Background
Methods
Search strategy
Selection of trials
Data extraction and quality assessment
Trial; Location | Study design; treatment/control groups | Dosage; duration | Active ingredients per daily dosage | Mean age; mean BMI | N treatment/control | Mean SBP (SD) in mmHg at start/end of treatment versus control | Mean DBP (SD) in mmHg at start/end of treatment versus control |
---|---|---|---|---|---|---|---|
Taubert et al. [10]; Germany | Crossovera,b
| 100 g/d; | 500 mg polyphenols | 59.5 yr; | 13/13 | Cocoa: 153.4 (4.4)/148.6 (2.4); | Cocoa: 84.5 (4.6)/82.9 (4.6); |
Dark/white chocolate | 14 d | 24.1 | Control: 153.6 (4.4)/154.0 (3.6) | Control: 84.2 (4.2)/84.5 (4.3) | |||
Murphy et al. [15]; Australia | Parallel; | 6 tablets/d | 234 mg flavanols; | 43.5 yr; | 13/15 | Cocoa: 118 (13)/120 (12); | Cocoa: 78 (12)/77 (10); |
High/low flavanol cocoa tablets | 28 d | Control: 6.4 mg | 26.0 | Control: 116 (9)/119 (8) | Control: 76 (8)/76 (7) | ||
Engler [11]; USA | Parallel; | 46 g/d; | 213 mg procyanidins | 32.1 yr; | 11/10 | Cocoa: 121 (17.9)/120 (13.3) | Cocoa: 68.1 (8.3)/69 (6.6) |
High/low flavanoid chocolate | 14 d | 22.6 | Control: 112.8 (8.9)/110 (6.3) | Control: 66.1 (5.4)/66 (6.3) | |||
Fraga et al. [12]; USA | Crossovera; | 105 g/d; | 168 mg flavanols | 18.0 yr; | 27/28 | Cocoa: 123 (11.2)/117 (7.5) | Cocoa: 72 (7.5)/67 (7.5) |
Dark/white chocolate | 14 d | 24.1 | Control: 123 (11.2)/121 (7.5) | Control: 71 (7.5)/70 (7.5) | |||
Grassi (normotensive arm) [13]; Italy | Crossovera,b; | 100 g/d; | 500 mg polyphenols | 33.9 yr; | 15/15 | Cocoa: 112.9 (8.5)/105.9 (6.6) | Cocoa: 74.0 (5.7)/69.8 (4.5) |
Dark/white chocolate | 15 d | 22.6 | Control: 113.2 (7.9)/112.7 (7.6) | Control: 73.8 (5.5)/73.5 (5.3) | |||
Grassi et al. (hypertensive arm [13]; Italy | Crossovera,b; | 100 g/d; | 500 mg polyphenols | 43.7 yr; | 20/20 | Cocoa: 141.3 (4.8)/129.3 (5.7); | Cocoa: 92.4 (3.8)/84.6 (5.6); |
Dark/white chocolate | 15 d | 25.4 | Control: 141.1 (5.4)/140.4 (4.6) | Control: 91.8 (4.7)/91.2 (4.7) | |||
Taubert et al. [16]; Germany | Parallela; | 6.3 g/d; | 30 mg polyphenols | 63.6 yr; | 22/22 | Cocoa: 147.7 (7.1)/144.8 (ng); | Cocoa: 86.4 (4.1)/84.5 (ng); |
Dark/white chocolate | 126 d (18 wk) | 24.0 | Control: 147.5 (8.0)/147.6 (ng) | Control: 86.7 (3.8)/86.7 (n.g.) | |||
Crews et al. [17]; USA | Parallela; | 37 g/d choc + 11 g/d drink; | 754 mg proanthocyanins; | 68.8 yr; | 45/45 | Cocoa: 126.8 (14.3)/123.3 (12.3); | Cocoa: 74.2 (8.2)/73.7 (7.5); |
Dark chocolate + cocoa drink/low flavanol chocolate + drink | 42 d (6 wk) | Control: 41.1 mg | 25.3 | Control: 128.6 (14.3)/125.5 (12.7) | Control: 75.0 (8.0)/74.4 (7.7) | ||
Grassi et al. [18]; Italy | Crossovera,b; | 100 g/d; | 1008 mg phenols | 44.8 yr; | 19/19 | Cocoa: 141.1 (3.4)/137.3 (4.0); | Cocoa: 91.2 (4.2)/87.3 (4.6); |
Dark/white chocolate | 15 d | 26.5 | Control: 140.9 (3.4)/140.8 (3.5) | Control: 91.1 (3.7)/90.9 (3.5) | |||
