HTN: Cocoa and Chocolate (2007)
Citation:
Study Design:
Class:
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Quality Rating:
Research Purpose:
To investigate whether cocoa flavonoids can improve endothelial function and measures of oxidative stress in human subjects and to evaluate the effects of flavonoid-rich dark chocolate on plasma epicatechin concentrations, lipoprotein profiles and blood pressure.
Inclusion Criteria:
Healthy adults in general good health and English speaking.
Exclusion Criteria:
- Known cardiovascular disease
- Diabetes
- Hyperlipidemia
- Thyroid disorders
- Smoking
- ±20% IBW
- Pregnancy
- Vegetarianism
- Extreme physical activity.
Description of Study Protocol:
- Recruitment: Methods not described
- Design: Randomized, placebo-controlled trial
- Blinding used: Double-blind
- Intervention: Subjects randomly assigned to high-flavonoid or low-flavonoid dark chocolate bars for two weeks.
Statistical Analysis
- Statistical analysis of outcomes determined by applying a repeated-measures ANOVA at alpha=0.05, with one between-subject's factor (group) with two levels (experimental and control) and one within-subject's factor (time) with two levels (baseline and post-intervention)
- This design allowed for three tests: The main effect of group, the main effect of time and the interaction of group by time
- If the test of the interaction was significant, tests of simple main effects were done to examine the difference between baseline and post-intervention within each group
- Eta-squared represents the percentage of explained variance.
Data Collection Summary:
Timing of Measurements
- At each visit, brachial artery endothelial function and blood pressure were measured, followed by height and weight measurements
- Blood samples also taken.
Dependent Variables
- Blood samples analyzed for total cholesterol, triacylglycerol, LDL, HDL, LDL oxidation, epicatechin, total antioxidant capacity and 8-isoprostanes
- Endothelial function of the brachial artery measured using a 15-MHz linear array vascular transducer and ultrasound system
- Blood pressure determined using automated blood pressure device
- Plasma epicatechin assessed through HPLC with electrochemical detection.
Independent Variables
- High-flavonoid (213mg procyanidins, 46mg epicatechin) or low-flavonoid dark chocolate bars (46g, 1.6oz) for two weeks
- Subjects asked to maintain usual diet and usual physical activity, except to refrain from flavonoid-rich foods and beverages, alcoholic beverages, vitamin supplements and NSAIDs two days before each visit
- Validated food frequency questionnaire completed at baseline, with three-day food records completed each week for two-week study
- Compliance measured by return of empty sample wrappers and by plasma epicatechin concentrations.
Description of Actual Data Sample:
- Initial N: 22 healthy adults; 11 men, 11 women
- Attrition (final N): 21 subjects
- Low-flavonoid: N=10, five men, five women
- High-flavonoid: N=11, six men, five women
- One person did not meet inclusion criteria.
- Age: Aged 21 to 55 years
- Low-flavonoid: 32.5±2.9 years
- High-flavonoid: 31.8±3.2 years.
- Ethnicity
- Low-flavonoid: Six Caucasian, four Asian/Pacific Islander
- High-flavonoid: Five Caucasian, six Asian/Pacific Islander.
- Anthropometrics: Differences in baseline characteristics of groups were examined by independent sample T-tests, but if the assumption of equal variance was not met, the separate variances T-test (Welch test) was used. Differences in baseline demographics were not statistically significant with the exception of age.
- Location: California.
Summary of Results:
|
Low-Flavonoid - Baseline | Low-Flavonoid - Two Weeks | High-Flavonoid - Baseline |
High-Flavonoid - Two Weeks |
BMI |
21.9±0.5 | 21.8±0.5 | 23.2±0.5 | 23.1±0.5 |
Weight (lbs) |
140±9 |
140.7±9 |
150.2±6.9 |
150.8±6.7 |
Total cholesterol (mmol per L) | 4.9±0.2 | 5.1±0.2 | 4.2±0.2 | 4.3±0.2 |
LDL cholesterol (mmol per L) | 2.5±0.1 | 2.7±0.2 | 2.1±0.1 | 2.0±0.1 |
HDL cholesterol (mmol per L) | 1.7±0.2 | 1.7±0.2 | 1.5±0.09 | 1.6±0.1 |
Triacylglycerol (mmol per L) | 1.2±0.1 | 1.3±0.05 | 1.2±0.1 | 1.5±0.1 |
Systolic BP (mm Hg) | 112.8±2.8 | 110±2 | 121.0±5.4 | 120±4 |
Diastolic BP (mm Hg) | 66.1±1.7 | 66±2 | 68.1±2.5 | 69±2 |
Brachial Artery Resting Diameter (mm) |
3.79±0.1 |
3.77±0.2 |
3.76±0.2 |
3.81±0.2 |
Other Findings
- Excellent compliance in all participants was documented
- Dietary intake of the subjects at baseline were similar in the low- and high-flavonoid groups, with the exception of polyunsaturated fat
- High-flavonoid chocolate consumption improved endothelium-dependent flow-mediated dilation of the brachial artery (mean change, 1.3±0.7%), as compared to low-flavonoid chocolate consumption (mean change, -0.96±0.5%)(P=0.024).
- No significant differences were noted in the resistance to LDL oxidation, total antioxidant capacity, 8-isoprostanes, blood pressure, lipid parameters, body weight or BMI between the two groups
- Plasma epicatechin concentrations were markedly increased at two weeks in the high-flavonoid group (204.4±18.5nmol per L, P<0.001), but not in the low-flavonoid group (17.5±9nmol per L, P=0.99).
Author Conclusion:
- In summary, flavonoid-rich dark chocolate improves endothelium-dependent vasodilation. This effect is associated with increased plasma epicatechin concentrations in healthy adults, though it is possible that flavonoids are a marker for some other bioactive constituent of chocolate. This could be evaluated by the administration of purified flavonoids.
- It is also acknowledged that the long-term clinical significance of the changes in endothelial function detected in the study are not known
- Our findings suggest a possible cardioprotective effect by flavonoid-rich chocolate, independent of changes in measures of oxidative stress and lipid profiles
- Further larger, long-term clinical trials with food sources rich in flavonoids, including chocolate, are certainly warranted.
Funding Source:
University/Hospital: | University of California SF School of Nursing |
Reviewer Comments:
Compliance measured through food diaries, empty sample wrappers and plasma epicatechin concentrations.
Quality Criteria Checklist: Primary Research
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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? | Yes | |
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? | Yes | |
2.2. | Were criteria applied equally to all study groups? | Yes | |
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? | Yes | |
3. | Were study groups comparable? | Yes | |
3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | Yes | |
3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | Yes | |
3.3. | Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) | Yes | |
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? | Yes | |
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? | Yes | |
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? | Yes | |
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? | Yes | |
6.4. | Was the amount of exposure and, if relevant, subject/patient compliance measured? | Yes | |
6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | Yes | |
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? | Yes | |
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 | |