Vitamin E

Neurochemical Aspects and Relevance to Nervous System Disorders
  • G. T. Vatassery


The history of vitamin E dates back to 1922 when Evans and Bishop (1922) discovered it as a nutritional factor that prevented resorption of the fetus in the laboratory rat. Since then innumerable investigations have been conducted to understand the role of vitamin E in maintaining the structure and function of various tissues. A few years ago this author reviewed selected aspects of the neurochemistry of vitamin E (Vatassery, 1992). The current article is intended to describe the state of the art with respect to the neurobiology of vitamin E, with special emphasis on human neurological diseases. The last section of the chapter summarizes part of the work done in our laboratory. During the last few years many new studies have appeared on this subject. The goal of the current review is not to present a comprehensive review of the field but to highlight some of the new information that has appeared in the literature.


Tardive Dyskinesia Alpha Tocopherol Passive Avoidance Response Gamma Tocopherol Linoleic Acid Hydroperoxide 
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  1. Adler, L. A., Peselow, E., Rotrosen, J., Duncan, E., Lee, M., Rosenthal, M., and Angrist, B., 1993, Vitamin E treatment of tardive dyskinesia, Am. J. Psychiatry 150:1405–1407.PubMedGoogle Scholar
  2. Amiel, J., Maziere, J. C., Beucler, I., Koenig, M., Reutenauer, L., Loux, N., Bonnefont, D., Feo, C., and Landrieux, R, 1995, Familial isolated vitamin E deficiency. Extensive study of a large family with a 5-year therapeutic follow up, J. Inker. Metab. Dis. 18:333–340.CrossRefGoogle Scholar
  3. Beal, M. F., 1995, Aging, energy, and oxidative stress in neurodegenerative disease, Ann. Neurol. 38:357–366.PubMedCrossRefGoogle Scholar
  4. Ben Hamida, M., Belal, S., Sirugo, G., Ben Hamida, C., Panayides, K., Ionannou, R, Beckmann, J., Mandel, J. L., Hentafi, F., Koenig, M., and Middleton, L., 1993, Friedrich’s ataxia phenotype not linked to chromosome 9 and associated with selective autosomal recessive vitamin E deficiency in two inbred Tunisian families, Neurology 43:2179–2183.PubMedCrossRefGoogle Scholar
  5. Burkhardt, C., Kelly, J. P., Lim, Y. H., Filley, C. M., and Parker, Jr., W. D., 1993, Neuroleptic medications inhibit complex I of the electron transport chain, Ann. Neurol. 33:512–517.PubMedCrossRefGoogle Scholar
  6. Burton, G. W., and Traber, M. G., 1990, Vitamin E: antioxidant activity, biokinetics, and bioavailability, Ann. Rev. Nutr. 10:357–382.CrossRefGoogle Scholar
  7. Cadet, J. L., and Kahler, L. A., 1994, Free radical mechanisms in schizophrenia and tardive dyskinesia, Neurosci. Biobehav. Rev. 18:457–467.PubMedCrossRefGoogle Scholar
  8. Chang, L. W., Gilbert, M., and Sprecher, J., 1978, Modification of methylmercury neurotoxicity by vitamin E, Environ. Res. 17:356–366.PubMedCrossRefGoogle Scholar
  9. Dexter, D. T., Ward, R. J., Wells, F. R., Daniel, S. E., Lees, A. J., Peters, T. J., Jenner, P., and Marsden, C. D., 1992, Alpha tocopherol levels in brain are not altered in Parkinson’s disease, Ann. Neurol. 32:591–593.PubMedCrossRefGoogle Scholar
  10. Dexter, D. T., Brooks, D. J., Harding, A. E., Burn, D. J., Muller, D. P. R., Goss-Sampson, M. A., Jenner, P. G., and Marsden, C. D., 1994, Nigrostriatal function in vitamin E deficiency: clinical, experimental, and positron emission tomographic studies, Ann. Neurol. 35:298–303.PubMedCrossRefGoogle Scholar
  11. Dowson, J. H., Fattoretti, P., Cairns, M., James, N. T., Wilton-Cox, H., and Bertoni-Feddari, C., 1992, The effects of aging and a vitamin E-deficienct diet on the lipopigment content of rat hippocampal and Purkinje neurons, Arch. Gerontol. Geriatr. 14:239–251.PubMedCrossRefGoogle Scholar
