Effect of cocoa on blood pressure

Karin Ried; Peter Fakler; Nigel P Stocks

doi:10.1002/14651858.CD008893.pub3

Cochrane Database of Systematic Reviews

Efecto del cacao sobre la presión arterial

Información

DOI:

https://doi.org/10.1002/14651858.CD008893.pub3 Copiar DOI

Base de datos:

Cochrane Database of Systematic Reviews

Versión publicada:

25 abril 2017see what's new

Tipo:

Intervention

Etapa:

Review

Grupo Editorial Cochrane:

Grupo Cochrane de Hipertensión

Copyright:

Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Cifras del artículo

Altmetric:

Citado por:

Citado 0 veces por enlace Crossref Cited-by

Contraer

Autores

Karin Ried

Correspondencia a: National Institute of Integrative Medicine, Melbourne, Australia

[email protected]

Discipline of General Practice, The University of Adelaide, Adelaide, Australia
Peter Fakler

Discipline of General Practice, The University of Adelaide, Adelaide, Australia
Nigel P Stocks

Discipline of General Practice, The University of Adelaide, Adelaide, Australia

Contributions of authors

Search strategy, obtain copies of studies, study selection, extract data: KR, PF

Data entry into RevMan: KR

Analysis and interpretation: KR, PF

Draft of the review: KR with contributions from PF and NS

Sources of support

Internal sources

The University of Adelaide, Australia.
National Institute of Integrative Medicine, Australia.

First author is employed as Director of Research at NIIM

External sources

No sources of support supplied

Declarations of interest

KR has been an investigator on two randomised controlled trials included in this review (Ried 2009, Massee 2015). KR has no other conflict of interest to declare.

NS has been an investigator on one randomised controlled trial included in this review (Ried 2009). NS has no other conflict of interest to declare.

PF has no conflict of interest to declare.

Acknowledgements

We are thankful for the assistance by N Funabashi (Shiina 2009), D Grassi (Grassi 2008), and B van den Bogaard (Bogaard 2010), who provided unpublished data for inclusion in our meta‐analysis.

We would like to acknowledge the assistance and advice received from the Cochrane Hypertension Group.

Version history

Published

Title

Stage

Authors

Version

2017 Apr 25

Effect of cocoa on blood pressure

Review

Karin Ried, Peter Fakler, Nigel P Stocks

https://doi.org/10.1002/14651858.CD008893.pub3

2012 Aug 15

Effect of cocoa on blood pressure

Review

Karin Ried, Thomas R Sullivan, Peter Fakler, Oliver R Frank, Nigel P Stocks

https://doi.org/10.1002/14651858.CD008893.pub2

2010 Dec 08

Effect of chocolate on blood pressure

Protocol

Karin Ried, Thomas R Sullivan, Peter Fakler, Oliver R Frank, Nigel P Stocks

https://doi.org/10.1002/14651858.CD008893

Differences between protocol and review

We added to the exclusion criteria: Trials of very low quality, specifically high losses to follow up of more than 50%, were excluded from meta‐analysis.

For clarity, we provided more detail of the approach for data analysis.
We modified:

Primary outcome measure: 'Difference in systolic and diastolic blood pressure at final follow‐up between cocoa and control group, adjusted for baseline.' Previously, the protocol had read: 'Changes in systolic and diastolic blood pressure from baseline compared with control.'
Measurement of treatment effect: 'Mean difference in SBP/DBP in mmHg from baseline to final follow‐up, adjusted for baseline differences.' Previously, the protocol had read: 'Change of mean difference in SBP/DBP from baseline to follow‐up in mmHg.'
Dealing with missing data: '....We assumed a correlation of 0.68 between the final follow‐up SBP/DBP results for the two treatment arms in a cross‐over trial.' Previously, the protocol had read: 'We will assume a correlation of 0.68 for the standard deviation of the differences from baseline to follow‐up.'
We modified the imputation of standard deviations as follows:
1. standard deviation of blood pressure at end of treatment taken in a different position from that of the blood pressure data used
2. standard deviation of blood pressure at baseline
3. mean standard deviation of blood pressure at end of treatment from other trials using the same intervention.

