Engelhart · JAMA 2002 · Prospective cohort study · n=5395

Dietary intake of antioxidants and risk of Alzheimer disease.

Cited 1078 times in the scientific literature.

Level 3 - non-randomized controlled study

Prospective population-based cohort study

PubMed 12076218 · doi:10.1001/jama.287.24.3223 · record verified 2026-08-30

What was done

Researchers analyzed data from the prospective Rotterdam Study in the Netherlands, evaluating 5,395 dementia-free, noninstitutionalized participants aged 55 years or older with reliable baseline dietary assessments (1990–1993). Participants were reexamined in 1993–1994 and 1997–1999 and continuously monitored for incident dementia over a mean follow-up of 6 years. The study assessed the association between dietary intake of beta carotene, flavonoids, vitamin C, and vitamin E and the risk of developing Alzheimer disease diagnosed by DSM-III-R and NINCDS-ADRDA criteria, adjusting for age, sex, Mini-Mental State Examination score, alcohol intake, education, smoking habits, pack-years, BMI, total energy intake, carotid plaques, and antioxidant supplement use.

What was found

During follow-up, 197 participants developed dementia, of whom 146 had Alzheimer disease. Per 1-SD increase in dietary intake, adjusted rate ratios (RRs) for incident Alzheimer disease were 0.82 (95% CI, 0.68–0.99) for vitamin C and 0.82 (95% CI, 0.66–1.00) for vitamin E. Among current smokers, the associations were pronounced: beta carotene RR was 0.49 (95% CI, 0.27–0.92), flavonoids RR was 0.54 (95% CI, 0.31–0.96), vitamin C RR was 0.65 (95% CI, 0.37–1.14), and vitamin E RR was 0.58 (95% CI, 0.30–1.12). Associations did not differ by education level or apolipoprotein E genotype.

Why it matters

This prospective study suggests that higher dietary intake of antioxidant vitamins, specifically C and E, is associated with a reduced risk of Alzheimer disease in older adults.

Limits

The study is observational and cannot establish causality or eliminate residual confounding from unmeasured lifestyle factors. Dietary intake was assessed at baseline only, and the subgroup analyses had relatively few incident cases resulting in wider confidence intervals.

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