Antioxidant Therapy in Neurological Disorders

  • D. P. R. Muller
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 264)


Oxygen derived free radical species have been implicated in an increasing number of disease processes (Halliwell and Gutteridge 1985a) including neurological disorders (Halliwell and Gutteridge 1985b), and as a result antioxidant therapy has been suggested for a number of diseases affecting the nervous system. in vivo antioxidant defenses can be divided into 2 categories. Firstly preventative antioxidants such as catalase and glutathione peroxidase which prevent the formation of free radical species, and secondly chain breaking antioxidants such as Superoxide dismutase, ascorbate, urate and vitamin E (alpha-tocopherol) which trap oxygen derived free radicals and halt the chain reaction. This paper will concentrate on the therapeutic role of vitamin E in neurological disorders, as in practice the administration of this fat soluble vitamin is a simple and safe way of altering antioxidant status in vivo. Alpha-tocopherol is also potentially important as it is the only well recognised lipid soluble chain breaking antioxidant in vivo (Burton et al 1983) and may, therefore, be expected to play an important role in such highly lipid structures as the brain, spinal cord and peripheral nerves.


Tardive Dyskinesia Antioxidant Therapy Neuronal Ceroid Lipofuscinoses Cholestatic Liver Disease Free Radical Species 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alade,S.L., Brown,R.E., and Paquet,A., 1986, Polysorbate 80 and E-Ferol toxicity, Pediatrics, 77:593.PubMedGoogle Scholar
  2. Anonymous, 1986, Vitamin E deficiency, Lancet, 1:423.Google Scholar
  3. Aranda, J.V., Chemtob, S., Laudignon, N., and Sasyniuk, B.I., 1986, Furosemide and vitamin E: two problem drugs in neonatology, Ped Clin N Amer., 33:583.Google Scholar
  4. Azizi, E., Zaidman, J. L., Eshchar, J., and Szeinberg, A., 1978, Abetalipoproteinemia treated with parenteral and oral vitamins A and E, and with medium chain triglycerides, Acta Paediatr Scand., 67:797.Google Scholar
  5. Bell, F.E., and Filer, L.J., 1981, The role of vitamin E in the nutrition of premature infants, Am J Clin Nutr., 34:414.PubMedGoogle Scholar
  6. Burton, G.W., Joyce, A., and Ingold, K.U., 1983, Is vitamin E the only lipid-soluble, chain-breaking antioxidant in human blood plasma and erythrocyte membranes?, Arch Biochem Biophys., 221:281.Google Scholar
  7. Cadet, J.L., Lohr, J.B., and Jeste, D.V., 1986, Free radicals and tardive dyskinesia, Trends Neurosci., 9:107.CrossRefGoogle Scholar
  8. Chiswick,M.L., Johnson, M., Woodhall, C., Gowland,M., Davies, J., Toner,N., and Sims,D.G., 1983, Protective effect of vitamin E (DL-alpha--tocopherol ) against intraventricular haemorrhage in premature babies, Br Med J., 287:81.CrossRefGoogle Scholar
  9. Committe on Fetus and Newborn, 1985, Vitamin E and the prevention of retinopathy of prematurity, Pediatrics., 76:313.Google Scholar
  10. Dexter, D.T., Carter, C.J., Wells, F.R., Javoy-Agid, F., Agid,Y., Lees,A., Jenner,P., and Marsden,C.D., 1989, Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease, J Neurochem., 52:38 1.CrossRefGoogle Scholar
  11. Fahn, S., High dosage antioxidants in early Parkinson’s disease, Ann NY Acad Sci., in press.Google Scholar
  12. Finer, N.N., Peters, K,L., Hayek, Z., and Merke] C.L., 1984, Vitamin E and necrotizing enterocolitis, Pediatrics, 73:3.Google Scholar
  13. Guggenheim, M.A., Ringel, S.P., Silvermart, A., and Grabert , B.E., 1982, Progressive neuromuscular disease in children with chronic cholestasis and vitamin E deficiency: diagnosis and treatment with alpha toeopherol, Pediatrics, 100:51.CrossRefGoogle Scholar
  14. Haga, P., Ek, J., and Kran, S., 1982, Plasma tocopherol levels and vitamin E/B-lipoprotein relationships during pregnancy and in cord blood, Am J Clin Nutr., 36:1200.PubMedGoogle Scholar
  15. Halliwell, B., and Gutteridge, J.M.C., 1985a, Oxygen radicals and the nervous system, Trends Neurosci., 8:22.CrossRefGoogle Scholar
  16. Halliwell, B., and Gutteridge, J.M.C., (1985b) Free Radicals in Biology and Medicine, Oxford University Press, Oxford .Google Scholar
  17. Harding, A.E., Matthews, S., Jones,S., Ellis, C.J.K., Booth,I.W., and Muller, D.P.R., 1985, Spinocerehe 11ar degeneration associated with a selective defect of vitamin E absorption, N Engl J Med., 313:32.PubMedCrossRefGoogle Scholar
  18. Harries, J.T., and Müller, D.P.R., 1971, Absorption of vitamin E in children with biliary obstruction, Gut, 12:579.PubMedCrossRefGoogle Scholar
  19. Herbert, P.N., Gotto, A.M., and Fredrickson, D.S., 1978, Familial lipoprotein deficiency, in: The Metabolic Basis of Inherited Diseases, Stanbury, J.B., Wyngaarden, J.B., Fredrickson, U.S., eds, McGraw Hill, New York.Google Scholar
