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(-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans.
Proc Natl Acad Sci U S A 2006; 103(4):1024-9PN

Abstract

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.

Authors+Show Affiliations

Department of Nutrition, University of California, Davis, CA 95616, USA. hschroeter@ucdavis.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16418281

Citation

Schroeter, Hagen, et al. "(-)-Epicatechin Mediates Beneficial Effects of Flavanol-rich Cocoa On Vascular Function in Humans." Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 4, 2006, pp. 1024-9.
Schroeter H, Heiss C, Balzer J, et al. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA. 2006;103(4):1024-9.
Schroeter, H., Heiss, C., Balzer, J., Kleinbongard, P., Keen, C. L., Hollenberg, N. K., ... Kelm, M. (2006). (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proceedings of the National Academy of Sciences of the United States of America, 103(4), pp. 1024-9.
Schroeter H, et al. (-)-Epicatechin Mediates Beneficial Effects of Flavanol-rich Cocoa On Vascular Function in Humans. Proc Natl Acad Sci USA. 2006 Jan 24;103(4):1024-9. PubMed PMID: 16418281.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. AU - Schroeter,Hagen, AU - Heiss,Christian, AU - Balzer,Jan, AU - Kleinbongard,Petra, AU - Keen,Carl L, AU - Hollenberg,Norman K, AU - Sies,Helmut, AU - Kwik-Uribe,Catherine, AU - Schmitz,Harold H, AU - Kelm,Malte, Y1 - 2006/01/17/ PY - 2006/1/19/pubmed PY - 2006/3/18/medline PY - 2006/1/19/entrez SP - 1024 EP - 9 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 103 IS - 4 N2 - 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. SN - 0027-8424 UR - https://www.unboundmedicine.com/medline/citation/16418281/____Epicatechin_mediates_beneficial_effects_of_flavanol_rich_cocoa_on_vascular_function_in_humans_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=16418281 DB - PRIME DP - Unbound Medicine ER -