Table 2.
Studies investigating cocoa and vascular function.
| Reference | Year | Study design | Population | Duration | Intervention | Outcome |
|---|---|---|---|---|---|---|
| Rodriguez-Mateos et al. (65) | 2015 | Randomized double-blind crossover | 15 healthy subjects | 1,2,3,4 h | CF-rich drink (1.4–10.9 mg/kg body weight) vs. nitrate or nutrient-matched flavanol-free drink | Improvement in FMD after flavanol and nitrate intake |
| Engler et al. (46) | 2004 | Randomized double-blind placebo-controlled | 21 heathy subjects | 2 weeks | High flavonoid chocolate (213 mg procyanidins, 46 mg epicatechin) vs. low-flavonoid chocolate | Improvement in FMD, increased epicatechin concentrations |
| Sansone et al. (27) | 2015 | Randomized double-blind controlled parallel | 100 healthy subjects | 30 days | CF-containing drink (450 mg) or a nutrient-matched flavanol-free control bi-daily | Improvement in FMD, decreased SBP and DBP, decreased PWV |
| Grassi et al. (23) | 2015 | Randomized double-blind crossover controlled | 20 healthy subjects | 5 weeks | Five treatments with daily intake of 10 g cocoa (0, 80, 200, 500, 800 mg flavonoids) | Dose-dependent improvement in FMD, decreased PWV, and BP |
| Schroeter et al. (66) | 2006 | Randomized crossover | 16 healthy subjects, isolated rabbit rings | 2 h | Drink with high flavonoid content | Improvement in FMD, paralleled the appearance of flavanols in plasma |
| Heiss et al. (67) | 2015 | Randomized double-blind controlled parallel | 42 healthy subjects | 14 days | CF-containing drink (450 mg bid) vs. CF-free drink | Improvement in FMD, decreased PWV, and in total peripheral resistances |
| Shiina et al. (47) | 2009 | Randomized single-blind | 39 healthy subjects | 2 weeks | 45 g commercially available dark chocolate vs. white chocolate | Improvement in coronary circulation as measured by coronary velocity flow reserve |
| Grassi et al. (51) | 2005 | Randomized crossover placebo-controlled | 20 untreated hypertensive patients | 15 days | 100 g dark chocolate (21.91 mg catechin, 65,97 mg epicatechin) vs. flavanol-free white chocolate | Improvement in FMD, decreased BP and LDL cholesterol, increased insulin sensitivity |
| Grassi et al. (54) | 2008 | Randomized crossover placebo-controlled | 19 hypertensive with IGT | 15 days | 100 g dark chocolate (36 mg catechin, 110 mg epicatechin) vs. flavanol-free white chocolate | Improvement in FMD, decreased SBP and DBP, decreased insulin resistance |
| Heiss et al. (69) | 2005 | Randomized double-blind crossover | 11 smokers | 2 h | 100 ml cocoa drink with high (176–185 mg) or low (<11 mg) flavanol content | Improvement in FMD and increased circulating NO pool. Increased flavanol metabolites |
| Hermann et al. (70) | 2006 | Randomized placebo-controlled | 20 smokers | 2 h | 40 g commercially available dark chocolate vs. white chocolate | Improvement in FMD, antioxidant status, and platelet function |
| Davison et al. (55) | 2008 | Randomized double-blind placebo-controlled parallel | 49 obese and overweight patients | 12 weeks | Dietary high (902 mg) vs. low (36 mg) flavanol intake | Improvement in FMD |
| Njike et al. (48) | 2011 | Randomized controlled crossover | 44 overweight patients | 6 weeks | Sugar-free cocoa beverage or placebo, sugar-sweetened cocoa beverage or placebo | Improvement in FMD, no change in weight |
| West et al. (71) | 2014 | Randomized double-blind crossover placebo-controlled | 30 overweight patients | 30 days | 37 g dark chocolate plus sugar-free cocoa beverage (flavanols 814 mg) vs. low-flavanol chocolate bar and cocoa-free and sugar-free beverage | Unchanged FMD, increased basal diameter and peak diameter of the brachial artery, increased basal blood flow, in women decreased augmentation index |
| Balzer et al. (72) | 2008 | Randomized double-blind | 41 diabetic patients | 30 days | Flavanol-rich cocoa (321 mg flavanols × 3) or a nutrient-matched control (25 mg flavanols × 3) | Improvement in FMD |
| Mellor et al. (73) | 2013 | Randomized double-blind crossover controlled | 10 diabetic patients | 2 h | 13.5 g of high vs. low-flavanol chocolate; 60 min later, a 75 g oral glucose load | Improved endothelial function assessed by reactive hyperemia peripheral artery tonometry |
| Heiss et al. (74) | 2003 | Randomized double-blind crossover | 20 patients with at least 1 CV risk factor | 2 h | Flavanol-rich cocoa drink (100 ml) | Improvement in FMD and increased levels of nitrosated and nitrosylated species |
| Heiss et al. (75) | 2010 | Randomized double-blind crossover controlled | 16 CHD patients | 30 days | Dietary high (375 mg bid) vs. low (9 mg bid) flavanol cocoa drink | Improvement in FMD and mobilization of endothelial progenitor cells |
| Flammer et al. (29) | 2012 | Randomized double-blind placebo-controlled | 20 heart failure patients | 2 h and 30 days | 40 g commercially available dark chocolate vs. flavonoid-free placebo chocolate | Improvement in FMD of platelet function |
| Flammer et al. (76) | 2007 | Randomized double-blind | 22 heart transplant patients | 2 h | 40 g commercially available dark chocolate vs. flavonoid-free placebo chocolate | Inducing coronary vasodilation, improvement in coronary endothelial function, and improvement in platelet function |
| Rassaf et al. (77) | 2016 | Randomized double-blind placebo-controlled | 57 hemodialytic patients | 30 days | CF-rich beverages (900 mg per study day) vs. flavanol-free beverages | Improvement in FMD decreased DBP. Ingestion of flavanols during HD alleviated HD-induced vascular dysfunction |
| Sansone et al. (68) | 2017 | Randomized double-blind crossover | 47 healthy subjects | High (820 mg)/low-flavanol cocoa drink with high (220 mg)/low methylxanthines content | CFs with methylxanthines increased epicatechin serum concentration, increased FMD decreased PWV and DBP compared with flavanols alone | |
Modified from Ref. (116).
FMD, flow-mediated dilation; endoPAT, reactive hyperemia peripheral artery tonometry; PWV, pulse wave velocity; CV, cardiovascular; NO, nitric oxide; CHD, coronary heart disease; HD, hemodialysis; BP, blood pressure; SBP, systolic blood pressure; DBP, diastolic blood pressure; LDL, low-density lipoprotein; CF, cocoa flavanol; IGT, impaired glucose tolerance.