Differences in versions of this review

The Ried 2012 version of this review incorporated a meta‐regression analysis which we have not conducted for this update, for practical reasons.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Adult; Humans;

PICO

Population

Intervention

Comparison

Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Figure 1

PRISMA Flow diagram

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 3

Forest plot of comparison: 1 Effect of cocoa on BP, outcome: 1.1 SBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 4

Forest plot of comparison: 1 Effect of cocoa on BP, outcome: 1.2 DBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 5

Forest plot of comparison: 2 Hypertensive or normotensive subjects, outcome: 2.1 SBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Figure 6

Forest plot of comparison: 2 Hypertensive or normotensive subjects, outcome: 2.2 DBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.1

Comparison 1 Effect of cocoa on BP, Outcome 1 SBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 1.2

Comparison 1 Effect of cocoa on BP, Outcome 2 DBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.1

Comparison 2 Hypertensive or normotensive participants, Outcome 1 SBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 2.2

Comparison 2 Hypertensive or normotensive participants, Outcome 2 DBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.1

Comparison 3 Flavanol‐free or low flavanol control, Outcome 1 SBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 3.2

Comparison 3 Flavanol‐free or low flavanol control, Outcome 2 DBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.1

Comparison 4 Double‐blinded or unblinded/single‐blinded, Outcome 1 SBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 4.2

Comparison 4 Double‐blinded or unblinded/single‐blinded, Outcome 2 DBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.1

Comparison 5 Participants ≥50 or <50 years old, Outcome 1 SBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 5.2

Comparison 5 Participants ≥50 or <50 years old, Outcome 2 DBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.1

Comparison 6 Study duration 2 ‐ 4 weeks or > 4 weeks, Outcome 1 SBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 6.2

Comparison 6 Study duration 2 ‐ 4 weeks or > 4 weeks, Outcome 2 DBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.1

Comparison 7 Sensitivity analysis: excl studies with industry employed authors, Outcome 1 SBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Analysis 7.2

Comparison 7 Sensitivity analysis: excl studies with industry employed authors, Outcome 2 DBP.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Summary of findings for the main comparison. Flavanol‐rich cocoa products for blood pressure

Flavanol‐rich cocoa products for blood pressure
Patient or population: adults with or without hypertension Settings: Primary healthcare practice, community Intervention: flavanol‐rich cocoa products versus control
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Flavanol‐rich cocoa products
Systolic blood pressure clinical digital sphygmomanometer Follow‐up: mean 9 weeks	The mean systolic blood pressure ranged across control groups from 107 to 154 mm Hg	The mean systolic blood pressure in the intervention groups was 1.76 mmHg lower (3.09 to 0.43 lower)		1804 (35 trials with 40 treatment comparisons)	⊕⊕⊕⊕ moderate^1,2,3,4
Diastolic blood pressure clinical digital sphygmomanometer Follow‐up: mean 9 weeks	The mean diastolic blood pressure ranged across control groups from 66 to 92 mm Hg	The mean diastolic blood pressure in the intervention groups was 1.76 mmHg lower (2.57 to 0.94 lower)		1772 (34 trials with 39 treatment comparisons)	⊕⊕⊕⊕ moderate^1,2,3,4
Withdrawals due to adverse effects	8 trials reported no withdrawals and no adverse effects. 9 trials reported adverse effects, including gastrointestinal complaints (cocoa groups: n = 8/760 (1%), control groups: n = 3/754 (0.4%)); dislike of the trial product (cocoa: n = 4/760; control: n = 1/754), headache (cocoa: n = 2/760; control: n = 1/754), and jitteriness (cocoa: n = 1/760, control: n = 0/754).			1514 (31 trials) reported on withdrawals and adverse effects	⊕⊕⊕⊕ moderate^1,2,3,4
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval;
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
^1.Downgraded to moderate quality due to high heterogeneity which cannot be explained by subgroup analyses. SBP/DBP: I² = 87%/78%. ^2.Good quality across 40 treatment comparisons. Only 5 trials (12.5%) had 2 items at high risk of bias, 19 trials (47.5%) had 1 item at high risk of bias, and 16 trials (40%) had no items at high risk of bias. 17 trials were unblinded or single‐blinded. 7 industry‐sponsored trials had authors employed by industry. Only 4 trials (10%) had more than 20% attrition. We explored influence of trials with items at high risk of bias by subgroup and sensitivity analysis. ^3.Statistically significant SBP: P = 0.009; DBP: P < 0.001. ^4.Sensitivity analysis excluding treatment comparisons (n = 7) with authors employed by trials sponsoring industry revealed reduced effect size and statistical significance.

Summary of findings for the main comparison. Flavanol‐rich cocoa products for blood pressure

