Oral Intake of Steriochemically Pure (‐)‐Epicatechin Enhances Endothelial Function in Humans

While the consumption of flavanol‐rich foods and beverages has been reported to decrease blood pressure and to improve endothelial function in humans, unequivocal evidence for a direct and causal link between flavanols and the observed effects has yet to be established. This becomes especially important when considering that flavanol‐rich foods can contain a large variety of other potentially bioactive phytochemicals. Thus, we investigated as to whether or not the oral administration of steriochemically pure (‐)‐epicatechin (EC) modulates cardiovascular function in humans. In a randomized, double‐blind, cross‐over study, human volunteers either ingested a single oral dose of EC dissolved in water or water alone. Endothelial function, as assessed by flow‐mediated dilation (FMD) and peripheral arterial tonometry (PAT), improved following the EC dose. Plasma concentrations of EC and EC metabolites were measured by HPLC and the efficacy of EC and major EC metabolites was assessed in vitro and ex vivo. EC and EC metabolites increased nitric oxide (NO) production, cGMP accumulation, and endothelial nitric oxide synthase (eNOS) phosphorylation in vitro, and relaxation response in pre‐contracted aortic rings ex vivo. Taken together, our results provide compelling evidence that the flavanol (‐)‐epicatechin mediates, at least in part, the beneficial vascular effects associated with the consumption of certain flavanol‐rich foods in humans. Furthermore, our findings strongly support the notion that EC and EC metabolites mediate vascular effects by modulating endothelial NO production. Research supported by Mars Inc.