Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-Related Cataract in a Randomized Trial of Women

Ophthalmic Epidemiol. 2016;23(1):32-9. doi: 10.3109/09286586.2015.1130845. Epub 2016 Jan 20.


Purpose: To examine the incidence of cataract and cataract extraction in a trial of folic acid and vitamins B6 and B12.

Methods: In a randomized, double-masked, placebo-controlled trial, 5442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or three or more CVD risk factors were randomly assigned to receive a combination of folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day), or placebo. A total of 3925 of these women did not have a diagnosis of cataract at baseline and were included in this analysis. The primary endpoint was age-related cataract, defined as an incident age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Extraction of incident age-related cataract was a secondary endpoint of the trial.

Results: During an average of 7.3 years of treatment and follow-up, 408 cataracts and 275 cataract extractions were documented. There were 215 cataracts in the combination treatment group and 193 in the placebo group (hazard ratio, HR, 1.10, 95% confidence interval, CI, 0.90-1.33; p = 0.36). For the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01-1.63; p = 0.04).

Conclusions: In this large-scale randomized trial of women at high risk of CVD, daily supplementation with a combination of folic acid, vitamin B6, and vitamin B12 had no significant effect on cataract, but may have increased the risk of cataract extraction.

Keywords: Cataract; Women’s Antioxidant Folic Acid Cardiovascular Study; folic acid; randomized controlled trial; supplements; vitamin B12; vitamin B6.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control
  • Cataract / epidemiology*
  • Cataract Extraction / statistics & numerical data*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Folic Acid / administration & dosage*
  • Health Personnel
  • Humans
  • Incidence
  • Middle Aged
  • Risk Factors
  • Vitamin B 12 / administration & dosage*
  • Vitamin B 6 / administration & dosage*
  • Vitamin B Complex / administration & dosage*


  • Drug Combinations
  • Vitamin B Complex
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12