Acetyl-L-carnitine and L-carnitine
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1 FACTSHEET Acetyl-L-carnitine and L-carnitine What is carnitine? L-carnitine is an amino acid found in red meat and acetyl-l-carnitine is another form of this nutrient. Carnitine can be made in small quantities by the brain, liver and kidneys. Among other things, this amino acid plays a role in helping to release energy from fat by moving fats to power plants within cells where fats can be burnt as fuel. These cellular power plants, called mitochondria, are responsible for making the energy a cell needs to survive and function. How does carnitine work? Carnitine appears to have antioxidant properties and may also play a role in maintaining blood sugar levels. According to at least one study, people with HIV can have normal levels of carnitine in their serum (the fluid part of the blood) while still having very low levels in the cells, where carnitine is needed. In people with HIV whose health has improved because of anti-hiv drugs (antiretroviral therapy, or ART), carnitine levels may not return to normal. When taken orally as a supplement, only a relatively small amount between 5% and 18% of carnitine is absorbed. Why do people with HIV use this supplement? Carnitine has many potential uses, including the following: 1. to help heal damaged nerves from peripheral neuropathy (PN) 2. to decrease levels of lactic acid in the blood 3. to reduce higher-than-normal levels of cholesterol and/or triglycerides 4. to avoid muscle wasting and fatigue 5. to delay or minimize fat wasting 1. To help heal damanged nerves from PN Levels of carnitine in the blood are sometimes lower in people who have HIV and PN (nerve damage that causes tingling, numbness or burning in the hands, feet and legs), particularly under the following conditions: damage from viral infections such as HIV and CMV (cytomegalovirus) the use of d drugs such as d4t, ddi and ddc the use of some anti-cancer drugs and antibiotics the consumption of large amounts of alcohol diabetes ACETYL-L-CARNITINE AND L-CARNITINE page 1 of 6
2 What the medications in the above list have in common is that they can damage the energy-producing parts of nerve cells the mitochondria. Injured mitochondria cannot supply sufficient energy and nerves begin to malfunction and can die. Nerves in the feet, legs and hands, particularly in the skin covering those body parts, appear to be especially susceptible to PN. Some researchers have noticed that people with both HIV and PN can develop abnormal sweating, suggesting that nerves in sweat glands can also be affected. One formulation of carnitine, acetyl-lcarnitine (ALCAR), may play a role in the management of PN. This compound helps mitochondria function and also appears to enhance the effect of a chemical that helps nerves grow nerve growth factor. Researchers in England conducted an extensive study of ALCAR in people who have both HIV and PN. Their findings revealed that most people with HIV showed some degree of recovery from nerve damage after taking 1.5 grams of ALCAR twice daily for up to 2¾ years. Seventy-six percent of participants had significantly reduced pain. Because this was not a controlled clinical trial comparing ALCAR to a placebo or another substance, researchers cannot be certain that the reduction in pain was indeed caused by ALCAR. To clarify this issue, placebo-controlled studies of ALCAR are needed. In the British study, analyses of skin samples taken during the clinical trial found that after six months of ALCAR use, nerve fibres were undergoing re-growth. The longer participants took the supplement, the greater the regrowth. Nerve fibres grow slowly so it takes many months, perhaps even years, for the damage from PN to heal. There were no significant changes to CD4+ and CD8+ cells or viral load measures during the study. The research team speculates that ALCAR may have helped nerves for the following reasons: Carnitine has antioxidant properties, which may protect nerve cells from the toxicity of the class of anti-hiv drugs known as nucleoside analogues (or nukes). By improving the transport of fats and sugar, carnitine may have helped cells become more energetic and active, perhaps stimulating their recovery. Carnitine could have helped nerve regrowth and repair by enhancing the effects of nerve growth factor. People living with both HIV and PN have been found to have decreased levels of ALCAR in their blood and the supplement may have reversed this. Overall, this study goes a long way toward helping researchers explore the role of carnitine, particularly ALCAR, as part of the management of PN. Two randomized, placebo-controlled studies for which participants took 500 mg/day or 1,000 mg/day have also found it to be beneficial in the management of PN in HIVnegative people with diabetes. 