Chocolate at heart: the anti-inflammatory impact of cocoa flavanols.

Mol Nutr Food Res. 2008 Nov;52(11):1340-8., Selmi C, Cocchi CA, Lanfredini M, Keen CL, Gershwin ME.

Chronic and acute inflammation underlies the molecular basis of atherosclerosis. Cocoa-based products are among the richest functional foods based upon flavanols and their influence on the inflammatory pathway, as demonstrated by several in vitro or ex vivo studies. Indeed, flavanols modify the production of pro-inflammatory cytokines, the synthesis of eicosanoids, the activation of platelets, and nitric oxide-mediated mechanisms. A relative paucity of data still characterizes the in vivo implications of these findings albeit there have been studies suggesting that the regular or occasional consumption of cocoa-rich compounds exerts beneficial effects on blood pressure, insulin resistance, vascular damage, and oxidative stress. Accordingly, rigorous controlled human studies with adequate follow-up and with the use of critical dietary questionnaires are needed to determine the effects of flavanols on the major endpoints of cardiovascular health.

The anti-inflammatory properties of cocoa flavanols.
J Cardiovasc Pharmacol. 2006;47 Suppl 2:S163-71; discussion S172-6., Selmi C, Mao TK, Keen CL, Schmitz HH, Eric Gershwin M.

Signs of chronic or acute inflammation have been demonstrated in most cardiovascular diseases of multifactorial pathogenesis, including atherosclerosis and chronic heart failure. The triggers and mechanisms leading to inflammation may vary between clinical conditions but they share many common mediators, including specific patterns of eicosanoid and cytokine production. Certain cocoa-based products can be rich in a subclass of flavonoids known as flavanols, some of which have been found in model systems to possess potential anti-inflammatory activity relevant to cardiovascular health. Indeed, experimental evidence demonstrates that some cocoa-derived flavanols can reduce the production and effect of pro-inflammatory mediators either directly or by acting on signaling pathways. However, it should be noted that the evidence for any beneficial effects of cocoa flavanols in providing a meaningful anti-inflammatory action has been gathered predominantly from in vitro experiments. Therefore, additional research in well-designed human clinical experiments, using cocoa properly characterized in terms of flavanol content, would be a welcome addition to the evidence base to determine unambiguously if this benefit does indeed exist. If so, then flavanol-rich cocoa could be a potential candidate for the treatment, or possibly prevention, of the broad array of chronic diseases that are linked to dysfunctional inflammatory responses.

Flavonoids of Cocoa Inhibit Recombinant Human 5-Lipoxygenase
Autors: T Schewe, H K?hn and H Sies
Publication: Journal of Nutrition. 132:1825-1829, 2002

Recently flavonoids, such as epicatechin, have been reported to improve health. Flavonoids protect the cardiovascular system by endothelium-dependent relaxation, increase of prostacyclin release, inhibition of oxidation of low density lipoproteins and inhibition of platelet aggregation. Flavonoids also act as anti-inflammatory agents by scavenging peroxynitrite and modulation of expression and secretion of interleukins. The phytochemical epicatechin and its oligomer procyanidin are present in relative high quantities in cacao and cacao products such as chocolate. The intake of cacao results in an increased plasma level of epicatechin, and a reduced plasma level of proinflammatory cysteinyl leukotrienes. These leukotrienes are formed via the 5-lipoxygenase pathway of arachidonic acid metabolism. The biological activity of procyanidins is still unclear. Previous in vivo studies have showed only limited breakdown of procyanidins into epicatechin. The purpose of this study was to investigate if flavonoids (epicatechin and its polymers) in cacao regulated 5-lipoxygenase.

The enzyme 5-lipoxygenase was allowed to react with arachidonic acid while using different dosages of epicatechin. The researchers found that epicatechin reduced hydrolysis and production of byproducts in a dose-dependent manner. The enzyme 5-lipoxygenases catalyze the dioxygenation of arachidonic acid to 5-HpETE and the conversion of 5-HpETE to 5,6-LTA4. Epicatechin and small procyanidins inhibited both processes. Dimers of epicatechin showed also inhibitory effects whereas larger polymers showed little to no activity. Other studies have shown that the intake of cacao decreased the plasma levels of cysteinyl leukotrienes by 30 percent.

The study concluded that epicatechin and its low-molecular procyanidins inhibit 5-lipoxygenase, which might explain the anti-inflammatory action of cacao.