnitine in the discrete brain regions. For creation of new methods and drugs overcoming fatigue, different types of animal models of fatigue were developed. By using such animal models, the green leaf odor, ascorbic acid, acetyl-carnitine, and tetrahydrobiopterin have been found to be effective.

Publication Types:

  • Review
  • Review, Tutorial


PMID: 12884756 [PubMed - indexed for MEDLINE]

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Neuroprotective effects of L-carnitine in induced mitochondrial dysfunction.

Binienda ZK.

Neurophysiology Laboratory, Division of Neurotoxicology, National Center for Toxicological Research/FDA, Jefferson, Arkansas 72079, USA. zbinienda@nctr.fda.gov

The neuroprotective action of l-carnitine (LC) in the rat model of 3-nitropropionic acid (3-NPA)-induced mitochondrial dysfunction was examined. 3-NPA is known to produce decreases in neuronal ATP levels via inhibition of the succinate dehydrogenase (SDH) at complex II of the mitochondrial electron transport chain. SDH is involved in reactions of the Krebs cycle and oxidative phosphorylation, and its inhibition leads to both necrosis and apoptosis. LC enhances mitochondrial metabolism and, together with its acetylated form, acetyl-l-carnitine (ALC), via the LC-ALC-mediated transfer of acetyl groups, plays an important modulatory role in neurotransmitter signal transduction pathways and gene expression in neuronal cells. In the study described here, adult male Sprague-Dawley rats were injected with 3-NPA alone or treated with LC prior to 3-NPA administration. Pretreatment with LC totally prevented the 3-NPA-induced decrease in brain temperature measured using temperature probes implanted intracranially. It appears that the protective effects of LC against 3-NPA-induced neurotoxicity are achieved via compensatory enhancement of several pathways of mitochondrial energy metabolism. The results of this and previous studies conducted by our division in the 3-NPA model of mitochondrial dysfunction demonstrate that 3-NPA may be employed in vivo to evaluate enhancers of mitochondrial function that might exert neuroprotective effects.

PMID: 12853320 [PubMed - indexed for MEDLINE]

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Effects of acetyl-L-carnitine in Alzheimer's disease patients unresponsive to acetylcholinesterase inhibitors.

Bianchetti A, Rozzini R, Trabucchi M.

Geriatric Research Group, Brescia, Italy. angelo.bianchetti@grg-bs.it

Acetyl-L-carnitine (ALC) is a compound acting as an intracellular carrier of acetyl groups across inner mitochondrial membranes. It also appears to have neuroprotective properties and it has recently been shown to reduce attention deficits in patients with Alzheimer's disease (AD) after long-term treatment. We performed an open study to evaluate the effect of ALC (2 g/day orally for 3 months) in association with donepezil or rivastigmine in 23 patients with mild AD who had not responded to treatment with acetylcholinesterase inhibitors (AChE-I). Clinical effects were evaluated by assessing cognitive functions, functional status and behavioural symptoms. The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of ALC, indicating that the combination of these two drugs may be a useful therapeutic option in AD patients. These data do not permit a conclusion as to the possible mechanism of action of the association of the two treatments.

Publication Types:

  • Clinical Trial


PMID: 12841930 [PubMed - indexed for MEDLINE]

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Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl-L-carnitine treatment.

McKay Hart A, Wiberg M, Terenghi G.

Blond-McIndoe Centre, Royal Free and University College Medical School, University Department of Surgery, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK.

Peripheral nerve trauma remains a major cause of morbidity, largely due to the death of approximately 40% of innervating sensory neurons, and to slow regeneration after repair. Acetyl-L-carnitine (ALCAR) is a physiological peptide that virtually eliminates sensory neuronal death, and may improve regeneration after primary nerve repair. This study determines the effect of ALCAR upon regeneration after secondary nerve repair, thereby isolating its effect upon neuronal regenerative capacity. Two months after unilateral sciatic nerve division 1 cm nerve graft repairs were performed (n=5), and treatment with 50 mg/kg/day ALCAR was commenced for 6 weeks until harvest. Regeneration area and distance were determined by quantitative immunohistochemistry. ALCAR treatment significant increased immunostaining for both nerve fibres (total area 264% increase, P<0.001; percentage area 229% increase, P<0.001), and Schwann cells (total area 111% increase, P<0.05; percentage area 86% increase, P<0.05), when compared to no treatment. Regeneration into the distal stump was greatly enhanced (total area 2,242% increase, P=0.008; percentage area 3,034% increase, P=0.008). ALCAR significantly enhances the regenerative capacity of neurons that survive peripheral nerve trauma, in addition to its known neuroprotective effects.

