Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease

• Published in: Circulation (New York, N.Y.) Vol. 99; no. 25; pp. 3234 - 3240
• Main Authors: GOKCE, N, KEANEY, J. F, FREI, B, HOLBROOK, M, OLESIAK, M, ZACHARIAH, B. J, LEEUWENBURGH, C, HEINECKE, J. W, VITA, J. A
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 29-06-1999; American Heart Association, Inc
• Subjects: Adult; Aged; Antioxidants - therapeutic use; Ascorbic Acid - therapeutic use; Biological and medical sciences; Biomarkers - blood; Blood Glucose - metabolism; Cardiology. Vascular system; Coronary Disease - blood; Coronary Disease - drug therapy; Coronary Disease - physiopathology; Coronary heart disease; Double-Blind Method; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Female; Free Radical Scavengers - therapeutic use; Glutathione - blood; Heart; Hemodynamics - drug effects; Humans; Lipids - blood; Male; Medical sciences; Middle Aged; Nitric Oxide - metabolism; Time Factors; Treatment Outcome; Human; Pharmacologic test; Ascorbic acid; Dysfunction; Cardiovascular disease; Hemodynamics; Antioxidant; Coronary heart disease; Long term; Endothelium
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.99.25.3234

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.
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 micromol/L after single-dose treatment and to 95. 0+/-36.1 micromol/L after long-term treatment (P<0.001).
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.