Ir a la tabla de la revisión

Table 1. Adverse events & withdrawals

Study	Study design	Participants Cocoa/ Control	Withdrawn Cocoa/Control	Reasons for withdrawal including adverse effects Cocoa/Control
Taubert 2003	C	13/13	0/0	‐
Murphy 2003	P	13/15	3 in total	Family illness (2) Non‐compliance in final week (1)
Engler 2004	P	11/10	0/0	‐
Fraga 2005	C	14/14	1/0	No reason given
Grassi 2005a	C	15/15	0/0	‐
Grassi 2005b	C	20/20	0/0	‐
Taubert 2007	P	22/22	0/0	‐
Crews 2008	P	45/45	6/5	Gastrointestinal upset/headache/cold sweat (2/1) Bronchitis (1/0) Jitteriness/increased energy (1/0) Atrial arrhythmia/medication change (1/0) Dislike of study product (1/1) Family illness (0/1) Unspecified reason (0/1) No adherence to trial regimen (0/1)
Grassi 2008	C	19/19	0/0	‐
Muniyappa 2008	C	20/20	5/4	Lost to follow‐up (0/1) Discontinued intervention (4/2) due to Intolerance to treatment, family emergencies, personal problems excluded from analysis (1/1)
Davison 2008a	P	12/11	7 in total	Time restrictions, personal circumstances (14) Non‐compliance (exercise or diet) (2)
Davison 2008b	P	13/13	5 in total
Al‐Faris 2008	P	30/29	0/0	‐
Shiina 2009	P	20/19	0/0	‐
Ried 2009	P	11/10	2/2	Study product unpalatable (2/0) Gastrointestinal upset (0/1) Illness unrelated to study (0/1)
Monagas 2009	C	42/42	0/0	Constipation (resolved with fibre intake)
Bogaard 2010	C	41/41	3 in total	Nausea (1) Headache (1) Arrythmia unrelated (1) Laxative effect (12/2) – did not withdraw
Heiss 2010	C	16/16	3 in total	Did not come to first visit
Davison 2010	P	13/14	7 in total	Mild gastric symptoms (1) Non‐compliance with study protocol (1) Withdrew due to personal circumstances (5)
Njike 2011	C	38/38	7 in total	Non‐compliance with study protocol (1) Withdrew for personal reasons (6)
Almoosawi 2012a	C	21/21	1/1	Personal reasons unrelated to study
Desideri 2012	P	30/30	0/1	Gastric discomfort (1)
Khan 2012	C	42/42	1/0	Constipation
Mogollon 2013	P	22/20	1/1	Unrelated to study (1)/headache (1)
Neufingerl 2013	P	10/10	1/1	Nausea (1)/unrelated (1)
Sorond 2013	P	29/29	1/1	No details provided
Esser 2014	C	41/41	3 in total	Medical reasons (1), disliked chocolate (1), poor compliance (1)
Ibero‐Baraibar 2014	P	24/23	2/1	Personal reason (2), poor compliance (1)
Nickols‐Richardson 2014	P	30/30	0/0	None
Sarria 2014 (a)	C	24/24 20/20	?	No information given
Heiss 2015 (a)	P	11/11 10/10	0/0	None
Massee 2015	P	19/19	1/1	Personal reasons (1)
Rostami 2015	P	32/28	2/6	No information given
Koli 2015	C	22/22	0/0	No side effects reported
Mastroiacovo 2015	P	30/30	1/0	Personal reasons (1) No side effects reported (1 gastric discomfort in IF (intermediate flavanol) group not included in this meta‐analysis)
Rull 2015	C	21/21	11	No details provided
Sansone 2015	P	50/50	?	No information given
C:Cross‐over P: Parallel

Table 1. Adverse events & withdrawals

Ir a la tabla de la revisión

Comparison 1. Effect of cocoa on BP

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SBP Show forest plot	40	1804	Mean Difference (Random, 95% CI)	‐1.76 [‐3.09, ‐0.43]

2 DBP Show forest plot	39	1772	Mean Difference (Random, 95% CI)	‐1.76 [‐2.57, ‐0.94]

Comparison 1. Effect of cocoa on BP

Ir a la tabla de la revisión

Comparison 2. Hypertensive or normotensive participants

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SBP Show forest plot	40	1804	Mean Difference (Random, 95% CI)	‐1.76 [‐3.09, ‐0.43]

1.1 Hypertensive (> 140 mmHg)	9	401	Mean Difference (Random, 95% CI)	‐4.00 [‐6.71, ‐1.30]
1.2 Prehypertensive (> 130 mmHg)	8	340	Mean Difference (Random, 95% CI)	‐2.43 [‐5.02, 0.17]
1.3 Normotensive	23	1063	Mean Difference (Random, 95% CI)	‐0.65 [‐2.13, 0.84]
2 DBP Show forest plot	39	1772	Mean Difference (Random, 95% CI)	‐1.76 [‐2.57, ‐0.94]

2.1 (Pre)hypertensive (> 80 mmHg)	16	735	Mean Difference (Random, 95% CI)	‐1.98 [‐3.38, ‐0.57]
2.2 Normotensive (< 80 mmHg)	23	1037	Mean Difference (Random, 95% CI)	‐1.57 [‐2.54, ‐0.61]

