CLINICAL STUDIES
Folic acid improves arterial endothelial function in adults with hyperhomocystinemia
Kam S. Woo, MD, FRACP, FACC*,
Ping Chook, MD*,
Yvette I. Lolin, PhD ,
John E. Sanderson, MD, FACC*,
Con Metreweli, MD, FRCR and
David S. Celermajer, PhD, FRACP
* Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
Department of Clinical Chemistry, Kent and Sussex Hospital, Kent, UK
Department of Diagnostic Radiology and Organ Imaging, The Chinese University of Hong Kong, Hong Kong
Department of Medicine, University of Sydney, Sydney, Australia
Manuscript received April 13, 1998;
revised manuscript received June 17, 1999,
accepted September 1, 1999.
Reprint requests and correspondence: Prof. K. S. Woo, c/o Department of Medicine and Therapeutics, Prince of Wales Hospital, Shatin N.T., Hong Kong
b208732{at}mailserv.cuhk.edu.hk
OBJECTIVES
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 µmol/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 µmol/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.
CONCLUSION
Folic acid supplementation improves arterial endothelial function in adults with relative hyperhomocystinemia, with potentially beneficial effects on the atherosclerotic process.
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Abbreviations and Acronyms
| | EDD | = endothelium-dependent dilation | | GTN | = glyceryltrinitrate (nitroglycerin) | | Hcy | = homocystine | | HHC | = hyperhomocystinemia | | tHcy | = total plasma homocystine |
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