Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women

Br J Psychiatry. 2015 Apr;206(4):324-31. doi: 10.1192/bjp.bp.114.148361. Epub 2015 Jan 8.


Background: Homocysteine-lowering nutrients may have preventive/ameliorative roles in depression.

Aims: To test whether long-term B-vitamin/folate supplementation reduces depression risk.

Method: Participants were 4331 women (mean age 63.6 years), without prior depression, from the Women's Antioxidant and Folic Acid Cardiovascular Study - a randomised controlled trial of cardiovascular disease prevention among 5442 women. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d) and vitamin B12 (1 mg/d) or a matching placebo. Average treatment duration was 7 years. The outcome was incident depression, defined as self-reported physician/clinician-diagnosed depression or clinically significant depressive symptoms.

Results: There were 524 incident cases. There was no difference between active v. placebo groups in depression risk (adjusted relative risk 1.02, 95% CI 0.86-1.21, P = 0.81), despite significant homocysteine level reduction.

Conclusions: Long-term, high-dose, daily supplementation with folic acid and vitamins B6 and B12 did not reduce overall depression risk in mid-life and older women.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Depression / diagnosis*
  • Depression / drug therapy*
  • Dietary Supplements
  • Drug Therapy, Combination
  • Female
  • Folic Acid / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Risk Factors
  • Self Report
  • Vitamin B 12 / therapeutic use*
  • Vitamin B 6 / therapeutic use*


  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12