HTN: Protein (2007)

Citation:

Goodman-Gruen D, Kritz-Silverstein D. Usual dietary isoflavone intake is associated with cardiovascular disease risk factors in postmenopausal women. J Nutr. 2001; 131: 1,202-1,206.

PubMed ID: 11285326
 
Study Design:
Cross-Sectional Study
Class:
D - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To examine the cross-sectional association between usual dietary isoflavone intake and CVD risk factors, including lipids and lipoproteins, BMI, BP and glucose metabolism.

Inclusion Criteria:
  • At least two years post-menopausal
  • Not using hormone replacement therapy for at least three months
  • Not currently using cholesterol-lowering drugs, anti-diabetic medications, tamoxifen or soy protein or herbal supplements.
Exclusion Criteria:
  • History of uncontrolled hypertension, stroke or transient ischemic attack
  • Cancer diagnosed less than five years ago
  • Myocardial infarction within six months.
Description of Study Protocol:

Recruitment

Women 45 to 74 years of age, who attended screening and baseline visits and were subsequently enrolled in the Soy Health Effects (SHE) Study, were also enrolled in the present study.

Design

Cross-sectional analysis of BP and other CVD risk factor data, based on usual genistein or daidzein intake.

Statistical Analysis

  • Analysis used log transformed data due to skewed distribution of outcomes data
  • ANOVA for continuous variables and chi-squared tests for categorical variables were used to test for differences in demographic and behavioral characteristics by category of genistein intake
  • ANCOVA was used to adjust mean risk factor levels by BMI and to compare adjusted means by daily genistein consumption
  • Linear contrasts in ANCOVA models tested for trends across tertiles of genistein intake
  • Multiple-regression analysis was used to assess the independent association between genistein intake and CVD risk factors, while controlling for age, BMI, ethnicity, total energy intake, total dietary fat intake, total dietary fiber intake and total dietary protein intake
  • All analyses were repeated using daidzein consumption and combining genistein and daidzein to approximate total isoflavone intake
  • P-values are two-tailed.
Data Collection Summary:

Timing of Measurements

  • At screening, data was collected regarding demographic and lifestyle characteristics
  • One month following the screening, a baseline visit occurred to assess diet using the Block Food Frequency Questionnaire, collect anthropometric data, measure BP and collect blood samples for lipid and glucose values. 

Dependent Variables

  • SBP and DBP measured twice with a mercury sphygmomanometer, after sitting quietly for at least five minutes
  • An average of the two measurements was used for analysis
  • Serum lipids
  • Fasting and two-hour BG
  • Fasting and two-hour insulin.

Independent Variables

  • Level of genistein usually consumed as analyzed by the Block Food Frequency Questionnaire with added sources of soy isoflavones
  • Level of daidzein usually consumed analyzed as above
  • Combined intake of genistein and daidzein. 

Control Variables

  • Age
  • Time post-menopausal
  • Smoking
  • Exercise
  • Daily alcohol intake
  • College completion
  • Ethnicity.
Description of Actual Data Sample:
  • Initial N: 210 women were enrolled
  • Attrition (final N): 208; one woman did not complete all of the baseline measurements and one woman reported isoflavone intake over four SD above the mean
  • Age: 56.7±6.4 years (mean±SD); range, 45 to 74 years.

Ethnicity

  • 77.9% Caucasian
  • 11.1% Hispanic
  • 5.3% Asian or Pacific Islander
  • 1.4% American Indian
  • 4.3% Black or African-American.

Other Relevant Demographics

  • Less than 25% were college graduates and almost 25% had at least one year of graduate-level education
  • 8.7% reported current smoking
  • 13.5% reported daily consumption of alcohol
  • 76% reported exercising at least three times per week.

Anthropometrics

  • BMI 26.2±4.4 for the tertile with no genistein intake, 26.6±4.6 for the moderate genistein intake group, 24.5±3.5 for the high genistein intake group
  • Waist circumference (cm) was 79.8±10.5 for the no genistein intake tertile, 80.4±10.5 for the moderate intake group and 75.8±7.9 for the high intake group
  • BMI and waist circumference were smaller in the tertile with the highest daily genistein intake, compared to those with no genistein intake, P<0.05.

Location

San Diego, CA.

Summary of Results:

Other Findings 

  • Consumption of genistein ranged from 0.0 to 13.9mg per day, with the average intake of 1.3±2.4mg per day. Asian women were most likely to report genistein consumption under 1.0mg per day.
  • There was no differences in age, years post-menopausal, education level, smoking, alcohol intake, total energy intake, total dietary fiber, protein, total fat or saturated fat intake or exercise by level of daily genistein intake, P<0.05
  • Women who reported moderate genistein intake (0.2±0.3mg per day) tended to have lower SBP (115.4±1.4mm Hg) than women who did not consume genistein (119.7±2.1mm Hg), P<0.10. SBP for women consuming high intakes of genistein was 118.9±1.9mm Hg. No significant differences by genistein intake were associated with DBP, total cholesterol, triglycerides, fasting and two-hour glucose or two-hour insulin. Repeating the analyses and substituting diadzein or total isoflavones did not change these findings. 
  • Women with moderate and high (4.4±3.0mg per day) genistein intake had higher HDL-C levels (P≤0.05) and fasting insulin levels (P≤0.05 and P≤0.10, respectively), compared with those who did not consume genistein. Results of multiple regression analysis adjusting for BMI, ethnicity and total daily energy intake indicated that total isoflavone intake was positively associated with HDL-C level (P=0.05, 0.008 and 0.03, respectively) and inversely associated with two-hour insulin concentration (P=0.04, 005 and 0.05, respectively).
Author Conclusion:

Results of this study suggest a protective cardiovascular effect of usual, unsupplemented, dietary isoflavone intake on obesity, HDL-C and fasting and post-challenge insulin to post-menopausal women.

Funding Source:
Government: NIH, NHLBI
Reviewer Comments:
  • Limitations included in the discussion suggest possibility of reporting error associated with food frequency questionnaires, yet errors are typically under-estimates of actual intake
  • The study recruited volunteers interested in joining a dietary soy supplementation study, so selection bias may have been present
  • There is a possibility that yet unidentified factors that covary with isoflavone exposure or a component of soy other than genistein or daidzein may be active compounds responsible for effects
  • Isoflavone intake was relatively low in this study
  • Daily genistein intake for the moderate group was 0.2±0.3mg per day and for the high group, 4.4±3.0mg per day
  • Daidzein for the moderate intake group was 0.06±0.1mg per day and for the high intake group, 1.4±1.2mg per day
  • Energy intakes for the groups were 1,547±506kJ per day for the group, with no isoflavone intake, 1,630±585kJ per day for the moderate intake group and 1,699±539kJ per day for the high intake group. This is in the range of 370-400kcal per day! However, protein intake is reported as 66.2±3.9g per day, 69.5±2.6g per day and 74.1±3.6g per day for the no genistein intake group, moderate intake group and high intake group, respectively.
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) N/A
  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) N/A
  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.) 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? Yes
  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? ???
  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? ???
  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.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? ???
  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? 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
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  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? N/A
  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? No
  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? ???
  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? ???
  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? No
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