Polyphenols from Cocoa and Vascular Health—A Critical Review
Abstract
:1. Introduction
2. Bioavailability of Polyphenols in Cocoa
3. Putative Health Benefits of Polyphenols from Cocoa and Chocolate
3.1. Studies in Vitro and in Cultured Cells
3.2. Studies in Laboratory Animals
3.3. Studies in Humans
4. Conclusions
References and Notes
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No. Subjects | Age range (mean) | BMI (kg/m2) | Dietary source of polyphenols | Polyphenol content | Plasma concentration | Reference |
---|---|---|---|---|---|---|
8 | 25–55 (40 ± 15) (± SD) | 23.94 ± 2.35 (± SD) | Dark chocolate: 40 g 80 g | Epicatechin: 82 mg 164 mg | Epicatechin: 0.383 μmol/L (t = 2 h) 0.7 μmol/L (t = 2.57 h) | [16] |
20 | 20–56 | 23.8 ± 0.79 (± SEM) | Semi-sweet chocolate baking bits: 27 g 53 g 80 g | Total procyanidins (epicatechin): 186 (46) mg 365 (90) mg 551 (136) mg | Epicatechin (t = 2 h): 0.133 μmol/L 0.258 μmol/L 0.355 μmol/L | [17] |
13 | 26–49 | 23.2 ± 1.2 (± SEM) | 105 g semi-sweet chocolate baking bits (of which 80 g procyanidin-rich chocolate) | 557 mg total procyanidins (137 mg epicatechin) | 0.257 μmol/L epicatechin (t = 2 h) | [10] |
5 | 30–33 (31 ± 1) (± SD) | 22.5 ± 1.3 (± SD) | 96 g chocolate 66 g cocoa | Total polyphenols (epicatechin): 2.74 g (760 μmoL) 2.73 g (760 μmoL) | Total epicatechin (t = 2 h): 4.77 μmol/L 4.92 μmol/L | [18] |
23 | 21–62 | – | 22 g cocoa powder + 16 g dark chocolate | 466 mg total procyanidins (111 mg monomers) | 0.036 nmol/L epicatechin (t = 2 h) | [19] |
11 | 20–55 (39 ± 5) (± SD) | 24 ± 3 (± SD) | 37 g high- vs. low-procyanidin chocolate | Total procyanidins: 4 mg/g vs. 0.9 mg/g | 0.212 μmol/L vs. 0.011 μmol/L epicatechin (t = 2 h) | [20] |
16 | 22–49 | – | 300 mL cocoa beverage (18.75 g flavanol-rich cocoa powder) | 897 mg total epicatechin & procyanidins | 1.043 μmol/L epicatechin (t=2 h) | [21] |
5 | 23–34 | – | Cocoa beverage (0.375 g cocoa/kg bw) | Per g cocoa: 12.2 mg monomers, 9.7 mg dimers, 28.2 mg procyanidins | 0.041 μmol/L dimer B2, 5.92 μmol/L epicatechin, 0.16 μmol/L catechin (t = 2 h) | [22] |
6 | 23–39 | 23.1 ± 0.7 (± SEM) | 400 mL flavanol-rich cocoa beverage (37.5 g cocoa); 2 days | Per g cocoa: 12.2 mg monomers, 9.7 mg dimers, 20.2 mg procyanidins | 0.08 μmol/L dimer B2, 4.11 μmol/L epicatechin, 0.4 μmol/L catechin (t = 2 h) | [23] |
18 | – | – | 25 g semi-sweet chocolate chips | 220 mg flavanols & procyanidins | 0.427 μmol/L epicatechin (t = 2 h) | [24] |
32 | 31–49 (40 ± 9) (± SD) | 26 ± 4 (± SD) | Cocoa flavanol & procyanidin supplementation for 28 days | 234 mg/d flavanols & procyanidins | 0.116 μmol/L epicatechin 0.091 nmol/L catechin (t = 28 d) | [25] |
Cell type | Treatment | Outcomes | Reference |
---|---|---|---|
Human LDL | Cocoa powder extract (5 μmol/L GAE°) vs. pure catechin (5 μmol/L) | LDL oxidation ↓ | [26] |
