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

ABSTRACT

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
• folic acid
• randomized controlled trial
• supplements
• vitamin B₆
• vitamin B₁₂
• Women’s Antioxidant Folic Acid Cardiovascular Study

Acknowledgments

Vitamin E and its placebo were provided by Cognis Corporation (LaGrange, IL). All other agents and their placebos were provided by BASF Corporation (Mount Olive, NJ). Cognis Corporation and BASF Corporation did not participate in the design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

This study was supported by research grants HL46959 from the National Heart, Lung, and Blood Institute and EY 06633 from the National Eye Institute.