PMID: 12453625 [PubMed - indexed for MEDLINE]

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Reversal of biochemical and behavioral parameters of brain aging by melatonin and acetyl L-carnitine.

Sharman EH, Vaziri ND, Ni Z, Sharman KG, Bondy SC.

Center for Occupational and Environmental Health, Department of Community and Environmental Medicine, University of California Irvine, Irvine, CA 92697-1825, USA.

The potential utility of dietary supplementation in order to prevent some of the oxidative and inflammatory changes occurring in the brain with age, has been studied. The cerebral cortex of 27-month-old male B6C3F1 mice had elevated levels of nitric oxide synthase 1 (EC 1.14.13.39) (nNOS) and peptide nitrotyrosine relative to cortices of younger (4-month-old) animals. After 25-month-old mice received basal diet together with 300 mg/l acetyl L-carnitine in the drinking water for 8 weeks, these levels were fully restored to those found in younger animals. A partial restoration was found when old animals received basal diet supplemented with 200 ppm melatonin in the diet. Levels of mRNA (messenger RNA) for nNOS were unchanged following these treatments implying translational regulation of nNOS activity. Behavioral indices indicative of exploratory behavior were also depressed in aged animals. Dietary supplementation with melatonin or acetyl L-carnitine partially reversed these changes. These findings suggest that dietary supplementation cannot merely arrest but indeed reverse some age-related increases in markers of oxidative and inflammatory events occurring with the cortex.

PMID: 12445964 [PubMed - indexed for MEDLINE]

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L-Acetylcarnitine induces analgesia by selectively up-regulating mGlu2 metabotropic glutamate receptors.

Chiechio S, Caricasole A, Barletta E, Storto M, Catania MV, Copani A, Vertechy M, Nicolai R, Calvani M, Melchiorri D, Nicoletti F.

Department of Pharmaceutical Science, University of Catania, Cataniea, Italy.

L-Acetylcarnitine (LAC, 100 mg/kg, s.c.), a drug commonly used for the treatment of painful neuropathies, substantially reduced mechanical allodynia in rats subjected to monolateral chronic constriction injury (CCI) of the sciatic nerve and also attenuated acute thermal pain in intact rats. In both cases, induction of analgesia required repeated injections of LAC, suggesting that the drug induces plastic changes within the nociceptive pathway. In both CCI- and sham-operated rats, a 24-day treatment with LAC increased the expression of metabotropic glutamate (mGlu) receptors 2 and 3 in the lumbar segment of the spinal cord, without changing the expression of mGlu1a or -5 receptors. A similar up-regulation of mGlu2/3 receptors was detected in the dorsal horns and dorsal root ganglia of intact rats treated with LAC for 5-7 days, a time sufficient for the induction of thermal analgesia. Immunohistochemical analysis showed that LAC treatment enhanced mGlu2/3 immunoreactivity in the inner part of lamina II and in laminae III and IV of the spinal cord. An increased mGlu2/3 receptor expression was also observed in the cerebral cortex but not in the hippocampus or cerebellum of LAC-treated animals. Reverse transcription-polymerase chain reaction combined with Northern blot analysis showed that repeated LAC injections selectively induced mGlu2 mRNA in the dorsal horns and cerebral cortex (but not in the hippocampus). mGlu3 mRNA levels did not change in any brain region of LAC-treated animals. To examine whether the selective up-regulation of mGlu2 receptors had any role in LAC-induced analgesia, we have used the novel compound LY 341495, which is a potent and systemically active mGlu2/3 receptor antagonist. LAC-induced analgesia was largely reduced 45 to 75 min after a single injection of LY 341495 (1 mg/kg, i.p.) in both CCI rats tested for mechanical allodynia and intact rats tested for thermal pain. We conclude that LAC produces analgesia against chronic pain produced not only by peripheral nerve injury but also by acute pain in intact animals and that LAC-induced analgesia is associated with and causally related to a selective up-regulation of mGlu2 receptors. This offers the first example of a selective induction of mGlu2 receptors and discloses a novel mechanism for drug-induced analgesia.

PMID: 11961116 [PubMed - indexed for MEDLINE]

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Effects of treatment with carnitines in infertile patients with prostato-vesiculo-epididymitis.

