Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease

OBJECTIVES The purpose of this study was to determine whether lowering homo cysteine levels with folic acid, with or without antioxidants, will improve endothelial dysfunction in patients with coronary artery disease (CAD). BACKGROUND Elevated plasma homocysteine levels are a risk factor for athero sclerosis. Homocysteine may promote atherogenesis through endothelial dysfu nction and oxidative stress. METHODS In a double-blind, placebo-controlled, randomized trial, we used va scular ultrasound to assess the effect of folic acid alone or with antioxid ants on brachial artery endothelium-dependent flow-mediated dilation (FMD). Seventy-five patients with CAD (screening homocysteine level greater than or equal to 9 mu mol/liter) were randomized equally to one of three groups: placebo, folic acid alone or folic acid plus antioxidant vitamins C and E. Patients were treated for four months. RESULTS Plasma folate, homocysteine, FMD and nitroglycerin-mediated dilatio n were measured before and after four months of treatment. Plasma folate, h omocysteine and FIL LD were unchanged in the placebo group. Compared with p lacebo, folic acid alone increased plasma folate by 475% (p < 0.001), reduc ed plasma homocysteine by 11% (p = 0.23) and significantly improved FMD fro m 3.2 +/- 3.6% to 5.2 +/- 3.9% (p = 0.04). The improvement in FMD correlate d with the reduction in homocysteine (r = 0.5, p = 0.01). Folic acid plus a ntioxidants increased plasma folate by 438% (p < 0.001), reduced plasma hom ocysteine by 9% (p = 0.56) and insignificantly improved FR ID from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo. Nitroglycerin-me diated dilation did not change significantly in any group. CONCLUSIONS Folic acid supplementation significantly improved endothelial d ysfunction in patients with coronary atherosclerosis. Further clinical tria ls are required to determine whether folic acid supplementation may reduce cardiovascular events. (C) 2000 by the American College of Cardiology.