Wageningen, the Netherlands - A randomized, placebo-controlled trial has shown daily folic acid significantly improves cognitive performance in older adults—specifically as it relates to memory and information processing [1].

The study, which included 818 subjects aged 50 to 70 who were folate deficient, showed those who took 800-µg oral folic acid daily for three 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 placebo.

"We have shown that three-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, led by Dr Jane Durga (Wageningen University, the Netherlands), write.

The study is published in the January 20, 2007 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 is investigating 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 cognitive performance.

The trial took place between November 1999 and December 2004. A total of 818 patients were randomly assigned to receive 800 µg/day of folic acid or placebo for three years.

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 <13 µmol/L or >26 µmol/L were excluded from the trial.

Baseline assessment of cognitive function included five separate tests, which measured five cognitive domains—memory, sensorimotor speed, complex speed, information-processing speed, and word fluency. In addition, patients also underwent the Mini-Mental State Examination 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; all other measurements were taken at the beginning and end of the study.

The authors report that 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 three-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," they write.

In an accompanying editorial, Drs Martha Clare Morris and Christine C Tangney (Rush University Medical Center, Chicago, IL) point out that many populations may have folate intakes similar to those of individuals in the study, which 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, they say.

"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," they write.