Improvement of endothelial function and insulin sensitivity with vitamin C in patients with coronary spastic angina : Possible role of reactive oxygen species

OBJECTIVES This study was designed to examine the effect of antioxidant supplementation on the endothelial function and insulin sensitivity in patients with coronary spastic angina (CSA). BACKGROUND Insulin resistance may play a key role in coronary heart disease, and there is a possible link between acetylcholine-induced coronary vasoconstriction and hyperinsulinemia in patients with CSA. Endothelial dysfunction is present in the systemic arteries in CSA patients, and reactive oxygen species may cause inactivation of nitric oxide in these patients. METHODS We measured flow-mediated dilation of the brachial artery using ultrasound technique in 22 patients with CSA and 20 control subjects. We also evaluated glucose tolerance using a 75-g oral glucose tolerance test and insulin sensitivity using steady-state plasma glucose (SSPG) methods in the same patients. RESULTS The incidence of impaired glucose tolerance was higher in the CSA group than in the control group. Vitamin C infusion augmented flow-mediated dilation and decreased SSPG levels in the CSA group (from 3.27 ± 0.77% to 7.00 ± 0.59% [p < 0.001 by analysis of variance (ANOVA)] and from 177.3 ± 13.3 to 143.1 ± 14.9 mg/dl [p = 0.047 by ANOVA], respectively) but not in the control group (from 6.47 ± 0.66% to 6.80 ± 0.60% and from 119.8 ± 11.7 mg/dl to 118.1 ± 11.3 mg/dl, respectively). The steady-state plasma insulin levels were not affected by vitamin C infusion in either group. CONCLUSIONS Vitamin C improves both endothelial function and insulin sensitivity in patients with CSA. Thus, reactive oxygen species and/or decreased nitric oxide bioactivity may play an important role in the genesis of both endothelial dysfunction and insulin resistance in patients with CSA.