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- Cocoa (Theobroma cacao, Malvaceae)
- Cardiovascular Health
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Date:
12-15-2015 | HC# 111531-534
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Re: Cocoa Flavanol Consumption Improves Vascular Function in Healthy Subjects
Sansone
R, Rodriguez-Mateos A, Heuel J, et al.; for the Flaviola Consortium, European
Union 7th Framework Program. Cocoa flavanol intake improves endothelial
function and Framingham Risk Score in healthy men and women: a randomised,
controlled, double-masked trial: the Flaviola Health Study. Br J Nutr. 2015;114(8):1246-1255.
Flavanol
intake has been associated with improvement in arterial function in persons
with cardiovascular disease (CVD) and in those at risk for developing the
disease. Published studies have specifically linked flavanol consumption with recovery
of endothelial function, decreased blood pressure (BP), and improved lipids and
insulin resistance, most often in individuals at increased cardiovascular risk.
Whether the intake of cocoa (Theobroma cacao, Malvaceae) flavanols (CFs) can
maintain or improve cardiovascular health in healthy individuals has not been
evaluated. These authors conducted the Flaviola Health Study, a randomized,
controlled, double-masked trial, to investigate the effects of dietary CF
intake on markers of cardiovascular risk in healthy, middle-aged individuals
without any history, signs, or symptoms of CVD.
The
primary endpoint of endothelial function was measured by flow-mediated dilation
(FMD); secondary endpoint assessments included plasma lipids, BP, and markers
of arterial stiffness – pulse wave velocity (PWV) and augmentation index (AIX).
Using the Framingham Risk Prediction model, the authors calculated the 10-year
risk for each subject to develop coronary heart disease (CHD) or CVD, to experience a myocardial infarction or stroke, or
to die from CHD or CVD.
The
study was conducted at the Division of Cardiology, Pulmonology and Vascular
Medicine at Duesseldorf University in Duesseldorf, Germany, from February 2013
to August 2014. Subjects were recruited through word of mouth and postings at
the university and its outpatient clinic. The authors selected 105 middle-aged
(35-60 years) healthy Caucasian men and women without any history, signs, or
symptoms of CVD and with a body mass index of 23-27 kg/m2.
An
open-label pilot study in 5 male subjects preceded the trial. Those 5 subjects
received 450 mg of CFs twice daily for 1 month to verify the efficacy of the
flavanol drink in increasing FMD and to assess the effect size and timing of
the main study. FMD was measured in fasting subjects and at 1 and 2 hours after
consumption of the first drink on days 1, 7, 14, 21, and 28. The authors
discovered that CF intake led to a time-dependent increase in endothelial
function that plateaued after 2 weeks.
The
remaining 100 subjects, assigned to 1 of 2 parallel groups of 50 subjects each,
then participated in the 1-month, double-masked, randomized, controlled trial.
Two interventions were provided as a low-energy, fruit-flavored beverage mix (provided
by Mars, Inc.; McLean, Virginia), which was combined with 50 mL water and
consumed twice daily, at breakfast and with the evening meal. A high-flavanol
Cocoapro®-processed cocoa extract (Mars, Inc.) was added to provide
450 mg total CFs per serving in the flavanol group drink, with (–)-epicatechin
being the predominant monomeric flavanol. The Cocoapro process used to extract CFs
from the beans helps to preserve and protect the flavanols usually destroyed
during normal cocoa processing, according to Mars, Inc. The control beverage
contained no cocoa extract; however, because of the natural presence of
theobromine and caffeine in the cocoa extract, both were added to the control
beverage to match the composition of the flavanol drink.
All
measurements were taken in fasting subjects at baseline and at 2 hours after
the first drink on day 1 and again at those time points after consuming the
last drink at the end of the trial. Subjects were asked to avoid excess amounts
of flavanol-rich foods for 24 hours before study visits. No significant
baseline differences were seen in demographic parameters between the 2 groups. Flavanol
intake was low among all subjects, and the subjects exhibited a low risk for
developing or dying from CVD.
The
results of this trial demonstrated that flavanol consumption increased FMD
significantly over the control drink by a difference of 1.2% after 1 month. In
a published meta-analysis, a 1% improvement in FMD was associated
with an 8% decrease in overall CVD risk over 3 to 6 years.1
Flavanol
consumption for 1 month also significantly decreased office systolic BP
(difference of 4.4 mm Hg) and diastolic BP (difference of 3.9 mm Hg) compared
with consumption of the control drink. Significant lowering was seen in central
systolic BP (by 4.3 mm Hg) and diastolic BP (by 4.7 mm Hg) responses in the
flavanol group compared with the control group. After 1 month, PWV and AIX decreased
by 0.4 m/s and by 5.3%, respectively, more in the flavanol group than in the
control group. The authors point out that no other study of this scale has
examined whether flavanols can decrease BP in healthy subjects with normal BP.
These findings suggest that improved elasticity of arteries or arterial
unloading, as evidenced by the decreases in PWV and AIX, may be related to systolic
BP lowering. Future studies of longer duration should verify the biological
relevance of these findings and examine the mechanisms involved, say the
authors.
Significant
differences in decreases were seen in total cholesterol (0.20 mmol/L or 7.7
mg/dL) and low-density lipoprotein cholesterol (0.17 mmol/L or 6.6 mg/dL), with
greater decreases observed in the flavanol group. High-density lipoprotein
cholesterol increased by 0.10 mmol/L, or 3.9 mg/dL, more at 1 month after
flavanol intake compared with control.
At
baseline on day 1, fasting levels of total plasma flavanols were not detectable
in 98 subjects. After 2 hours, acute ingestion of CFs led to a significant
increase in plasma flavanols and metabolites, with values similar to those
observed after acute ingestion on day 1 of the study. After 1 month of CF
consumption and following an overnight fast, the levels were again below the
limit of detection in all but 7 subjects.
The
authors reported significant correlations between the increase in FMD and the increase
in plasma flavanols 2 hours after consumption (P<0.0001) and between chronic
FMD improvements at 1 month and the acute increase in plasma flavanols at 2
hours after consumption as an index of individual flavanol bioavailability
(P<0.0001).
Compared
with the control group, flavanol consumption led to significant decreases in
CVD risks as measured by Framingham Risk Scores. The decreases in the flavanol
group compared with baseline were as follows: to be diagnosed with CHD (21%) or
CVD (22%); to experience myocardial infarction (31%); and to die from CHD (37%)
or CVD (30%).
In
this study, CF consumption improved the parameters of vascular function in
healthy, middle-aged subjects. "Our findings support the notion that CF
intake has the potential to support the maintenance of cardiovascular
health," write the authors.
This
study was partially funded by Mars, Inc. One of the authors (H. Schroeter)
reported a conflict of interest, as he is employed by Mars, Inc., a company
engaged in flavanol research and flavanol-related commercial activities and a
member of the Flaviola Research Consortium.
―Shari Henson
Reference
1Ras RT, Streppel MT,
Draijer R, Zock PL. Flow-mediated dilation and cardiovascular risk prediction:
a systematic review with meta-analysis. Int
J Cardiol. 2013;168(1):344-351.
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