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. 2016 May 26;8(6):321. doi: 10.3390/nu8060321

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)
E-selectin I: o
C: o
ICAM-1 I: ↓
C: o
I < C (d28)
VCAM-1 I: o
C: o
MCP-1 I: o
C: o
IL-6 I: o
C: o
Monocytes LFA-1 I: o
C: o
Mac-1 I: o
C: o
VLA-4 I: ↓
C: o
I < C (d28)
SLex I: o
C: o
CD36 I: ↓
C: o
I < C (d28)
CD40 I: ↓
C: o
I < C (d28)
T cells LFA-1 I: o
C: o
VLA-4 I: o
C: o
SLex I: o
C: o
CD40 I: o
C: o
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
TNF-α I: ↓
C: o
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.