(Circulation. 1999;100:335-338.)
© 1999 American Heart Association, Inc.
Brief Rapid Communications |
Effects of Oral Folic Acid Supplementation on Endothelial Function in Familial Hypercholesterolemia
A Randomized Placebo-Controlled Trial
From the Departments of Nephrology and Hypertension (M.C.V., H.A.K., T.J.R.) and Clinical Chemistry (R.M.F.W.), University Hospital Utrecht; Department of Vascular Medicine, Academic Medical Center Amsterdam (J.J.P.K.); and Department of Clinical Chemistry, Antonius Hospital Nieuwegein (D.v.L.), Netherlands; and the Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Md (S.M.).
Correspondence to Ton J. Rabelink, Department of Nephrology and Hypertension, University Hospital Utrecht, PO Box 85500, 3508 GA Utrecht, Netherlands. E-mail t.rabelink{at}digd.azu.nl
Background—Folates have been suggested to be of benefit in reducing cardiovascular risk. The present study was designed to examine whether oral folic acid supplementation could improve endothelial function as an intermediate end point for cardiovascular risk in patients with increased risk of atherosclerosis due to familial hypercholesterolemia (FH).
Methods and Results—In a prospective, randomized, double-blind, placebo-controlled study with crossover design, we evaluated the effects of 4 weeks of treatment with oral folic acid (5 mg PO) on endothelial function in FH. In 20 FH patients, forearm vascular function was assessed at baseline, after 4 weeks of folic acid treatment, and after 4 weeks of placebo treatment by venous occlusion plethysmography, with serotonin and sodium nitroprusside used as endothelium-dependent and -independent vasodilators. In addition, we examined the vasoconstrictor response to the NO synthase inhibitor NG-monomethyl-L-arginine to assess basal NO activity. In FH patients, folic acid supplementation restored the impaired endothelium-dependent vasodilation, whereas it did not significantly influence endothelium-independent vasodilation or basal forearm vasomotion. There was a trend toward improvement in basal NO activity.
Conclusions—These data demonstrate that oral supplementation of folic acid can improve endothelial function in patients with increased risk of atherosclerotic disease due to hypercholesterolemia, without changes in plasma lipids.
Key Words: endothelium • nitric oxide • folate • hypercholesterolemia
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