Can an antioxidant-rich diet help protect against the progression of debilitating conditions like Alzheimer's disease (AD)? Research suggests a protective role for several key antioxidants, notably vitamin E, but a clear link between antioxidant status and cognition has yet to be established. Two studies published in a recent issue of the Journal of the American Medical Association add to what we know of this complex issue.

Diet analyses

In one analysis, 815 Chicago area residents --- all at least 65 years old and free of clinical signs of dementia --- were followed for an average of 4 years. Food frequency questionnaires completed during the study were used to assess usual intake of vitamins C and E and beta-carotene from food and dietary supplements. A total of 131 participants were diagnosed with AD during the study. After adjusting for potential confounders --- including age, gender, and apo-E status --- the researchers found that those who consumed the most vitamin E from foods (> 50 IU/day) were 70% less likely to develop Alzheimer's disease than those who consumed the least (< 7.9 IU/day) (RR=0.30, 95% CI 0.10, 0.92). Vitamin E from dietary supplements, however, did not have the same effect. Likewise, vitamin C and beta-carotene intake had no significant effect on risk.

A second study followed 5395 Dutch residents --- all at least 55 years old and deemed free of dementia --- for an average of 6 years. Again, food frequency questionnaires were used to assess usual diet. During the study's span, 146 people developed AD. The results, adjusted for potential confounders, showed that those with the highest intake of vitamin C from foods and supplements were 18% less likely than those with the lowest intake to develop AD (RR= 0.82, 95% CI 0.68, 0.99). High intake of vitamin E from foods and supplements showed a trend toward a protective effect (RR=0.82, 95% CI 0.66, 1.00).

Both sets of researchers then analyzed their data by apo-E status and got different results. In the Chicago study, the protective effect of vitamin E was limited to those without the apo E-4 allele. On the other hand, the Dutch study found no significant association between apo-E status and disease risk.

What's the connection?

The antioxidant-brain health connection seems obvious --- the brains of Alzheimer's victims clearly show signs of damage associated with exposure to free radicals. Antioxidants help to limit such damage by deactivating free radicals. In addition, in vitro studies indicate that antioxidants may blunt the impact of beta-amyloid protein, a known genetic risk factor. But it remains to be seen if manipulating diet can have a measurable effect on the risk of developing a multi-faceted disease like Alzheimer's.

Why didn't supplements have more of an effect?

Earlier research has suggested that antioxidant supplements, especially vitamin E, may be able to slow the cognitive decline that marks Alzheimer's, but supplements did not appear to have a major impact on the results of these studies. It's not clear why, but the author of the editorial that accompanied these reports commented that both studies were of relatively short duration, and may have not captured enough data on long-term supplement use.

Advice to patients

More work needs to be done to give researchers a clear picture of which nutrients, in what amounts, might help reduce Alzheimer's risk. Note, though, that participants who consumed the most antioxidants from foods were likely eating a variety of fruits, vegetables, whole grains, seeds, and nuts. Such a diet tends to be high in vitamins, minerals, and phytochemicals --- any combination of which may help keep people healthy as they age.