- Cocoa (Theobroma cacao)
- Blood Pressure
12-31-2012 ||HC# 081224-463
Re: Nonlinear Meta-analysis of Cocoa Effects on Blood Pressure Finds It Provides a Dose-dependent Benefit
Ellinger S, Reusch A,
Stehle P, Helfrich HP. Epicatechin ingested via cocoa products reduces blood
pressure in humans: a nonlinear regression model with a Bayesian approach. Am J Clin Nutr. 2012;95(6):1365-1377.
meta-analyses have been performed on the effects of cocoa (Theobroma cacao) on blood pressure (BP), all showing that it
provides a benefit. It is thought that these effects are due to the dose of
epicatechin; if so, this may explain the differences in results in the studies
used in the meta-analyses. This paper reports on the novel use of an alternate
meta-analysis using a nonlinear regression model with a Bayesian approach and which
includes a Markov chain Monte Carlo method that takes full account of the
nonlinearity of the regression model. The authors hoped to thereby understand
whether the dose of epicatechin is related to the magnitude of its BP-lowering
effect and if this can explain between-study differences in effects.
Medline was searched
until July 2011 for randomized, controlled trials (RCTs), which were included
if they met the following criteria: (1) control substances were of low-flavanol
composition; (2) BP was measured after an overnight fast; (3) mean or median
systolic BP (SBP) or diastolic BP (DBP), standard deviations (SDs), standard
error of the mean (SEM), 95% credible intervals (CIs), or P-values for changes
were given; and (4) data on epicatechin intake were recorded.
Twenty-six RCTs were
identified, of which 13 met the inclusion criteria. An additional study was
obtained from an author; and 1 study had 3 arms, each of which was considered
separately. This yielded a total of 16 studies for consideration (16 on SBP and
15 on DBP).
The regression curve
showed that reductions in SBP and DBP were dependent on the dose of
epicatechin. The estimated asymptotic value K
of the treatment effect was -4.6 mmHg (95% CI: -5.4, -3.9 mmHg) for SBP and -2.1
mmHg (95% CI: -2.7, -1.6 mmHg) for DBP (Figure 3). The coefficient c reflecting the initial slope of the
curve was -2.5 mmHg/mg for SBP (95% CI: -8.4, -0.6 mmHg/mg). For DBP, the mean
value for c was -4.3 mmHg/mg (95% CI:
-9.6, -0.2 mmHg/mg).
From this curve, a
mean reduction for a dose of 25 mg of epicatechin for SBP could be estimated to
be -4.1 mmHg (95% CI: -4.6, -3.6 mmHg) and for DBP, a mean reduction of -2.0 mmHg
(95% CI: -2.4, -1.5 mmHg) could be estimated.
Because the 95% CIs
are narrower in the nonlinear regression model than in the regular
meta-analyses, the authors conclude that the dose of epicatechin is responsible
for the heterogeneity of the studies, and that their model estimates the
treatment effects more precisely than the linear regression model. They argue
that the likelihood of confounding effects was low and that the merging of data
from both ambulatory and 24-hour BP readings should not affect the results
since they are very similar in magnitude. Limitations include the inability to
understand the effects of low doses of epicatechin (because of lack of data for
such doses) and the fact that the data cannot be readily extrapolated to normotensive
subjects, since only 25% of the studies examined that population.
The authors conclude
that a dose of 25-30 g of high-flavanol cocoa should lower SBP by -4.1 mmHg and
DBP by -2.0 mmHg. The cocoa should be consumed in a form that will not lead to
unwanted weight gain.