The blood pressure-lowering DASH diet also reduces
levels of the amino acid homocysteine, according to a National Heart, Lung,
and Blood Institute (NHLBI)-funded study. A high level of homocysteine appears
to increase the risk of heart disease, stroke, and peripheral vascular disease.
The study appears in the August 22 issue of
Circulation: Journal of the American Heart Association.
DASH stands for Dietary Approaches to Stop Hypertension.
This new report is based on data from the DASH trial, which found that a diet
rich in fruits, vegetables, and low fat dairy foods and low in saturated fat,
total fat, and cholesterol significantly and quickly lowers blood pressure.
The diet also included whole grains, poultry, fish, and nuts.
The DASH trial involved four sites and a coordinating
center. The homocysteine results come from the Johns Hopkins University site
in Baltimore, MD.
Homocysteine levels are affected by various factors,
including intake of folic acid (or folate) and vitamins B6 and B12. In the trial,
participants followed one of three diets-a control diet similar to what most
Americans eat, a diet rich in fruits and vegetables, and the DASH diet. Compared
with homocysteine levels of those on the control diet, homocysteine levels of
those on the DASH diet were significantly lower, with levels of those on the
fruits and vegetables diet being intermediate. Changes in the homocysteine levels
were significantly associated with changes in folate levels.
People with elevated levels of homocysteine in
the blood had nearly double the risk of developing Alzheimer's disease (AD),
according to a new report from scientists at Boston University. The findings,
in a group of people participating in the long-running Framingham Study, are
the first to tie homocysteine levels measured several years before with later
diagnosis of AD and other dementias. The report, which appears in the February
14, 2002, issue of The New England Journal of Medicine, provides some
of the most powerful evidence yet of an association between high plasma homocysteine
and later, significant memory loss.
The relationship between AD and the amino acid
homocysteine is of particular interest because blood levels of homocysteine
can be reduced, for example, by increasing intake of folic acid (or folate)
and vitamins B6 and B12. The therapeutic use of these compounds is being explored
as scientists try to understand better homocysteine's role in AD or other types
of dementia as well as its possible link to various forms of heart disease.
The dementia/AD study is being conducted by Philip
A. Wolf, M.D., Boston University (BU), and colleagues at BU and Tufts University,
who authored the new findings. The study was supported by the National Institute
on Aging (NIA), part of the National Institutes of Health (NIH). The researchers
were also funded by NIH's National Institute of Neurological Disorders and Stroke
(NINDS). The Framingham Heart Study is supported by the NIH's National Heart,
Lung, and Blood Institute (NHLBI).
"The Framingham population gave us the perfect
opportunity to look at homocysteine levels in a group of people without memory
problems over a period of several years, well before any evidence of dementia,"
Wolf pointed out. "This is the clearest demonstration yet of the relationship
between elevated homocysteine levels and dementia," he noted.
"The evidence is beginning to mount regarding
homocysteine's role in dementia," according to Neil Buckholtz, Ph.D., chief
of the Dementias of Aging program at the NIA. "The good news is that we may
have found a potential risk factor for AD that is modifiable. We don't know
yet whether reducing homocysteine levels will reduce dementia risk, but this
is something that can and will be tested in clinical trials." Buckholtz noted
that the NIA-sponsored Alzheimer's Disease Cooperative Study, a nationwide consortium
of research centers, is already planning a clinical trial of folate and vitamins
B6 and B12 to test whether reducing homocysteine levels with high doses of these
vitamin supplements can slow the rate of cognitive decline in people diagnosed
with AD.
Wolf and colleagues followed 1,092 people in
a "dementia-free" group of the Framingham cohort. Participants in this group,
whose average age was 76, were enrolled in the study between 1976 and 1978.
Plasma homocysteine levels were measured between 1979 and 1982 and between 1986
and 1990. Researchers also considered age, sex, vascular risk factors other
than homocysteine, and plasma levels of folate and vitamins B6 and B12 of the
participants. Information from the participants was also available on the late-onset
AD genetic risk factor APOE-e4.
From the 1986-1990 examinations through December
2000, some 111 people developed dementia, including 83 diagnosed specifically
with AD. Elevated homocysteine levels (defined as greater than 14 mmol/liter)
doubled the chance that a participant would develop AD and each 5 mmol/liter
elevation increased the risk of AD by 40 percent. The analysis showed further
that people with consistently high levels of homocysteine throughout the period
of the study were at highest risk for dementia and AD. The researchers also
examined whether the earlier levels of homocysteine, measured between 1979 and
1982, had any relationship to the development of dementia or AD later on; this
analysis, too, linked elevated levels at least 8 years prior to a later diagnosis
of dementia and AD. The association between homocysteine and AD was found to
be strong and independent of other factors, such as age, gender, APOE genotype,
and other known or suspected risk factors for dementia and AD.
There was no direct association in this study
between the serum levels of folate and vitamins B6 and B12 and the development
of dementia among the participants. As the relationship between these B vitamin
levels, homocysteine, AD, and cardiovascular disease continues to be studied,
scientists speculate that consuming adequate amounts of B vitamins by diet or
supplementation might help reduce levels of homocysteine in some individuals.
Findings from the NHLBI-supported DASH (Dietary Approaches to Stop Hypertension)
study suggest that a diet rich in green leafy vegetables, low-fat dairy products,
citrus fruits and juices, whole wheat bread, and dry beans can significantly
lower levels of homocysteine. The Food and Drug Administration (FDA) now requires
the addition of folic acid to enriched breads, cereals, flours, corn meals,
pastas, rice, and other grain products. "Although there is no evidence that
actually reducing homocysteine levels will prevent AD or cardiovascular disease,
a healthy diet low in fat and rich in nutrients is always a good idea," says
BU's Wolf.
The NIA leads the Federal effort to support and
conduct basic, clinical, and social and behavioral studies on aging and AD.
It supports the Alzheimer's Disease Education and Referral (ADEAR) Center, which
provides information on AD research, including clinical trials, to the public,
health professionals, and the media. ADEAR can be contacted toll free at 1-800-438-4380
weekdays or by visiting the website
www.alzheimers.org.
Press releases, fact sheets, and other materials about aging and aging research
can be viewed at the NIA's general information website,
www.nia.nih.gov.
The NHLBI is the nation's leading supporter of
biomedical research on diseases of the heart, blood vessels, and lung; sleep
disorders; and on the management of blood resources. The Institute's Framingham
Heart Study began in 1948 as the first long-term population-wide epidemiological
study and has led to such medical breakthroughs as identifying the risk factors
for heart disease, including high blood cholesterol and high blood pressure.
Information about Framingham is available online at
www.nhlbi.nih.gov/about/framingham.
NHLBI press releases, fact sheets, and other materials are available on the
NHLBI website at
www.nhlbi.nih.gov.
The National Institute on Aging is a component
of the National Institutes of Health, U.S. Department of Health and Human Services.
