Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Communication
  • Published:

Low serum carnitine in HIV-infected children on antiretroviral treatment

Abstract

Objective: HIV-infection and antiretroviral therapies are associated with energy dysfunction and lipid metabolism in adults. Our aim was to detect a possible carnitine deficiency in HIV-infected children on antiretroviral treatments. We analysed the relation among serum carnitine, its amino-acid precursors (methionine and lysine), clinical evaluation and antiretroviral therapy.

Design and setting: Cross-sectional study performed in a tertiary care hospital.

Subjects: A total of 79 HIV-infected children on antiretroviral therapy, monitored prospectively in our hospital.

Interventions: Antiretroviral therapy included nucleoside analogues plus protease inhibitors and/or non-nucleoside analogues. Carnitine was analysed by an enzymatic–spectrometric procedure, and amino acids by ion exchange chromatography. Reference values of carnitine and amino acids were established in apparently healthy children who underwent presurgical analysis for minor surgery.

Results: Serum free and total carnitine, acylcarnitines, methionine and lysine were significantly lower in HIV-infected children compared with our reference values for similar ages (P<0.0001; Student's t-test). Low carnitine values were observed in 37% of our HIV-infected children. A significantly positive correlation was observed between serum total carnitine and methionine or lysine (P<0.0001 and P=0.005, respectively; Pearson test). No relation was observed between serum carnitine and clinical stage of HIV infection, immunological or nutritional status or lipodystrophy. Free and total carnitine were significantly lower (P=0.002 and 0.033, respectively) in HIV-infected patients on protease inhibitors (N=56) compared with those on other treatments (N=23).

Conclusions: Low serum carnitine concentration was observed in 37% of our HIV-infected children on antiretroviral therapy. Malabsorption or defective synthesis may also account for the low serum carnitine values detected in these patients.

Sponsorship: Grant FIS 99/1270.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  • Arnaudo E, Dalakas M, Shanke S, Moraes CT, DiMauro S & Schon EA (1991): Depletion of muscle mitochondrial DNA in AIDS patients with zidovudine-induced myopathy. Lancet 337, 508–510.

    Article  CAS  Google Scholar 

  • Artuch R, Quintana M, Moyano D, Moreno J, Puig R & Vilaseca MA (1997): Determinación de carnitina en plasma por un procedimiento espectrométrico. Valores de referencia para una población pediátrica. Química Clín. 16, 397–400.

    Google Scholar 

  • Bogden JD, Baker H, Frank O, Perez G, Kemp F, Bruening K & Louria D (1990): Micronutrient status and human immunodeficiency virus (HIV) infection. Ann. NY Acad. Sci. 587, 189–195.

    Article  CAS  Google Scholar 

  • Brinkman K, Hofsteder HJM, Burger DM, Smeitink JAM & Koopmans PP (1998): Adverse effect of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway. AIDS 12, 1735–1744.

    Article  CAS  Google Scholar 

  • Brinkman K, Smeitink JA, Romijn JA & Reiss P (1999): Mitochondrial toxicity induced by nucleoside-analogue reverse-transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy. Lancet 354, 1112–1115.

    Article  CAS  Google Scholar 

  • Campos Y & Arenas J (1994): Muscle carnitine deficiency associated with zidivudine-induced mitochondrial myopathy. Ann. Neurol. 36, 680–681.

    Article  CAS  Google Scholar 

  • Carr A, Miller J, Law M & Cooper DA (2000): A syndrome of lipoatrophy, lactic acidaemia and liver dysfunction associated with HIV nucleoside analogue therapy: contribution to protease inhibitor-related lipodystrophy syndrome. AIDS 14, F25–F32.

    Article  CAS  Google Scholar 

  • Carr A, Smaras K, Burton S, Law M, Freund J, Chisholm DJ & Cooper DA (1998a): A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin-resistance in patients receiving HIV protease inhibitors. AIDS 12, F51–F58.

    Article  CAS  Google Scholar 

  • Carr A, Samaras K, Chisholm DJ & Cooper DA (1998b): Pathogenesis of HIV-1protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin-resistance. Lancet 351, 1881–1883.

