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Jae Hee Kang, ScD; Nancy Cook, ScD; JoAnn Manson, MD, DrPH; Julie E. Buring, ScD; Francine Grodstein, ScD

Arch Intern Med. 2006;166:2462-2468.

Background  Oxidative stress may play a key role in the development of cognitive impairment. Long-term supplementation with vitamin E, a strong antioxidant, may provide cognitive benefits.

Methods  The Women's Health Study is a randomized, double-blind, placebo-controlled trial of vitamin E supplementation (600 IU [-tocopherol acetate], on alternate days) begun between 1992 and 1995 among 39 876 healthy US women. From 1998, 6377 women 65 years or older participated in a cognitive substudy. Three cognitive assessments of general cognition, verbal memory, and category fluency were administered by telephone at 2-year intervals. The primary outcome was a global composite score averaging performance on all tests. Repeated measures analyses were conducted to examine mean performance and mean differences in cognitive change, and logistic regression was used to estimate relative risks of substantial decline.

Results  There were no differences in global score between the vitamin E and placebo groups at the first assessment (5.6 years after randomization: mean difference, –0.01; 95% confidence interval [CI], –0.04 to 0.03) or at the last assessment (9.6 years of treatment: mean difference, 0.00; 95% CI, –0.04 to 0.04). Mean cognitive change over time was also similar in the vitamin E group compared with the placebo group for the global score (mean difference in change, 0.02; 95% CI, –0.01 to 0.05; P = .16). The relative risk of substantial decline in the global score in the vitamin E group compared with the placebo group was 0.92 (95% CI, 0.77 to 1.10).

Conclusion  Long-term use of vitamin E supplements did not provide cognitive benefits among generally healthy older women.

Author Affiliations: Channing Laboratory (Drs Kang, Manson, and Grodstein) and Division of Preventive Medicine (Drs Cook, Manson, and Buring), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, and Department of Epidemiology, Harvard School of Public Health (Drs Manson, Buring, and Grodstein), Boston, Mass.

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