Name:	Alpha-tocopherol
Other Names:	Vitamin E
Development Status:	investigational in U.S.
FDA Phase:	Phase III
Primary Medical Role:	An essential vitamin that function as an antioxidant. Previous research has shown that vitamin E can help prevent cardiovascular disease and increase immune response.
Role in Alzheimer's Disease:	Thought to prevent brain cell damage by destroying toxic free radicals.
Pharmacological Role:	Binds to free radicals normally found in blood stream. Reduce the oxidation process, which may seriously damage cells.
Side Effects:	When taken in high dose, may cause bleeding and gastrointestinal problems. In Alzheimer's disease study, a slight increase in the number of falls and sycopal episodes were noted in the treated patients. A study published in November 2004 concluded that high-dosage (>/=400 IU/d) vitamin E supplements may increase all- cause mortality and should be avoided.
Evidence pro its efficacy:	A recent, pretty big, double-blinded placebo-controlled multicenter study supported the use of Vit. E in Alzheimer's disease. It found that those taking 2000 IU a day are less likely to come to bad primary outcomes than people taking placebo (similar to the outcome found using selegeline). The results were hence encouraging but were far from mind-blowing. In fact, technically, there was no statistically significant difference between the groups in this study (the findings mentioned above were declared after statistical adjustments were made).
Evidence con its efficacy:	The use of this drug over the long term has not been examined. Moreover, the results of the single study that indicated that it is efficacious were not overly terrific.
Notes:	Phase III clinical trials testing vitamin E in AD or mild cognitive impairment are ongoing (NCT00040378, NCT00235716, NCT00903695). This record was last updated October 17, 2010.

References

Miller ER, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality. Ann Intern Med. 2004 Nov 10 [Epub ahead of print] Abstract

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Klatte ET, Scharre DW, Nagaraja HN, Davis RA, Beversdorf DQ. Combination therapy of donepezil and vitamin E in Alzheimer disease. Alzheimer Dis Assoc Disord. 2003 Apr- Jun ;17(2):113-6. Abstract

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Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology. 2000 Mar 28;54(6):1265-72. POW link

Grundman M. Vitamin E and Alzheimer disease: the basis for additional clinical trials. Am J Clin Nutr. 2000 Feb;71 (2):630S-636S. POW link

Behl C. Vitamin E protects neurons against oxidative cell death in vitro more effectively than 17-beta estradiol and induces the activity of the transcription factor NF- kappaB. J Neural Transm. 2000;107(4):393-407. POW link

Vatassery GT, Bauer T, Dysken M. High doses of vitamin E in the treatment of disorders of the central nervous system in the aged. Am J Clin Nutr. 1999 Nov;70(5):793-801. POW link

Yatin SM, Aksenov M, Butterfield DA. The antioxidant vitamin E modulates amyloid beta-peptide-induced creatine kinase activity inhibition and increased protein oxidation: implications for the free radical hypothesis of Alzheimer's disease. Neurochem Res. 1999 Mar;24(3):427-35. Abstract

Butterfield DA, Koppal T, Subramaniam R, Yatin S. Vitamin E as an antioxidant/free radical scavenger against amyloid beta-peptide-induced oxidative stress in neocortical synaptosomal membranes and hippocampal neurons in culture: insights into Alzheimer's disease. Rev Neurosci. 1999;10 (2):141-9. Abstract

Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, Woodbury P, Growdon J, Cotman CW, Pfeiffer E, Schneider LS, Thal LJ. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med 1997 Apr 24;336(17):1216-22. POW link