Table 3.

Effect of regular cocoa consumption on inflammation in patients with pre-/hypertension—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	Untreated grade I hypertension, NS Age: 44 ± 2 BMI: 25.4 ± 0.3 CRP: 0.4 ± 0.1	I: Flavanol-rich 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 chocolate free run-in and washout
								ICAM-1	I: o C: o
			C: White chocolate (Milka, Kraft Foods), 90 g/day, matched for energy, macro-, micronutrients	C: 0
Wang-Polagruto et al., 2006 [60]	32	Hypertension stage 1 or prehypertension, hypercholesterolemia, NS Age: 57 ± 1 BMI: 25.1 ± 0.6 CRP: n.d.	I: Flavanol-rich cocoa drink with 18.8 g cocoa powder (Mars), sucrose, 240 mL/day	n.d.	42	Double-blind, parallel group	Plasma	P-selectin	I: o C: o	No flavonoid-rich food 24 h before study, 2 weeks run-in with flavanol-poor cocoa drink, 3 × 3 days Food records, Compliance: empty packets
								E-selectin	I: o C: o
			C:_Flavanol-poor cocoa drink, 240 mL/day	n.d.				ICAM-1	I: o C: o
								VCAM-1	I: ↓ C: o ΔI > ΔC
Grassi et al., 2008 [61]	19	Untreated stage I hypertension, impaired glucose tolerance, 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
Muniyappa et al., 2008 [62]	20	Stage 1 hypertension, overweight/obesity, NS, antihypertensive medication (n = 6) discontinued Age: 51 ± 2 BMI: 33.2 ± 1.4 CRP: n.d.	I: Flavanol-rich cocoa drink with cocoa powder (CocoaPro, Mars), water, 300 mL/day	I: 174	14	Placebo-controlled, double-blind, crossover	Serum or plasma	E-selectin	I: o C: o	1 week Run-in and 1 week washout with low-flavanol diet, Compliance: cocoa powder or placebo packets
								ICAM-1	I: o C: o
								VCAM-1	I: o C: o
			C: Flavanol-poor placebo drink, with water, matched for energy, macronutrients, similar in color, taste and packaging, 300 mL/day	C: 2				MCP-1	I: o C: o
								IL-6	I: o C: o
								TNF-α	I: o C: o

^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; I: cocoa intervention; IL-6: interleukin-6; IP: intervention period; n.d.: no data available; MCP-1: monocyte chemoattractant protein-1; TNF-α: tumor necrosis factor-α; VCAM-1: vascular cell adhesion molecule-1; ↓: decrease; o: no changes; ∆ difference pre- vs. post-consumption values. Data on age (years), BMI (kg/m²), and CRP (mg/L) are means ± SEM. 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.