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

Abstract

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 (2.5mg/d), vitamin B6 (50mg/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. Declaration of interest: Vitamin E and its placebo were supplied by Cognis Corporation (LaGrange, Illinois, USA). All other agents and their placebos were supplied by BASF Corporation (Mount Olive, New Jersey, USA). Pill packaging was provided by Cognis and BASF.