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 N27 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:
Mars, Inc.
Food Company:
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
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