Liposomes & human LDL | Cocoa catechin monomers & procyanidin fractions (0.1–10.0 μg/mL) | LDL oxidation ↓ | [27] |
LDL | 220 mL cocoa drink (cocoa concentration: 1.5, 2.0, 2.5, 3.0, 3.5%) | LDL oxidation ↓ dose-dependent | [28] |
LDL | Catechin, epicatechin, procyanidin B2, procyanidin C1, cinnamtannin A2 (0.125, 0.25, 0.5, 1.0, 2.0 μg/mL) | LDL oxidizability ↓ | [29] |
Human LDL & VLDL | Dark chocolate, cocoa, milk chocolate, hot cocoa mixes (126, 224, 52.2, 8.2 μmol/g total phenols) | Lag time of LDL & VLDL oxidation ↑ | [30] |
LDL & VLDL | Dark chocolate & cocoa powder (containing fat or defatted) vs. cocoa butter | LDL & VLDL oxidizability ↓ | [49] |
Rat liver microsomes | Cacao liquor | NADPH-dependent lipid peroxidation ↓ Linoleic acid autoxidation ↓ | [33] |
Recombinant human 5-LOX | Cocoa epicatechin & procyanidins (10 μmol/L) | 5-LOX activity ↓ Proinflammatory mediators (LTB4, LTC4, LTD4) ↓ | [32] |
Isolated rabbit 15-LOX-1 Recombinant human platelet 12-LOX | Cocoa procyanidins (monomers through decamers; 2.9 mg/mL) Epicatechin & procyanidin decamer | 15-LOX-1 activity ↓ dose-dependent 12-LOX activity ↓ dose-dependent | [31] |
Human PBMC * | Cocoa procyanidins (monomers through decamers; 25 μg/mL) | IL-1β secretion ↑ IL-2 expression ↓ IL-4 expression & secretion ↓ | [34] |
Human PBMC * | Cocoa procyanidins (monomers through decamers; 25 μg/mL) | IL-1β transcription & secretion ↑ (pentamers-decamers) IL-1β transcription & secretion ↓ (monomers-tetramers) | [36] |
Human PBMC * | Cocoa procyanidins (monomers through decamers; 25 μg/mL) | Secretory IL-4 ↑ | [35] |
Human PBMC * | Cocoa procyanidins (monomers through decamers; 25 μg/mL) | TNF-α secretion ↑ | [37] |
Human PBMC * | Cocoa procyanidins (monomers through decamers; 25 μg/mL) | IL-5 secretion ↑ (monomers-trimers) IL-5 secretion ↓ (hexamers-decamers) | [38] |
Human PBMC° | Short- (monomers-pentamers) & long-chain (hexamers-decamers) flavanol fractions (20 μg/mL) | Inflammatory mediators (IL-1β, IL-6, IL-10, TNF-α) ↑ | [53] |
Whole blood | Purified trimeric & pentameric cocoa procyanidins (3, 10 μmol/L) | PAC-1 binding & P-selectin expression ↑ in unstimulated platelets Epinephrine-induced platelet activation ↓ | [54] |
Isolated rabbit aortic rings | Procyanidin-rich cocoa extracts | Endothelium-dependent relaxation ↑ NOS activity ↑ | [45] |
ACE from rabbit lung | Epicatechin, dimeric & hexameric procyanidins (0–500 μmol/L) | ACE activity ↓ molecular weight-dependent | [47] |
Murine EL4BOU6 lymphocytes | Cocoa extract (5–80 μg/mL total polyphenols) vs. epicatechin (60–120 μg/mL total polyphenols) | IL-2 secretion ↓ IL-4 secretion↑ T lymphocyte activation ↓ | [41] |
Murine RAW264.7 macrophages # Rat NR8383 macrophages # | Cocoa extract (5–100 μg/mL total polyphenols) vs. epicatechin (60–120 μg/mL total polyphenols) Cocoa extract (10–50 μg/mL total polyphenols) vs. epicatechin (30–60 μg/mL total polyphenols) | inducible NO ↓ Proinflammatory mediators (TNF-α, MCP-1, IL-1α, IL-6) ↓ | [42] |
