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

Table 2.

Effect of regular cocoa consumption on inflammation in healthy subjects—results from randomized, controlled trials.

Study (Reference) n Participants Intervention EC (mg) IP (d) Study Design Sample Parameter Results Annotations
Grassi et al., 2005 [51] 20 Healthy NS
Age: 34 ± 2
BMI: 22.6 ± 0.6
CRP: 0.3 ± 0.1		 I: Dark chocolate (Ritter Sport, Halbbitter, Ritter), 100 g/day I: 66 15 Crossover Serum CRP a I: o
C: o		 No flavonoid-rich food, food diaries, 1 week run-in and 1 week washout without chocolate
C: White chocolate (Milka, Kraft Foods), 90 g/day C: 0 ICAM-1 I: o
C: o
Kurlandsky and Stote, 2006 [52] 24 Healthy NS, serum cholesterol 4.1–7.8 mmol/L, no lipid lowering medication
Age: 43 ± 2
BMI: 25.0 ± 0.8
CRP: 4.7 ± 1.5		 I: Dark chocolate (Dove Silky Dark Chocolate, Mars), 41 g/day n.d. 42 Parallel group Serum CRP a I: o
C: o		 Flavonoid-rich food limited, 3 days food records before and in week 2, 4, and 6 ofintervention
C: No chocolate ICAM-1 I: ↓
C: o
VCAM-1 I: o
C: o
Crews et al., 2008 [53] 88 Healthy subjects with prehypertension
Age: 69 ± 1
BMI: 25.3 ± 0.5
CRP: 1.6 ± 0.2		 I: Dark chocolate, 37 g/day, + cocoa beverage, 237 mL/day (Hershey) n.d. 42 Placebo-controlled, double-blind, parallel group Serum CRP a ΔI = ΔC No flavonoid-rich food, 1 week run-in without flavonoid-rich food, compliance: daily records
C: Cocoa-free placebo products (Hershey) n.d.
Njike et al., 2011 [54] 44 Healthy NS, overweight/obese
Age: 52 ± 2
BMI: 30.2 ± 3.4
CRP: 0.9 (median)		 I: Cocoa-rich beverage with water (Hershey), 454 g/day
I1: sugared
I2: sugar- free (I2)		 I1: 48
I2: 48		 42 Double-blind, crossover Serum CRP a I1: o
I2: o
C: o		 No flavonoid-rich food 24 h before, 3 days food diary during each treatment, 4 weeks washout
C: Cocoa-free sugared placebo beverage (Hershey), 454 g/day C: 0
Tzounis et al., 2011 [55] 22 Healthy subjects
Age: 30 ± 3
BMI: 23.2 ± 0.4
CRP: 0.3 ± 0.1		 I: Flavanol-rich cocoa drink (Mars), 150 mL/day I: 89 28 Placebo-controlled, double-blind, crossover Plasma CRP a I: ↓
C: o		 2 weeks run-in, 4 weeks washout, no flavonoid-rich food, 4 days food diaries during run-in, 3rd week of both treatments, and during 4th week washout compliance: % used cocoa sachets, self-reported intake >95%
C: Low-flavanol cocoa drink (Mars), 150 mL/day C: 3
Ibero-Baraibar et al., 2014 [56] 50 Healthy NS, overweight/obese
Age: 57 ± 1
BMI: 30.6 ± 0.3
CRP: n.d.		 I: Cocoa extract (1.4 g/day; Nutrafur) in ready-to-eat meals, within a hypocaloric diet (energy restriction of 15%) I: 153 28 Double-blind, parallel group Plasma ICAM-1 I: ↓
C: ↓		 1 week run-in without cocoa, 3 days before low-polyphenol-diet; exclude polyphenol-rich foods; compliance >98%
C: Ready-to-eat meals not enriched with cocoa extract, within a hypocaloric diet (energy restriction of 15%) C: 0 VCAM-1 I: o
C: o
Sarriá et al., 2014 [57] 44 Healthy NS, normocholesterolemic (n = 24; N) or moderately hypercholesterolemic (n = 20; H)
