HTN: Cocoa and Chocolate (2007)
Citation:
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To examine the effects of flavanol-rich and flavanol-poor cocoa on the blood pressure response to inhibition of nitric oxide synthase and on vasodilation in the finger of healthy humans.
Inclusion Criteria:
Healthy individuals.
Exclusion Criteria:
- None specifically mentioned
- Subjects were not taking medications and had no cardiovascular, endocrine or renal disease.
Description of Study Protocol:
- Recruitment: Methods not specified
- Design: Non-randomized clinical trial
- Blinding used: Participants were blinded to intervention, the endpoint was objective and blinded
- Intervention: Five days of flavanol-rich cocoa. Flavanol-poor cocoa tested in seven subjects.
Statistical Analysis
- Group means are presented, with the SEM as the index of dispersion
- Differences between means of responses measured before and after intervention (administration of either cocoa or L-NAME) were tested for significance using paired T-tests.
Data Collection Summary:
Timing of Measurements
- Measurements made before and after five days of cocoa consumption
- Specific nitric oxide synthase inhibitor was infused intravenously on Day One, before cocoa and on Day Five, after cocoa.
Dependent Variables
- Pulse wave amplitude measured on the finger with a volume-sensitive validated calibrated plethysmograph
- Blood pressure measured with automated indirect recording sphygmomanometer.
Independent Variables
- Five days of consumption of flavanol-rich cocoa [920ml cocoa daily in four doses of 230ml each, 821mg of flavanols per day, quantitated as (-)-epicatechin, (+)-catechin and related procyanidin oligomers]
- Nitric oxide synthase inhibitor [NG-nitro-L-arginine methyl ester (L-NAME)] infused intravenously in 18 participants
- Seven participants underwent additional testing with flavanol-poor cocoa.
Description of Actual Data Sample:
- Initial N: 27 healthy people; 11 men, 16 women
- Attrition (final N): 27 subjects
- Age: Mean age, 44±3.4 years, range 18 to 72 years
- Ethnicity: 26 were white, one was black
- Other relevant demographics: Four were smokers, but none smoked on the study days
- Location: Boston.
Summary of Results:
Peripheral Arterial Tomography (PAT) Responses to Cocoa and L-NAME
|
Basal Volume (ml) | Response to Ischemia (ml) |
Day One - Baseline |
7.3±0.7 |
10.1±1.1 |
Day One - 60 minutes after L-NAME |
7.0±1.1 |
11.4±1.2 |
Day Five - Baseline |
9.4±1.0, P<0.01 |
11.9±1.2 |
Day Five - 90 minutes after cocoa | 12.5±1.1, P<0.01 | 14.8±1.6, P<0.03 |
Day Five - 60 minutes after L-NAME | 8.0±0.7, P<0.004 | 13.1±1.0 |
Other Findings
- Four days of flavanol-rich cocoa induced consistent and striking peripheral vasodilation (P=0.009)
- On Day Five, pulse wave amplitude exhibited a large additional acute response to cocoa (P=0.01)
- L-NAME completely reversed this vasodilation (P=0.004)
- In addition, intake of flavanol-rich cocoa augmented the vasodilator response to ischemia. Flavanol-poor cocoa induced much smaller responses (P=0.005) and none was induced in the time-control study.
- Flavanol-rich cocoa also amplified the systemic pressor effects of L-NAME (P=0.005)
- Blood pressure responses to L-NAME were assessed in 18 individuals. Cocoa by itself had no effect upon blood pressure; basal blood pressure remained unchanged after four days of cocoa and also after acute dosing.
Author Conclusion:
In healthy humans, flavanol-rich cocoa induced vasodilation via activation of the nitric oxide system, providing a plausible mechanism for the protection that flavanol-rich foods induce against coronary events.
Funding Source:
Government: | NIH | ||
Industry: |
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Reviewer Comments:
- Flavanol-poor cocoa testing only completed in seven subjects
- Recruitment methods and inclusion and exclusion criteria not well defined
- Compliance not assessed
- Only five days.
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? | ??? | |
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? | 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? | ??? | |
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? | ??? | |
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)? | N/A | |
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 | |