Jane Durga, Martin P J van Boxtel, Evert G Schouten, Frans J Kok, Jelle Jolles, Martijn B Katan, Petra Verhoef

Background Low folate and raised homocysteine concentrations in blood are associated with poor cognitive performance in the general population. As part of the FACIT trial to assess the eff ect of folic acid on markers of atherosclerosis in men and women aged 50–70 years with raised plasma total homocysteine and normal serum vitamin B12 at screening, we report here the fi ndings for the secondary endpoint: the eff ect of folic acid supplementation on cognitive performance.

Methods Our randomised, double blind, placebo controlled study took place between November, 1999, and December, 2004, in the Netherlands. We randomly assigned 818 participants 800 μg daily oral folic acid or placebo for 3 years.

The effect on cognitive performance was measured as the difference between the two groups in the 3-year change in performance for memory, sensorimotor speed, complex speed, information processing speed, and word fluency.

Analysis was by intention-to-treat. This trial is registered with clinicaltrials.gov with trial number NCT00110604.

Findings Serum folate concentrations increased by 576% (95% CI 539 to 614) and plasma total homocysteine concentrations decreased by 26% (24 to 28) in participants taking folic acid compared with those taking placebo. The 3-year change in memory (diff erence in scores 0・132, 95% CI 0・032 to 0・233), information processing speed (0・087, 0・016 to 0・158) and sensorimotor speed (0・064, –0・001 to 0・129) were signifi cantly better in the folic acid group than in the placebo group.

Interpretation Folic acid supplementation for 3 years signifi cantly improved domains of cognitive function that tend to decline with age.