Folic acid improves arterial endothelial function in adults with hyperhomocystinemia.
OBJECTIVE
To evaluate whether oral folic acid supplementation might improve endothelial function in the arteries of asymptomatic adults with hyperhomocystinemia.


BACKGROUND
Hyperhomocystinemia is an independent risk factor for endothelial dysfunction and occlusive vascular disease. Folic acid supplementation can lower homocystine levels in subjects with hyperhomocystinemia; however, the effect of this on arterial physiology is not known.


METHODS
Adults subjects were recruited from a community-based atherosclerosis study on healthy volunteers aged 40 to 70 years who had no history of hypertension, diabetes mellitus, hyperlipidemia, ischemic heart disease or family history of premature atherosclerosis (n = 89). Seventeen subjects (aged 54 +/- 10 years, 15 male) with fasting total homocystine levels above 75th percentile (mean, 9.8 +/- 2.8 micromol/liter) consented to participate in a double-blind, randomized, placebo-controlled and crossover trial; each subject received oral folic acid (10 mg/day) and placebo for 8 weeks, each separated by a washout period of four weeks. Flow-mediated endothelium-dependent dilation (percent increase in diameter) of the brachial artery was assessed by high resolution ultrasound, before and after folic acid or placebo supplementation.


RESULTS
Compared with placebo, folic acid supplementation resulted in higher 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 micromol/liter, p = 0.03) and significant improvement in endothelium-dependent dilation (8.2 +/- 1.6% vs. 6 +/- 1.3%, p < 0.001). Endothelium-independent responses to nitroglycerin were unchanged. No adverse events were observed.


CONCLUSIONS
Folic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process.
Woo
K S
KS
Department of Medicine and Therapeutics, The Chinese University of Hong Kong. b208732@mailserv.cuhk.edu.hk
Chook
P
P
Lolin
Y I
YI
Sanderson
J E
JE
Metreweli
C
C
Celermajer
D S
DS
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001161:Arteriosclerosis / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D006397:Hematinics / Q000008:administration & dosage / Q000627:therapeutic use*; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D016896:Treatment Outcome; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D006397:Hematinics; D006710:Homocysteine; D005492:Folic Acid; D002784:Cholesterol