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Serum carnitine levels and levocarnitine supplementation in institutionalized Huntington’s disease patients

Abstract

Along with antioxidant properties, carnitine is an important regulator of lipid metabolism in humans. While beneficial effects of carnitine have been demonstrated in animal models of Huntington’s disease (HD), metabolism of carnitine has not been studied in humans with this illness. In this retrospective database review from 23 patients admitted to a HD-specialized nursing home unit, we found a relatively high prevalence of hypocarnitinemia (6 cases, 26%). Our review suggests that catabolism and chronic valproate use predisposed our patients to develop hypocarnitinemia. The patients with low serum carnitine levels who received levocarnitine supplementation, during a mean period of 7.3 months, showed improvement in motor, cognitive and behavioral measures. We hypothesize that observed improvement related to the resolution of reversible metabolic encephalopathy and myopathy associated with secondary carnitine deficiency. In conclusion, notwithstanding its limitations, this is the first study to report measurements of carnitine levels in HD patients, revealing relatively high prevalence of hypocarnitinemia in our population. Our findings suggest that HD patients with hypocarnitinemia may benefit from low-dose levocarnitine supplementation. Further studies of carnitine metabolism and supplementation in HD patients are warranted.

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References

  1. 1.

    Chen Q, Surmeier DJ, Reiner A (1999) NMDA and non-NMDA receptor-mediated excitotoxicity are potentiated in cultured striatal neurons by prior chronic depolarization. Exp Neurol 159:283–296

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Perluigi M, Poon HF, Maragos W, Pierce WM, Klein JB, Calabrese V, Cini C, De Marco C, Butterfield DA (2005) Proteomic analysis of protein expression and oxidative modification in r6/2 transgenic mice: a model of Huntington disease. Mol Cell Proteomics 4:1849–1861

    PubMed  Article  CAS  Google Scholar 

  3. 3.

    Klepac N, Relja M, Klepac R, Hećimović S, Babić T, Trkulja V (2007) Oxidative stress parameters in plasma of Huntington’s disease patients, asymptomatic Huntington’s disease gene carriers and healthy subjects: a cross-sectional study. J Neurol 254:1676–1683

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Antonini A, Leenders KL, Spiegel R, Meier D, Vontobel P, Weigell-Weber M, Sanchez-Pernaute R, de Yébenez JG, Boesiger P, Weindl A, Maguire RP (1996) Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington’s disease. Brain 119(Pt 6):2085–2095

    PubMed  Article  Google Scholar 

  5. 5.

    Martin LJ, Blackstone CD, Huganir RL, Price DL (1992) Cellular localization of a metabotropic glutamate receptor in rat brain. Neuron 9:259–270

    PubMed  Article  CAS  Google Scholar 

  6. 6.

    Schilling G, Coonfield ML, Ross CA, Borchelt DR (2001) Coenzyme Q10 and remacemide hydrochloride ameliorate motor deficits in a Huntington’s disease transgenic mouse model. Neurosci Lett 315:149–153

    PubMed  Article  CAS  Google Scholar 

  7. 7.

    Rebouche CJ (2004) Kinetics, pharmacokinetics, and regulation of l-carnitine and acetyl-l-carnitine metabolism. Ann N Y Acad Sci 1033:30–41

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Evans AM, Fornasini G (2003) Pharmacokinetics of l-carnitine. Clin Pharmacokinet 42:941–967

    PubMed  Article  CAS  Google Scholar 

  9. 9.

    Malaguarnera M, Vacante M, Motta M, Malaguarnera M, Volti GL, Galvano F (2009) Effect of l-carnitine on the size of low-density lipoprotein particles in type 2 diabetes mellitus patients treated with simvastatin. Metabolism 58:1618–1623

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Malaguarnera M, Vacante M, Avitabile T, Malaguarnera M, Cammalleri L, Motta M (2009) l-Carnitine supplementation reduces oxidized LDL cholesterol in patients with diabetes. Am J Clin Nutr 89:71–76

    PubMed  Article  CAS  Google Scholar 

  11. 11.

    Galvano F, Volti GL, Malaguarnera M, Avitabile T, Antic T, Vacante M, Malaguarnera M (2006) Effects of simvastatin and carnitine versus simvastatin on lipoprotein(a) and apoprotein(a) in type 2 diabetes mellitus. Expert Opin Pharmacother 10:1875–1882

    Article  Google Scholar 

  12. 12.

    Rani PJA, Panneerselvam C (2001) Carnitine as a free radical scavenger in aging. Exp Gerontol 6:1713–1726

    Google Scholar 

  13. 13.

    Koudelová J, Mourek J, Drahota Z, Rauchová H (1994) Protective effect of carnitine on lipoperoxide formation in rat brain. Physiol Res 43:387–389

    PubMed  Google Scholar 

  14. 14.

    Malaguarnera M, Cammalleri L, Gargante MP, Vacante M, Colonna V, Motta M (2007) l-Carnitine treatment reduces severity of physical and mental fatigue and increases cognitive functions in centenarians: a randomized and controlled clinical trial. Am J Clin Nutr 86:1738–1744

    PubMed  CAS  Google Scholar 

  15. 15.

    Malaguarnera M, Vacante M, Motta M, Giordano M, Malaguarnera G, Bella R, Nunnari G, Rampello L, Pennisi G (2011) Acetyl-l-carnitine improves cognitive functions in severe hepatic encephalopathy: a randomized and controlled clinical trial. Metab Brain Dis 26:281–289

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Malaguarnera M, Bella R, Vacante M, Giordano M, Malaguarnera G, Gargante MP, Motta M, Mistretta A, Rampello L, Pennisi G (2011) Acetyl-l-carnitine reduces depression and improves quality of life in patients with minimal hepatic encephalopathy. Scand J Gastroenterol 46:750–759

    PubMed  Article  CAS  Google Scholar 

  17. 17.

