Cocoa beans as the starting ingredients in manufacturing dark chocolate

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3 Cocoa beans as the starting ingredients in manufacturing dark chocolate

4 Raw cocoa beans contain large amounts of flavanols Polyphenols Flavonoids Flavonols Flavones Isoflavones Flavanones Anthocyanidins Flavanols Catechin and epicatechin (monomers) Procyanidins (=dimers, oligomers und polymers of epicatechin and catechin) Manach, Am J Clin Nutr 2004

5 Presumed beneficial effects of flavanols Decrease in blood pressure Improvement in endothelial function Improved insulin sensitivity Reduced platelet activity (inhibition of aggregation and adhesion) Antioxidant properties Corti, Circulation 2009

6 Enhanced nitric oxide bioavailability as most likely mechanism for flavanol effects Nitric oxide relaxes smooth muscle cells vasodilation prevents leukocyte adhesion and migration prevents smooth muscle cell proliferation inhibits platelet adhesion and aggregation Reduced bioavailability: endothelial dysfunction/atherosclerosis Flavanols increase enos activity and lower arginase activity Corti, Circulation 2009

7 Variation in flavanol content Regional origin Ripeness of cocoa pod Manufacturing (i.e. fermentation, roasting): Raw cocoa powder dark chocolate milk chocolate

8 Flavanol content in selected foods Catechin/Epicatechin content (mg/kg or mg/l) Chocolate Beans Apricots Cherries Grapes Peaches Blackberries 130 Apples Green tea Black tea Red wine Cider 40 Manach, Am J Clin Nutr 2004

9 Cocoa-containing products and blood pressure Desch, Am J Hypertension 2010

10 Limitations of randomized trials of cocoa for Mostly short-term trials the lowering of blood pressure Low number of participants Flavanol intake on average higher than in commercially available products White chocolate as control In most studies, total daily consumption of chocolate/cocoa beverage too high for potential long-term treatment (energy, fat, and sugar content)

11 Effects of low habitual cocoa intake on blood pressure Methods: 44 adults with prehypertension/stage 1 hypertension Randomized to 6.3 g/day of flavanol-rich dark chocolate or flavanol-free white chocolate 18 weeks Primary outcome measure: Blood pressure Results Significant reduction in systolic blood pressure by 2.9 mmhg and 1.9 mmhg in diastolic blood pressure Conclusion Small amounts of flavanol-rich dark chocolate might reduce blood pressure Taubert, JAMA 2007

12 Reduction in blood pressure paralleled by increase in serum levels of S-nitrosoglutathione Taubert, JAMA 2007

13 Low vs. higher-dose dark chocolate and blood pressure in cardiovascular high-risk patients 102 patients at high cardiovascular risk and highnormal/stage 1 hypertension Low dose (n=51) 6g of dark chcoolate/day High dose (n=51) 25g of dark chcoolate/day Primary Endpoint: Blood pressure at 3 months Desch, Am J Hypertension 2010

14 Desch, Am J Hypertension 2010

15 Epidemiological evidence Zutphen Elderly Study Methods: 470 elderly men free of chronic disease Assessment of habitual intake of cocoa-containing food Median cocoa intake in highest tertile: 4.2 g/day (equals 10 g/day of dark chocolate) 15 years of clinical follow-up Results Significant benefit in cardiovascular and all-cause mortality for participants in highest tertile of cocoa consumption compared to lowest tertile (adjusted analysis, relative risk 0.50; 95% CI ) Mean systolic blood pressure 3.7 mmhg lower in highest compared to lowest tertile of cocoa intake (diastolic blood pressure: -2.1 mmhg) Buijsse, Archives of Int Med 2006

16 Meta-analysis of epidemiological evidence Cardiovascular disease: Myocardial infarction, stroke, ischaemic heart disease, heart failure, diabetes and metabolic syndrome Buitrago-Lopez, BMJ 2011

17 Shortcomings of epidemiological chocolate studies Possibility of condounding No differentiation between dark chocolate and milk chocolate Reporting bias Heterogeneity (when pooling results across studies)

18 Overview of large scale double-blind randomized placebo-controlled trials of dark chocolate versus control...

19 Problems in setting up a large-scale double-blind randomized placebocontrolled trial of dark chocolate versus control Funding Placebo chocolate Standardizing content (especially with regard to flavanols)

20 Should we recommend to consume (small amounts) of flavanol-rich dark chocolate for cardiovascular health reasons? Classes of recommendation Definitions Levels of evidence Definitions Class I Class IIb Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective. Usefulness/efficacy is less well established by evidence/opinion. Level of evidence A Data derived from multiple randomized clinical trials or metaanalyses. Class II Conflicting evidence and/or a Level of Data derived from a single divergence of opinion about the evidence B randomized clinical trial or large non-randomized studies. usefulness/efficacy of the given Suggestive data, but no proof from adequately treatment or procedure. Class IIa Weight of evidence/opinion is Level of Consensus of opinion of the designed interventional favour of usefulness/efficacy. evidence C experts studies and/or small studies, retrospective studies, registries. Class III Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may be harmful.

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