HTN: Protein (2007)

Citation:

Hermansen K, Hansen B, Jacobsen R, Clausen P, Dalgaard M, Dinesen B, Holst JJ, Pedersen E, Astrup A. Effects of soy supplementation on blood lipids and arterial function in hypercholesterolaemic subjects. Eur J Clin Nutr. 2005; 59: 843-850.

PubMed ID: 15900307
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
  • To compare the long-term effects (24 weeks) of supplementation of the soy-based dietary supplement, Abalon, with a control (casein) on LDL-cholesterol and other cardiovascular risk factors (including endothelial function) in subjects with hypercholesterolaemia
  • BP as a secondary outcome.
Inclusion Criteria:
  • Women and men between 40 and 80
  • Total cholesterol over 6mmol per L or LDL-cholesterol over 3.5mmol per L.
Exclusion Criteria:
  • Fasting TG over 4.5mmol per L
  • Major cardiovascular events within three months prior to inclusion
  • Diabetes mellitus
  • Severe hypertension (over 180/110mm Hg)
  • BMI higher than 40
  • Taking supplements or therapy for lowering blood lipids.

 

Description of Study Protocol:

Design

  • Prospective double-blind randomized, placebo-controlled parallel-group, two-center trial
  • Randomization to groups was based on a computer generated randomization list
  • Subjects were stratified by LDL-C at screening
  • Screening was followed by a two-week run-in period that preceded the 24-week intervention.

Blinding Used

Double-blinded.

Intervention

  • Soy supplementation group: 30g soy protein, 9g cotyledon fiber and 100mg isoflavones were taken daily, one in the morning and one in the evening, as two sachets mixed in water for 24 weeks
  • Control group: Matching casein sachets (30g) administered identically as the soy supplement.

Statistical Analysis

  • Mann-Whitney test was used to compare height and age for the groups at randomization
  • ANOVA was used to analyze for difference within and between treatment groups. 
Data Collection Summary:

Timing of Measurements

  • BP measurements were taken at baseline and at the end of the 24-week intervention
  • Blood measurements were conducted on the first day of the study, after 12 weeks and at the end of the intervention. 

Dependent Variables

  • SBP and DBP (methods not described)
  • Pulse rate
  • Blood glucose, serum insulin, flow-mediated vasodilation, serum lipids, TNF-alpha, homocysteine, GIP.

Independent Variables

  • Soy supplementation
  • Casein supplementation placebo.

Control Variables

Subjects were asked to maintain their usual physical activity.

Description of Actual Data Sample:
  • Initial N: 100 (58 women, 42 men)
  • Attrition (final N): 89 (46 in soy group, 46 in placebo group) completed the study; however, all 100 were included in the data as intent-to-treat
  • Age: 58±4.6 years (mean±SD) for placebo group; 60.6±3.4 years for the soy group
  • Ethnicity: 99% Caucasian.

Anthropometrics

  • Weight: 75.3±3.4kg placebo group at baseline, 75.4±3.7kg at 24 weeks; 77.1±3.6kg soy group at baseline, 76.6±13.6 at 24 weeks
  • BMI: 25.6±3.4 for placebo group at baseline, 25.8±3.4 at 24 weeks; 26.4±3.6 for soy group at baseline, 26.5±3.7 at 24 weeks.

Location

Copenhagen.

 

Summary of Results:

Blood Pressure and Pulse Rate of 100 Original Subjects at the Start and End of the 24-Week Intervention

  Placebo at Baseline Placebo at 24 Weeks Soy Group at Baseline Soy Group at 24 Weeks
SBP (mm Hg) 133±16.1 131±16.2 133±17.7 133±16.5
DBP (mm Hg) 81.4±9.1 79.6±9.1 80.2±9.2 79.2±10.2
Pulse rate (beats per minute) 67.5±9.2 65.9±8.3 66.1±8.1 64.4±8.9

Mean±SD
P-values were not given.

Other Findings

There was no difference in serum lipids or arterial function due to intervention.

 

Author Conclusion:
  • No significant effects on blood lipids were observed in the main study to a soy supplementation in hypercholesterolaemic subjects after 24 weeks
  • In the sub-study, the soy supplementation reduced LDL and total cholesterol, but did not influence markers of arterial function
  • Blood pressure was not a primary outcome of the study
  • No conclusive comment was made regarding BP.
Funding Source:
Industry:
Nutripharma ASA
Food Company:
Reviewer Comments:
  • Activity, weight change, BMI, smoking, alcohol intake and diet were variables included in analysis
  • Compliance was measured by diet records and counting returned supplements
  • No discussion or level of significance is mentioned regarding baseline or post-intervention BP
  • All 100 subjects were included in the analysis as intent-to-treat, even though 89 of the original 100 subjects completed the study.
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? 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) 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? 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? Yes
  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.) ???
  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? 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
  6.3. 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
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  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? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? ???
  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
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? No
  8.1. Were statistical analyses adequately described and the results reported appropriately? No
  8.2. Were correct statistical tests used and assumptions of test not violated? ???
  8.3. Were statistics reported with levels of significance and/or confidence intervals? 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
  8.6. Was clinical significance as well as statistical significance reported? N/A
  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? ???