Home Journal Excerpts Alzheimer Disease and Antioxidants Dietary intake of antioxidants and risk of Alzheimer disease
Dietary intake of antioxidants and risk of Alzheimer disease PDF Print E-mail
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Thursday, 29 January 2004 00:00
“CONTEXT: Laboratory findings have suggested that oxidative stress may contribute to the pathogenesis of Alzheimer disease. Therefore, the risk of Alzheimer disease might be reduced by intake of antioxidants that counteract the detrimental effects of oxidative stress.”

“OBJECTIVE: To determine whether dietary intake of antioxidants is related to risk of Alzheimer disease.”

“DESIGN AND SETTING: The Rotterdam Study, a population-based, prospective cohort study conducted in the Netherlands.”

“PARTICIPANTS: A total of 5395 participants who, at baseline (1990-1993), were aged at least 55 years, free of dementia, and noninstitutionalized and had reliable dietary assessment. Participants were reexamined in 1993-1994 and 1997-1999 and were continuously monitored for incident dementia.”

“MAIN OUTCOME MEASURES: Incidence of Alzheimer disease, based on Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria and National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) criteria, associated with dietary intake of beta carotene, flavonoids, vitamin C, and vitamin E.”

“RESULTS: After a mean follow-up of 6 years, 197 participants developed dementia, of whom 146 had Alzheimer disease. When adjustments were made for age, sex, baseline Mini-Mental State Examination score, alcohol intake, education, smoking habits, pack-years of smoking, body mass index, total energy intake, presence of carotid plaques, and use of antioxidative supplements, high intake of vitamin C and vitamin E was associated with lower risk of Alzheimer disease (rate ratios [RRs] per 1-SD increase in intake were 0.82 [95% confidence interval [CI], 0.68-0.99] and 0.82 [95% CI, 0.66-1.00], respectively). Among current smokers, this relationship was most pronounced (RRs, 0.65 [95% CI, 0.37-1.14] and 0.58 [95% CI, 0.30-1.12], respectively) and also was present for intake of beta carotene (RR, 0.49 [95% CI, 0.27-0.92]) and flavonoids (RR, 0.54 [95% CI, 0.31-0.96]). The associations did not vary by education or apolipoprotein E genotype.”

“CONCLUSION: High dietary intake of vitamin C and vitamin E may lower the risk of Alzheimer disease.”

“Several findings suggest that oxidative stress may plan an important role in the pathogenesis of Alzheimer disease. First, the brains of patients with Alzheimer disease contain lesions that are typically associated with exposure to free radicals. In addition, oxidative stress in brains of Alzheimer patients is indicated by elevated cerebral levels of endogenous antioxidants that scavenge free radicals. Moreover, in vitro studies suggest that exogenous antioxidants reduce the toxicity of ß-amyloid in brains of Alzheimer patients. Based on these findings, it has been hypothesized that antioxidants from food many reduce the risk of Alzheimer disease.”

“A pervious randomized controlled trial found that patients taking vitamin E supplement had a slower progression of Alzheimer disease than patients taking placebo. It is thus possible that high intake of antioxidants may also prevent the onset of dementia, because antioxidants may reduce neuronal loss due to oxidative damage.”

“Two studies examined the longitudinal relationship between antioxidants from supplements and risk of Alzheimer disease. These studies found conflicting results: vitamin C supplement use was related to lower risk of Alzheimer disease in one study, whereas the other found no association for combined use of vitamin C and vitamin E supplements. However, studies on supplement use are prone to bias because people who use supplements may also have more health problems and more health-seeking behavior. In addition, use of supplements is generally of short duration.”

“To date, only 1 study has prospectively examined the association between dietary antioxidants and risk of dementia, and found a reduced risk of dementia associated with increased intake of flavonoids. We investigated whether intake of a range of antioxidants from food, namely beta carotene, flavonoids, vitamin C, and vitamin E, was associated with the risk of Alzheimer disease, using data from a population-based cohort study.”

“We found that high intake of vitamin C and vitamin E from food may be associated with a lower incidence of Alzheimer disease after a mean follow-up period of 6 years. The risk reduction associated with intake of all 4 antioxidants was consistently largest for current smokers, although the differences in RRs [Rate Ratios] for beta carotene and flavonoids between smokers and nonsmokers were of marginal statistical significance, while those for vitamin C and vitamin E were not significant. Nonetheless, these associations persisted after controlling for a number of potentially confounding variables, such as use of vitamin supplements, education, and alcohol use.”

“Several studies have examined the relationship between Alzheimer disease and intake of vitamin C and vitamin E from supplements. A case-controlled study and a prospective study in men showed no association between supplement intake and Alzheimer disease. Another prospective study found that use of supplements, in particular vitamin C but not vitamin E, was associated with a lower risk of Alzheimer disease. The only controlled trial of supplemented antioxidant intake and Alzheimer disease was preformed within patients who were already diagnosed with Alzheimer disease. This study reported that patients who took vitamin E supplements had a slower progression of the disease than patients who took placebo.”

“In our study, the risk of Alzheimer disease associated with vitamin C and vitamin E was lowest in current smokers and beta carotene, and flavonoids seemed inversely related to Alzheimer disease in current smokers only. Because smoking itself is associated with increased risk of Alzheimer disease, high antioxidant intake may partly counteract the excess risk of Alzheimer disease for smokers. This is supported by the finding of smokers' increased load of free radicals, which may be reduced by antioxidants.”

“Several biological mechanisms could explain a possible relationship between antioxidant from food and Alzheimer disease. First, antioxidants may decrease the level of oxidative stress in the brain. Antioxidants may thereby reduce the amount of DNA damage, neuronal cell death, and aggregation of ß-amyloid within the brain. These phenomena are all important neuropathological features in Alzheimer disease; by preventing the genesis of the features, the risk of dementia might be reduced. Second, because Alzheimer disease is associated with both cardiovascular risk factors and atherosclerosis, and oxidative processes are involved in atherogenesis, high intake of antioxidants could also decrease the risk of dementia by reducing the risk of atherosclerosis. However, because additional adjustments for carotid plaques as a measure of atherosclerosis did not change our results, we doubt that atherosclerosis is an important intermediary in the relationship between antioxidants and risk of Alzheimer disease.”

“In conclusion, our results suggests that higher intake of vitamin C and vitamin E from food may be associated with a lower risk of Alzheimer disease. Whether this reflects a causal association remains to be elucidated. Randomized controlled trials can help evaluate a possible causal relationship between antioxidant intake form supplements and risk of Alzheimer disease. However, the effect of short-term supplement use in clinical trials may not be comparable with long-term intake from dietary sources. Therefore, more cohort studies are needed to further investigate the relationship between dietary intake and risk of Alzheimer disease.”


Engelhart, Marianne J., MD, MSc; Geerlings, Mirjam I., PhD; Ruitenberg, Annemieke, MD, PhD; van Swieten, John C.; Hofman, Albert MD, PhD; Witteman, Jacqueline, C. M. PhD; and Breteler, Monique M. B., MD, PhD, "Dietary intake of antioxidants and risk of Alzheimer disease", JAMA, January 9, 2004, Vol. 287, Num. 24, pp. 3223-3229

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