Muniyappa et al. [20]; USA | Crossovera,b; | 31 g/d cocoa; | 900 mg polyphenols; | 51.0 yr; | 20/20 | Cocoa: 141 (13)/139 (9); | Cocoa: 91 (13) 88 (9); |
High flavanol cocoa/low flavanol drink | 14 d | Control: 28 mg | 33.2 | Control: 141 (13)/140 (9) | Control: 91 (13)/87 (9) | ||
Davison et al. (nonexercise arm) [21]; Australia | Parallel; | 300 ml drink mix/d; | 902 mg flavanols; | 44.9 yr; | 12/11 | Cocoa: 124 (10.4)/122.1 (ng); | Cocoa: 76 (6.2)/74.2 (ng); |
High flavanol cocoa/low flavanol drink | 84 d (12 wk); | Control: 36 mg | 33.6 | Control: 124 (5.97)/128.2 (ng) | Control: 77 (5.0)/79.8 (ng) | ||
Davison (exercise arm)[21]; Australia | Parallel; | 300 ml drink mix/d; | 902 mg flavanols; | 45.4 yr; | 13/13 | Cocoa: 126 (10.4)/127.1 (ng); | Cocoa: 78 (8.7)/77.5 (ng); |
High flavanol cocoa/low flavanol drink | 84 d (12 wk) | Control: 36 mg | 33.4 | Control: 121 (13.0)/120.5 (ng) | Control: 74 (5.8)/73.8 (ng) | ||
Shiina et al. [22]; Japan | Parallela; | 45 g/d | 550 mg polyphenols | 29.8 yr; | 20/19 | Cocoa: 116.4 (12.7)/121.0 (12.7); | Cocoa: 64.7 (11.7)/71.3 (10.8); |
Dark/white chocolate | 14 d | 22.6 | Control: 121.6 (14.9)/125.6 (11.4) | Control: 72.2 (13.8)/77.4 (11.6) | |||
Ried et al. (phase 1) [23]; Australia | Parallel; | 50 g/d; | 750 mg polyphenols | 53.1 yr; | 11/10 | Cocoa: 135.0 (12.5)/133.1 (11.7)c; | Cocoa: 83.6 (10.6)/84.5 (11.6); |
Dark chocolate/placebo pill | 56 d (8 wk) | 26.6 | Control: 135.7 (12.4)/130.8 (18.3)c
| Control: 77.8 (8.6)/77.3 (10.0) | |||
Monagas et al. [24]; Spain | Crossover; | 40g/d + 250 skim milk; control: 500 ml skim milk | 495 mg polyphenols | 69.7 yr; | 42/42 | Cocoa: 138 (26)/138 (16); | Cocoa: 84 (13)/82 (13); |
Cocoa powder in milk/milk only | 28 d | 27.6 | Control: 138 (26)/135 (24) | Control: 84 (13)/81 (13) |
Trial; location | Study design; treatment/control groups | Dosage; duration | Active ingredients per daily dosage | Mean age; mean BMI | N treatment/control | Reason for exclusion |
---|---|---|---|---|---|---|
Grassi et al. [19]; Italy | Crossovera,c
| 100 g/d | 500 mg polyphenols | 33.9 yr; | 15/15 | Same population and protocol as studied in Grassi et al. [11] |
Dark/white chocolate | 15 d | 22.6 | ||||
Crossoverb; | 22g/d | Not reported | 44.7 yr; | 44/44 | No cocoa-free control group | |
Chocolate + plant sterols/chocolate + no plant sterols | 28 d (4 wk) | 27.8 | ||||
Balzer et al. [36]; USA | Parallel; | 3 drink mix/d | 963 mg flavanols; | 63.8 yr; | 21/20 | No mean SBP/DBP (SD) reported |
High/low-flavanol drink | 30 d (4 wk) | control: 75 mg flavanols | 32.1 | |||
Faridi et al. [37]; USA | Crossovera,c; | 74 g bar with 22 g cocoa/d; | 821 mg flavanols | 53 yr; | 44/44 | Duration < 2 wk |
Dark chocolate/placebo bar | Single dose, 1 d | 30 | ||||
Ried et al. (phase 2) [23]; Australia | Crossoverd; | 50 g/d; control: 1 capsule/d; | 750 mg polyphenols; | 53.1 yr; | 26/26 | Crossover of two active treatment groups, no true control group |
Dark chocolate/Tomato extract capsules | 56 days (8 wks) | control: tomato extract (15 mg lycopene) | 26.6 | |||
