Improved vascular endothelial function after oral B vitamins - An effect mediated through reduced concentrations of free plasma homocysteine

Background-Hyperhomocysteinemia is an independent risk factor for coronary heart disease (CHD). Dietary supplementation with B vitamins lowers plasma homocysteine by up to 30%. However, little is known about the potential ben eficial effects of homocysteine lowering on vascular function in patients w ith CHD. Methods and Results-We investigated 89 men with CHD (aged 56 [range 39 to 6 7] years). Brachial artery flow-mediated dilatation (endothelium dependent) and nitroglycerin-induced dilatation (endothelium independent) were measur ed before and 8 weeks after treatment with either (1) folic acid (5 mg) and vitamin B-12 (1 mg) daily (n=59) or (2) placebo (n=30). Total, protein-bou nd, and free plasma homocysteine, serum folate, and vitamin B,, were measur ed at baseline and at 8 weeks. Flow-mediated dilatation improved after trea tment with B vitamins (2.5+/-3.2% to 4.0+/-3.7%, P=0.002) but not placebo ( 2.3+/-2.6% to 1.9+/-2.6%, P=0.5). Vitamin therapy lowered plasma concentrat ions of total homocysteine (from 13.0+/-3.4 to 9.3+/-1.9 mu mol/L, P<0.001) , protein-bound homocysteine (from 8.7+/-2.8 to 6.2+/-1.4 <mu>mol/L, P<0.00 1), and free homocysteine (from 4.3+/-1.2 to 3.0+/-0.6 <mu>mol/L, P<0.001) and raised concentrations of serum folate (from 10.3+/-4.3 to 33.2+/-10.8 n g/mL, P<0.001) and vitamin B-12 (from 314+/-102 to 661+/-297 pg/mL, P<0001) . In regression analysis, improved flow-mediated dilatation correlated clos ely with the reduction in free plasma homocysteine (r= -0.26, P=0.001), ind ependent of changes in protein-bound homocysteine, folate, and vitamin B-12 . Nitroglycerin-induced dilatation was unchanged after both B vitamins and placebo. Conclusions-Folic acid and vitamin B-12 supplementation improves vascular e ndothelial function in patients with CHD, and this effect is likely to be m ediated through reduced concentrations of free plasma homocysteine concentr ations. Our data support the view that lowering homocysteine, through B vit amin supplementation, may reduce cardiovascular risk.