  12. Einarson, L., and Telford, I. R., 1960, Effect of vitamin E deficiency on the central nervous system in various laboratory animals, Danske Videnskabernes Selskab 11:1–81.Google Scholar
  13. Evans, H. M., and Bishop, K. S., 1922, On the existence of a hitherto unrecognized dietary factor essential for reproduction, Science 56:650–661.PubMedCrossRefGoogle Scholar
  14. Fish, W. H., Cohen, M., Franzek, D., Williams, J. M., and Lemons, J. A., 1990, Effect of intramuscular vitamin E on mortality and intracranial hemorrhage in neonates of 1000 grams or less, Pediatrics 85:578–584.PubMedGoogle Scholar
  15. Goss-Sampson, M. A., MacEvilly, C. J., and Muller, D. P. R., 1988, Longitudinal studies of the neurobiology of vitamin E and other antioxidant systems, and neurological function in vitamin E deficient rats, J. Neurol Sci. 87:25–35.PubMedCrossRefGoogle Scholar
  16. Gotoda, T., Arita, M., Arai, H., Inoue, K., Yokota, T., Fukuo, Y., Yazaki, Y, and Yamada, N„ 1995, Adult-onset spinocerebellar dysfunction caused by a mutation in the gene for the alpha tocopherol-binding protein, New Engl. J. Med. 333:1313–1318.PubMedCrossRefGoogle Scholar
  17. Halks-Miller, M., Henderson, M., and Eng, L. F., 1986, Alpha tocopherol decreases lipid peroxidation, neuronal necrosis, and reactive gliosis in reaggregate cultures of fetal rat brain. J. Neuropath. Exp. Neurol. 45:471–484.PubMedCrossRefGoogle Scholar
  18. Hensley, K., Carney, J. M., Mattson, M. P., Aksenova, M., Harris, M., Wu, J. F., Floyd, R. F, and Butterfield, D. A., 1994, A model for beta amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer’s disease, Proc. Natl. Acad. Sci. USA 91:3270–3274.PubMedCrossRefGoogle Scholar
  19. Ichitani, Y, Okaichi, H., Yoshikawa, T., and Ibata, Y, 1992, Learning behavior in chronic vitamin E-deficient and supplemented rats: radial arm maze learning and passive avoidance response, Beh. Brain Res. 51:157–164.CrossRefGoogle Scholar
  20. Jankovic, J., 1995, Tardive syndromes and other drug-induced movement disorders, Clin. Neuropharmacol. 18:197–214.PubMedCrossRefGoogle Scholar
  21. Kayden, H. J., and Traber, M. G., 1986, Clinical, nutritional and biochemical consequences of apolipoprotein B deficiency, Adv. Exp. Biol. Med. 201:67–81.Google Scholar
  22. Landrieu, P., Selva, J., Alvarez, F., Ropert, A., and Metral, S., 1985, Peripheral nerve involvement in children with chronic cholestasis and vitamin E deficiency, Neuropediatrics 16:194–201.PubMedCrossRefGoogle Scholar
  23. Mecocci, P., MacGarvey, U., and Beal, M. F., 1994, Oxidative damage in mitochondrial DNA is increased in Alzheimer’s disease, Ann. Neurol. 36:747–751.PubMedCrossRefGoogle Scholar
  24. Metcalfe, T., Bowen, D. M., and Muller, D. P. R., 1989, Vitamin E concentrations in human brain of patients with Alzheimer’s disease, fetuses with Down’s syndrome, centennarians and controls. Neurochem. Res. 14:1209–1212.PubMedCrossRefGoogle Scholar
  25. Muller, D. P. R., and Goss-Sampson, M. A., 1990, Neurochemical, neurophysiological, and neuropathological studies in vitamin E deficiency, Critical Reviews in Neurobiology 5:239–263.PubMedGoogle Scholar
  26. Muller, D. P. R., Lloyd, J. K., and Wolff, O. H., 1983, Vitamin E and neurological function, Lancet 199(8318):225–228.CrossRefGoogle Scholar
  27. Nakajima, M., Kashiwagi, K., Hayashi, Y, Saito, M., Kawashima, T., Furukawa, S., and Kobayashi, K., 1991, Alpha tocopherol supports the survival and neurite extension of neurons cultured from various region of fetal rat brain, Neurosci. Lett. 133:49–52.PubMedCrossRefGoogle Scholar
