Two studies in the June 26 JAMA report that high intake of vitamins E and C was correlated with reduced risk of AD, pointing to the role of antioxidant activity in warding off the disease. The finding held only when the vitamins were consumed from foods, not in the form of supplements.

Both reports were drawn from large-scale, prospective community studies of aging, one in Rotterdam, the Netherlands, and the other in Chicago, Illinois (the latter being noteworthy for having equal numbers of black and white participants). In their analysis of data from the Rotterdam study, Monique Breteler and colleagues at Erasmus Medical Center there found a protective effect in those whose diets were high in vitamins E and C. The Chicago data, reported by Martha Morris and colleagues, showed a protective effect only of vitamin E. Other dietary antioxidants examined (beta carotene in both studies, flavonoids in the Chicago study) did not correlate with AD risk.

Interestingly, neither study found a protective effect for vitamin supplements. This could mean that supplements are useless in protecting against AD because their biological activity differs from vitamins in food, but other possible explanations exist, as well. Breteler et al. point out that users of supplements tend to either have existing health problems or engage in a range of other “health-seeking” behaviors, any of which might affect the progression of AD. Numerous confounding factors argue against deriving conclusions from this kind of epidemiological data.

Echoing the authors' cautionary remarks, Daniel Foley of U.S. National Institute on Aging in Bethesda, Maryland, and Lon White of the Pacific Health Research Institute in Honolulu, Hawaii, present some of the arguments for reserving judgment until results from long-term clinical trials become available. Among their concerns about the present data are the reliability of the questionnaires on dietary habits, which ask about large numbers of foods consumed over long periods of time. There is an inherent possibility that people in preclinical stages of AD would be increasingly unable to provide accurate data. Similarly, preclinical disease might affect eating habits or the use of supplements.

“Nonetheless, the idea that vitamin E and vitamin C might have beneficial effects on the underlying AD process makes sense, and it seems unlikely that antioxidant-rich foods would negatively affect brain aging,” conclude Foley and White in an accompanying editorial.—Hakon Heimer


  1. Interventions to modify oxidant balance to provide protection from Alzheimer disease (AD) are as hotly debated as it has been for other age-related diseases. In recent studies ( Engelhart et al., Foley and White, Morris, et al.), dietary intake of vitamin E and C was associated with a mild lowered risk of AD, yet vitamins supplied by supplements had no benefit. That dietary antioxidants provide protections should be of little surprise given the massive oxidative damage that is a prominent and early feature of AD (Nunomura, et al). However, oxidative phenomena are well-regulated events such that in AD there is a compensatory antioxidant response (Smith, et al., Russel, et al.) and regulatory control of oxidative damage (Wataya, et al). Uni-dimensional antioxidants found in supplements would only perturb this system whereas complex antioxidants found in fruits and vegetables would synergize with endogenous protectants, and may increase neuronal signaling to increase the efficacy of conventional treatments, or may serve to prevent the disease in individuals genetically predisposed to AD (Joseph et al., 1998, 1999; Casadesus et al., 2002). To expect health from a bottle may be too much , but it hopefully heralds a new direction for treatment and prevention.

    George Perry, Gemma Casadesus*, James A. Joseph*, and Mark A. Smith Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio; *USDA-HNRC at Tufts University, 711 Washington Street, Boston, Massachusetts


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    . Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol. 2001 Aug;60(8):759-67. PubMed.

    . Increased neuronal glucose-6-phosphate dehydrogenase and sulfhydryl levels indicate reductive compensation to oxidative stress in Alzheimer disease. Arch Biochem Biophys. 1999 Oct 15;370(2):236-9. PubMed.

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  2. As a background reading please do not miss the following article:

    Brain Cholesterol Pathology is the cause of Alzheimer’s disease [ Full Text ]

    View all comments by Alexei Koudinov
  3. As a followup on the subject of 'diet and Alzheimer's disease' please do not miss the following article:

    Brain Cholesterol Pathology is the cause of Alzheimer’s disease [ Full Text ]

    View all comments by Alexei Koudinov

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Primary Papers

  1. . Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. 2002 Jun 26;287(24):3223-9. PubMed.
  2. . Dietary intake of antioxidant nutrients and the risk of incident Alzheimer disease in a biracial community study. JAMA. 2002 Jun 26;287(24):3230-7. PubMed.
  3. . Dietary intake of antioxidants and risk of Alzheimer disease: food for thought. JAMA. 2002 Jun 26;287(24):3261-3. PubMed.