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      Association between chocolate consumption and risk of coronary artery disease: a systematic review and meta-analysis

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          (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans.

          Epidemiological and medical anthropological investigations suggest that flavanol-rich foods exert cardiovascular health benefits. Endothelial dysfunction, a prognostically relevant key event in atherosclerosis, is characterized by a decreased bioactivity of nitric oxide (NO) and impaired flow-mediated vasodilation (FMD). We show in healthy male adults that the ingestion of flavanol-rich cocoa was associated with acute elevations in levels of circulating NO species, an enhanced FMD response of conduit arteries, and an augmented microcirculation. In addition, the concentrations and the chemical profiles of circulating flavanol metabolites were determined, and multivariate regression analyses identified (-)-epicatechin and its metabolite, epicatechin-7-O-glucuronide, as independent predictors of the vascular effects after flavanol-rich cocoa ingestion. A mixture of flavanols/metabolites, resembling the profile and concentration of circulating flavanol compounds in plasma after cocoa ingestion, induced a relaxation in preconstricted rabbit aortic rings ex vivo, thus mimicking acetylcholine-induced relaxations. Ex vivo flavanol-induced relaxation, as well as the in vivo increases in FMD, were abolished by inhibition of NO synthase. Oral administration of chemically pure (-)-epicatechin to humans closely emulated acute vascular effects of flavanol-rich cocoa. Finally, the concept that a chronic intake of high-flavanol diets is associated with prolonged, augmented NO synthesis is supported by data that indicate a correlation between the chronic consumption of a cocoa flavanol-rich diet and the augmented urinary excretion of NO metabolites. Collectively, our data demonstrate that the human ingestion of the flavanol (-)-epicatechin is, at least in part, causally linked to the reported vascular effects observed after the consumption of flavanol-rich cocoa.
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            Effects of cocoa extracts on endothelium-dependent relaxation.

            The aim of this study was to examine the effects of procyanidins derived from cocoa on vascular smooth muscle. Two hypotheses were tested: 1) extracts of cocoa, which are rich in procyanidins, cause endothelium-dependent relaxation (EDR), and 2) extracts of cocoa activate endothelial nitric oxide synthase (NOS). The experiments were carried out on aortic rings obtained from New Zealand White rabbits. The polymeric procyanidins (tetramer through decamer of catechin) caused an EDR. In addition, the Ca(2+)-dependent NOS activity, measured by the L-arginine to L-citrulline conversion assay, was significantly increased in aortic endothelial cells exposed to polymeric procyanidins, whereas monomeric compounds had no such effect. These findings demonstrate that polymeric procyanidins cause an EDR that is mediated by activation of NOS.
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              Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: randomized, double-masked controlled studies.

              Cocoa flavanol intake, especially that of (-)-epicatechin, has been linked to beneficial effects on human cardiovascular function. However, cocoa also contains the methylxanthines theobromine and caffeine, which may also affect vascular function.
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                Author and article information

                Journal
                European Journal of Preventive Cardiology
                Eur J Prev Cardiolog
                SAGE Publications
                2047-4873
                2047-4881
                July 22 2020
                : 204748732093678
                Affiliations
                [1 ]Section of Cardiology, The Michael E DeBakey VA Medical Center, USA
                [2 ]Section of Cardiology, Baylor College of Medicine, USA
                [3 ]The Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, USA
                [4 ]Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, USA
                [5 ]Division of Health Care Policy and Research, Mayo Clinic, USA
                [6 ]Department of Cardiovascular Diseases, Einstein Medical Center, USA
                [7 ]Mayo Clinic Libraries, Mayo Clinic, USA
                [8 ]Department of Cardiovascular Medicine, Cleveland Clinic, USA
                Article
                10.1177/2047487320936787
                dae59df2-b4c6-4640-b4cb-b3cd168d6a9f
                © 2020

                http://journals.sagepub.com/page/policies/text-and-data-mining-license

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