Full text also follows:
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-4, 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-4 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-4 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.alzheimers.org.
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.
###