2. To help reduce levels of lactic acid in the blood One of the complications that can occur in users of the anti-hiv drugs called nucleoside analogues is the development of higher-thannormal levels of lactic acid. If levels become very high, the following signs/symptoms may occur as part of a condition called lactic acidosis: unexpected tiredness abdominal pain swollen, fatty liver shortness of breath nausea and/or vomiting ACETYL-L-CARNITINE AND L-CARNITINE page 2 of 6
3 The following blood tests help identify lactic acidosis: lactate levels of 5 mmol/l or greater bicarbonate levels of 20 mmol/l or lower Anecdotal reports suggest that L-carnitine may play a role in helping people with HIV to recover from lactic acidosis. In a pilot study of six people with HIV who were extremely ill and who had high levels of lactic acid in their blood from drug-related side effects, researchers gave them intravenous L-carnitine at doses between 50 mg and 100 mg/kg of body weight per day. Despite this treatment, only three of the participants survived and recovered from lactic acidosis. Other researchers have intervened at earlier stages of lactic acidosis with oral supplements of B vitamins and L-carnitine with successful results. 3. To reduce high levels of cholesterol and/or triglycerides in the blood Having higher-than-normal levels of lipids cholesterol and triglycerides in the blood increases the risk of cardiovascular disease. In a small, controlled trial of HIV-positive people, carnitine caused triglyceride levels to drop significantly after two weeks at a dose of six grams daily. However, this study was done in 1993, when AZT was the only antiretroviral drug being used. In 2001, results of a pilot study in Montreal were released. L-carnitine at a dose of 3 grams daily was used by 16 people with HIV who were also taking anti-hiv drugs. Triglyceride levels decreased significantly within the first month and by the end of the study had deceased by about 35%. By the end of the study, 70% of participants had their triglyceride levels return to the normal range. In the same year, a German study found that L-carnitine at a dose of 1 gram twice daily for three months lowered cholesterol but not triglyceride levels in 12 people living with HIV. 4. To avoid muscle wasting and fatigue Some HIV-positive people use carnitine supplements to treat muscle wasting and fatigue due to anti-hiv drugs. A 1994 study of 21 men with AZT-related muscle wasting (myopathy) showed that the men s muscle tissue had been damaged and that lipids (fats) had built up in the tissue. The study also showed that the most badly damaged muscle had the lowest levels of carnitine. A test-tube study done the same year suggested that carnitine supplements might improve AZT-related myopathy, although no trials in HIV-positive people have been done to assess this compound s impact on muscle wasting and fatigue. 5. To delay or minimize fat wasting L-carnitine has been tested in Germany as a potential treatment to stop the loss of fat that can occur from the HIV lipodystrophy syndrome. Twelve people with HIV were given 1 gram of L-carnitine twice daily for three months. This supplement did not prevent fat loss, though cholesterol levels fell significantly (triglyceride levels did not). For more information about lipodystrophy and ways to manage HIV drug-related side effects, please see CATIE s Practical Guide to Managing Drug Side Effects at sideeffects_e.nsf. Side effects 1. Gastrointestinal Nausea, vomiting and diarrhea may occur, especially in people who take more than 4 grams per day. 2. Neurological Seizures have been reported by some people taking carnitine supplements, regardless of whether or not these people had seizures in the past. ACETYL-L-CARNITINE AND L-CARNITINE page 3 of 6
