Chronic Consumption of Flavanol-rich Cocoa Improves Endothelial Function and Decreases Vascular Cell Adhesion Molecule in Hypercholesterolemic Postmenopausal Women

Abstract

Endothelial dysfunction characterizes many disease states including subclinical atherosclerosis. The consumption of flavanol-rich cocoa and cocoa-based products has been shown to improve endothelial function in both compromised and otherwise normal, healthy individuals when administered either acutely or over a period of several days, or weeks. Women experience increased risk for cardiovascular disease after menopause, which can be associated with endothelial dysfunction. Whether a flavanol-rich cocoa-based product can improve endothelial function in hypercholesterolemic postmenopausal women is not known. The purpose of the present study was to determine whether chronic dietary administration of flavanol-rich cocoa improves endothelial function and markers of cardiovascular health in hypercholesterolemic postmenopausal women. Thirty-two postmenopausal hypercholesterolemic women were randomly assigned to consume a high-flavanol cocoa beverage (high cocoa flavanols (CF)--446 mg of total flavanols), or a low-flavanol cocoa beverage (low CF--43 mg of total flavanols) for 6 weeks in a double-blind study (n=16 per group). Endothelial function was determined by brachial artery-reactive hyperemia. Plasma was analyzed for lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol), hormones (follicle-stimulating hormone), total nitrate/nitrite, activation of cellular adhesion markers (vascular cell adhesion molecule 1, intercellular adhesion molecule 1, E-Selectin, P-Selectin), and platelet function and reactivity. Changes in these plasma markers were then correlated to brachial reactivity. Brachial artery hyperemic blood flow increased significantly by 76% (P<0.05 vs. baseline) after the 6-week cocoa intervention in the high CF group, compared with 32% in the low CF cocoa group (P=ns vs. baseline). The 2.4-fold increase in hyperemic blood flow with high CF cocoa closely correlated (r2=0.8) with a significant decrease (11%) in plasma levels of soluble vascular cell adhesion molecule-1. Similar responses were not observed after chronic use of low CF. There were no significant differences between high and low CF in other biochemical markers and parameters measured. This study is the first to identify beneficial vascular effects of flavanol-rich cocoa consumption in hypercholesterolemic postmenopausal women. In addition, our results suggest that reductions in plasma soluble vascular cell adhesion molecule-1 after chronic consumption of a flavanol-rich cocoa may be mechanistically linked to improved vascular reactivity.

Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects

“…While these studies provide clear evidence of an effect of short-term consumption of cocoa flavanols on endothelial function, the lack of placebo control prevents a definitive interpretation of the results as being directly caused by the cocoa flavanols. A previous placebo-controlled study conducted in postmenopausal hypercholesterolemic women was able to demonstrate an increase in brachial artery blood flow following 6 weeks of HF cocoa consumption (446 mg flavanols per day) but fell marginally short of showing a significant improvement in FMD, 16 potentially due to a lack of statistical power. Prior to the present study, Grassi et al 17 had provided the strongest evidence for benefits of chronic consumption of cocoa-containing flavanols on FMD when it was demonstrated, using a cross-over design, that consuming 100 g of dark chocolate each day (containing around 500 mg of cocoa 'polyphenols') for 15 days resulted in significant improvements in FMD, BP and insulin sensitivity compared with consuming white choco- Figure 2 Changes in blood pressure and heart rate from baseline to weeks 6-12.…”

Effects of cocoa products/dark chocolate on serum lipids: a meta-analysis

“…Four studies were dropped because flavanol was part of a mixed dietary test regimen Mustad et al, 1993;Allen et al, 2008) or due to lack of randomization (Baba et al, 2007). Five studies were not included because they did not report sufficient details on blood lipid measurements (Kris-Etherton and Polagruto et al, 2006;Wang-Polagruto et al, 2006;Taubert et al, 2007;Grassi et al, 2008). One study was excluded because of the lack of a control group (Hamed et al, 2008).…”

“…(http://www.nal.usda.gov/fnic/ foodcomp/search/), the latter two being saturated fats. Cocoa products are also very rich in plant phytochemicals, especially flavonoids, which are now objects of increased scientific attention due to their potential health benefits (Engler et al, 2004;Grassi et al, 2005a;Wang-Polagruto et al, 2006;Almoosawi et al, 2010).…”

“…Previous studies have suggested that dark chocolate consumption reduces blood pressure (Grassi et al, 2005b;Grassi et al, 2008), improves insulin sensitivity as shown by significantly higher QUICKI (quantitative insulin sensitivity check index) measurements (Grassi et al, 2008), improves vascular endothelial function and reverses vascular dysfunction (Engler et al, 2004;Grassi et al, 2005b;Wang-Polagruto et al, 2006), reduces insulin resistance as evidenced by significantly lower HOMA-IR (homeostasis model assessment of insulin resistance) (Grassi et al, 2005a) measurements, and increases serum total antioxidant capacity (Wan et al, 2001).…”

A New Process To Develop a Cocoa Powder with Higher Flavonoid Monomer Content and Enhanced Bioavailability in Healthy Humans

“…Flavonoid-rich cocoa products and chocolate have demonstrated relevant biological activity (6)(7)(8). The consumption of flavanol-rich cocoa has been reported to improve endothelial function (9), and this effect has been directly linked to the presence of procyanidin-derived metabolites in plasma (4). In this context, the bioavailability of food polyphenols is essential to understand their biological activity.…”