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W02 Nutr150 - Document - cocoaAndBloodPressure
W02 Nutr150 - Document - cocoaAndBloodPressure
Background was −4.5 mm Hg (95% confidence interval (CI), −5.9 to −3.2, P < 0.001)
Cocoa products such as dark chocolate and cocoa beverages c onsumption of cocoa-containing food was inversely
may have blood pressure (BP)–lowering properties due to their a ssociated with BP.3 Mean systolic and diastolic BP were 3.7
high content of plant-derived flavanols.1 Initial observations of and 2.1 mm Hg lower in participants in the highest tertile
the possible antihypertensive effects of cocoa-rich food came of cocoa intake as compared to those in the lowest tertile.
from the Kuna Indians, a native population living on islands Furthermore, cocoa intake was inversely related to cardiovas-
off the Panama coast. Hypertension is very rare in the island cular and all-cause mortality.
Kuna Indians, and there is no age-dependent increase in BP. Sparked by these epidemiological observations, several ran-
These effects are likely environmental because they are lost domized clinical trials examining the effect of cocoa-rich prod-
upon migration to urban Panama City. One striking dietary ucts on BP have been undertaken. In 2007, a meta-analysis
feature of the Kuna Indians living offshore is the consumption of randomized studies examining the effect of cocoa- and
of large amounts of natural cocoa drinks rich in flavanols.2 In flavanol-rich dark chocolate consumption on BP reported
contrast, Kuna Indians living in Panama City consume cocoa beneficial effects as compared to chocolate containing no or
from grocery stores largely devoid of flavanols leading to the only negligible amounts of flavanols.4 However, only five small
hypothesis that intake of flavanol-rich cocoa might be causally trials were included in the analysis with a total of 96 partici-
linked to the low prevalence of hypertension in island-dwelling pants. Several randomized controlled trials have been pub-
Kuna Indians. lished since suggesting an updated meta-analysis with a more
Further epidemiological evidence comes from a cohort reliable assessment of the antihypertensive effects of flavanol-
of 470 men from the Dutch Zutphen Elderly Study. Habitual rich cocoa products.
c ocoa-containing beverages on arterial BP. Furthermore, we mean difference of the treatments. In one trial, the SD could be
hand-searched bibliographic citations from the retrieved calculated from confidence intervals (CIs).6 In the other three
papers and from review articles. No language restrictions were parallel-group trials, we estimated the SD based on the SD of
applied. BP at the end of treatment. For crossover trials, the treatment
MEDLINE and EMBASE were searched using the term effect was defined as the mean within-subject difference of the
“cacao” (major subject heading) OR the text words “cacao” treatments (change from baseline in BP) assuming no carry-
OR “cocoa” OR “chocolate.” The search was limited to the over or period effect. To properly analyze crossover trials, it is
criteria “clinical trials” and “human.” CENTRAL and the necessary that the mean difference of the treatments and the
ClinicalTrials.gov Web site were searched with “chocolate OR corresponding standard error (which can be calculated from
cocoa OR cacao” as free terms without further restrictions SD or CIs, and sample size) are available.7–9 In one trial, the
applied to the search. standard error could be calculated from the sample size and
Two investigators (S.D. and J.S.) independently screened the SD of the mean difference of the treatments.10 In another
the titles and abstracts resulting from the search strategies. trial, the standard error was estimated from a P value for the
Articles were rejected on initial screening if titles or abstracts mean difference of the treatments.11 If the standard error for
were clearly irrelevant. The full text of potentially relevant arti- the within-person differences could not be extracted, correla-
trials included and the lack of studies with large sample sizes • Study design did not meet
prespecified criteria (e.g., single-dose
preclude a meaningful interpretation. trial, control group not applicable,
nonrandomized trial), n = 16
• Blood pressure reporting insufficient
Statistical analysis. The change in systolic and diastolic BP to calculate effect size, n = 1
between the intervention and control groups was defined as • Publication/study did not examine
the primary outcome measure. For parallel-group trials, the blood pressure, n = 13
content). Data synthesis and statistical analyses were done The populations studied were either healthy normotensive
using the Cochrane Collaboration Review Manager (RevMan, adults or patients with prehypertension/stage 1 hypertension
version 5.0.18; The Cochrane Collaboration, Copenhagen, without a ntihypertensive medication. The majority of stud-
Denmark). The study was performed in compliance with the ies used office BP to assess treatment effects. Treatment dura-
Quality of Reporting of Meta-analyses guidelines.19 tion ranged from 2 to 18 weeks. Flavanol intake varied widely
across studies, e.g., between 5 and 174 mg for the flavanol sub-
Results compound epicatechin (Table 1).
