A randomized, placebo-controlled trial has shown
Folic acid significantly improves cognitive
performance in older adults specifically as it relates to memory and
The study, which included 818 subjects, aged 50
to 70 years who were folate deficient, showed that those who took 800 µg
daily of oral folic acid for 3 years had significantly better memory and
information processing speed than subjects in the placebo group.
Furthermore, serum folate concentrations
increased by 576% and plasma total homocysteine concentrations decreased
by 26% in participants taking folic acid compared with those taking
"We have shown that 3-year folic acid
supplementation improves performance on tests that measure
information-processing speed and memory, domains that are known to
decline with age, in older adults with raised total homocysteine
concentrations," the authors write.
Led by Jane Durga, PhD, of the Wageningen
University, the Netherlands, the study is published in the January 20
issue of The Lancet.
Study subjects were men and women from the
Netherlands who were participating in the Folic Acid and Carotid
Intima-media Thickness (FACIT) trial, which investigated the effect of
folic acid supplementation on atherosclerotic progression.
However, this article reports on one of the
study's secondary outcomes the effect of folic acid supplementation on
The trial took place between November 1999 and
December 2004 in the Netherlands. A total of 818 patients were randomly
assigned to receive 800 µg of daily oral folic acid or placebo for 3
Patients with high concentrations of plasma
total homocysteine were selected for the study based on the likelihood
they would benefit from the homocysteine-lowering effects of folic acid
to reduce vascular disease risk. As a result, individuals with total
plasma homocysteine levels of less than 13 µmol/L or greater than 26
µmol/L were excluded from the trial.
Baseline assessment of cognitive function
included 5 separate tests, which measured 5 cognitive domains memory,
sensorimotor speed, complex speed, information processing speed, and
word fluency. In addition, patients also underwent the Mini-Mental State
Examination (MMSE) to screen for possible dementia.
Genotype and educational level were established
at the beginning of the trial. Plasma total homocysteine serum folate,
vitamin B12 concentrations, and information about medical status and
drug use were recorded annually, and all other measurements were taken
at the beginning and end of the study.
Slower Rate of Decline
The authors report participants in both groups
were well matched with similar baseline scores.
At the end of the study, the effect of folic
acid on cognitive performance was measured as the difference in
cognitive performance between the folic acid and placebo groups.
Among individuals in the placebo group
sensorimotor speed, information-processing speed, and complex speed
declined significantly. In contrast, those in the folic acid group
experienced a much slower rate of decline.
Furthermore, the 3-year change in cognitive
function was significantly better in the folic acid group in terms of
information-processing speed. However, folic acid had no effect on
complex speed or word fluency.
"The effect of folic acid might be restricted to
basic aspects of speed and information processing, rather than high
order information processing. Word fluency was not affected by folic
acid supplementation, perhaps not surprisingly because encyclopedic
memory is a component of crystallized intelligence that stays relatively
intact as one grows older," the authors write.
Folate Intake Too Low
In an accompanying editorial, Martha Clare
Morris, ScD and Christine C Tangney, PhD, both of Rush University
Medical Center in Chicago, Illinois, point out, many populations may
have folate intakes, similar to those of individuals in the study, that
may be suboptimal for physiological functioning.
In part, they note, this is due to a lack of
knowledge regarding optimum levels of dietary folate. To make more
informed dietary recommendations, the medical community needs more
randomized trials, like the FACIT study.
"In particular, future trials should specify
inclusion and exclusion criteria that target individuals at various
stages of nutrient balance. They should also include comprehensive
monitoring of biochemical concentrations of folate and folate
metabolites in addition to monitoring of system function, such
as cognitive function," the editorialists write.
Copyright credit: Lancet. 2007;369:208-216.
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