Effects of 6-Month Folic Acid Supplementation on Cognitive Function and Blood Biomarkers in Mild Cognitive Impairment: A Randomized Controlled Trial in China

J Gerontol A Biol Sci Med Sci. 2016 Oct;71(10):1376-83. doi: 10.1093/gerona/glv183. Epub 2015 Oct 27.


Background: This study is to examine the effects of folic acid supplementation on cognitive function in Chinese older adults with mild cognitive impairment who are unexposed to folic acid fortification and assess cognitive functioning in relation to folate, homocysteine, and vitamin B12 values at baseline.

Methods: This was a single-center, randomized, controlled trial in Tianjin, China; 180 individuals aged 65 years and older who had mild cognitive impairment were assigned randomly to one of two groups: (a) those treated with oral folic acid (400 µg/day) and (b) those treated via conventional treatment. Tests of cognitive performance and biomarkers were measured at baseline, 3 months, and 6 months. Analysis was by intention-to-treat. Changes in cognitive or clinical function were analyzed by repeated-measure analysis of variance or mixed-effects models. This trial has been registered with the trial number ChiCTR-TRC-13003227.

Results: Total of 159 participants (intervention group: 80; control group: 79) completed the trial. Repeated-measure analysis of variance showed significant improvements in serum folate (ηp (2) = 0.712, p = .009), homocysteine (ηp (2) = 0.119, p = .017), serum vitamin B12 (ηp (2) = 0.144, p = .022), and S-adenosylmethionine (ηp (2) = 0.117, p = .033) in the intervention group over the control group. Folic acid supplementation improved Full Scale IQ (p = .031; effect size d = 0.168), Digit Span (p = .009; d = 0.176), and Block Design (p = .036; effect size d = 0.146) scores at 6 months in comparison to the control. There were no significant findings for all other cognitive measures.

Conclusion: There was a beneficial effect from relatively short-term folate supplementation on cognitive functioning in later life. Larger-scale, randomized, controlled trials of longer duration in selected age groups are needed.

Keywords: Cognitive function; Folic acid; Homocysteine; Mild cognitive impairment; Randomized controlled trial.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • China
  • Cognitive Dysfunction / drug therapy*
  • Female
  • Folic Acid / administration & dosage*
  • Homocysteine / blood
  • Humans
  • Male
  • Treatment Outcome
  • Vitamin B 12 / blood


  • Biomarkers
  • Homocysteine
  • Folic Acid
  • Vitamin B 12