  28. Nelson, J. S., 1980, Pathology of vitamin E deficiency, in: Vitamin E: A Comprehensive Treatise (L. J. Machlin, ed.), Marcel Dekker, New York, pp. 391–428.Google Scholar
  29. Nelson, J. S., Fitch, C. D., Fischer, V. W., Broun Jr., G. O., and Chou, A. C., 1981, Progressive neuro-pathologic lesions in vitamin E-deficient rhesus monkeys, J. Neuropathol. Exp. Neurol. 40:166–186.PubMedCrossRefGoogle Scholar
  30. Ouahchi, K., Arita, M., Kayden, H. J., Hentati, F., Ben Hamida, M., Sokol, R., Arai, H., Inoue, K., Mandel, J. L., and Koenig, M., 1995, Ataxia with isolated vitamin E deficiency is caused by mutations in the alpha tocopherol transfer protein, Nature Genetics 9:141–145.PubMedCrossRefGoogle Scholar
  31. Pappenheimer, A. M., and Goettsch M., 1931, A cerebellar disorder in chicks, apparently of nutritional origin, J. Exp. Med. 53:11–26.PubMedCrossRefGoogle Scholar
  32. Pappolla, M. A., Omar, R. A., Kim, K. S., and Robakis, N. K., 1992, Immunohistochemical evidence of antioxidant stress in Alzheimer’s disease, Am. J. Pathol. 140,621–628.PubMedGoogle Scholar
  33. Parker, Jr., W. D., Parks, J., Filley, C. M., and Kleinschmidt-DeMasters, B. K., 1994, Electron transport chain defects in Alzheimer’s disease brain, Neurology 44,1090–1096.PubMedCrossRefGoogle Scholar
  34. The Parkinson’s Study Group, 1993, Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease, New Engl. J. Med. 328:176–183.CrossRefGoogle Scholar
  35. Pascoe, G. A., Olafsdottir, K., and Reed, D. J., 1987, Vitamin E protection against chemical-induced cell injury. I. Maintenance of cellular protein thiols as a cytoprotective mechanism, Arch. Biochem. Biophys. 256:150–158.PubMedCrossRefGoogle Scholar
  36. Pentschew, A., and Schwarz, K., 1962, Systemic axonal dystrophy in vitamin E deficient adult rats, Acta Neuropath. 1:313–334.CrossRefGoogle Scholar
  37. Perumal, A. S., Gopal, V. B., Tordzro, W. K., Cooper, T. B., and Cadet, J. L., 1992, Vitamin E attenuates the toxic effects of 6-hydroxydopamine on free radical scavenging systems in rat brain, Brain Res. Bull. 29:699–701.PubMedCrossRefGoogle Scholar
  38. Rader, D. J., and Brewer, J. H. B., 1993, Abetalipoproteinemia: New insights into lipoprotein assembly and vitamin E metabolism from a rare genetic disease, J. Am. Med. Assoc. 270:865–869.CrossRefGoogle Scholar
  39. Sahu, S. N., Edwards-Prasad, J., and Prasad, K. N., 1988, Effects of alpha tocopheryl succinate on adenylate cyclase activity in murine neuroblastoma cells in culture, J. Am. Coll. Nutr. 7:285–293.PubMedGoogle Scholar
  40. Sato, Y., Hagiwara, K., Arai, H., and Inoue, K., 1992, Purification and characterization of the alpha tocopherol transfer protein from rat liver. FEBS Lett. 288:41–45.CrossRefGoogle Scholar
  41. Shoulson, I., 1992, Antioxidative therapeutic strategies for Parkinson’s disease, Ann. N. Y. Acad. Sci. 648:37–42.PubMedCrossRefGoogle Scholar
  42. Shriqui, C. L., Bradwejn, J., Annable, L., and Jones, B. D., 1992, Vitamin E in the treatment of tardive dyskinesia: a double-blind placebo-controlled study, Am. J. Psychiatry 140:391–393.Google Scholar
  43. Sokol, R. J., 1989, Vitamin E and neurologic function in man, Free Rad. Biol. Med. 6:189–207.PubMedCrossRefGoogle Scholar
  44. Subbarao, K. V, Richardson, J. S., and Ang, L. C., 1990, Autopsy samples of Alzheimer’s cortex show increased lipid peroxidation in vitro, J. Neurochem. 55:342–345.PubMedCrossRefGoogle Scholar
  45. Towfighi, J., 1981, Effects of chronic vitamin E deficiency on the nervous system of the rat, Acta Neuropathol. 54:261–267.PubMedCrossRefGoogle Scholar
