Vitamin B Deficiency Linked to Cognitive Impairment;
Senior Citizens Often Low on B6
Nutrition research center on aging at Tufts U.
releases second recent study on vitamin B
Cereal often rich in B vitamins
Sept. 2, 2008 Just a few months ago, researchers
identified senior citizens as a group that tended to have levels of
vitamin B6 that are consistently too low. The same research center
released a new study today showing that a deficiency of B-vitamins may
cause cognitive impairment. Mice with a deficiency of three B-vitamins -
folate, B12 and B6 - developed cognitive dysfunction in the study.
(See
sidebar on right for study on B6 deficiency in seniors.)
Researchers at the Jean Mayer USDA Human Nutrition
Research Center on Aging (HNRCA) at Tufts University used an
experimental model to examine the metabolic, cognitive, and
microvascular effects of dietary B-vitamin deficiency. Their findings
appear in the August 26, 2008 issue of Proceedings of the National
Academy of Sciences (PNAS).
"Metabolic impairments induced by a diet deficient
in three B-vitamins - folate, B12 and B6- caused cognitive dysfunction
and reductions in brain capillary length and density in our mouse
model," says Aron Troen, PhD, the study's lead author. "The vascular
changes occurred in the absence of neurotoxic or degenerative changes."
Troen, who is an assistant professor at Tufts
University's Friedman School of Nutrition Science and Policy, explains,
"Mice fed a diet deficient in folate and vitamins B12 and B6
demonstrated significant deficits in spatial learning and memory
compared with normal mice."
Troen and colleagues observed similar but less
pronounced differences between normal mice and a third group of mice
that were fed a diet enriched with methionine.
"The B-vitamin-deficient mice also developed plasma
homocysteine concentrations that were seven-fold higher than the
concentrations observed in mice fed a normal diet," adds Troen.
Homocysteine is produced by the breakdown of a
dietary protein called methionine. B-vitamins, including folate, vitamin
B12, and vitamin B6, are required to convert homocysteine back to
methionine, thereby reducing the blood concentration of homocysteine.
Studies have linked elevations in plasma
homocysteine with an increased risk for cognitive impairment.
The elevated levels of homocysteine that were
associated with vascular cognitive impairment in the mice in the study
are comparable to the levels that are associated in older adults with an
increased risk for Alzheimer's disease and cerebrovascular disease, the
latter of which manifests with conditions such as stroke and
atherosclerosis, according to Irwin Rosenberg, MD, director of the
Nutrition and Neurocognition Laboratory at the HNRCA.
Senior Citizens
Among Those Found with Low Levels of Vitamin B6
In the earlier study released in May, the
Tufts University researchers looked just at vitamin B6 levels.
Vitamin B6, a nutrient essential for red blood cell function and
important for maintaining a healthy immune system and blood
glucose levels.
Across the study population, we noticed
participants with inadequate vitamin B6 status even though they
reported consuming more than the Recommended Daily Allowance of
vitamin B6, which is less than 2 milligrams per day, says
Martha Savaria Morris, PhD, an epidemiologist at the Jean Mayer
USDA Human Nutrition Research Center on Aging at Tufts
University.
Morris identified four subgroups where
this trend seemed most prominent:
● women of reproductive age, especially current and former
users of oral contraceptives,
● male smokers,
● non-Hispanic African-American men, and
● men and women over age 65.
Someone with inadequate vitamin B6 status
is at risk of becoming vitamin B6 deficient should their vitamin
B6 levels drop too low.
The RDAs for vitamin B6 in men and women
who are not pregnant or lactating are as follows: 1.3 mg per day
for men and women ages 19-50, 1.7 mg per day for men over age 50
and 1.5 mg for women over age 50.
Because the study shows association and
not causation, Morris stresses that further research is
necessary to determine whether the RDA for vitamin B6 is high
enough.
We have identified populations with a
high prevalence of apparently inadequate vitamin B status,
Morris says.
However, it is important to recognize
that signs of deficiency are not seen at plasma PLP
concentrations of 20 nmol/L and that dietary assessment is
imperfect.
According to the National Institutes of
Health (NIH), vitamin B6 deficiency is rare in the United
States, but it can cause a form of anemia similar to iron
deficiency anemia.
Vitamin B6 is widely distributed in the
American diet, and baked potatoes, bananas, 100 percent
fortified cereals and chicken are particularly good sources.
Morris says, The question our study
raises is whether, due to aging, genetics, or exposures, some
population subgroups need supplements to achieve the current
biochemical definition of adequate status.
This study was supported by the National
Institutes of Health and by the U.S. Department of Agriculture.
These findings may indicate that microvascular
changes mediate the association between high homocysteine levels and
human age-related cognitive decline," Rosenberg added.
"However," Troen says, "it has not been determined
that homocysteine is directly responsible. Based on the findings of our
study, we theorize that a deficiency of B-vitamins induces a metabolic
disorder that manifests with high homocysteine, as well as cerebral
microvascular dysfunction."
Troen and colleagues divided their study mice into
three groups and fed each group a different diet for 10 weeks. While the
control (comparison) group was fed a normal diet containing methionine
and B-vitamins, the other two diets were designed to induce high
homocysteine levels but through different metabolic mechanisms.
One was methionine-enriched, and the other was
deficient in B vitamins.
Researchers measured blood concentrations of
B-vitamins and homocysteine and assessed the brain anatomy and
vasculature. They also evaluated psychomotor function by a battery of
age-sensitive tests, such as holding on to a wire and walking a beam,
and assessed spatial learning and memory with the Morris water maze, a
well-validated and sensitive test of rodent cognitive function.
"It took longer, on average, for the
B-vitamin-deficient mice to maneuver the water maze, compared with
controls," says Troen.
"Longer latencies were associated with higher
plasma homocysteine levels and shorter capillaries, particularly in the
brain region called the hippocampus."
Troen adds, "Despite the vascular changes, the
brain anatomy appeared normal, and there was no evidence of a cellular
proliferation process called gliosis, which typically accompanies
neurodegeneration."
Troen and colleagues write that their study helps
to " define more precisely the mechanisms underlying cerebral
microvascular disease, independent of or prior to the onset of
irreversible neurodegeneration." According to Troen, this work, which
was funded by the U.S. Department of Agriculture, "may provide a model
system in which to study the role of the brain's microvascular
circulation in cognitive function."
Editors Notes:
The Gerald J. and Dorothy R. Friedman School of
Nutrition Science and Policy at Tufts University is the only independent
school of nutrition in the United States. The school's eight centers,
which focus on questions relating to famine, hunger, poverty, and
communications, are renowned for the application of scientific research
to national and international policy. For two decades, the Jean Mayer
USDA Human Nutrition Research Center on Aging at Tufts University has
studied the relationship between good nutrition and good health in aging
populations. Tufts research scientists work with federal agencies to
establish the USDA Dietary Guidelines, the Dietary Reference Intakes,
and other significant public policies.
Troen AM, Shea-Budgell M, Shukitt-Hale B, Smith DE,
Selhub J, Rosenberg IH. Proceedings of the National Academy of Sciences.
2008 (Aug. 26); 105 (34): 12474-12479. "B-vitamin deficiency causes
hyperhomocysteinemia and vascular cognitive impairment in mice."
