Drugs & Aging

, Volume 13, Issue 4, pp 263–268

Is NADH Effective in the Treatment of Parkinson’s Disease?

  • Russell H. Swerdlow
Leading Article

Abstract

Most Parkinson’s disease (PD) treatments palliate symptoms by increasing nigrostriatal dopaminergic tone. A unique strategy for accomplishing this pharmacological end-point proposes using reduced nicotinamide adenine dinucleotide (NADH) to boost endogenous dopamine production, since NADH indirectly supplies reducing equivalents to the rate-limiting, tyrosine hydroxylase-catalysed step of dopamine synthesis. Support for using NADH in PD treatment includes claims that NADH stimulates tyrosine hydroxylase and dopamine biosynthesis in tissue culture and humans, as well as case series associating intravenous and oral NADH administration with PD rating scale improvements. Theoretical and practical arguments against NADH include underlying NADH disposal impairment in PD and failure of a placebo-controlled trial to show any clear benefit. While NADH may yet prove to ameliorate parkinsonism, recommendations for its use in PD are premature.

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References

  1. 1.
    McGeer PL, McGeer EG. Enzymes associated with the metabolism of catecholamines, acetylcholine and GABAin human controls and patients with Parkinson’s disease and Huntington’s chorea. J Neurochem 1976; 26: 65–76PubMedGoogle Scholar
  2. 2.
    Reiderer P, Rausch WD, Birkmayer W, et al. CNS modulation of adrenal tyrosine hydroxylase in Parkinson’s disease and metabolic encephalopathies. J Neural Transm 1978; Suppl. 14: 121–31Google Scholar
  3. 3.
    Nagatsu T, Yamaguchi T, Kato T, et al. Biopterin in human brain and urine from controls and parkinsonian patients: application of a new radioimmuneassay. Clin Chim Acta 1981; 109: 305–11PubMedCrossRefGoogle Scholar
  4. 4.
    Lewitt PA, Miller LP, Newman RP, et al. Tyrosine hydroxylase cofactor (tetrahydrobiopterin) in parkinsonism. In: Hassler RG, Christ JF, editors. Advances in Neurology 40, New York: Raven Press, 1984: 459–62Google Scholar
  5. 5.
    Moore AP, Behan PO, Jacobsen W, et al. Biopterin in Parkinson’s disease. J Neurol Neurosurg Psychiatry 1987; 50: 85–7PubMedCrossRefGoogle Scholar
  6. 6.
    Birkmayer W, Birkmayer JGD. Iron, a new aid in the treatment of Parkinson patients. J Neural Transm 1986; 67: 287–92PubMedCrossRefGoogle Scholar
  7. 7.
    Birkmayer JGD, Birkmayer W. Improvement of disability and akinesia of patients with Parkinson’s disease by intravenous iron substitution. Ann Clin Lab Sci 1987; 17: 32–5PubMedGoogle Scholar
  8. 8.
    Lhermitte J, Kraus WM, McAlpine B. On the occurrence of abnormal deposit of iron in the brain in parkinsonism with special reference to its localization. J Neural Psychopath 1924; 5: 1810–2Google Scholar
  9. 9.
    Jenner P, Olanow CW. Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 1996; 47 (6 Suppl. 3): S161–170PubMedCrossRefGoogle Scholar
  10. 10.
    Sengstock GJ, Olanow CW, Menzies RA, et al. Infusion of iron into the rat substantia nigra: nigral pathology and dose-dependent loss of striatal dopaminergic markers. J Neurosci Res 1993; 35: 67–82PubMedCrossRefGoogle Scholar
  11. 11.
    Dexter DT, Jenner P, Marsden CD. Oxyferrixcorbone elevates the total iron content of blood but not brain. Mov Disord 1989; 4: 176–82PubMedCrossRefGoogle Scholar
  12. 12.
    Birkmayer GJD, Birkmayer W. Stimulation of endogenous L-dopa biosynthesis: a new principle for the therapy of Parkinson’s disease. Acta Neurol Scand 1989; 126: 183–7CrossRefGoogle Scholar
  13. 13.
    Birkmayer W, Birkmayer GJD. Nicotinamidadenindinucleotide (NADH): the new approach in the therapy of Parkinson’s disease. Ann Clin Lab Sci 1989; 19: 38–43PubMedGoogle Scholar
  14. 14.
    Birkmayer W, Birkmayer GJD, Vrecko K, et al. The coenzyme nicotinamide adenine dinucleotide (NADH) improves the disability of Parkinsonian patients. J Neural Trans (P-D Sect) 1989; 1: 297–302CrossRefGoogle Scholar
