Table 5.
Human intervention trials with cocoa and chocolate.
| No. Subjects | Age range (mean) | BMI (kg/m2) | Intervention | Polyphenol content | Outcomes | Reference |
|---|---|---|---|---|---|---|
| 12 | 39 ± 4.0 | – | Cocoa | – | LDL oxidation ↓ | [57] |
| 15 | (32.5 ± 6.4) | 21.7 ± 2.1 | 12 g cocoa powder x3/d for 2 weeks, vs. sugar | 2610 mg total polyphenols/d (244 mg epicatechin) | LDL oxidation ↓ No change in plasma lipids or antioxidants Urinary excretion of epicatechin/metabolites ↑ |
[58] |
| 23 | 21–62 (36) | – | 22 g cocoa powder + 16 g dark chocolate/d for 4 weeks, vs. average American diet | 466 mg procyanidins/d (111 mg monomers) | LDL oxidation ↓ Serum antioxidant capacity ↑ HDL cholesterol ↑ |
[19] |
| 25 | 20–6 (32.4 ± 7.4) | 24.4 ± 3.4 | 37 g dark chocolate & 31 g cocoa powder in a drink/d for 6 weeks, vs. none | 651 mg total procyanidins/d (chocolate = 168 mg/d, cocoa = 483 mg/d) | LDL oxidizability ↓ No effect on inflammation markers, or plasma antioxidant capacity |
[81] |
| 45 | 19–49 (26) | 21.5 ± 2.9 /24.1 ± 3.5 | 75 g dark chocolate or high-phenolic dark chocolate for 3 weeks, vs. 75 g white chocolate | Total polyphenols (epicatechin): Dark = 274 (114) mg/d High = 418 (170) mg/d |
HDL cholesterol ↑ Lipid peroxidation ↓ No change in plasma antioxidant capacity |
[60] |
| 25 | (38 ± 1) | 22.1 ± 0.4 | 26 g/d cocoa powder for 12 weeks |
Per 100 g: 377 mg epicatechin, 135 mg catechin, 158 mg procyanidin B2, 96.1 mg procyanidin C1 |
LDL oxidation ↓ HDL-cholesterol ↑ |
[59] |
| 20 | 20–56 | 23.8 ± 0.79 | Semi-sweet chocolate baking bits (27, 53, 80 g), vs. none | Total procyanidins (epicatechin): 186 (46) mg 365 (90) mg 551 (136) mg |
Plasma epicatechin ↑ dose-dependent Antioxidant capacity ↑ TBARS ↓ |
[17] |
| 13 | 26–49 | 23.2 ± 1.2 | 105 g (of which 80 g chocolate) semi-sweet baking bits, vs. vanilla milk chips | 557 mg total procyanidins (137 mg epicatechin) | Plasma epicatechin ↑ Total antioxidant capacity ↑ TBARS ↓ |
[10] |
| 20 | 20–40 | – | 100 ml high- vs. low-flavanol cocoa drink | 187 mg vs. 14 mg total monomers & oligomeric procyanidins | Plasma F2-isoprostanes ↓ | [62] |
| 12 | 25–35 (32.2 ± 1.0) | 21.9 ± 0.4 | 100 g dark chocolate (with & without 200 mL milk), vs. 200 g milk chocolate | Not stated but FRAP values (147.4 μmol FE/100 g) | Plasma antioxidant capacity & epicatechin ↑, in absence of milk | [9] |
| 30 | 24–49 | – | Cocoa beverage (300 ml, 18.75 g procyanidin-rich cocoa powder), caffeinated beverage, or water | 897 mg total epicatechin & oligomeric procyanidins | Platelet activation & function ↓ | [61] |
| 18 | – | – | 25 g semi-sweet chocolate chips, vs. none | 220 mg flavanols & procyanidins | Plasma epicatechin ↑ Platelet function ↓ |
[24] |
| 32 | 40 ± 9 | 26 ± 4 | Cocoa flavanol/procyanidin tablets for 28 d, vs. placebo | 234 mg flavanols & procyanidins/d | Platelet aggregation ↓ Plasma ascorbic acid ↑ No change in oxidation status markers Plasma epicatechin & catechin ↑ |
[25] |
| 30 | 20–58 (30.6) | – | Dark (75% cocoa), vs. milk (20% cocoa) or white (no flavonoids) chocolate High polyphenol vs. low | – | Collagen–induced platelet aggregation ↓ | [82] |
| 27 | 18–72 (44 ± 3.4) | 26.9 ± 0.9 | flavanol cocoa drink (4x 230 mL/d for 4 d) | 821 mg/d total flavanols (epicatechin, catechin & related oligomers) | Improved peripheral vasodilation | [63] |
| 20 | 41 ± 14 | 25 ± 4 | 100 mL high polyphenol vs. low flavanol cocoa drink | 176 mg total flavanols (70 mg monomers, 106 mg procyanidins) | NO bioactivity ↑ Arterial FMD ↑ |
