Effects of Two-Year Vitamin B 12 and Folic Acid Supplementation on Depressive Symptoms and Quality of Life in Older Adults with Elevated Homocysteine Concentrations: Additional Results from the B-PROOF Study, an RCT

Nutrients. 2016 Nov 23;8(11):748. doi: 10.3390/nu8110748.


Lowering elevated plasma homocysteine (Hcy) concentrations by supplementing vitamin B12 and folic acid may reduce depressive symptoms and improve health-related quality of life (HR-QoL) in older adults. This study aimed to test this hypothesis in a randomized controlled trial. Participants (N = 2919, ≥65 years, Hcy concentrations ≥12 µmol/L) received either 500 µg vitamin B12 and 400 µg folic acid daily or placebo for two years. Both tablets contained 15 µg vitamin D₃. Depressive symptoms were measured with the Geriatric Depression Scale-15 (GDS-15). HR-QoL was assessed with the SF-12 Mental and Physical component summary scores and the EQ-5D Index score and Visual Analogue Scale. Differences in two-year change scores were analyzed with Analysis of Covariance (ANCOVA). Hcy concentrations decreased more in the intervention group, but two-year change scores of the GDS-15 and three of four HR-QoL measures did not differ between groups. The EQ-5D Index score declined less in the intervention group than in the placebo group (mean change 0.00 vs. -0.02, p = 0.004). In conclusion, two-year supplementation with vitamin B12 and folic acid in older adults with hyperhomocysteinemia showed that lowering Hcy concentrations does not reduce depressive symptoms, but it may have a small positive effect on HR-QoL.

Keywords: depressive symptoms; folic acid; homocysteine; hyperhomocysteinemia; older adults; quality of life; randomized controlled trial; vitamin B12.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Affect*
  • Age Factors
  • Aged
  • Biomarkers / blood
  • Depression / diagnosis
  • Depression / etiology
  • Depression / prevention & control*
  • Depression / psychology
  • Dietary Supplements*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Folic Acid / administration & dosage*
  • Homocysteine / blood*
  • Humans
  • Hyperhomocysteinemia / blood
  • Hyperhomocysteinemia / diagnosis
  • Hyperhomocysteinemia / drug therapy*
  • Male
  • Netherlands
  • Psychiatric Status Rating Scales
  • Quality of Life*
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Vitamin B 12 / administration & dosage*


  • Biomarkers
  • Drug Combinations
  • Homocysteine
  • Folic Acid
  • Vitamin B 12