Comparison 2. Hypertensive or normotensive participants

Ir a la tabla de la revisión

Comparison 3. Flavanol‐free or low flavanol control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SBP Show forest plot	40	1804	Mean Difference (Random, 95% CI)	‐1.76 [‐3.09, ‐0.43]

1.1 Flavanol‐free control	26	1116	Mean Difference (Random, 95% CI)	‐1.80 [‐3.46, ‐0.13]
1.2 Low flavanol control	14	688	Mean Difference (Random, 95% CI)	‐1.67 [‐4.03, 0.69]
2 DBP Show forest plot	39	1772	Mean Difference (Random, 95% CI)	‐1.76 [‐2.57, ‐0.94]

2.1 Flavanol‐free control	26	1116	Mean Difference (Random, 95% CI)	‐1.82 [‐2.95, ‐0.68]
2.2 Low flavanol control	13	656	Mean Difference (Random, 95% CI)	‐1.62 [‐2.56, ‐0.68]

Comparison 3. Flavanol‐free or low flavanol control

Ir a la tabla de la revisión

Comparison 4. Double‐blinded or unblinded/single‐blinded

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SBP Show forest plot	40	1804	Mean Difference (Random, 95% CI)	‐1.76 [‐3.09, ‐0.43]

1.1 Double‐blind	23	1059	Mean Difference (Random, 95% CI)	‐0.95 [‐2.77, 0.86]
1.2 Unblinded, single‐blinded	17	745	Mean Difference (Random, 95% CI)	‐2.71 [‐4.66, ‐0.76]
2 DBP Show forest plot	39	1772	Mean Difference (Random, 95% CI)	‐1.76 [‐2.57, ‐0.94]

2.1 Double‐blind	21	927	Mean Difference (Random, 95% CI)	‐1.16 [‐2.05, ‐0.27]
2.2 Unblinded, single‐blinded	18	845	Mean Difference (Random, 95% CI)	‐2.33 [‐3.62, ‐1.04]

Comparison 4. Double‐blinded or unblinded/single‐blinded

Ir a la tabla de la revisión

Comparison 5. Participants ≥50 or <50 years old

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SBP Show forest plot	38	1762	Mean Difference (Random, 95% CI)	‐1.36 [‐2.79, 0.06]

1.1 < 50 years	18	726	Mean Difference (Random, 95% CI)	‐1.79 [‐4.05, 0.48]
1.2 ≥ 50 years	20	1036	Mean Difference (Random, 95% CI)	‐0.98 [‐2.87, 0.90]
2 DBP Show forest plot	37	1688	Mean Difference (Random, 95% CI)	‐1.62 [‐2.49, ‐0.76]

2.1 < 50 years	18	726	Mean Difference (Random, 95% CI)	‐2.01 [‐3.45, ‐0.58]
2.2 ≥ 50 years	19	962	Mean Difference (Random, 95% CI)	‐1.28 [‐2.32, ‐0.24]

Comparison 5. Participants ≥50 or <50 years old

Ir a la tabla de la revisión

Comparison 6. Study duration 2 ‐ 4 weeks or > 4 weeks

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SBP Show forest plot	40	1804	Mean Difference (Random, 95% CI)	‐1.76 [‐3.09, ‐0.43]

1.1 2 ‐ 4 week duration	24	1043	Mean Difference (Random, 95% CI)	‐1.37 [‐3.23, 0.49]
1.2 > 4 week duration	16	761	Mean Difference (Random, 95% CI)	‐2.37 [‐4.30, ‐0.44]
2 DBP Show forest plot	39	1772	Mean Difference (Random, 95% CI)	‐1.76 [‐2.57, ‐0.94]

2.1 2 ‐ 4 week duration	23	1011	Mean Difference (Random, 95% CI)	‐1.55 [‐2.71, ‐0.39]
2.2 > 4 week duration	16	761	Mean Difference (Random, 95% CI)	‐2.04 [‐3.18, ‐0.91]

Comparison 6. Study duration 2 ‐ 4 weeks or > 4 weeks

Ir a la tabla de la revisión

Comparison 7. Sensitivity analysis: excl studies with industry employed authors

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 SBP Show forest plot	33	1482	Mean Difference (Random, 95% CI)	‐1.08 [‐2.60, 0.43]

2 DBP Show forest plot	33	1482	Mean Difference (Random, 95% CI)	‐1.37 [‐2.31, ‐0.43]

Comparison 7. Sensitivity analysis: excl studies with industry employed authors

Ir a la tabla de la revisión

The Cochrane Library

Scolaris Language Selector Scolaris Language Selector

Idioma de la Revisión Cochrane

Idioma de la web

Scolaris Content Language Banner Portlet Scolaris Content Language Banner Portlet

Scolaris Content Display Scolaris Content Display

Efecto del cacao sobre la presión arterial

Información