Jurkat T cells | Catechin, epicatechin & B-type oligomers (1.7–17.2 μmol/L) | PMA-induced NF-κB activation ↓ IL-2 expression & secretion ↓ | [55] |
VSMC | Cocoa procyanidins (0–100 μg/mL) & procyanidin B2 (0–100 μmol/L) | MMP-2 expression & activation ↓ VSMC invasion & migration ↓ MT1-MMP & MEk1 activities ↓ | [46] |
HUVEC | Epicatechin & flavanol metabolites mixture vs. control | Arginase-2 mRNA expression ↓ Arginase activity ↓ dose-dependent | [44] |
|
Species | No. animals | Experimental duration (wk) | Treatment | Outcomes | Reference |
---|---|---|---|---|---|
Rats | 5 | – | Oral administration of 1 g cocoa powder/kg bw (7.8 mg epicatechin) | Lipid peroxides in plasma ↓ Oxidant-induced α-tocopherol consumption ↓ | [4] |
Rats | 5–6 | – | Gastric intubation with 100 mg cocoa extract | Plasma antioxidant capacity ↑ Erythrocyte hemolysis ↓ | [56] |
Rats | 48 | 2 | Diet containing by weight 0.5–2.0% flavanol- and procyanidin-rich cocoa (12.2 mg/g epicatechin, 2.8 mg/g catechin, 53.3 mg/g procyanidins) | Oxidative DNA damage in testes ↓ No effect on plasma F2-isoprostane and TBARS | [52] |
Hypercholesterolemic rabbits | 12 | 24 | Diet containing 10% cocoa powder (0.78 g total polyphenols) | TBARS in plasma↓ No effects on plasma cholesterol, TG & phospholipids LDL oxidation lag time ↑ Area of atherosclerotic lesions in aorta ↓ | [48] |
Hamsters | 27 | 10 | Brownie (10 g vs. 1 g cocoa powder) | LDL & TG levels ↓ HDL ↑ dose-dependent LDL-oxidizability ↓ | [49] |
Obese-diabetic rats | 40 | 4 | Cocoa extract (600 mg/kg bw/d) | Blood glucose levels ↓ Plasma free fatty acids ↓ 8-isoprostane levels ↓ Superoxide dismutase activity ↑ No change in catalase activity | [51] |
Rats | 10 | 4 | 40 g cocoa powder per kg diet (11.0 mg/g epicatechin, 2.8 mg/g catechin, 43.0 mg/g procyanidins), vs. none | Renal arginase activity ↓ | [44] |
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] |
© 2009 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
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Rimbach, G.; Melchin, M.; Moehring, J.; Wagner, A.E. Polyphenols from Cocoa and Vascular Health—A Critical Review. Int. J. Mol. Sci. 2009, 10, 4290-4309. https://doi.org/10.3390/ijms10104290
Rimbach G, Melchin M, Moehring J, Wagner AE. Polyphenols from Cocoa and Vascular Health—A Critical Review. International Journal of Molecular Sciences. 2009; 10(10):4290-4309. https://doi.org/10.3390/ijms10104290
Chicago/Turabian StyleRimbach, Gerald, Mona Melchin, Jennifer Moehring, and Anika E. Wagner. 2009. "Polyphenols from Cocoa and Vascular Health—A Critical Review" International Journal of Molecular Sciences 10, no. 10: 4290-4309. https://doi.org/10.3390/ijms10104290