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Abstract

Background: The aim of this study was to determine whether reducing plasma homocysteine concentrations with long-term, combined treatment with folic acid, vitamin B₆, and vitamin B₁₂ alters plasma biomarkers of inflammation and endothelial dysfunction in women at increased risk of cardiovascular disease.

Methods and results: We conducted a blood substudy of 300 treatment-adherent participants (150 in the active treatment group, 150 in the placebo group) in the WAFACS (Women's Antioxidant and Folic Acid Cardiovascular Study), a randomized, double-blind, placebo-controlled trial testing a daily combination of folic acid (2.5 mg), vitamin B₆ (50 mg), vitamin B₁₂ (1 mg), or matching placebo, in cardiovascular disease prevention among women at increased risk of cardiovascular disease. Plasma concentration of 3 biomarkers of inflammation (C-reactive protein, interleukin-6, and fibrinogen) and a biomarker of endothelial dysfunction (intercellular adhesion molecule 1) were measured at baseline and at the end of treatment and follow-up. After 7.3 years of combined treatment with folic acid, vitamin B₆, and vitamin B₁₂, homocysteine concentrations were reduced by 18% in the active treatment group as compared with the placebo group (P<0.001). However, there was no difference between treatment groups in change in blood concentration from baseline to follow-up for C-reactive protein (P=0.77), interleukin-6 (P=0.91), intercellular adhesion molecule 1 (P=0.38), or fibrinogen (P=0.68).

Conclusions: These findings indicate that long-term, combined treatment with folic acid, vitamin B₆, and vitamin B₁₂ lowers homocysteine concentrations, but does not alter major biomarkers of vascular inflammation, consistent with the lack of clinical cardiovascular disease benefit in the trial.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000541.

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