Age: 29 ± 1
BMI: 23.6 ± 0.5
CRP: n.d.		 I: Cocoa drink with cocoa, 30 g/day, rich in dietary fiber (Nutrexpa), with 400 mL semi-skimmed milk I: 9.3 28 Crossover Plasma CRP n.d. 2 weeks run-in and during intervention, polyphenol-rich foods were restricted, 3-day food records, compliance measured
IL-1β I: o
C: o (N, H)
IL-6 I: o
C: o (N, H)
C: Cocoa-free drink with semi-skimmed milk, 400 mL/day C: 0 IL-8 I: o
C: o (N, H)
IL-10 I: ↓
C: ↓
Ip < Cp (N, H)
TNF-α I: o
C: o (N, H)
MCP-1 I: o
C: o (N, H)
VCAM-1 I: o
C: o (N, H)
ICAM-1 I: o
C: o (N, H)
West et al., 2014 [58] 13 Healthy NS, Overweight/obese
Age: 52 ± 0.3
BMI: 27.8 ± 0.2
CRP: n.d.		 I: Dark chocolate, 37 g/day + cocoa drink with 22 g cocoa/day I: 73.6 42 Placebo-controlled, crossover Plasma CRP a n.d. 2 days before no flavonoid-rich foods, 2 weeks washout
C: Low-flavanol chocolate + cocoa-free drink as color matched control IL-1β I: o
C: o
C: 0.9 IL-6 I: o
C: o
TNF-α I: o
C: o
McFarlin et al., 2015 [59] 24 Healthy subjects with normal weight (n = 10; N), overweight (n = 7; O), or obesity (n = 7; B),
Age: 22 ± 2
BMI: 21.6 ±1.9 (N), 27.0 ± 1.4 (O), 34.9 ± 9.9 (B)
CRP: n.d.		 I: Cocoa bars with 12.7 g natural cocoa (Hershey)
C: Cocoa-free placebo bar (Hershey), matched for energy content and macronutrient composition		 I: 48.0
C: 0		 42 Placebo-controlled, crossover Serum/Plasma CRP a n.d. no chocolate during study, 2 weeks washout
AGP n.d.
AMG n.d.
Adipsin n.d.
Haptoglobin I: o (N,O), ↓ (B)
C: o (N, O, B)
t0: B > O > N
E-selectin I: o (N, O, B)
C: o (N, O, B)
t0: B > O, N
SAP n.d.
Endocan-1 I: o
C: o (N, O, B)
IL-1β n.d.
IL-6 n.d.
IL-8 n.d.
TNF-α n.d.
Non-inflammatory monocytes (CD16-) CD11b n.d.
Proinflammatory monocytes (CD16+) CD11b n.d.
All Monocytes CD62L I: ↑ (N) o (O), ↓ (B)
C: o (N, O, B)
t0: B > O > N
Proinflammatory monocytes (CD16+) CD62L I: ↑ (N, O), ↓ (B)
C: o (N, O, B)
t0: B > O > N
EMP in whole blood EMP concentration I: o (N, O), ↓ (B)
C: o (N, O, B)
t0: B > O > N

a determined by high-sensitivity test kits for C-reactive protein. AGP: alpha-2 acid glycoprotein; AMP: alpha-2 macroglobulin; B: obese; BMI: body mass index; C: control; Cp: value after intervention; d: days; CRP: C-reactive protein; EC: epicatechin; EMP: endothelial microparticles (CD42a-/45-/144+); H: hypercholesterolemic; I: intervention; IP: intervention period; IL: interleukin; Ip: value after intervention; ICAM-1: intracellular adhesion molecule 1; IL-1β: interleukin-1β; IL-6: interleukin-6; n.d; no data available; NS: non-smoker; MCP-1: monocyte chemoattractant protein-1; N: normocholesterolemic; O: overweight; SAP: serum amyloid P; TNF-α: tumor necrosis factor-α; VCAM-1: vascular cell adhesion molecule-1; wk: week; ↑: increase; ↓: decrease; o: no changes, Δ: difference pre- vs. post-consumption value. 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 which data on inflammatory markers were available.