• Lisa A Boothby and Paul L Doering.
• Harrison School of Pharmacy, Auburn University, AL, USA. lisa.boothby@crhs.net
• Ann Pharmacother. 2005 Dec 1;39(12):2073-80.

ObjectiveTo evaluate the literature on supplemental vitamin C and vitamin E therapy in the prevention and treatment of Alzheimer's disease (AD).Data SourcesLiterature retrieval was accessed through MEDLINE (1966-March 2005) using the key words antioxidants, vitamin C, vitamin E, Alzheimer's disease, and dementia. International Pharmaceutical Abstracts (1970-March 2005), Current Contents (1996-March 2005), Cochrane Database of Systematic Reviews (1994-March 2005), and Ebsco's Academic Search Elite (1975-March 2005) were searched with the same key words.Study Selection And Data ExtractionArticles related to the objective that were identified through PubMed were included.Data SynthesisOral supplementation of vitamin C (ascorbic acid) and vitamin E (D-alfa-tocopherol acetate) alone and in combination have been shown to decrease oxidative DNA damage in animal studies in vivo, in vitro, and in situ. Recent results of a prospective observational study (n = 4740) suggest that the combined use of vitamin E 400 IU daily and vitamin C 500 mg daily for at least 3 years was associated with the reduction of AD prevalence (OR 0.22; 95% CI 0.05 to 0.60) and incidence (HR 0.36; 95% CI 0.09 to 0.99). Contradicting this is a previous prospective observational study (n = 980) evaluating the relationship between 4 years of vitamin C and E intake and the incidence of AD, which detected no difference in the incidence of AD during the 4-year follow-up. Recent meta-analysis results suggest that doses of vitamin E > or =400 IU daily for more than one year are associated with increased all-cause mortality. Mega-trial results suggest that vitamin E doses > or =400 IU daily for 6.9 years in patients with preexisting vascular disease or diabetes mellitus increase the incidence of heart failure, with no other outcome benefits noted.ConclusionsIn the absence of prospective, randomized, controlled clinical trials documenting benefits that outweigh recently documented morbidity and mortality risks, vitamin E supplements should not be recommended for primary or secondary prevention of AD. Although the risks of taking high doses of vitamin C are lower than those with vitamin E, the lack of consistent efficacy data for vitamin C in preventing or treating AD should discourage its routine use for this purpose.

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