Vitamin C improves endothelial function in healthy estrogen-deficient postmenopausal women

Abstract

Objective: Estrogen deficiency is associated with increased cardiovascular risk and endothelial dysfunction. Improvements in endothelial function with antioxidants, including vitamin C, have been reported. We aimed to determine the acute effect of vitamin C on endothelial function in healthy women with established menopause. Subjects: Subjects (aged 47-59 years) were at least 1 year postmenopause. Ten (serum estradiol < 50 pmol/l) were not receiving hormone replacement therapy, while eight hysterectomized subjects received subcutaneous estradiol. Design: Forearm blood flow (FBF; strain-gauge plethysmography) responses to intrabrachial artery infusions of incremental doses of acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) were determined at baseline, and following 1.5 g vitamin C given intravenously. Results: At baseline, estrogen-treated subjects had a lower index of insulin resistance (homeostasis model assessment, HOMA) and lower fibrinogen than those of estrogendeficient subjects. There was a trend towards higher baseline FBF and larger baseline FBF response to acetylcholine in estrogen-treated subjects. FBF responses to acetylcholine were significantly enhanced after vitamin C in estrogen-deficient subjects (area under the dose-response curve (AUC): estrogen-deficient 9.9 ± 2.6 vs. 15.1 ± 3.2 (mean ± SEM), p = 0.02; estrogen-treated 17.0 ± 2.9 vs. 21.0 ± 3.2, p = 0.07). Resting FBF and response to sodium nitroprusside were unchanged in either group by vitamin C. Plasminogen activator inhibitor-1 levels fell after vitamin C in the estrogen-deficient group (17.0 ± 1.6 vs. 14.7 ± 0.9 IU/ml, p = 0.03). Conclusions: These results indicate that endothelial function may be improved acutely by antioxidant treatment in postmenopausal women with established estrogen deficiency.