1. L-CARNITINE, L-ACETYLCARNITINE INDICATIONS:

L-carnitine has numerous applications including angina(1), recovery from myocardial infarction(2), arrhythmia(3), congestive heart failure(4), peripheral vascular disease(5) and enhancing physical performance(6). Acetyl -L-carnitine in particular has shown application in Alzheimer's disease(7), senile depression(8), age-related memory defect(9) and Down's syndrome(10). L-carnitine has also shown benefit in kidney disease and hemodialysis(11), diabetes(12), liver disease(13), low sperm counts and depressed sperm mobility(15), chronic obstructive pulmonary disease(16), AIDS(17), inborn errors of amino acid metabolism(18), and protection against drug toxicity(19). Low levels are noted in muscular dystrophy(14).

DOSAGE:

The daily dosage of L-carnitine is usually between 1,500 and 4,000 mg in divided doses(around 20 mg/kg). Lower doses should be used in patients on hemodialysis because of a paradoxical effect on triglyceride levels and platelet aggregation. Slightly higher doses of 3 gm/day have been used in chronic renal failure.

SIDE EFFECTS AND INTERACTIONS:

There are no side effects of L-carnitine. D-carnitine can produce side effects as well as interfering with the function of L-carnitine. Carnitine, coenzyme Q10 and pantethine work together synergistically. Choline supplementation results in a conservation of carnitine and may increase intracellular levels. Carnitine, a water-soluble amino acid, is an essential cofactor of several enzymes necessary for the transport of free long-chain fatty acids into the mitochondrial matrix for beta-oxidation. In the cytoplasm of the cell, long-chain fatty acids are linked with Coenzyme A, forming acylCoA which is then esterified to acylcarnitine before it can cross the mitochondrial membrane. Acylcarnitine transferase I and carnitine translocase assist this process. Inside the mitochondria, acylcarnitine transferase II transforms acylcarnitine back into acylCoA for beta-oxidation. Carnitine is found in all tissues with high amounts in skeletal muscle and myocardium. Free L-carnitine levels are much lower in infarcted myocardial tissue than normal resulting in an accumulation of free fatty acids and long-chain acylCoA and higher lactate production which may lead to tissue damage. L-carnitine is also involved in the conversion of keto-acid analogues of the branched chain amino acids valine, leucine and isoleucine, an important function during fasting, starvation and exercise. Acetyl-L-carnitine, the acetyl derivative of L-carnitine, traverses the mitochondrial inner membrane, providing a transport mechanism for acetyl groups. These arise during the beta oxidation of fatty acids in the mitochondria and then recombine with acetyl-CoA in the cytosol. It is structurally similar to acetylcholine and appears to have similar actions in the CNS, both directly and by a supportive effect on choline acetyltransferase, the generative enzyme for acetylcholine. It also has a scavenger effect on the superoxide anion and increases reduced glutathione and coenzymeQ10, thereby decreasing membrane lipid peroxidation, protecting the membrane. It also enhances mitochondrial energy production by several mechanisms. Carnitine's ability to improve oxygen utilization and energy metabolism in myocardial tissue explains its benefit in angina, recovery from myocardial infarction, arrythmia and congestive heart failure. Similarly, these same improvements in non-cardiac muscle benefits patients with peripheral vascular disease, chronic obstructive pulmonary disease, and enhances physical performance. L-acetylcarnitine's structural similarity to acetylcholine led to its use, with positive results, in Alzheimer's disease, senile depression, age-related memory defect, and Down's Syndrome. It's use in kidney disease relates to a deficiency in these patients secondary to diminished production by the kidney, the major source of carnitine, and carnitine loss in hemodialysis. Its role in fatty acid metabolism may explain its benefit in liver disorders secondary to fatty acid infiltration, a common pathology in the liver. L-carnitine is critical to sperm energy metabolism explaining it's benefit in low sperm counts and decreased motility. Its benefit in AIDS relates to diminished levels and the prevention of toxicity of AZT on muscle mitochondria. A similar mechanism may be involved in protection of heart muscle against adriamycin.

1. Bartels GL, et al., Effects of L-propionylcarnitine on ischemia-induced myocardial dysfunction in men with angina pectoris. Am J Cardiol 74, 125-130, 1994
2. Davini P, et al., Controlled study on L-carnitine therapeutic efficacy in post-infarction. Drugs Exp Clin Ress 18, 355-365, 1992
3. Goa KL and Brogden RN, L-carnitine- A preliminary review of its pharmacokinetics, and its therapeutic use in ischemic cardiac disease and primary and secondary carnitine deficiencies in relationship to its role in fatty acid metabolism. Drugsa 34, 1-24, 1987
4. Pucciarelli G, et al., The clinical and hemodynamic effects of propionyl-L-carnitine in the treatment of congestive heart failure. Clin Ther 141, 379-384, 1992
5. Sabba C, et al., Comparison between the effect of L-propionylcarnitine, L-acetylcarnitine and nitroglycerin in chronic peripheral arterial disease: A haemodynamic double-blind echo-doppler study. Eur Heart J 15, 1348-1352, 1994
6. Huertas R, et al., Respiratory chain enzymes in muscles of endurance athletes: Effect of L-carnitine. Biochem Biophy Res Comm 188, 102-107, 1992
7. Pettegrew JW, et al., Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer-s disease. Neurobiol Aging 16, 1-4, 1995
8. Garyza G, et al., Evaluation of the effects of L-acetylcarnitine on senile patients suffering from depression. Drugs Exp Clin Res 101, 106, 1990
9. Salvioli G and Neri M, L-acetylcarnitine treatment of mental decline in the elderly. Drugs Exp Clin Res 20, 169-176, 1994
10. DeFalco FA, et al., Effect of the chronic treatment with L-acetylcarnitine in Down's syndrome. Clin Ther 144, 123-127, 1994
11. Golper TA, et al., Multicenter trial of L-carnitine in maintenance hemodialysis. Kidney International 38, 904-918, 1990
12. Greco AV, et al., Effects of proprionyl-L-carnitine in the treatment of diabetic angiopathy: Controlled double-blind trial versus placebo. Drugs Exp Clin res 18, 69-80, 1992
13. Noto R, et al., Free fatty acids and carnitine in patients with liver disease. Curr Ther Res 40, 35-39, 1986
14. Carrier HN and Berthiller G, Carnitine levels in normal children and adults and in patients with diseased muscle. Muscle Nerve 3, 326-334, 1980
15. Costa M, et al., L-carnitine in idiopathic asthenozoospermia: A multicenter study. Andrologia 26, 155-159, 1994
16. Dal Negro R, et al., L-carnitine and physiokinesiotherapy in chronic respiratory insufficiency. Clinical Trials J 22, 353-360, 1985
17. De Simone C, et al., Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: Effect of oral L-carnitine. AIDS 8, 655-660, 1994
18. Seccombe DW, James L, and Booth F, L-carnitine treatment in glutaric aciduria type I, Neurology 36, 264-267. 1986
19. Freeman JM, Does carnitine administration improve the symptoms attributed to anticonvulsant medications? A double-blinded, crossover study. Pediatrics 93, 893-895, 1994

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