4 3. Thyroid hormones The hormones produced by the thyroid gland are called T3 (triiodothyronine) and T4 (thyroxine). Thyroid hormones help control the body s ability to produce energy and regulate its temperature. In lab experiments, L-carnitine blocks the ability of cells to respond to these hormones. In studies in HIVnegative people, L-carnitine, at doses of 2 or 4 grams per day, reduced thyroid hormone levels. We are not sure what effect lower doses of carnitine might have on thyroid hormone levels. If thyroid hormone levels fall below normal, a range of symptoms may develop, including the following: unexpected tiredness feeling cold dry skin muscle weakness forgetfulness and difficulty concentrating impaired hearing If you are taking carnitine supplements, your doctor may wish to regularly monitor the health of your thyroid gland. 4. Pregnancy Carnitine has not been studied in pregnant women. Therefore, the manufacturer suggests that carnitine be used by pregnant women only if it is clearly needed. Drug interactions Always tell your doctor and other members of your healthcare team about all the medications prescription and nonprescription herbs and supplements that you are taking. Carnitine may interfere with the following drugs: drugs to treat or prevent blood clots acenocoumarol/nicoumalone (Sintrom) thyroid hormones Dosage and formulations Carnitine is produced by the Sigma-Tau company, in Italy, in two formulations: L-carnitine acetyl-l-carnitine The dose usually recommended for people with HIV varies from 500 mg to 3,000 mg (3 grams) a day. This can be divided into several doses and taken with food. Availability L-carnitine is sold under the brand name Carnitor and is available by prescription in North America. Acetyl-L-carnitine (ALCAR) is sold under the brand name Nicetile in Italy and some countries of the European Union. Sigma- Tau does not appear to market ALCAR in North America. In Canada and the United States, some health food stores also sell different brands and formulations of carnitine. All formulations of carnitine are expensive. ALCAR is more often used in studies of neuropathy and may be most useful for this condition. Both formulations of carnitine have been used in trials related to HIV, although some HIV nutritional experts have suggested the acetyl form may be more useful. References Carnitor (levocarnitine). Product Monograph. Compendium of Pharmaceutical Specialties Vaz FM and Wanders RJ. Carnitine biosynthesis in mammals. Biochemical Journal. 2002;361(Pt 3): De Simone C, Tzantzoglou S, Jirillo E et al. L-carnitine deficiency in AIDS patients. AIDS. 1992;6(2): De Simone C, Famularo G, Tzantzoglou S et al. Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of oral L-carnitine. AIDS. 1994;8: Vilaseca MA, Artuch R, Sierra C et al. Low serum carnitine in HIV-infected children on antiretroviral treatment. European Journal of Clinical Nutrition. 2003;57(10): Famularo G, De Simone C. Carnitine stands on its own in HIV infection treatment. Archives of Internal Medicine May;159: ACETYL-L-CARNITINE AND L-CARNITINE page 4 of 6
5 Evans AM and Fornasini G. Pharmacokinetics of L-carnitine. Clinical Pharmacokinetics. 2003;42(11): Famularo G, Moretti S, Marcellini S et al. Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. AIDS Feb;11(2): Ilias I, Manoli I, Blackman MR et al. L-Carnitine and acetyl-lcarnitine in the treatment of complications associated with HIV infection and antiretroviral therapy. Mitochondrion Jul;4(2-3): Sima AA, Calvani M, Mehra M et al. Acetyl-L-carnitine improves pain, nerve regeneration, and vibratory perception in patients with chronic diabetic neuropathy: an analysis of two randomized placebo-controlled trials. Diabetes Care Jan;28(1): Hart AM, Wilson AD, Montovani C et al. Acetyl-l-carnitine: a pathogenesis based treatment for HIV-associated antiretroviral toxic neuropathy. AIDS. 2004;18(11): Vrouenraets SM, Treskes M, Regez RM et al. Hyperlactataemia in HIV-infected patients: the role of NRTI-treatment. Antiviral Therapy. 2002;7(4): Brinkman K, Vrouenraets S, Kauffmann R et al. Treatment of nucleoside reverse transcriptase inhibitor-induced lactic acidosis. AIDS. 2000;14(17): Carter RW, Singh J, Archambault C and Arrieta A. Severe lactic acidosis in association with reverse transcriptase inhibitors with potential response to L-carnitine in a pediatric HIV-positive patient. AIDS Patient Care and STDs. 2004;18(3): Dalakas MC, Leon-Monzon ME et al. Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. Annals of Neurology April;35(4): Georges B, Galland S, Rigault C et al. Beneficial effects of L-carnitine in myoblastic C2C12 cells. Interaction with zidovudine. Biochemical Pharmacology May;65(9): Mauss S and Schmutz G. L-Carnitine in the treatment of HIVassociated lipodystrophy syndrome. HIV Medicine Jan;2(1): Benvenga S, Amato A, Calvani M and Trimarchi F. Effects of carnitine on thyroid hormone action. Annals of the New York Academy of Sciences Nov;1033: Bachmann HU and Hoffmann A. Interaction of food supplement L-carnitine with oral anticoagulant acenocoumarol. Swiss Medical Weekly Jun 26;134(25-26):385. Ferraresi R, Troiano L, Roat E et al. Protective effect of acetyl-l-carnitine on oxidative damage induced by antiretroviral drugs. Program and abstracts of the 7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV; November, Dublin, Ireland. Poster 84. Author: Hosein SR Published: 2012 Claessens YE, Cariou A, Monchi M et al. Detecting lifethreatening lactic acidosis related to nucleoside-analog treatment of human immunodeficiency virus-infected patients, and treatment with L-carnitine. Critical Care Medicine. 2003;31(4): Muller DM, Seim H, Kiess W et al. Effects of oral L-carnitine supplementation on in vivo long-chain fatty acid oxidation in healthy adults. Metabolism. 2002;51(11): De Simone C, Tzantzoglou S et al. High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients. Immunopharmacology and Immunotoxicology Jan;15(1):1-12. Loignon M and Toma E. L-Carnitine for the treatment of highly active antiretroviral therapy-related hypertriglyceridemia in HIV-infected adults. AIDS Jun 15;15(9): Mingrone G. Carnitine in type 2 diabetes. Annals of the New York Academy of Sciences Nov;1033: Day L, Shikuma C and Gerschenson M. Acetyl-L-carnitine for the treatment of HIV lipoatrophy. Annals of the New York Academy of Sciences. 2004;1033: ACETYL-L-CARNITINE AND L-CARNITINE page 5 of 6
6 Contact us by telephone by fax by by mail Richmond Street West Toronto ON M5V 3B1 Disclaimer Decisions about particular medical treatments should always be made in consultation with a qualified medical practitioner knowledgeable about HIV- and hepatitis C-related illness and the treatments in question. CATIE (Canadian AIDS Treatment Information Exchange) in good faith provides information resources to help people living with HIV and/or hepatitis C who wish to manage their own healthcare in partnership with their care providers. Information accessed through or published or provided by CATIE, however, is not to be considered medical advice. We do not recommend or advocate particular treatments and we urge users to consult as broad a range of sources as possible. We strongly urge users to consult with a qualified medical practitioner prior to undertaking any decision, use or action of a medical nature. We do not guarantee the accuracy or completeness of any information accessed through or published or provided by CATIE. Users relying on this information do so entirely at their own risk. Neither CATIE nor the Public Health Agency of Canada nor the Ontario Ministry of Health and Long-Term Care, nor any of their employees, directors, officers or volunteers may be held liable for damages of any kind that may result from the use or misuse of any such information. The views expressed herein or in any article or publication accessed or published or provided by CATIE are solely those of the authors and do not reflect the policies or opinions of CATIE nor the views of the Public Health Agency of Canada nor the Ontario Ministry of Health and Long-Term Care. Permission to reproduce This document is copyrighted. It may be reprinted and distributed in its entirety for non-commercial purposes without prior permission, but permission must be obtained to edit its content. The following credit must appear on any reprint: This information was provided by the Canadian AIDS Treatment Information Exchange (CATIE). For more information, contact CATIE at Funding has been provided by the Public Health Agency of Canada. CATIE Ordering Centre No: ATI (aussi disponible en français, ATI-50061) CATIE fact sheets are available for free at ACETYL-L-CARNITINE AND L-CARNITINE page 6 of 6
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