(Circulation. 1999;99:3234-3240.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Long-Term Ascorbic Acid Administration Reverses Endothelial Vasomotor Dysfunction in Patients With Coronary Artery Disease
From the Evans Memorial Department of Medicine, Cardiology Section, and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass (N.G., J.F.K., M.H., M.O., B.J.Z., J.A.V.); the Linus Pauling Institute at Oregon State University, Corvallis (B.F.); and the Department of Internal Medicine, Washington University School of Medicine, St Louis, Mo (J.W.H., C.L.).
Correspondence to Joseph A. Vita, MD, Section of Cardiology, Boston Medical Center, 88 E Newton St, Boston, MA 02118. E-mail jvita{at}bu.edu
Background—Loss of endothelium-derived nitric oxide (EDNO) contributes to the clinical expression of coronary artery disease (CAD). Increased oxidative stress has been linked to impaired endothelial vasomotor function in atherosclerosis, and recent studies demonstrated that short-term ascorbic acid treatment improves endothelial function.
Methods and Results—In a randomized, double-blind, placebo-controlled study, we examined the effects of single-dose (2 g PO) and long-term (500 mg/d) ascorbic acid treatment on EDNO-dependent flow-mediated dilation of the brachial artery in patients with angiographically established CAD. Flow-mediated dilation was examined by high-resolution vascular ultrasound at baseline, 2 hours after the single dose, and 30 days after long-term treatment in 46 patients with CAD. Flow-mediated dilation improved from 6.6±3.5% to 10.1±5.2% after single-dose treatment, and the effect was sustained after long-term treatment (9.0±3.7%), whereas flow-mediated dilation was 8.6±4.7% at baseline and remained unchanged after single-dose (7.8±4.4%) and long-term (7.9±4.5%) treatment with placebo (P=0.005 by repeated-measures ANOVA). Plasma ascorbic acid concentrations increased from 41.4±12.9 to 115.9±34.2 µmol/L after single-dose treatment and to 95.0±36.1 µmol/L after long-term treatment (P<0.001).
Conclusions—In patients with CAD, long-term ascorbic acid treatment has a sustained beneficial effect on EDNO action. Because endothelial dysfunction may contribute to the pathogenesis of cardiovascular events, this study indicates that ascorbic acid treatment may benefit patients with CAD.
Key Words: coronary disease • endothelium • vitamins
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