DF: Cardiovascular Disease (2008)
Citation:
Jacobs DR Jr., Pereira MA, Stumpf K, Pins JJ, Adlercreutz H. Whole grain food intake elevates serum enterolactone. Br J Nutr. 2002 Aug; 88 (2): 111-116. PMID: 12144714.
PubMed ID: 12144714Study Design:
Crossover feeding study
Class:
A - Click here for explanation of classification scheme.
Quality Rating:

Research Purpose:
The purpose was to identify the role of whole grain foods high in phytochemicals, such as phytoestrogens on modifying serum enterolactone levels in hyperinsulinemic men and women.
Inclusion Criteria:
- Males and females, aged 26 to 54
- BMI from 27 to 36
- Fasting insulin, 96pmol to 288 pmol per L
- Non-smokers
- Non-diabetic.
Exclusion Criteria:
Individuals with current antibiotic use.
Description of Study Protocol:
- Recruitment: Six men and six women, recruited from University of Minnesota and the surrounding community
- Design: Randomized, non-blinded, crossover controlled feeding trial.
Intervention (if Applicable)
- Subjects were assigned to two six-week controlled feeding periods, separated by a wash-out period of six to nine weeks
- During the feeding periods, participants were fed all meals by the GCRC
- The food quantity provided was calculated for weight maintenance, based on the Harris-Benedict equation
- Compliance was assessed through daily subject surveys.
The meal composition is shown in the table below:
Diet | Carbohydrate (%) | Fiber (grams per 2000 Kcal) | Protein (%) | Fat (%) |
Whole Grain | 54.2% | 28g | 17.1% | 31.7% |
Refined | 54.6% | 17g | 15.7% | 30.7% |
The following data were collected at baseline and at Weeks Two, Four and Six of the two diet periods:
- Height
- Weight
- Blood pressure
- Serum enterolactone.
Statistical Analysis
- Parametric (effect of diet on enterolactone)
- Repeated-measures regression (treatment, time, feeding period, gender).
- Non-parametric analysis (effect of diet on enterolactone) Sign test.
Data Collection Summary:
- Timing of measurements: Data collected at Weeks Two, Four and Six of the two diet periods
- Dependent variables: Serum enterolactone
- Independent variables: Whole grain intake
- Compliance to the diets was assessed by daily reports from the participants.
Description of Actual Data Sample:
- Initial N: Six males, six females
- Attrition (final N): 11 (five males, six females)
- Age: 26 to 54 years
- Ethnicity: Not described
- Other relevant demographics: No statistical differences in quantity of energy consumed on diets
- Location: General Clinical Research Center, University of Minnesota.
Summary of Results:
Findings
- Baseline serum enterolactone varied between subjects (14.3nmol per L) and within subjects (SD 9.3nmol per L)
- Non-significant (P=0.17) higher baseline enterolactone in females vs. males
- No significant difference in baseline serum enterolactone between treatments
- Significantly higher enterolactone, during consumption of whole grain diet (non-parametric, P=0.028; parametric, P=0.0008)
- This difference was evident, following two weeks of whole grain intake and continued over six weeks
- Difference in enterolactone between diet groups similar in men (5.6nmol per L, P=0.04) and women (6.7nmol per L, P=0.009).
- In non-parametric and parametric analysis, serum enterolctone was higher while on the whole grain diet. A difference in serum enterolactone between the two diets was noted after two weeks.
Author Conclusion:
Serum enterolactone is increased by a whole grain diet.
Funding Source:
Government: | NCRR, NHLBI |
Reviewer Comments:
- Small sample size
- Did not include intent-to-treat analysis
- No power calculation presented
- No data collected or presented on serum glucose and insulin levels
- No description of randomization scheme.
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 | |
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 | |
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 | |
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 | |
4. | Is the intervention or procedure feasible? (NA for some epidemiological studies) | Yes | |
Validity Questions | |||
1. | Was the research question clearly stated? | Yes | |
1. | Was the research question clearly stated? | Yes | |
1.1. | Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? | Yes | |
1.1. | 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 | |
1.2. | Was (were) the outcome(s) [dependent variable(s)] clearly indicated? | Yes | |
1.3. | Were the target population and setting specified? | Yes | |
1.3. | Were the target population and setting specified? | Yes | |
2. | Was the selection of study subjects/patients free from bias? | 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 | |
2.1. | 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 | |
2.2. | Were criteria applied equally to all study groups? | Yes | |
2.3. | Were health, demographics, and other characteristics of subjects described? | 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 | |
2.4. | Were the subjects/patients a representative sample of the relevant population? | Yes | |
3. | Were study groups comparable? | 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) | No | |
3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | No | |
3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | 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 | |
3.3. | 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 | |
3.4. | 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 | |
3.5. | 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 | |
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. | Was method of handling withdrawals described? | Yes | |
4.1. | Were follow-up methods described and the same for all groups? | 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 | |
4.2. | 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 | |
4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | Yes | |
4.4. | Were reasons for withdrawals similar across groups? | N/A | |
4.4. | 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 | |
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? | No | |
5. | Was blinding used to prevent introduction of bias? | No | |
5.1. | In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? | 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 | |
5.2. | 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 | |
5.3. | 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 | |
5.4. | 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 | |
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. | 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 | |
6.1. | 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 | |
6.2. | 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 | |
6.3. | 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 | |
6.4. | 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? | N/A | |
6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | N/A | |
6.6. | Were extra or unplanned treatments described? | No | |
6.6. | Were extra or unplanned treatments described? | No | |
6.7. | Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? | Yes | |
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? | Yes | |
6.8. | In diagnostic study, were details of test administration and replication sufficient? | Yes | |
7. | Were outcomes clearly defined and the measurements valid and reliable? | Yes | |
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 | |
7.1. | 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 | |
7.2. | 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 | |
7.3. | 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 | |
7.4. | 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 | |
7.5. | 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 | |
7.6. | Were other factors accounted for (measured) that could affect outcomes? | Yes | |
7.7. | Were the measurements conducted consistently across groups? | 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? | No | |
8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | No | |
8.1. | Were statistical analyses adequately described and the results reported appropriately? | No | |
8.1. | Were statistical analyses adequately described and the results reported appropriately? | No | |
8.2. | Were correct statistical tests used and assumptions of test not violated? | 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 | |
8.3. | 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)? | No | |
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)? | No | |
8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | Yes | |
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? | No | |
8.6. | Was clinical significance as well as statistical significance reported? | No | |
8.7. | If negative findings, was a power calculation reported to address type 2 error? | No | |
8.7. | If negative findings, was a power calculation reported to address type 2 error? | No | |
9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
9.1. | Is there a discussion of findings? | Yes | |
9.1. | Is there a discussion of findings? | Yes | |
9.2. | Are biases and study limitations identified and discussed? | 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. | Is bias due to study's funding or sponsorship unlikely? | Yes | |
10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |
10.2. | Was the study free from apparent conflict of interest? | Yes | |