Table 4.
Effect of regular cocoa consumption on inflammation in patients with type 2 diabetes or impaired glucose tolerance—results from randomized, controlled trials.
Study (Reference) | n | Participants | Intervention | EC (mg) | IP (d) | Study Design | Sample | Parameter | Results | Annotations |
---|---|---|---|---|---|---|---|---|---|---|
Balzer et al., 2008 [63] | 41 | Type 2 diabetes, stably-treated, NS Age: 64 ± 1 BMI: 31.6 ± 0.8 CRP: 4.9 ± 1.1 |
I: Flavanol-rich cocoa drink, with CocoaPro cocoa powder (Mars), 750 mL/day | I: 203 | 30 | Double-blind, parallel group | Plasma | CRP | I: o C: o |
No dietary restrictions, dietary intake not determined, compliance: empty cocoa sachets, epicatechin in plasma |
C: Flavanol-poor cocoa drink with CocoaPro cocoa powder (Mars), similar in taste, matched for energy and macro-, micronutrient composition, 750 mL/day | C: 17 | |||||||||
Grassi et al., 2008 [61] | 19 | Impaired glucose tolerance, untreated stage I hypertension, NS Age: 45 ± 1 BMI: 26.5 ± 0.3 CRP: n.d. |
I: Flavanol-rich chocolate (Cuorenero, Sugar Company), 100 g/day | I: 111 | 15 | Crossover | Serum | CRP a | I: o C: o |
No flavonoid-rich food, 1 week cocoa-free run-in and washout, food records daily |
C: White chocolate (Milka, Kraft Foods), 100 g/day | C: 0 | |||||||||
Monagas et al., 2009 [64] | 42 | Diabetes or ≥3 cardiovascular disease risk factors (smoking, hypertension, hypercholesterolemia, obesity, family history of premature coronary heart disease) Age: 70 ± 2 BMI: 27.6 ± 0.8 CRP: 0.5 ± 0.3 |
I: Cocoa drink, prepared with cocoa powder (Nutrexpa) and skim milk, 500 mL/day | I: 46 | 28 | Crossover | Serum or plasma | CRP a | I: o C: o |
Flavonoid-rich food limited, 3 × 3 days food records, ompliance: patient reports and epicatechin metabolites in plasma and urine, 2 weeks run-in, no washout-period |
C: Skim milk, 500 mL/day | C: 0 | P-selectin | I: ↓ C: o I < C (d28) |
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E-selectin | I: o C: o |
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ICAM-1 | I: ↓ C: o I < C (d28) |
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VCAM-1 | I: o C: o |
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MCP-1 | I: o C: o |
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IL-6 | I: o C: o |
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Monocytes | LFA-1 | I: o C: o |
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Mac-1 | I: o C: o |
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VLA-4 | I: ↓ C: o I < C (d28) |
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SLex | I: o C: o |
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CD36 | I: ↓ C: o I < C (d28) |
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CD40 | I: ↓ C: o I < C (d28) |
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T cells | LFA-1 | I: o C: o |
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VLA-4 | I: o C: o |
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SLex | I: o C: o |
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CD40 | I: o C: o |
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Mellor et al., 2010 [65] | 12 | Type 2 diabetes, no steroids, no changes in chronic medication Age: 68 (median); 42–71 (range) BMI: n.d. CRP: 2.8 ± 0.5 |
I: Polyphenol-rich chocolate (Nestlé), 45 g/day | I: 17 | 56 | Double-blind, crossover | Serum or plasma | CRP a | I: o C: o |
4 weeks washout, compliance: empty wrappers: 93.8%, no changes in diet and lifestyle, dietary recalls |
C: Polyphenol-free chocolate (Nestlé), 45 g/day, matched for energy and macronutrients | C: <2 | |||||||||
Stote et al., 2012 [66] | 19 | Impaired or normal glucose tolerance, obese, NS Age: 46 ± 1 BMI: 36.8 ± 0.2 CRP: n.d. |
I: Cocoa drink with 28 g cocoa (different flavanol content, Mars), water, 300 mL/day | I1: 184 I2: 72 I3: 34 | 5 | Single-blind, crossover | Serum or plasma (0, 0.5, 1, 1.5, 2.0 h after an oral 75-g-glucose load) | CRP a | ↓ by dose | 10 days washout, no dietary changes |
ICAM-1 | o by dose | |||||||||
IL-6 | ↓ by dose | |||||||||
C: Flavanol-poor drink with water (Mars), 300 mL/day, matched for energy, macro-, micronutrients | C: 4 | |||||||||
Parsaeyan et al., 2014 [67] | 100 | Type 2 diabetes Age: 54 ± 1 BMI: 28 ± 0.5 CRP: n.d. |
I:_Cocoa drink (10 g cocoa, 10 g milk powder, 250 mL water), 2 drinks/day | n.d. | 42 | Parallel group | Serum | CRPa | I: ↓ C: o |
Dietary records, no restrictions |
IL-6 | I: ↓ C: o |
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TNF-α | I: ↓ C: o |
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C: Cocoa-free drink (10 g milk powder, 250 mL water), 2 drinks/day | n.d. | |||||||||
Rostami et al., 2015 [68] | 60 | Type 2 diabetes, blood pressure ≥140/90 mm Hg, stable medication, NS Age: 60 ± 1 BMI: 29.8 ± 0.6 CRP: unclear |
I: Dark chocolate (Farmand), 25 g/day | n.d. | 56 | Placebo-controlled, double-blind, parallel group | Serum | CRP a | I: ↓ C: o; No effect by ANCOVA adjusted for age, sex, energy intake |
No further chocolate, 3 days food records |
C: White chocolate (Farmand), 25 g/day, isocaloric, same color and shape, identically wrapped | n.d. |
a determined by high-sensitivity test kits for C-reactive protein. BMI: body mass index; C: control; d: days; CRP: C-reactive protein; EC: epicatechin; I: cocoa intervention; ICAM-1: intercellular adhesion molecule-1; IL-6: interleukin-6; IP: intervention period; LFA-1: lymphocyte function-associated antigen-1; MCP-1: monocyte chemoattractant protein; n.d.: no data available; SLex: sialil Lewis X, CD15s; VCAM-1: vascular cell adhesion molecule-1; VLA-4: very late activation antigen-4; ↓: decrease; o: no changes; Δ difference pre- vs. post-consumption values. Data on age (years), BMI (kg/m2), and CRP (mg/L) are means ± SEM if not indicated otherwise. Means were calculated as weighted means from the data of individual groups if not provided by the authors. Missing SEMs were calculated by SDs, of individual groups. n refers to the number of participants for whom data on inflammatory markers were available.