[64] |
| 10 | – | – | 200 mL high- vs. low-flavanol cocoa beverage | 985 vs. 80.4 mg total flavanols | Erythrocyte arginase activity ↓ | [44] |
| 13 | 55–64 | 21.9–26.2 | 100 g dark chocolate/d for 14 d, vs. 90 g white chocolate in hypertensive subjects | 500 mg/d total polyphenols | Systolic & diastolic blood pressure ↓ | [72] |
| 15 | (33.9 ± 7.6) | 22.6 ± 3.0 | 100 g dark chocolate, vs. 90 g white chocolate for 15 d | 500 mg total polyphenols | Insulin sensitivity ↑ Insulin resistance ↓ Systolic blood pressure ↓ |
[70] |
| 28 | – | – | 105 g/d milk chocolate for 14 d, vs. cocoa butter chocolate; hypertensive subjects | 168 mg/d flavanols (39 mg monomers, 126 mg polymers) 2.62 g procyanidins | Diastolic & mean blood pressure ↓ LDL cholesterol ↓ Oxidative stress markers ↓ |
[69] |
| 17 | 24–32 (28.9) | <27.0 | 100 g dark chocolate, vs. none | (0.54 g monomers & dimers, 0.76 g trimer-heptamers) | Improved endothelial function Vasodilation of brachial artery No change in blood pressure |
[67] |
| 20 | (43.65 ± 7.8) | 25.4 ± 1.7 | 100 g/d dark chocolate for 15 d, vs. 90 g white chocolate in hypertensive subjects | 88 mg/d flavanols (22 mg catechin, 66 mg epicatechin) | Improved insulin sensitivity Systolic & diastolic blood pressure ↓ LDL cholesterol ↓ Improved FMD |
[71] |
| 11 | (31 ± 1) | 21.8 ± 0.8 | 100 mL high- vs. low-polyphenol cocoa drink | 176–185 mg flavanols (70–74 mg monomers, 20–22 mg epicatechin, 106–111 mg procyanidins) | Circulating NO & FMD ↑ | [65] |
| 16 | 25–32 | 19–23 | 300 mL high- vs. low-flavanol cocoa drink | 917 mg flavanols (19% epicatechin) | Circulating NO species ↑ FMD response of conduit arteries ↑ Microcirculation ↑ |
[66] |
| 20 | – | – | 40 g dark chocolate, vs. white chocolate | Same brand as used for Vlachopoulos et al. (2005) | Improved FMD Platelet function ↓ Plasma total antioxidant status ↑ |
[83] |
| 34 | 18–74 (47.9 ± 3.0) | 28.0 ± 1.9/28.4 ± 1.3 | High polyphenol cocoa drink 4x 230 mL/d for 4–6 d, vs. none |
Per 100 mL: 9.2 mg epicatechin, 10.7 mg catechin, 69.3 mg flavanol oligomers (821 mg/d) |
NO synthesis ↓ FMD ↑ Pulse wave amplitude ↑ |
[84] |
| 40 | 61 ± 9 | 27.1 ± 3.9 | 48 g flavanol-rich chocolate bar + 18 g cocoa beverage/d, vs. placebo for 6 weeks in subjects with coronary artery disease | 444 vs. 19.6 mg/d total flavanols (107 vs. 4.7 mg epicatechin) | No acute or chronic changes in FMD, systemic arterial compliance, forearm blood flow, soluble cellular adhesion molecules | [75] |
| 32 | 57.7 ± 2.2/55.4 ± 1.7 | 24.9 ± 1.0/25.3 ± 0.8 | High- vs. low-flavanol cocoa beverage for 6 weeks in hypercholesterolemic subjects | 446 vs. 43 mg total flavanols | FMD ↑ Brachial artery hyperaemic blood flow ↑ VCAM-1 ↓ |
[85] |
| 11 | 22–32 (27 ± 1) | 22 ± 1 | 100 mL high-flavanol vs. low-phenolic cocoa drink x3/d for 1 week |
Per 100 ml: 59 mg epicatechin, 15 mg catechin, 232 mg flavanol oligomers (918 mg/d procyanidins) |
FMD ↑ No change in biomarkers of oxidative stress |
[86] |
| 45 | 30–75 (52.8 11.0) ± | 30.1 ± 3.3 | 74 g solid dark chocolate (22 g cocoa powder); 240 ml liquid cocoa (sugar-free vs. sugared) | 821 mg total flavanols; 805.2 & 8.5 mg total flavanols | Improved FMD Systolic & diastolic blood pressure ↓ |
[68] |
FE: Ferric equivalents; FMD: Flow-mediated dilation; FRAP: Ferric-reducing ability of plasma;
TBARS: Thiobarbituric acid reactive substances.
All data refer to healthy subjects unless otherwise stated.