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A new population-based study of antioxidants, appearing in the June 26, 2002, Journal of the American Medical Association (JAMA), suggests that a diet rich in foods containing vitamin E may help protect some people against Alzheimer's disease (AD). The study is also noteworthy for its finding that vitamin E in the form of supplements was not associated with a reduction in the risk of AD. The latest in a series of reports on vitamin E and dementia, the study findings heighten interest in the outcome of clinical trials now underway to test the effectiveness of vitamin E and other antioxidants in preventing or postponing cognitive decline and AD.
The JAMA study was conducted by Martha Clare Morris, Sc.D., of the Rush Institute for Healthy Aging at Rush-Presbyterian-St.Luke's Medical Center, Chicago, IL, Denis A. Evans, M.D., and colleagues. A related study by Morris and colleagues, in press in the July 2002 Archives of Neurology, a JAMA publication, also associates vitamin E with protection against more general cognitive decline. (Reporting of additional detail on this study is embargoed for July 14, 2002, 4 p.m. ET.) Both studies were supported by the National Institute on Aging (NIA) at the National Institutes of Health.
The June 26 issue of JAMA includes similar findings from scientists in The Netherlands, who also reported a link between high dietary intake of vitamins C and E and protection against AD in certain people. In addition, the journal contains an editorial on the epidemiological study of dietary intake of antioxidants and the risk of AD by Daniel J. Foley, M.S., of the NIA's Laboratory of Epidemiology, Demography, and Biometry, and Lon White, M.D., Pacific Health Research Institute, Honolulu.
"This and a number of important population studies have pointed to vitamin E as possibly protective against oxidative damage or other mechanisms associated with cognitive decline and dementia," says Neil Buckholtz, Ph.D., head of the Dementias of Aging Branch at the NIA. "The only way this association can really be tested is through clinical studies and trials now underway. These will help us determine whether vitamin E in food or in supplements—or taken together—can prevent or slow down the development of mild cognitive impairment or AD."
It is not recommended, based on current evidence, that people take high-dose vitamin E supplements or other antioxidant pills in an effort to prevent mental decline, Buckholtz says. While population-based studies and animal research have suggested that antioxidants may be neuroprotective, clinical trials to test that notion are currently in progress. Little is known about safety, effectiveness, and dosages of various antioxidant supplements that are proposed for neuroprotective purposes, Buckholtz emphasizes. In excessively high doses (above 2,000 International Units daily, or IU/d), for example, vitamin E may be associated with increased risk of bleeding, and patients taking anti-coagulant medications may be especially at risk. Interactions with other medications commonly taken by older people are also of potential concern. People are advised to consult with their physicians before taking high doses of supplemental vitamin E or other antioxidants.
The 815 people participating in the Morris study were part of the Chicago Health and Aging Project (CHAP), a study of a large, diverse community of people age 65 and older. Participants were free of dementia at the start of the study and followed for an average of 3.9 years. At an average of 1.7 years from their baseline assessment, participants completed a questionnaire, asking them in detail about the kinds and quantities of foods consumed in the previous year.
Some 131 participants had been diagnosed with AD by the end of the study period, when researchers examined the relationship between intake of antioxidants, including dietary and supplemental vitamins E and C, beta carotene, and a multivitamin, and development of AD. The most significant protective effect was found among people in the top fifth of dietary vitamin E intake (averaging 11.4 IU/d), whose risk of AD was 67 percent lower when compared to people in the group with the lowest vitamin E consumption from food (averaging 6.2 IU/d). (The recommended dietary allowance of vitamin E is 22 IU/d.) No significant change in risk of AD was found when the scientists looked at vitamin E supplements, the other antioxidants and their supplements, or a general multivitamin. There was some evidence, though not statistically significant, that increased intake of dietary vitamin C and beta carotene was moving in a "protective direction," the researchers said.
The data were also analyzed to see if age, gender, race, education, or possible genetic risk for AD would influence the findings. Only the presence or lack of apoE-ε4, one form of a protein associated with increased risk of late-onset AD, seemed to matter: the protective effect of vitamin E from food was strongest among people who did not have the apoE-ε4 risk factor allele. "Dietary vitamin E may protect against Alzheimer's disease," says Morris, "but the protection may only occur among people without the apoE-ε4 allele."
Morris suggests that further study in key areas is needed to confirm and explain some of the study's findings, including the link with apoE status and the study's striking distinction between dietary intake of vitamin E and use of supplements. For example, the lack of a protective effect for the supplements could be explained by several factors. Some participants in the study started taking supplements only recently and there may not have been sufficient time for the supplement to be found effective. Also, people who believe they have memory problems could be more likely to take the supplements in the first place. Another possible explanation might be variations in the forms of vitamin E, scientists note. Most vitamin E supplements consist of alpha tocopherol while foods are generally more rich in gamma tocopherol. These forms of vitamin E scavenge different types of free radicals, with one possibly more important than another in potentially reducing risk of cognitive decline. To help determine whether vitamin E might play a role in preventing AD, or at least in delaying its onset, a number of clinical trials are now being supported by the NIA. These include:
- Memory Impairment Study—This study targets people with mild cognitive impairment, or MCI, testing the usefulness of vitamin E and donepezil to slow or stop the conversion from MCI to AD. (Study has completed recruitment.) Principal investigator: Dr. Ronald Petersen, Mayo Clinic, Rochester, MN.
- Prevention of AD by Vitamin E and Selenium (PREADVISE)—An add-on to the National Cancer Institute's Selenium and Vitamin E Prostate Cancer Prevention Trial (SELECT), this investigation is testing vitamin E and selenium in healthy men age 60 and older for preventing cognitive decline and AD. (Some study sites have begun recruitment and others will begin enrolling participants over the next few months. See below on obtaining more information from NIA's ADEAR Center.) Principal investigator: Dr. William Markesberry, University of Kentucky.
- Women's Antioxidant Cardiovascular Study (WACS)—Testing vitamin E, vitamin C, beta carotene, and folate for slowing cognitive decline in women age 65 and older at high risk of cardiovascular disease, the WACS is funded by the National Heart, Lung, and Blood Institute (NHLBI). An add-on for cognitive testing is supported by the NIA. (Recruitment and some cognitive testing of participants have been completed.) Principal investigator: Dr. Francine Grodstein, Harvard University.
- Women's Health Study (WHS)—Testing aspirin and vitamin E in healthy women age 65 and older for slowing cognitive decline, the WHS is supported by the NHLBI and the National Cancer Institute. An add-on for the cognitive studies is supported by the NIA. (Recruitment and some cognitive testing of participants have been completed.) Principal investigator: Dr. Francine Grodstein, Harvard University.
- Physician's Health Study II (PHS II)—Testing beta carotene, vitamin E, vitamin C and multivitamin with folate in healthy men age 65 and older for slowing cognitive decline. NIA supports the cognitive supplement to this privately funded study. (Recruitment and baseline cognitive testing of participants have been completed.) Principal investigator: Dr. Francine Grodstein, Harvard University.
More information on these studies, as it becomes available, will appear on the NIA-supported Alzheimer's Disease Education and Referral (ADEAR) Center Web site at www.nia.nih.alzheimers . The ADEAR Center also provides general information on AD research for health professionals, the media, and the general public. ADEAR can be contacted weekdays, toll free, at 1-800-438-4380.
The NIA leads the Federal effort supporting and conducting biomedical, clinical, social, and behavioral research on aging and on Alzheimer's disease specifically. Press releases, fact sheets, and other materials about aging and aging research can be viewed at the NIA's general information Web site, www.nia.nih.gov .