Food and Behaviour Research

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A randomized trial of vitamin E supplementation and cognitive function in women.

Kang JH, Cook N, Manson J, Buring JE, Grodstein F. (2006) Archives of Internal Medicine 166(22) 2462-8 American Medical Association

Web URL: read full abstract via PubMed here


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 (alpha-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.


Many aspects of physical and mental degeneration associated with aging involve ‘oxidative stress’ - in which damaging substances called free radicals overwhelm the body’s antioxidant defences. Vitamin E is a potent antioxidant, so this study was designed to test whether it might offer some protection against age-related cognitive decline if provided as a dietary supplement.

In a long-term randomized controlled trial (RCT), 6377 women aged 65 years or older from the larger ‘Women’s Health study’ were given either Vitamin E supplements or placebo every other day for almost 10 years. After more than 5 years of supplementation they were then assessed (by telephone) on measures of general cognition, verbal memory, and category fluency three times at 2-year intervals. Scores on these tests were combined to provide a total ‘cognitive function’ score on which the women taking Vitamin E supplements (in the form of alpha-tocopherol acetate, 600 IU) were compared at each timepoint with those taking placebo.

No significant differences were found between the two groups on any of these measures at any timepoint. The researchers concluded that long-term use of vitamin E supplements did not provide cognitive benefits among generally healthy older women.


Population studies have indicated that diets rich in Vitamin E may offer protection from a number of conditions linked with oxidative stress, including age-related cognitive decline. However, RCTs (such as this trial) are the only kind of study that can provide definitive evidence of cause-and-effect relationships.

No obvious benefits for cognitive function were found in women aged over 65 years who took Vitamin E supplements for several years. The supplements provided only one (synthetic) form of Vitamin E, however, which is found naturally in at least 8 different forms. Even more important is the fact that foods rich in vitamin E (such as nuts, seeds and whole grains) also provide many other micronutrients, macronutrients and dietary fibre. Nutrients work in ‘synergy’ – meaning that their combined effects on physical and mental health are likely to be more important that the effects of any one nutrient in isolation.

It may well be that Vitamin E per se is not a critical factor in protecting against age-related cognitive decline. But it would be wrong to dismiss the potential benefits of Vitamin E (or any other nutrients) purely on the basis of controlled trials like this one, which are far better suited to the assessment of pharmaceutical drugs. Changes in actual diet are extremely difficult to study under controlled conditions like this, of course – but to improve our understanding of the role of nutrition in health this challenge needs to be addressed, and the overall balance of different kinds of evidence should always be considered.