Folic acid improves arterial endothelial function in adults with hyperhomocystinemia

OBJECTIVES To evaluate whether oral folic acid supplementation might improv e endothelial function in the arteries of asymptomatic adults with hyperhom ocystinemia. BACKGROUND Hyperhomocystinemia is an independent risk factor for endothelia l dysfunction and occlusive vascular disease. Folic acid supplementation ca n lower homocystine levels in subjects with hyperhomocystinemia; however, t he effect of this on arterial physiology is not known. METHODS Adults subjects were recruited from a community-based atheroscleros is study on healthy volunteers aged 40 to 70 years who had no history of hy pertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or fa mily history of premature atherosclerosis (n = 89). Seventeen subjects (age d 54 +/- 10 years, 15 male) with fasting total homocystine levels above 75t h percentile (mean, 9.8 +/- 2.8 mu mol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each sub ject received oral folic acid (10 mg/day) and placebo for 8 weeks, each sep arated by a washout period of four weeks. Flow-mediated endothelium-depende nt dilation (percent increase in diameter) of the brachial artery was asses sed by high resolution ultrasound, before and after folic acid or placebo s upplementation. RESULTS Compared with placebo, folic acid supplementation resulted in highe r serum folate levels (66.2 +/- 7.0 vs. 29.7 +/- 14.8 nmol/liter; p < 0.001 ), lower total plasma homocystine levels (8.1 +/- 3.1 vs. 9.5 +/- 2.5 mu mo l/liter, p = 0.03) and significant improvement in endothelium dependent dil ation (8.2 +/- 1.6% vs. 6 +/- 1.3%, p < 0.001). Endothelium-independent res ponses to nitroglycerin were unchanged. No adverse events were observed. CONCLUSIONS Folic acid supplementation improves arterial endothelial functi on in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process. (C) 1999 by the American College o f Cardiology.