  46. Traber, M. G., Sokol, R. J., Ringel, S. P., Neville, H. E., Thellman, C. A., and Kayden, H. J., 1987, Lack of tocopherol in peripheral nerves of vitamin E-deficient patients with peripheral neuropathy, New. Engl. J. Med. 317:262–265.PubMedCrossRefGoogle Scholar
  47. Traber, M. G., Sokol, R. J., Burton, G. W., Ingold, K. U., Papas, A. M., Huffaker, J. E., and Kayden, H. J., 1990, Impaired ability of patients with familial isolated vitamin E deficiency to incorporate alpha tocopherol into lipoproteins secreted by the liver, J. Clin. Invest. 85:397–407.PubMedCrossRefGoogle Scholar
  48. Uenohara, H., Imaizumi, S., Suzuki, J., and Yashimoto, T., 1988, The protective effect of mannitol, vitamin E and glucocorticoid on ischaemic brain injury: evaluation by chemiluminescence, energy metabolism and water content, Neurosurg. Res. 10:73–80.Google Scholar
  49. Vatassery, G. T., 1992, Vitamin E: neurochemistry and implications for Parkinson’s disease, Annals of the New York Academy of Science, 669:97–110.CrossRefGoogle Scholar
  50. Vatassery, G. T., 1993, Oxidation of alpha tocopherol in subcellular fractions from rat brain and its possible involvement in nerve function, Biochem. Pharmacol. 45:2295–2301.PubMedCrossRefGoogle Scholar
  51. Vatassery, G. T., 1995, In vitro oxidations of vitamins C and E, cholesterol, and thiols in rat brain synaptosomes, Lipids 30:1007–1013.PubMedCrossRefGoogle Scholar
  52. Vatassery, G. T., and Schut, L. J., 1987, Changes in vitamin E concentration in red blood cells and plasma of patients with olivopontocerebellar ataxia within the Schut-Swier kindred, J. Am. Coll. Nutr. 6:151–156.PubMedGoogle Scholar
  53. Vatassery, G. T., Angerhofer, C. K., Knox, C. A., and Deshmukh, D. S., 1984a, Concentrations of vitamin E in various neuroanatomical regions and subcellular fractions and the uptake of vitamin E by specific areas of rat brain, Biochim. Biophys. Acta 792:118–122.PubMedCrossRefGoogle Scholar
  54. Vatassery, G. T., Angerhofer, C. K., and Peterson, F. J., 1984b, Vitamin E concentrations in the brains and some selected peripheral tissues of selenium-deficient and vitamin E-deficient mice. J. Neurochem. 42:554–558.PubMedCrossRefGoogle Scholar
  55. Vatassery, G. T., Smith, W. E., and Quach, H. T., 1994, Increased suceptibility to oxidation of vitamin E in mitochondrial fractions compared with synaptosomal fractions from rat brains, Neurochem. Int. 24:29–35.PubMedCrossRefGoogle Scholar
  56. Vatassery, G. T., Smith, W. E., Quach, H. T., and Lai, J. C. K., 1995, In vitro oxidation of vitamin E, vitamin C, thiols and cholesterol in rat brain mitochondria incubated with free radicals, Neurochem. Int. 26:527–535.PubMedCrossRefGoogle Scholar
  57. Von Voigtlander, P. F., Burian, M. A., Althaus, J. S., and Williams, L. R., 1990, Effects of chronic haloperidol on vitamin E levels and monoamine metabolism in rats fed normal and vitamin E-deficient diets, Res. Comm. Chem. Path. Pharmacol. 68:343–352.Google Scholar
  58. Wood, P. L., and Boegman, R. J., 1975, Increased rate of rapid axonal transport in vitamin E deficient rats, Brain Res. 84:325–328.PubMedCrossRefGoogle Scholar
  59. Yoshida, H., Yusin, M., Ren, I., Kuhlenkamp, J., Hirano, T., Stolz, A., and Kaplowitz, N., 1992, Identification, purification, and immunochemical characterization of a tocopherol-binding protein in rat liver cytosol, J. Lipid Res, 33:343–350.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • G. T. Vatassery
    • 1
    • 2
  1. 1.Research Service and the Geriatric Research Education and Clinical Center (GRECC)Veterans Affairs Medical CenterMinneapolisUSA
  2. 2.Department of PsychiatryUniversity of MinnesotaMinneapolisUSA

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