Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men

Background: Dietary flavonoids may improve endothelial function and ultimately lead to beneficial cardiovascular effects. Objective: The objective was to assess whether pure dietary fla-vonoids can modulate nitric oxide and endothelin-1 production and thereby improve endothelial function. Design: A randomized, placebo-controlled, crossover trial in 12 healthy men was conducted to compare the acute effects of the oral administration of 200 mg quercetin, ()-epicatechin, or epigallo-catechin gallate on nitric oxide, endothelin-1, and oxidative stress after nitric oxide production was assessed via the measurement of plasma S-nitrosothiols and plasma and urinary nitrite and nitrate concentrations. The effects on oxidative stress were assessed by measuring plasma and urinary F2-isoprostanes. Plasma and urinary concentrations of quercetin, ()-epicatechin, and epigallocatechin gallate were measured to establish the absorption of these fla-vonoids. Results: Relative to water (control), quercetin and ()-epicatechin resulted in a significant increase in plasma S-nitrosothiols, plasma nitrite, and urinary nitrate concentrations (P 0.05), but not in plasma nitrate or urinary nitrite. Epigallocatechin gallate did not alter any of the measures of nitric oxide production. Quercetin and ()-epicatechin resulted in a significant reduction in plasma endothelin-1 concentration (P 0.05), but only quercetin signifi-cantly decreased the urinary endothelin-1 concentration. None of the 3 treatments significantly changed plasma or urinary F2-isoprostane concentrations. Significant increases in the circulating concentra-tions of the 3 flavonoids were observed (P 0.05) after the corre-sponding treatment. Conclusions: Dietary flavonoids, such as quercetin and ()-epicatechin, can augment nitric oxide status and reduce endothelin-1 concentrations and may thereby improve endothe-lial function. Am J Clin Nutr 2008;88:1018 –25