    Malaguarnera M, Pistone G, Astuto M, Vecchio I, Raffaele R, Lo Giudice E, Rampello L (2006) Effects of l-acetylcarnitine on cirrhotic patients with hepatic coma: randomized double-blind, placebo-controlled trial. Dig Dis Sci 51:2242–2247

    PubMed  Article  CAS  Google Scholar 

  18. 18.

    Malaguarnera M, Pistone G, Elvira R, Leotta C, Scarpello L, Liborio R (2005) Effects of l-carnitine in patients with hepatic encephalopathy. World J Gastroenterol 11:7197–7202

    PubMed  CAS  Google Scholar 

  19. 19.

    Mock CM, Schwetschenau KH (2012) Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy. Am J Health Syst Pharm 69:35–39

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Vamos E, Voros K, Vecsei L, Klivenyi P (2010) Neuroprotective effects of l-carnitine in a transgenic animal model of Huntington’s disease. Biomed Pharmacother 64:282–286

    PubMed  Article  CAS  Google Scholar 

  21. 21.

    Folstein M, Folstein SE, McHugh PR (1975) “Mini-Mental State” a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Huntington Study Group (1996) Unified Huntington’s Disease Rating Scale: reliability and consistency. Mov Disord 11:136–142

    Article  Google Scholar 

  23. 23.

    National Academy of Sciences (1996) Summary of WIC nutrition risk criteria: a scientific assessment. Committee on Scientific Evaluation of WIC Nutrition Risk Criteria Food and Nutrition Board, Institute of Medicine. J Am Diet Assoc 96:925–930

    Article  Google Scholar 

  24. 24.

    Cuturic M, Abramson RK, Moran RR, Hardin JW, Hall AV (2011) Clinical correlates of low serum carnitine levels in hospitalized psychiatric patients. World J Biol Psychiatry 12(1):73–79

    PubMed  Article  Google Scholar 

  25. 25.

    Cuturic M, Abramson RK, Moran RR, Hardin JW (2010) Clinical outcomes and low-dose levocarnitine supplementation in psychiatric inpatients with documented hypocarnitinemia: a retrospective chart review. J Psychiatr Pract 16:5–14

    PubMed  Article  Google Scholar 

  26. 26.

    Longo N, di San Amat, Filippo C, Pasquali M (2006) Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet 142C:77–85

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Proulx F, Lacroix J, Qureshi IA, Nadeau D, Gauthier M, Lambert M (1997) Acquired carnitine abnormalities in critically ill children. Eur J Pediatr 156:864–869

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Wennberg A, Hyltander A, Sjöberg A, Arfvidsson B, Sandström R, Wickström I, Lundholm K (1992) Prevalence of carnitine depletion in critically ill patients with undernutrition. Metabolism 41:165–171

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Coppola G, Epifanio G, Auricchio G, Federico RR, Resicato G, Pascotto A (2006) Plasma free carnitine in epilepsy children, adolescents and young adults treated with old and new antiepileptic drugs with or without ketogenic diet. Brain Dev 28:358–365

    PubMed  Article  Google Scholar 

  30. 30.

    Pratley RE, Salbe AD, Ravussin E, Caviness JN (2000) Higher sedentary energy expenditure in patients with Huntington’s disease. Ann Neurol 47:64–70

    PubMed  Article  CAS  Google Scholar 

  31. 31.

    Breningstall GN (1990) Carnitine deficiency syndromes. Pediatr Neurol 6:75–81

    PubMed  Article  CAS  Google Scholar 

  32. 32.

    Lheureux PE, Penaloza A, Zahir S et al (2005) Science review: carnitine in the treatment of valproic acid-induced toxicity—what is the evidence? Crit Care 9:431–440

    PubMed  Article  Google Scholar 

  33. 33.

    Pons R, De Vivo DC (1995) Primary and secondary carnitine deficiency syndromes. J Child Neurol 10(suppl. 2):8–24

    Google Scholar 

  34. 34.

    Malaguarnera M, Gargante MP, Cristaldi E, Vacante M, Risino C, Cammalleri L, Pennisi G, Rampello L (2008) Acetyl-l-carnitine treatment in minimal hepatic encephalopathy. Dig Dis Sci 53:3018–3025

    PubMed  Article  CAS  Google Scholar 

  35. 35.

    Goety CG, Tanner CM, Cohen JA, Thelen JA, Carroll VS, Klawans HL, Fariello RG (1990) l-Acetyl-carnitine in Huntington’s disease: double-blind placebo controlled crossover study of drug effects on movement disorder and dementia. Mov Disord 5:263–265

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Eder K, Felgner J, Becker K et al (2005) Free and total carnitine concentrations in pig plasma after oral ingestion of various l-carnitine compounds. Int J Vitam Nutr Res 75:3–9

    PubMed  Article  CAS  Google Scholar 

  37. 37.

    (2007) Carnitor (levocarnitine) prescribing information. Sigma-Tau Pharmaceuticals Inc, Gaithersburg

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The authors certify that there is no actual or potential conflict of interest in relation to this article.

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Correspondence to Miroslav Cuturic.

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Cuturic, M., Abramson, R.K., Moran, R.R. et al. Serum carnitine levels and levocarnitine supplementation in institutionalized Huntington’s disease patients. Neurol Sci 34, 93–98 (2013). https://doi.org/10.1007/s10072-012-0952-x

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Keywords

  • Carnitine
  • Catabolism
  • Huntington’s disease
  • Levocarnitine
  • Valproic acid