    Article  CAS  Google Scholar 

  • Carter AL, Abney TO & Lapp DF (1995): Biosynthesis and metabolism of carnitine. J. Child Neurol. 10(Suppl), 2S3–2S7.

    Article  Google Scholar 

  • Cifone MG, Alesse E, Di Marzio L, Ruggeri B, Zazzeroni F, Moretti S, Famularo G, Steinberg SM, Vullo E & De Simone C (1997): Effect of L-carnitine treatment in vivo on apoptosis and ceramide generation in peripheral blood lymphocytes from AIDS patients. Proc. Assoc. Am. Physicians 109, 146–153.

    CAS  PubMed  Google Scholar 

  • Claessens YE, Cariou A, Chiche JD, Dauriat G & Dhainaut JF (2000): L-carnitine as a treatment of life-threatening lactic acidosis induced by nucleoside analogues. AIDS 14, 472–473.

    Article  CAS  Google Scholar 

  • Dalakas M, Illa I, Pezeshkpour GH, Laikaitis JP, Cohen B & Griffin JL (1990): Mitochondrial myopathy caused by long-term zidovudine therapy. N. Eng. J. Med. 322, 1098–1105.

    Article  CAS  Google Scholar 

  • Dalakas MC, Leon-Monzon M, Bernardini I, Gahl WA & Jay CA (1994): Zidovudine-induced mitochondrial myopathy is associated with muscle carnitine deficiency and lipid storage. Ann. Neurol. 35, 482–487.

    Article  CAS  Google Scholar 

  • Davis HJ, Miene LJ, van der Westhuizen N, et al (1998): L-carnitine and magnesium as a supportive supplement with antiviral drugs. Int. Conf. AIDS 12, 851.

    Google Scholar 

  • De Simone C, Famularo G, Tzantzoglou S, Trinchieri V, Moretti S & Sorice F (1994): Carnitine depletion in peripheral blood mononuclear cells from patients with AIDS: effect of oral L-carnitine. AIDS 8, 655–660.

    Article  CAS  Google Scholar 

  • De Simone C, Tzantzoglou S, Famularo G, Moretti S, Paoletti F, Vullo V & Delia S (1993): High dose L-carnitine improves immunologic and metabolic parameters in AIDS patients. Immunopharmacol. Immunotoxicol. 15, 1–12.

    Article  CAS  Google Scholar 

  • De Simone C, Tzantzoglou S, Jirillo E, et al (1992): Carnitine deficiency in AIDS. AIDS 6, 203–205.

    Article  CAS  Google Scholar 

  • Famularo G, De Simone C & Cifone G (1999): Carnitine stands on its own in HIV infection treatment. Arch. Intern. Med. 159, 1143–1144.

    Article  CAS  Google Scholar 

  • Famularo G, Moretti S, Marcellini S, Trinchieri V, Tzantzoglou S, Santini G, Longo A & De Simone C (1997): Acetyl-carnitine deficiency in AIDS patients with neurotoxicity on treatment with antiretroviral nucleoside analogues. AIDS 11, 185–190.

    Article  CAS  Google Scholar 

  • Kotler DP (1998): Human immunodeficiency virus-related wasting: malabsorption syndromes. Semin. Oncol. 25, Suppl 6), 70–75.

    CAS  PubMed  Google Scholar 

  • Lenzo NP, Garas BA & French MA (1997): Hepatic steatosis and lactic acidosis associated with stavudine treatment in an HIV patient: a case report. AIDS 11, 1294–1296.

    Article  CAS  Google Scholar 

  • Megarbane B, Brivet F, Guerin JM & Baud FJ (1999): Lactic acidosis and multi-organ failure secondary to anti-retroviral therapy in HIV-infected patients. Presse Med. 28, 2257–2264.

    CAS  PubMed  Google Scholar 

  • Melegh B, Pap M, Bock I & Rebouche CJ (1993): Relationship of carnitine and carnitine precursors lysine, N-trimethyllysine, and γ-butyrobetaine in drug-induced carnitine depletion. Pediatr. Res. 34, 460–464.

    Article  CAS  Google Scholar 

  • Mintz M (1995): Carnitine in human immunodeficiency virus type 1 infection/acquired immune deficiency syndrome. J. Child Neurol. 10(Suppl), 2S40–2S44.

    Article  Google Scholar 

  • Moretti S, Alesse E, Di Marzio L, Zazzeroni F, Ruggeri B, Marcellini S, Famularo G, Steinberg SM, Boschini A, Cifone MG & De Simone C (1998): Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study. Blood 91, 3817–3824.

    CAS  PubMed  Google Scholar 

  • Moyano D, Vilaseca MA, Artuch R & Lambruschini N (1998): Plasma amino acids in anorexia nervosa. Eur. J. Clin. Nutr. 52, 684–689.

    Article  CAS  Google Scholar 

  • Mutomba MC, Yuan H, Konyavko M, Adachi S, Yokoyama CB, Esser V, McGarry JD, Babior BM & Gottlieb RA (2000): Regulation of the activity of caspases by L-carnitine and palmitoylcarnitine. FEBS Lett. 478(1–2), 19–25.

    Article  CAS  Google Scholar 

  • Periquet BA, Jammes NM, Lambert WE, Tricoire J, Moussa MM, Garcia J, Ghisolfi J & Thouvenot J (1995): Micronutrient levels in HIV-1-infected children. AIDS 9, 887–893.

    Article  CAS  Google Scholar 

  • Pons R & De Vivo DC (1995): Primary and secondary carnitine deficiency syndromes. J. Child Neurol. 10(Suppl): 2S8–2S24.

    Article  Google Scholar 

  • Revell P, O'Doherty MJ, Tang A & Savidge GF (1991): Folic acid absorption in patients infected with the human immunodeficiency virus. J. Intern. Med. 230, 227–231.

    Article  CAS  Google Scholar 

  • Semino-Mora MC, Leon-Monzon ME & Dalakas MC (1994): The effect of L-carnitine on the AZT-induced destruction of human myotubes. Part II: treatment with L-carnitine improves the AZT-induced changes and prevents further destruction. Lab. Invest. 71, 773–781.

    CAS  PubMed  Google Scholar 

  • Simpson DM (1992): Neuromuscular complications of human immunodeficiency virus infection. Semin. Neurol. 12, 34–42.

    Article  CAS  Google Scholar 

  • Sundar K (1997): Zidovudine-induced fatal lactic acidosis and hepatic failure in patients with acquired immunodeficiency syndrome: report of two patients and review of the literature. Crit. Care Med. 8, 1425–1430.

    Article  Google Scholar 

  • Vilaseca MA, Briones P, Ferrer I, Campistol J, Riverola A, Castillo P & Ramon F (1993): Controlled diet in Phenylketonuria may cause serum carnitine deficiency. J. Inher. Metab. Dis. 16, 101–104.

    Article  CAS  Google Scholar 

  • Vilaseca MA, Sierra C, Colomé C, Artuch R, Valls C, Muñoz MC, López-Vilches MA & Fortuny C (2001): Hyperhomocysteinemia and folate deficiency in HIV-infected children on antiretroviral treatment. Eur. J. Clin. Invest. 31, 992–998.

    Article  CAS  Google Scholar 

  • Walter EB, Drucker RP, McKinney RE & Wilfert CM (1991): Myopathy in human immunodeficiency virus-infected children receiving long-term zidovudine therapy. J. Pediatr. 119, 152–155.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was sponsored by Grant FIS 99/1270. We are very grateful to Rosa Puig for her skilful technical assistance.

Author information

Authors and Affiliations

Authors

Contributions

Guarantor: MA Vilaseca.

Contributors: MAV, CS and CF designed the study. MAV, CS and RA created the databases, performed the statistical analysis, and wrote the paper. JP carried out the carnitine determinations and CM-A the viral load quantification. MAL-V collected the clinical data. CF was in charge of the paediatric evaluation of HIV patients and critically reviewed the contents of the manuscript.

Corresponding author

Correspondence to M A Vilaseca.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vilaseca, M., Artuch, R., Sierra, C. et al. Low serum carnitine in HIV-infected children on antiretroviral treatment. Eur J Clin Nutr 57, 1317–1322 (2003). https://doi.org/10.1038/sj.ejcn.1601694

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1601694

Keywords

This article is cited by

Search

Quick links