There is an increasing body of evidence that subgroups of patients infected with human immunodeficiency virus type 1 possess carnitine deficiency. Secondary carnitine deficiencies in these individuals may result from nutritional deficiencies, gastrointestinal disturbances, renal losses, or shifts in metabolic pathways. However, tissue depletion precipitated by drug toxicities, particularly zidovudine, is a major etiology and concern. Carnitine deficiency may impact on energy and lipid metabolism, causing mitochondrial and immune dysfunction. There are convincing laboratory data showing the in vitro ameliorative effects of L-carnitine supplementation on zidovudine-induced myopathies and lymphocyte function. Studies measuring the impact of L-carnitine supplementation on clinical characteristics are ongoing. (J Child Neurol 1995; 10(Suppl):2540-2544).
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References
1.
Mintz M.: Clinical comparison of adult and pediatric neuroAIDS. Adv Neuroimmunol1995;4:207-221.
2.
Epstein L., Gendelman HE: Human immunodeficiency virus type 1 infection of the nervous system: Pathogenetic mechanisms. Ann Neurol1993 ;33:429-436.
3.
Surtees R., Hyland K., Smith I.: Central-nervous-system methyl-group metabolism in children with neurological complications of HIV infection. Lancet1990 ;335:619-621.
4.
Grunfeld C., Feingold RK: Metabolic disturbances and wasting in the acquired immunodeficiency syndrome . N Engl J Med1992;327:329-337.
5.
Herzlich BC, Schiano TD: Reversal of apparent AIDS dementia complex following treatment with vitamin B12. J Intern Med1993;233:495-497.
6.
Smith I., Howells DW, Kendall B., et al: Folate deficiency and demyelination in AIDS. Lancet1987;2:215.
7.
Stein TP, Nutinsky C., Condolucci D. et al: Protein and energy substrate metabolism in AIDS patients. Metabolism1990;39: 876-881.
8.
Aguilar JJ, Anel A., Torres JM, et al: Changes in lipid composition of human peripheral blood lymphocytes infected by HIV. AIDS Res Hum Retroviruses1991;7:761-765.
9.
Apostolov K. , Barker W., Galpin SA, et al: Syncytia formation in HIV-1-infected cells is associated with an increase in cellular oleic acid . FEBS Lett1989;250:241-244.
10.
Klein A., Mercure L., Gordon P., et al: The effect of HIV-1 infection on the lipid fatty acid content in the membrane of cultured lymphocytes. AIDS1990;4:865-867.
11.
Lynn WS, Tweedale A., Cloyd MW: Human immunodeficiency virus (HIV-1) cytotoxicity: Perturbation of the cell membrane and depression of phospholipid synthesis. Virology1988;163: 43-51.
12.
Memon RA, Feingold KR, Moser AH, et al: In vivo effects of interferon-alpha and interferon-gamma on lipolysis and ketogenesis. Endocrinology1992 ;131:1695-1702.
13.
DeSimone C. , Famularo G., Tzantzoglou S., et al: Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: Effect of oral L-carnitine . AIDS1994;8:655-660.
14.
DeSimone C. , Tzantzoglou S., Famularo G., et al: High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients. Immunopharmacol Immunotoxicol1993;15:1-12.
15.
Winter HS, Miller TL: Gastrointestinal and nutritional problems in pediatric HIV disease , in Wilfert CM, Pizzo PA (eds): Pediatric AIDS: The Challenge of HIV Infection in Infants, Children, and Adolescents. Baltimore, Williams & Wilkins, 1994, pp 513-534.
16.
Tomaka FL, Cimoch PJ, Reiter WM, et al: Prevalence of nutritional deficiencies in patients with HIV-1 infection, abstract no. PB0898. Int Conf AIDS1994;10:221.
17.
DeSimone C. , Tzantzoglou S., Jirillo E., et al: L-Carnitine deficiency in AIDS patients . AIDS1992;6:203-205.
18.
Bogden JD, Baker H., Frank O., et al: Micronutrient status and human immunodeficiency virus (HIV) infection. Ann N Y Acad Sci1990;587:189-195.
19.
Bohmer T., Rydning A., Solberg HE: Carnitine levels in human serum in health and disease. Clin Chim Acta1974;57:55-61.
Deufel T.: Determination of L-carnitine in biological fluids and tissues. J Clin ChemBiochem1990;28:307-311.
22.
Sekas G., Paul HS: Pyrimethamine and sulfadiazine administration produces carnitine deficiency, abstract. Presented at Current Concepts in Carnitine Research, Atlanta, 1991.
23.
Herzberg VL : Human T lymphocytes require lipid as either lipoprotein or nonesterified fatty acid for in vitro activation. Immunol Invest1991;20:507-513.
24.
Monti D., Cossarizza A., Troiano L., et al: Immunomodulatory properties of L-acetylcarnitine on lymphocytes from young and old humans, in DeSimone C, Arrigoni-Martelli E (eds): Stress, Immunity and Ageing. A Role for L-Acetylcarnitine. Amsterdam, Elsevier, 1989, pp 83-96.
25.
DeSimone C. , Ferrari M., Meli D., et al: Reversibility by L-carnitine of immunosuppression induced by an emulsion of soya bean oil, glycerol and egg lecithin. Drug Res1982;32:1485-1488.
26.
DeSimone C. , Tzantzoglou S., Moretti S., et al: Carnitine deficiency in HIV-infected subjects: Carnitine modulates S and Gr M phase lymphocytes . Ann N Y Acad Sci, in press.
27.
Grunfeld C. , Pang M., Doerrler W., et al: Lipids, lipoproteins, triglyceride clearance and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab1992; 74:104.r1052.
28.
Mildvan D., Machado SG, Wilets I., Grossberg SE: Endogenous interferon and triglyceride concentrations to assess response to zidovudine in AIDS and advanced AIDS-related complex. Lancet1992;339:453-456.
29.
Feingold KR, Grunfeld C.: Role of cytokines in inducing hyperlipidemia. Diabetes1992;41:97-101.
30.
Brew BJ, Bhalla RB, Paul M., et al: Cerebrospinal fluid beta-2 microglobulin in patients with AIDS dementia complex: An expanded series including response to zidovudine treatment . AIDS1992;6:461-465.
31.
Wesselingh SL , Power C., Glass JD, et al: Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dementia . Ann Neurol1993;33:576-582.
32.
Mintz M., Rapaport R., Oleske JM, et al: Elevated serum levels of tumor necrosis factor are associated with progressive encephalopathy in children with acquired immunodeficiency syndrome. Am J Dis Child1989;143:771-774.
33.
Simpson DM: Neuromuscular complications of human immunodeficiency virus infection . Semin Neurol1992;12:34-42.
34.
Walter EB, Drucker RP, McKinney RE, Wilfert C.: Myopathy in human immunodeficiency virus-infected children receiving long-term zidovudine therapy. J Pediatr1991 ;119:152-155.
35.
Dalakas MC, Illa I., Pezeshkpour GH, et al: Mitochondrial myopathy caused by long-term zidovudine therapy . N Engl J Med1990;322:1098-1105.
36.
Pezeshkpour GH, Illa I., Dalakas MC: Ultrastructural characteristics and DNA immunocytochemistry in HIV and AZT-associated myopathies. Hum Pathol1991;22:1281-1288.
37.
Arnaudo E., Dalakas M., DiMauro S., Schon EA: Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathies. Lancet1991;337:508-510.
38.
Dalakas MC, Leon-Monzon ME, Bernardini I., et al: Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. Ann Neurol1994;35:482-487.
39.
Campos Y., Huertas R., Bautista J., et al: Muscle carnitine deficiency and lipid storage myopathy in patients with mitochondrial myopathy. Muscle Nerve1993;16:778-781.
40.
Campos Y., Huertas R., Lorenzo G., et al: Plasma carnitine insufficiency and effectiveness of L-carnitine therapy in patients with mitochondrial myopathy. Muscle Nerve1993;16:150-153.
41.
Semino-Mora MC, Leon-Monzon ME, Dalakas MC: Effect of L-carnitine on the zidovudine-induced destruction of human myotubes. Part I: L-carnitine prevents the myotoxicity of AZT in vitro. Lab Invest1994;71:102-112.
42.
Semino-Mora MC, Leon-Monzon ME, Dalakas MC: Effect of L-carnitine on the zidovudine-induced destruction of human myotubes. Part II: Treatment with L-carnitine improves the AZT-induced changes and prevents further destruction . Lab Invest1994;71:773-781.
43.
Campos Y., Arenas J.: Muscle carnitine deficiency associated with zidovudine-induced mitochondrial myopathy, letter. Ann Neurol1994;36:680-681.
44.
Chen C-H., Cheng Y-C.: Delayed cytotoxicity and selective loss of mitochondrial DNA in cells treated with the anti-human immunodeficiency virus compound 2',3'-dideoxycytidine . J Biol Chem1989;264:11934-11937.
45.
Lipton SA: Human immunodeficiency virus-infected macrophages, gp 120 and N-methyl-D-aspartate neurotoxicity. Ann Neurol1993;33:227-228.
46.
Genis P., Jett M., Bernton EW: Cytokines and arachidonic metabolites produced during human immunodeficiency virus (HIV)-infected macrophage-astroglia interactions: Implications for the neuropathogenesis of HIV disease. J Exp Med1992; 176: 1703-1718.
47.
Lipton SA, Gendelman HE: Dementia associated with acquired immunodeficiency syndrome. N Engl J Med1995;332:934-940.
48.
Fauci A.: Multifactorial nature of human immunodeficiency virus disease: Implications for therapy. Science1993;262: 1011-1018.
49.
Stiehm ER, Bryson YJ, Frendel LM, et al: Prednisone improves human immunodeficiency virus encephalopathy in children. Pediatr Infect Dis J1992;11:49-50.
50.
Dezube BJ, Pardee AB, Chapman B., et al: Pentoxifylline decreases tumor necrosis factor expression and serum triglycerides in people with AIDS. J Acquir Immune Defic Syndr1993;6:787-794.
