EAL

HTN: Cocoa and Chocolate (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To compare the effects of either dark or white chocolate bars (high- or low-polyphenol content), on the glucose and insulin responses to an oral glucose challenge and on blood pressure in healthy subjects.

Inclusion Criteria:

Young subjects without metabolic diseases and cardiovascular disease risk factors.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment: Recruited from medical staff
Design: Randomized controlled crossover trial
Blinding used: Blood pressure measured by same physician, unaware of study design, results and purpose
Intervention: Consumption of white or dark chocolate.

Statistical Analysis

Within each treatment group, changes in blood pressure and metabolic indexes from baseline values analyzed by paired Student's T-test
For multiple comparisons, data were analyzed with a two-factor repeated-measures ANOVA with time and treatment as the two factors
Post hoc comparisons were performed by Tukey's honestly significant difference test
Statistical analysis and power calculation were performed with SAS.

Data Collection Summary:

Timing of Measurements

After a seven-day cocoa-free run-in phase, subjects were assigned to receive dark or white chocolate for 15 days, followed by another seven-day cocoa-free washout phase and then 15 days of the other condition
Oral glucose tolerance tests and routine hematological checks performed at the end of each phase, blood pressure and heart rate checked daily.

Dependent Variables

Oral glucose tolerance tests to calculate the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI)
Blood pressure measured with standard mercury sphygmomanometer
Heart rate
Body weight
Routine hematological check: Serum electrolytes, total cholesterol, HDL-cholesterol, LDL-cholesterol and triacylglycerol concentrations.

Independent Variables

90g white (no polyphenols) or 100g dark chocolate (500g polyphenols) for 15 days in each phase, each providing 480kcals
Seven days of cocoa-free run-in and washout phases; subjects were asked to substitute foods of similar energy and macronutrient composition
Diet assessed by a diary of daily food intake
Tailored isocaloric diet equal in total energy, energy density, dietary fiber and macronutrient composition and providing approximately 1,400kcal per day (excluding chocolate kcals) provided to participants.

Description of Actual Data Sample:

Initial N: 15 subjects; seven men, eight women
Attrition (final N): 15 subjects
Age: Mean, 33.9±7.6 years
Ethnicity: Not mentioned
Other relevant demographics: Not mentioned
Location: Italy.

Summary of Results:

	Dark - Before	Dark - After	White - Before	White - After
BMI	22.6±3.0	22.6±3.0	22.6±3.0	22.6±3.0
Body weight (kg)	63.6±10.3	63.6±10.3	63.6±10.3	63.6±10.3
Total cholesterol (mmol/L)	4.6±0.6	4.7±0.4	4.7±0.4	4.7±0.4
LDL cholesterol (mmol/L)	2.8±0.5	2.8±0.4	2.8±0.4	2.8±0.4
HDL cholesterol (mmol/L)	1.5±0.3	1.6±0.3	1.6±0.3	1.6±0.3
Triacylglycerols (mmol/L)	0.7±0.3	0.7±0.4	0.7±0.4	0.8±0.3
Heart rate (beats/min)	67.5±6.3	67.6±4.5	66.8±5	66.8±5.1

Other Findings

The homeostasis model assessment of insulin resistance (HOMA-IR) was significantly lower after dark than after white chocolate ingestion (0.94±0.42, compared with 1.72±0.62; P<0.001) and the quantitative insulin sensitivity check index (QUICKI) was significantly higher after dark than white chocolate ingestion (0.398±0.039, compared with 0.356±0.023; P=0.001)
Insulin sensitivity index was found to be significantly higher after dark than after white chocolate (15.18±7.69 ,compared with 7.4±3.5; P=0.001).
For glucose and insulin concentrations, two-factor repeated-measures ANOVA showed a significant effect of both treatment (P<0.0001 for both) and time (P<0.0001 for both) as well as a significant treatment-by-time interaction (P=0.0039 for glucose, P=0.0191 for insulin)
Although within normal values, systolic blood pressure was lower after dark than after white chocolate ingestion (107.5±8.6, compared with 113.9±8.4mm Hg; P< 0.05).
There were no influences of sex on the effects of chocolate on HOMA-IR, QUICKI, ISI or blood pressure
No significant changes in the lipid profile were observed.

Author Conclusion:

In conclusion, the current study showed that polyphenol-rich dark chocolate, but not white chocolate (which contains cocoa butter), decreases blood pressure and improves insulin sensitivity in healthy persons
These findings indicate that dark chocolate may exert a protective effect on the vascular endothelium also by improving insulin sensitivity
Obviously, large scale trials are needed to confirm these protective actions of dark chocolate or other flavanol-containing foods in populations affected by insulin-resistant conditions, such as essential hypertension and obesity.

Funding Source:

University/Hospital:

Italian Ministero della Universitae della Ricerca Scientifica

Reviewer Comments:

Recruitment methods, inclusion criteria and exclusion criteria were not well-defined
Relatively small sample size
Compliance not described
Body weight did not change at all even with an additional approximately 500kcal per day
15 days is short term.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	Yes
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	Yes
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	Yes
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		???
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	???
	2.2.	Were criteria applied equally to all study groups?	???
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
3.	Were study groups comparable?		N/A
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		Yes
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		???
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	???
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	Yes
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	???
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	Yes
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	Yes
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	N/A
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes