HTN: Protein (2007)

Citation:

Sagara M, Kanda T, Jelekera MN, Teramoto T, Armitage L, Birt N, Birt C, Yamori Y. Effects of dietary intake of soy protein and isoflavones on cardiovascular disease risk factors in high risk, middle-aged men in Scotland. J Am Coll Nutr. 2003; 23 (1): 85-91.

 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To investigate the effects of soy protein and isoflavones on cardiovascular (CVD) risk factors, such as blood pressure (BP) and total cholesterol among high-risk middle-aged people in Scotland.

Inclusion Criteria:
  • SBP at least 130mm Hg or
  • Total cholesterol at least 220mg per dL
  • Inhabitants of the Isles of Lewis and Harris (northwest part of Scotland)
  • Male adults.
Exclusion Criteria:
  • Diabetes mellitus or any other chronic illness that could affect BP, blood lipids or ability to participate in the study
  • Use of anti-hypertensive medication, cholesterol-lowering medication or any other medication that could affect BP or blood lipids.
Description of Study Protocol:

Recruitment

Randomly identified potential subjects from age-gender registers of 12 local general practitioners and recruited by letter. 

Design

Health survey for screening of high-risk subjects followed by a randomized placebo-controlled, double-blind parallel-group trial.

Blinding Used

Double-blind, but method not discussed.

Intervention

  • Soy group: Soy powder containing at least 20g of soy protein and 80mg isoflavones per day mixed in cereals, biscuits and bread rolls in addition to the usual diet. The cereals, biscuits and bread rolls were any combination of two bread rolls and two cereal bars or two bread rolls and a packet of biscuits to be consumed daily at any time of the day. The "usual diet" was not defined.
  • Control group: Received a placebo of cereals, biscuits and bread rolls similar to the intervention products without soy that were consumed with the usual diet.

Statistical Analysis

  • Frequency differences were analyzed by chi-squared test
  • Between-groups differences were analyzed by unpaired Student's T-tests
  • Within groups differences were analyzed by paired Student's T-tests.
Data Collection Summary:

Timing of Measurements

  • Stage One: Health survey to screen for high risk (not defined), anthropometric measures, BP, fasting blood samples urinary isoflavones
  • Stage Two: Five-week intervention
  • Follow-up Stage: Weight, BP and blood lipid and urinary isoflavone measures.

Dependent Variables

  • SBP, DBP measured using a sphygmometer after a 10-minute seated rest; measures were repeated three times
  • Serum levels of total cholesterol, HDL-C, non-HDL-C, non-HDL-C:HDL-C ratio.

Independent Variables

  • Soy supplementation of grain products
  • Placebo of grain products without soy.
Description of Actual Data Sample:
  • Initial N: 156 male subjects identified from age-gender registers; 61 of these males were identified as high-risk by initial screening survey
  • Attrition (final N): 50 male subjects; of the 61 original subjects, eight withdrew during the intervention, two subjects were excluded due to missing blood samples, one subject was excluded due to non-compliance.

Age
 

  • Mean age for soy group: 52.2±3.9 years (SEM)
  • Placebo group: 52.2±4.3 years.
     

Ethnicity

Inhabitants of NW Scotland.

Baseline Anthropometric Values for Each Group

 

 

  Soy Group Placebo Group
Weight (kg) 85.1±10.9 83.8±11.7
BMI 27.6±2.7 27.2±3.1
  • The groups were not different in weight or BMI at baseline
  • Weight was maintained for both groups throughout the study 84.3±2.1 and 83.6±2.3 for the soy and placebo groups, respectively
  • Weight was not different between groups following intervention.
Summary of Results:

 BP in the Groups at Baseline and Following Intervention

  Soy Baseline Soy at Five Weeks Placebo Baseline Placebo at Five Weeks
SBP (mm Hg) 142±3.0 131.2±3.1* 134.0±3.2 130.4±3.3
DBP (MM Hg) 87.1±1.8 82.0±1.8* 80.8±10.2 79.1±2.1

*P<0.01, compared with baseline values.

Other Findings

  • TC, HDL-C, non HDL-C, and non HDL-C:HDL-C ratio were lower than baseline for the soy group, P<0.05 for TC, P<0.01 for other outcomes
  • HDL-C was greater than baseline for the placebo group, P<0.01 and the ratio was lower than baseline for the placebo group, P<0.01
  • Urinary isoflavones following intervention were greater than at baseline for the soy group (P<0.01) and greater than those of the placebo group following intervention (P<0.01).
Author Conclusion:

At least 20g of soy protein and at least 80mg of isoflavones for five weeks improved BP, TC, HDL-C and non-HDL-C in high-risk, middle-aged men in Scotland.

Funding Source:
Government: Ministry of Education Science, Sports and Culture
Reviewer Comments:
  • No mention is made regarding controlling for physical activity, smoking or alcohol intake
  • Olive oil was used in the placebo, which may have had an effect
  • Compliance was measured by food records with the prescribed diet; however, the prescribed diet is not described.
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? 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? No
  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? ???
  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%.) ???
  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? 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? ???
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? 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? ???
  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? 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? 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? No
  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)? ???
  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