  20. Johnson, L., Schaffer, D., and Goggs, T.R., 1974, The premature infant, vitamin E deficiency and retro 1 enta 1 fibroplasia, Am J Clin Nutr., 25:1158.Google Scholar
  21. Johnson, L., Bowen F.W., Abbasi,S., Herrmann,N., Weston, M., Sacks,L., Porat,R., Stahl,G., Peckham, G., Delivoria-Papadopoulos, M., Quinn,G., and Schaffer, D., 1985, Relationship of prolonged pharmacologio serum levels of vitamin E to incidence of sepsis and necrotizing enterocolitis in infants with birth weight 1,500 grams or less, Pediatrics, 75:619.PubMedGoogle Scholar
  22. Johnson, L., Abbasi,S., Quinn, G.E., Otis, C., and Bowen, F.W., 1988, Vitamin E and retinopathy of prematurity, Pediatrics, 81:329.PubMedGoogle Scholar
  23. Kinsey, V.E., 1956, Retrolental fibroplasia: cooperative study of retrolental fibroplasia and the use of oxygen, Arch Ophthalmol., 56:481.CrossRefGoogle Scholar
  24. Lohr, J.B., Cadet J.L., Lohr, M.A., Jeste, D.V., and Wyatt, R.J., 1987, Alpha-tocohperol in tardive dyskinesia, Lancet, 1:913.PubMedCrossRefGoogle Scholar
  25. Lorch,B., Murphy, D., Hoersten, L.R., Harris,E., Fitzgerald, J., and Sinha, S.N., 1985, Unusual syndrome among premature infants: association with a new intravenous vitamin E product, Pediatrics, 75:598.PubMedGoogle Scholar
  26. Muller, D.P.R., Harries, J.T., and Lloyd, J.K., 1974, The relative importance of the factors involved in the absorption of vitamin E in children, Gut, 15:966.PubMedCrossRefGoogle Scholar
  27. Muller, D.P.R., Lloyd, J.K., and Bird, A.C., 1977, Long-term management of abetalipoproteinaemia, possible role for vitamin E, Arch Dis Childh., 52:209.Google Scholar
  28. Muller, D.P.R., Lloyd, J.K., and Wolff, O.H., 1983, Vitamin E and neurological function, Lancet, 1:225.PubMedCrossRefGoogle Scholar
  29. Müller, D.P.R., 1987, Free radical problems of the newborn, Proc Nutr Soc., 46:69.PubMedCrossRefGoogle Scholar
  30. Nelson, J.S., Fitch, C.D., Fischer, V.W., Broun, G.O., and Chou, A.C., 1981, Progressive neuropathologic lesions in vitamin E-deficient rhesus monkeys, J Neuropath Exp Neurol., 40:166.PubMedCrossRefGoogle Scholar
  31. Owens, W.C., and Owens, E.U., 1941, Retrolental fibroplasia in premature infants. II. Studies on the prophylaxis of the disease. The use of alphatocophery1 acetate, Am J Ophthalmol., 32:1631.Google Scholar
  32. Phe1ps, D.L., 1982, Vitamin E and retrolental fibroplasia in 1982, Pediatrics, 70:420.Google Scholar
  33. Phelps, D.L., Rosenbaum, A.L., Isenberg, S.J., Leake, R.D., and Dorey, F.J., 1987, Tocopherol efficacy and safety for preventing retinopathy of prematurity: a randomized, controlled, double-masked trial, Pediatrics , 79 : 489 .Google Scholar
  34. Santavuori, P., Heiskala, H., Westermarck, T., Sainio, K., and Moren, R., 1988, Experience over 17 years with antioxidant treatment in Spielmeyer-Sjogren disease, Am J Med Gen Suppl., 5:265.CrossRefGoogle Scholar
  35. Sinha, S., Davies, J., Toner, N., Bogle, S.. and Chiswick, M., 1987, Vitamin E supplementation reduces frequency of peri ventricular haemorrhage in very preterm babies, Lancet., 1:466.PubMedCrossRefGoogle Scholar
  36. Sokol, K.J., Guggenheim, M., lannaccone, S.T., Barkhaus, P.E., Miller, C., Silverman, A., Balistreri, W.F., and Heubi, J.E., 1985, Improved neurologic function after long-term correction of vitamin E deficiency in children with chronic cholestasis, N Engl J Mod., 313:1580.CrossRefGoogle Scholar
  37. Sokol, R.J., Kayden, H.J., Bettis, D.B., Traber, M.G., Neville, H., Ringel, S., Wilson, W.B., and Stumpf D.A., 1988, Isolated vitamin E deficiency in the absence of fat malabsorption -familial and sporadic cases: characterization and investigation of causes, J Lab Ci in Med., 111:548.Google Scholar
  38. Sokol, R.J., Butler-Simon, N.A., Bettis, D., Smith, D.J., and Silverman, A., 1987, Tocopheryl polyethylene glycol 1000 succinate therapy for vitamin E deficiency during chronic childhood cholestasis: neurological outcome, J Peds., 111:830.CrossRefGoogle Scholar
  39. Speer, M.E., Blifeld, C., Rudolph, A.J., Chadda, P., Holbein, M.E.B., and Hittner, H.M., 1984, Intraventricular hemorrhage and vitamin E in the very low-birth-weight infant: evidence for efficacy of early intramuscular vitamin E administration, Pediatrics, 74:1107.PubMedGoogle Scholar
  40. Stead, R. J., Muller, D.P.R., Matthews, S., Hodson, M.E., and Batten, J.C., 1986, Effect of abnormal liver function on vitamin E status and supplementation in adults with cystic fibrosisr Gut, 27:714.PubMedCrossRefGoogle Scholar
  41. Terry, T.L., 1942, Extreme prematurity and fibroplastic overgrowth of persistent vascular sheath behind each crysalline lens, Am J Ophthalmol., 25:203.Google Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • D. P. R. Muller
    • 1
  1. 1.Department of Child HealthInstitute of Child HealthLondonUK

Personalised recommendations