Vicari E, Calogero AE.

Section of Andrology, Endocrinology and Internal Medicine, Department of Biomedical Sciences, University of Catania, Italy. acalogere@unict.it

BACKGROUND: We have recently shown that patients with prostato-vesiculo-epididymitis (PVE) have a greater reactive oxygen species (ROS) overproduction than patients with prostatitis or prostato-vesiculitis. Since this biochemical stress persists even after treatment with antimicrobials, it may relate to an imbalance between pro- and anti-oxidant factors at the epididymal level. METHODS: To evaluate the effects of antioxidant treatment of patients with PVE, whether in the presence or absence of pro-oxidant factors, abacterial PVE infertile patients with normal (<1x10(6)/ml, group A, n = 34) or abnormal (>1x10(6)/ml, group B, n = 20) seminal white blood cell (WBC) concentrations received carnitines (L-carnitine 1 g and acetyl-carnitine 0.5 g twice/day) for 3 months followed by a wash-out period of 3 months. Semen parameters, ROS production and pregnancy outcome were evaluated before, during and following carnitine treatment. RESULTS: Carnitines increased sperm forward motility and viability in group A patients. This was associated with a significant reduction in ROS production which persisted during wash-out. Carnitines increased only the percentage of viable spermatozoa in group B patients. Within 3 months after the discontinuation of carnitines, the rate of spontaneous pregnancy in group A patients was significantly higher than that of group B patients, being 11.7% (4/34) compared with 0%. CONCLUSION: These results indicate that carnitines are only an effective treatment in patients with abacterial PVE and elevated ROS production when seminal WBC concentration is normal.

PMID: 11679516 [PubMed - indexed for MEDLINE]

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Effect of acetylcarnitine treatment in oligoasthenospermic patients.

Moncada ML, Vicari E, Cimino C, Calogero AE, Mongioi A, D'Agata R.

First Department of Internal Medicine, University of Catania Medical School, Italy.

Acetylcarnitine (AC), present in human spermatozoa and seminal fluid, plays an important role in sperm metabolism. To further investigate the effect of AC on sperm quality, AC (4 g/day) was given to 20 patients with idiopathic oliogasthenospermia for 60 days. AC had no effects on sperm density and total motility, but it did significantly increase progressive sperm motility (mean +/- SEM: 21.7 +/- 3.2% vs 38.2 +/- 4.7). The increment in sperm motility was sustained ( > or = 40%) in 12 patients (mean increment 2.7 fold). This parameter returned to basal value 4 months after therapy discontinuation. Five pregnancies occurred during treatment and only 2 during the 4 months follow-up ensuing therapy discontinuation.

PMID: 1343182 [PubMed - indexed for MEDLINE]

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Neuroprotective effects of acetyl-L-carnitine after stroke in rats.

Lolic MM, Fiskum G, Rosenthal RE.

Department of Emergency Medicine, Ronald Reagan Institute of Emergency Medicine, Washington, DC, USA.

STUDY OBJECTIVE: To test the hypothesis that acetyl-L-carnitine (ALCAR) promotes neurologic recovery from experimental focal cerebral ischemia (stroke) in rats. METHODS: We conducted a prospective, randomized, blinded study in which adult male Sprague-Dawley rats were subjected to coagulative occlusion of the distal right middle cerebral artery (MCA) and temporary occlusion of both common carotid arteries (CCAs) for 60 minutes. After the onset of ischemia each rat was given ALCAR (200 mg/kg) or a similar volume of drug vehicle. Neurologic evaluation was performed on postoperative days 1, 2, 3, and 7. Postoperative weight loss was measured at day 7. Infarct volume was measured in separate groups of rats at 24 hours. RESULTS: Neurologic outcomes, as assessed with an 11-point neurologic deficit scoring system, were significantly improved in ALCAR-treated rats on days 1, 2, and 3 (P < .05). Improvement approached significance on day 7. Rats treated with ALCAR also demonstrated significantly less weight loss on day 7 compared with the vehicle-treated controls. We detected no differences, however, in infarct volumes measured between treatment groups. CONCLUSION: Although we noted no differences in infarct volume, postischemic treatment with ALCAR did improve early clinical recovery and prevented significant weight loss in this rat model of focal cerebral ischemia.

PMID: 9174521 [PubMed - indexed for MEDLIN]

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