(09-11-11) Cocoa polyphenols and inflammatory mediators

Helmut Sies, Tankred Schewe, Christian Heiss, and Malte Kelm


ABSTRACT
Cocoa products are sources of flavan-3-ols, which have attracted interest regarding cardiovascular health. This review provides a sur- vey of our research on the effects of cocoa polyphenols on leukotri- ene and nitric oxide (NO) metabolism and on myeloperoxidase- induced modification of LDL. Because intake of flavonoid-rich chocolate by human subjects was reported to decrease the plasma concentrations of proinflammatory cysteinyl leukotrienes, we as- sessed whether cocoa polyphenols inhibited human 5-lipoxygenase, the key enzyme of leukotriene synthesis. (-)-Epicatechin and other cocoa flavan-3-ols proved to be inhibitory at the enzyme level. This action may confer antileukotriene action in vivo. In a double-blind crossover study, 20 individuals at risk for cardiovascular diseases received cocoa beverages with high or low contents of flavan-3-ols. NO-dependent, flow-mediated dilation of the brachial artery and concentrations of nitroso compounds in plasma were measured, and it was shown that ingestion of the high-flavanol coca drink but not the low-flavanol cocoa drink significantly increased plasma concentra- tions of nitroso compounds and flow-mediated dilation of the bra- chial artery. Therefore, ingested flavonoids may reverse endothelial dysfunction through enhancement of NO bioactivity. Oxidative modification of LDL appears to be crucial for atherogenesis, and one of the mediators is the proinflammatory proatherogenic enzyme myeloperoxidase. Micromolar concentrations of (-)-epicatechin or other flavonoids were found to suppress lipid peroxidation in LDL induced by myeloperoxidase in the presence of physiologically rel- evant concentrations of nitrite, an NO metabolite. Adverse effects of NO metabolites, such as nitrite and peroxynitrite, were thus attenuated.

Am J Clin Nutr 2005;81(suppl):304S?12S.

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