Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomised, double blind, controlled trial.
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 effect 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 findings for the secondary endpoint: the effect 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 mug 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.


RESULTS
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 (difference in Z 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 significantly better in the folic acid group than in the placebo group.


CONCLUSIONS
Folic acid supplementation for 3 years significantly improved domains of cognitive function that tend to decline with age.
Durga
Jane
J
Division of Human Nutrition, Wageningen University, 6700 EV Wageningen, Netherlands. jane.durga@rdls.nestle.com
van Boxtel
Martin P J
MP
Schouten
Evert G
EG
Kok
Frans J
FJ
Jolles
Jelle
J
Katan
Martijn B
MB
Verhoef
Petra
P
D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics; D003071:Cognition / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016014:Linear Models; D008297:Male; D008568:Memory / Q000187:drug effects; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D009426:Netherlands; D011581:Psychological Tests; D014803:Vitamin B Complex / Q000097:blood / Q000627:therapeutic use*
D001057:Apolipoproteins E; D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)