Effects of oral folic acid supplementation on endothelial function in familial hypercholesterolemia. A randomized placebo-controlled trial

Circulation. 1999 Jul 27;100(4):335-8. doi: 10.1161/01.cir.100.4.335.


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 N(G)-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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Blood Vessels / drug effects
  • Blood Vessels / physiopathology
  • Cross-Over Studies
  • Double-Blind Method
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Folic Acid / therapeutic use*
  • Forearm / blood supply
  • Hematinics / therapeutic use*
  • Humans
  • Hyperlipoproteinemia Type II / drug therapy*
  • Male
  • Prospective Studies
  • Regional Blood Flow / drug effects
  • Vasoconstriction / drug effects
  • Vasodilation / drug effects
  • Vasodilation / physiology
  • omega-N-Methylarginine / pharmacology


  • Enzyme Inhibitors
  • Hematinics
  • omega-N-Methylarginine
  • Folic Acid