Reduced Risk of Alzheimer Disease in Users of Antioxidant Vitamin Supplements: The Cache County Study
Peter P. Zandi, PhD; James C. Anthony, PhD; Ara S. Khachaturian, PhD; Stephanie V. Stone, PhD; Deborah Gustafson, PhD; JoAnn T. Tschanz, PhD; Maria C. Norton, PhD; Kathleen A. Welsh-Bohmer, PhD; John C. S. Breitner, MD; for the Cache County Study Group
Arch Neurol. 2004;61:82-88.
Background Antioxidants may protect the aging brain against oxidative damage associated with pathological changes of Alzheimer disease (AD).
Objective To examine the relationship between antioxidant supplement use and risk of AD.
Design Cross-sectional and prospective study of dementia. Elderly (65 years or older) county residents were assessed in 1995 to 1997 for prevalent dementia and AD, and again in 1998 to 2000 for incident illness. Supplement use was ascertained at the first contact.
Setting Cache County, Utah.
Participants Among 4740 respondents (93%) with data sufficient to determine cognitive status at the initial assessment, we identified 200 prevalent cases of AD. Among 3227 survivors at risk, we identified 104 incident AD cases at follow-up.
Main Outcome Measure Diagnosis of AD by means of multistage assessment procedures.
Results Analyses of prevalent and incident AD yielded similar results. Use of vitamin E and C (ascorbic acid) supplements in combination was associated with reduced AD prevalence (adjusted odds ratio, 0.22; 95% confidence interval, 0.05-0.60) and incidence (adjusted hazard ratio, 0.36; 95% confidence interval, 0.09-0.99). A trend toward lower AD risk was also evident in users of vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B–complex supplements.
Conclusions Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD.
From the Department of Mental Health, Bloomberg School of Public Health (Drs Zandi, Anthony, and Khachaturian), and Advanced Academic Programs: Developmental Psychology (Dr Stone), The Johns Hopkins University, Baltimore, Md; Departments of Nutrition and Food Sciences (Dr Gustafson), Psychology (Drs Tschanz and Norton), and Family, Consumer, and Human Development (Dr Norton), and the Center for Epidemiologic Studies (Drs Tschanz and Norton), Utah State University, Logan; Department of Psychiatry and Behavioral Sciences and the Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University Medical Center, Durham, NC (Dr Welsh-Bohmer); and Veterans Affairs Puget Sound Health Care System and Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle (Dr Breitner). A list of the additional members of the Cache County Study Group appears in the box.
What the New York Times has to say...
Vitamin E, C Supplements May Prevent Alzheimer's Mon January 19, 2004 05:09 PM ET
By Megan Rauscher
NEW YORK (Reuters Health) - A study involving more than 4700 participants strongly suggests that the combination of vitamin C and E lowers the risk of developing Alzheimer's disease.
As the lead investigator Dr. Peter P. Zandi told Reuters Health, properly conducted prevention trials are needed to confirm the results.
However, "because vitamins E and C are relatively non-toxic and are believed to have wide-ranging health benefits, they may offer a very attractive strategy for preventing Alzheimer's disease."
The findings come from the Cache County Study, which looked at the prevalence of Alzheimer's disease and other dementias in terms of genetic and environmental risk factors. As part of the study, people aged 65 and older were assessed for dementia between 1995 and 1997 and again between 1998 and 2000.
The participants were categorized as "vitamin E users" if they took an individual vitamin E tablet or a multivitamin containing more than 400 international units of vitamin E every day. They were classified as "vitamin C users" if they took at least 500 milligrams per day of vitamin C as a stand-alone tablet or in a multivitamin. If they took multivitamins containing lower doses of these two vitamins, they were categorized as "multivitamin users."
Zandi, at The Johns Hopkins University Bloomberg School of Public Health in Baltimore, and colleagues identified 200 cases of Alzheimer's disease between 1995 and 1997 and 104 new cases during follow-up of 4740 participants.
According to the team's analysis, reported in The Archives of Neurology, use of vitamin E and C supplements in combination lowered the odds of having Alzheimer's disease at the start of the study by about 78 percent, and the odds of developing the disease by about 64 percent during the follow-up period.
There was also a trend toward reduced Alzheimer's risk among people who took vitamin E and multivitamins containing vitamin C.
In contrast, there was "no evidence of a protective effect with the use of vitamin E or C supplements alone, with multivitamins alone, or with vitamin B-complex supplements."
Currently, the recommended daily allowance for vitamin E is 22 IU (15 mg) and for vitamin C, 75 to 90 mg, the team points out. Although multivitamin preparations typically contain approximately these levels, individual supplements commonly contain doses up to 1000 IU of vitamin E and 500 to 1000 mg or more of vitamin C.
"Our findings suggest that vitamins E and C may offer protection against AD when taken together in the higher doses available from individual supplements," the researchers conclude.
Zandi also pointed out that there may be a biological reason why the two vitamins together produce a benefit, related to the different duration of their antioxidant effects.
"Vitamin E is a lipid-soluble vitamin that sticks around in fat tissues of the body for a relatively long time," he explained. "In contrast, vitamin C is a water-soluble vitamin and is rapidly excreted from the body. Vitamin C may act to 'recharge' the antioxidant capacities of vitamin E so that the vitamin E can sustain its job of soaking up free radicals and relieving oxidative stress in the body."