Almoosawi et al. [38]; UK | Crossovera,c; | 20 g/d; | 1000 mg polyphenols; | 31 yr; | 14/14 | Two dosages, no true control group |
Dark chocolate dosage 1/dosage 2 | 14 days | control: 500 mg | 27.7 |
Trial ID | Total score | Blinding | Outcome measure: blood pressure | Loss to follow-up | Funding source | Compliance; other chocolate diary |
---|---|---|---|---|---|---|
Scores given | 1: choc + control blinded | 1: Primary | 1: < 20% | 1: Sponsor not involved in data collection, analysis | 1: Compl assessed; no sign diff between groups | |
0.5: control blinded | 0.5: Secondary | 0: ≥ 20% | 0: Sponsor involved | 1: Compl assessed, sign diff included in analysis | ||
0: No blinding | 0: Compl not assessed | |||||
Taubert et al. [10] | 4 | 0: dark/white | 1 | 1: none | 1 | 1 |
Murphy et al. [15] | 3.5 | 1: cocoa tablets | 0.5 | 1: 9.5% (4 of 42) | 0: supported by Mars | 1: tablet count, 7 day weight food records x2 |
Engler et al. [11] | 5 | 1: flav bar matched | 1 | 1: none | 1 | 1 |
Fraga et al. [12] | 2.5 | 0: dark/white | 1 | 1: 3.6% (1 of 28) | 0: 3 authors from Mars | 0.5: reported what consumed, no diary |
Grassi et al. [13] | 3.5 | 0: dark/white | 1 | 1: none | 0.5: unclear | 1: daily diary |
Grassi et al. [13] | 3.5 | 0: dark/white | 1 | 1: none | 0.5: unclear | 1: daily diary |
Taubert et al. [16] | 4 | 0: dark/white | 1 | 1: none | 1 | 1: food diary |
Crews et al. [17] | 2.5 | 0.5: flav drink; > 50% assumed correct group they were in | 1 | 0.5: 11% (11 of 101) | 0.5: independent industry research grant, supplier | 0: not reported |
Grassi et al. [18] | 3.5 | 0: dark/white | 1 | 1: none | 0.5: unclear | 1: diary |
Muniyappa et al. [20] | 3 | 1: flav drink; blinding assessed ok | 1 | 0: 31% (9 of 29) | 1 | 0: not reported |
Davison et al. [21] | 3 | 1: flav drink | 1 | 0: 21% (14 of 65) | 0: Mars Financial support | 1: diet + background exercise |
Davison et al. [21] | 3 | 1: flav drink | 1 | 0: 21% (14 of 65) | 0: Mars Financial support | 1: diet + background exercise |
Shiina et al. [22] | 2 | 0: dark/white | 0 | 1: none | 1 | 0 |
Ried et al. [23] | 4.5 | 0.5: control blinded | 1 | 1: 8% (3 of 39) | 1 | 1: diary |
Monagas et al. [24] | 3.5 | 0: cocoa powder in milk/milk | 0.5 | 1: none | 1 | 1: diet monitoring (3-day food questionnaires x3) |
Analysis
Results
Summary of included studies
Meta-analysis
Meta-regression and sensitivity analysis
Subgroups | SBP | DBP | |||||
---|---|---|---|---|---|---|---|
Mean difference in mmHg (95% CI) |
P
|
I
2
| Mean difference in mmHg (95% CI) |
P
|
I
2
| ||
Study design | -4.91 (-7.94, -1.88) | 0.002 | 80% | -3.24 (-5.36, -1.12) | 0.003 | 67% | |
-2.01 (-3.42, -0.60) | 0.005 | 9% | -1.20 (-2.29, -0.11) | 0.03 | 12% | ||
-0.43 (-2.80, 1.94) | 0.72 | 0% | -0.25 (-1.83, 1.33) | 0.75 | 0% | ||
Type of control | -4.21 (-6.65, -1.77) | 0.0007 | 82% | -2.81 (-4.52, -1.10) | 0.001 | 70% | |
0.74 (-2.92, 4.40) | 0.69 | 53% | -0.38 (-2.00, 1.24) | 0.65 | 0% |