  15. 15.
    Birkmayer W, Birkmayer JGD, Vrecko K, et al. The clinical benefit of NADH as stimulator of endogenous L-dopa biosynthesis in Parkinsonian patients. In: Korczyn AD, Melamed E, Youdin MBH, editors. Advances in Neurology 53. New York, Raven Press, 1990: 545–9Google Scholar
  16. 16.
    Langston JW, Ballard PA, Tetrud JW, et al. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983; 219: 979–80PubMedCrossRefGoogle Scholar
  17. 17.
    Forno LS, Langston JW, DeLanney LE, et al. Locus ceruleus lesions and eosinophilic inclusions in MPTP-treated monkeys. Ann Neurol 1986; 20: 449–55PubMedCrossRefGoogle Scholar
  18. 18.
    Parker WD, Byson SJ, Parks JK. Electron transport chain abnormalities in idiopathic Parkinson’s disease. Ann Neurol 1989; 26: 719–23PubMedCrossRefGoogle Scholar
  19. 19.
    Schapira AHV, Coloper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson’s disease [letter]. Lancet 1989; I: 1289Google Scholar
  20. 20.
    Mizuno Y, Ohta S, Tanaka M, et al. Deficiencies in complex I subunits of the respiratory chain in Parkinson’s disease. Biochem Biophys Res Commun 1989; 163: 1450–5PubMedCrossRefGoogle Scholar
  21. 21.
    Swerdlow RH, Parks JK, Miller SW, et al. Origin and functional consequences of the complex I defect in Parkinson’s disease. Ann Neurol 1996; 40: 663–71PubMedCrossRefGoogle Scholar
  22. 22.
    Lawen A, Martinus RD, McMullen GL, et al. The universality of bioenergetic disease: the role of mitochondrial mutation and the putative inter-relationship between mitochondria and plasma membrane NADH oxidoreductase. Mol Aspects Med 1994; 15 Suppl.: S13–27PubMedCrossRefGoogle Scholar
  23. 23.
    Jenkins BG, Brouillet E, Chen YCI, et al. Non-invasive neurochemical analysis of focal excitotoxic lesions in models of neurodegenerative illness using spectroscopic imaging. J Cereb Blood Flow Metab 1996; 16: 450–61PubMedCrossRefGoogle Scholar
  24. 24.
    Bender DA, Earl CJ, Lees AJ. Niacin depletion in Parkinsonian patients treated with L-dopa, benserazide and carbidopa. Clin Sci 1979; 56: 89–93PubMedGoogle Scholar
  25. 25.
    Birkmeyer JGD, Vrecko C, Vole D, et al. Nicotinamide adenine dinucleotide (NADH): a new therapeutic approach to Parkinson’s disease. Acta Neurol Scand 1993; 146: 32–5Google Scholar
  26. 26.
    Vrecko K, Birkmayer JG, Krainz J. Stimulation of dopamine biosynthesis in cultured PC 12 phaeochromocytoma cells by the coenzyme nicotinamide adeninedinucleotide (NADH). J Neural Transm Park Dis Dement Sect 1993; 5: 147–56PubMedCrossRefGoogle Scholar
  27. 27.
    Shoffner JM, Watts RL, Juncos JL, et al. Mitochondrial oxidative phosphorylation defects in Parkinson’s disease. Ann Neurol 1991; 30: 332–9PubMedCrossRefGoogle Scholar
  28. 28.
    Dizdar N, Kagedal B, Lindvall B. Treatment of Parkinson’s disease with NADH. Acta Neurol Scand 1994; 90: 345–7PubMedCrossRefGoogle Scholar
  29. 29.
    Kuhn W, Muller T, Winkel R, et al. Parenteral application of NADH in Parkinson’s disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis. J Neural Transm 1996; 103: 1187–93PubMedCrossRefGoogle Scholar
  30. 30.
    Birkmayer W, Birkmayer JGD, Vrecko C, et al. Nicotinamide adenine dinucleotide (NADH) as medication for Parkinson’s disease: experience with 415 patients. New Trends Clin Neuropharm 1990; 4: 7–24Google Scholar
  31. 31.
    Birkmayer W, Neumayr E. Die moderne medikamentose behandlung des Parkinsonismus. Z Neurol 1972; 202: 257–80PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1998

Authors and Affiliations

  • Russell H. Swerdlow
    • 1
  1. 1.The Center for the Study of Neurodegenerative Diseases and the Department of NeurologyUniversity of VirginiaCharlottesvilleUSA
  2. 2.Department of NeurologyUniversity of Virginia Health Sciences CenterCharlottesvilleUSA

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