The study selection process is shown in Figure 1. Among Results of the quality assessment are summarized in Figure 2.
the trials excluded from the analysis, two studies compar- Among the trials using a “dark vs. white chocolate” design (as
ing low-flavanol vs. high-flavanol beverages could not be opposed to cocoa beverages or tablets), adequate blinding of
considered20,21 because the amount of flavanols ingested in the participants was not possible due to the obvious differences
low-flavanol control arm was significantly higher than those in appearance and taste. However, investigators and end point
reported to possess significant BP-lowering capacity.6 Another assessment were blinded in most studies. Other minor sources
study reported mean pressures only and was therefore not of potential bias included the following: the majority of trials (i)
included in the analysis.22 In total, 10 randomized control- did not describe the methods of sequence generation in the ran-
−10 −5 0 5 10
Favors cocoa Favors control
−10 −5 0 5 10
Favors cocoa Favors control
Figure 3 | Effect of cocoa product intake on (a) systolic blood pressure and (b) diastolic blood pressure. BP, blood pressure; CI, confidence interval.
Study (ref. 10) (ref. 17) (ref. 12) (ref. 13) (ref. 15) (ref. 14) (ref. 6) 16) (ref. 18) (ref. 11)
Intervention Flavanol-rich Flavanol-rich Flavanol-rich Flavanol-rich Flavanol-rich Flavanol-rich Flavanol-rich Flavanol-rich Flavanol-rich Flavanol-rich
dark chocolate tablets vs. dark chocolate dark chocolate milk chocolate dark chocolate dark chocolate dark chocolate dark chocolate cocoa drink vs.
vs. flavanol-free flavanol-poor vs. flavanol- vs. flavanol-free vs. flavanol-poor vs. flavanol-free vs. flavanol-free vs. flavanol-free and flavanol-rich flavanol-poor
white chocolate tablets free white white chocolate chocolate white chocolate white chocolate white chocolate cocoa beverage cocoa drink
chocolate vs. matching
placebo
Flavanol intake Catechin 234 mg Cocoa, 46 mg 168 mg 168 mg 168 mg Catechin Catechin 754 mg 902 mg
in intervention 27 mg/d flavanols, and Epicatechin/d Flavanols/d Flavanols/d Flavanols/d 1.7 mg/d 36 mg/d Procyanidins/d Flavanols/d
group Epicatechin procyanidins 213 mg 22 mg 39 mg Catechin 22 mg Catechin Epicatechin Epicatechin (catechin and Catechin 62 mg/d
81 mg/d (catechin and Procyanidins/d Catechin and epicatechin 66 mg 5.1 mg/d 111 mg/d epicatechin Epicatechin
epicatechin 66 mg 126 mg Epicatechin values 174 mg/d
values not stated) Epicatechin Procyanidins not stated) Procyanidins
676 mg/d
Flavanol intake Negligible Negligible Negligible Negligible Negligible Negligible Negligible Negligible Negligible Negligible
in control group
Design Randomized, Randomized, Randomized, Randomized, Randomized, Randomized, Randomized, Randomized, Randomized, Randomized,
crossover, parallel-group, parallel-group, crossover, crossover, crossover, parallel-group, crossover, parallel-group, crossover,
14 days 28 days controlled, 15 days 14 days 15 days 18 weeks 15 days 6 weeks 2 weeks
2 weeks
Population Patients with Healthy Healthy Healthy Healthy Patients with Patients with Patients with Healthy, older Patients with
isolated systolic normotensive normotensive normotensive normotensive hypertension prehypertension hypertension adults hypertension
hypertension adults adults adults young male (grade 1) or hypertension (grade 1) and (grade 1)
(grade 1) adults (grade 1) impaired glucose
tolerance
Number of 13 32 22 15 28 20 44 19 101 29
participants (28 analyzed) (21 analyzed) (27 analyzed) (90 analyzed) (20 analyzed)
Missing 0 4 1 0 1 0 0 0 11 9
participants
101
Downloaded from http://ajh.oxfordjournals.org/ at Brigham Young University on August 6, 2013
original contributions Cocoa and Blood Pressure
Table 2 | Subgroup analyses by trial duration, baseline BP, and flavanol content
Mean difference in systolic BP Mean difference in diastolic BP
Subgroups (mm Hg, 95% CI) (mm Hg, 95% CI)
Short-term trials10–16 −5.2 (−6.9 to −3.5) −2.9 (−4.6 to −1.2)
Medium-term trials6,17,18 −3.0 (−3.5 to −2.5) −1.8 (−2.5 to −1.0)
Lower baseline BP12,13,15,17,18 −3.6 (−5.5 to −1.8) −3.6 (−5.5 to −1.8)
Higher baseline BP6,10,11,14,16 −5.3 (−7.9 to −2.6) −5.3 (−7.9 to −2.6)
Lower flavanol content6,12–15 −5.2 (−7.0 to −3.3) −5.2 (−7.0 to −3.3)
Higher flavanol content10,11,16–18 −4.0 (−5.6 to −2.3) −4.0 (−5.6 to −2.3)
BP, blood pressure.
excluding the studies (−3.9 mm Hg, 95% CI, −4.9 to −2.9, P < reduction in systolic BP of 2.9 mm Hg (95% CI, 3.9–2.0, P <
0.001). However, for diastolic BP, significant heterogeneity was 0.001) and diastolic BP of 1.9 mm Hg (95% CI, 2.7–1.1, P <
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