Vitamin E in Alzheimer’s disease

Salamanca R. (1997). Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer s disease. J Neural Transm. 104(6-7) 703-10. 

Berman K. and Brodaty H. (2004). Tocopherol (vitamin E) in Alzheimer s disease and other neu-rodegenerative disorders. CNS Drugs 18 807-825. 

The importance of cell death mediated by oxidative damage has led to the popularity of antioxidants as potential therapeutics. A variety of naturally occurring (vitamin C, vitamin E) and synthetic (lazaroids) antioxidants have been smdied as possible remedies for a wide variety of ailments. Large doses of vitamin E have been studied as a putative therapy in Alzheimer s disease, functioning through the inhibition of amyloid-induced oxidative destruction of neuronal membranes within the brain. 

Today s healthcare policy-makers, including government officials, health insurance companies and managed-care organizations, are faced with the reality of limited resources for healthcare and the knowledge that much medical care is of uncertain value. The value of vitamin E therapy in Alzheimer s disease, for example, is still unclear, but some physicians have recommended it for years without any real measures of its effect on the disease. 

The substantia nigra and globus pallidus are rich in iron yet cerebrospinal fluid has very little iron-binding capacity (H2). Moreover, any injury to the CNS may result in the release of iron, which by Fenton/Haber-Weiss chemistry, catalyzes free radical production. Iron has also been shown to accelerate the production of CNS lipofuscin (increased in Alzheimer s disease), while various antioxidants (vitamin E, GSH, selenium) reduce its concentration (E5). 

Hyland S, Muller D, Hayton S, Stoeckhn E, BareUa L (2(X)6) Cortical gene expression in the vitamin E-deficient rat possible mechanisms for the electrophysiological abnormalities of visual and neural function. Ann Nutr Metab 50(5) 433-441 Heroux M, Raghavendra Rao VL, Lavoie J, Richardson JS, Butterworth RF (1996) Alterations of thiamine phosphorylation and of thiamine-dependent enzymes in Alzheimer s disease. Metab Brain Dis ll(l) 81-88... 

Other substances that are being evaluated in Alzheimer s disease include the antioxidant vitamin E, the monoamine oxidase type B inhibitor, selegeline (see p. 425) and the plant extract gingko biloba, which is though to have antioxidant and cholinergic activity. Oestrogens and nonsteroidal anti-inflammatory agents may also have protective effects. 

Neurological Mutations in SOD 1 result in human ALS and transgenic animal models rescued by antioxidants. NMDA-receptor stimulation produces superoxide. Defects in the function of complex 1 seen in Parkinson s disease. Vitamin E not protective in early Parkinson s disease. Vitamin E beneficial in Alzheimer s disease. A-acetylcysteine does not effect survival in ALS. 

Mangialasche F, Kivipelto M, Mecocci P, Rizzuto D, Palmer K, Winblad B, Fratiglioni L. (2010) High plasma levels of vitamin E forms and reduced Alzheimer s disease risk in advanced age. J Alzheimers Dis 20 1029-1037. 

Metcalfe T., Bowen D. M., and Muller D. P. (1989). Vitamin E concentrations in human brain of patients with Alzheimer s disease, fetuses with Down s syndrome, centenarians, and controls. Neurochem. Res. 14 1209-1212. 

CCS Case-control 4750 M-F Use of vitamin E and C supplements in combination reduces the prevalence of Alzheimer s disease (208)... 

The occurrence of mitochondrial damage and oxidative stress has been repeatedly found in the chnical setting and in e q)erimental models of Parkinson s disease [52]. Treatment of Parkinson s disease patients with vitamin E has not provided definite positive results however, a combination of antioxidants [46, 53], including vitamins such as niacin and riboflavin, is strongly recommended [46,54]. Treatment of patients with Alzheimer s disease with vitamin E (2000 mg day ) has been reported to improve the patients event-free-sur-vival (cognitive activity) [55]. It has also been claimed that an increased intake of vitamin E lowers the risk of Alzheimer s disease [56,57]. 

Forette F, Seux M-L, Staessen JA et al. Prevention of dementia in randomised double-blind placebo-controlled systolic hypertension in Europe (Syst-Eur) trial. Lancet 1998 351 1347-51 Morris MC, Beckett LA, Scherr PA et al. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis Assoc Disord 1998 12 121-6 National Institute for Clinical Excellence Technology Appraisal Guidance No. 19. Guidance on the use of donepezil, rivastigmine and galantamine for the treatment of Alzheimer s disease, 2001. http //www. nice, org. uk/... 

Before drawing this chapter to a close with some parallels in other age-related diseases, what have we learnt from Alzheimer s disease First, the known genetic mutations affect a small fraction of people with Alzheimer s disease and their effects are delayed until middle age. This delay implies that, as in mice and monkeys, oxidative stress must cross a threshold before neurons die en masse and dementia can be diagnosed clinically. Second, all other known risk factors for Alzheimer s disease, including Down syndrome, ApoE4 and herpes simplex infection, are associated with a rise in oxidative stress. Third, oxidative stress alone is sufficient to cause dementia in old age in people with no known risk factors (about half the people who succumb to dementia in old age). Fourth, factors that lower oxidative stress, such as aspirin and vitamin E, can postpone the onset of dementia by a few years, if not indefinitely. 

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