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DFA: Conjugated Linoleic Acid (CLA) Supplementation and Intermediate Health Outcomes (2011)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

The purpose of this study was to examine the effect of conjugated linoleic acid (CLA) on atherosclerosis in humans. After six months of supplementation with CLA in overweight and obese adults, aortic pulse wave velocity (a marker of atheroslerosis) and other cardiovascular risk factors were examined.

Inclusion Criteria:
  • Apparently healthy men and women
  • Aged 40-70 years
  • BMI≥25kg/m2.
Exclusion Criteria:
  • Systolic blood pressure≥160mm Hg
  • Diastolic blood pressure≥90mm Hg
  • Current use of blood pressure-lowering drugs
  • Total cholesterol of≥8mmol/L
  • Current use of lipid lowering drugs
  • Inability to perform PWV measurements
  • BMI<25kg/m2
  • Glucose >7mmol/L
  • Glucose lowering drugs
  • Alcohol abuse.
Description of Study Protocol:

Recruitment

The Julius Center "POKA" database, which is made up of subjects interested in participating in studies, was used for recruitment. Additional recruitment was from municipal registries from a large and middle-large town in the Netherlands. Invitations to participate were by mail. 

Design

A single-center, double-blind, randomized placebo-controlled group trial was performed to examine the effects of placebo vs. c9t11 CLA over six months of supplementation. A web-based application was used to randomly assign participants to the study groups, c9, t11 CLA or placebo. A 1:1 ratio with a minimalization procedure was implemented and randomization was stratified for sex. Changes in aortic PWV as well as changes in insulin resistance, blood pressure, anthropometrics and concentrations of blood lipids, glucose, insulin and CRP were measured. 

Blinding used

  • Study capsules provided in individual, numbered bottles (blinded)
  • Investigators did not know treatment allocations during the study. 

Intervention 

Participants received either placebo or c9t11 CLA supplements. Both were soft gel capsules and each provided 1g of oil daily (four capsules). Lipid Nutrition (Wormerveer, Netherlands) manufactured the capsules. 

c9t11 CLA supplements:

  • Made from safflower oil
  • Provided 80% CLA isomers of which 80% (2.5 grams per day) was c9t11 CLA and 20% (0.6 grams per day) was t10c12 CLA
  • c9t11 CLA provided about 1% of energy and t10c12 provided about 0.3% of energy (based on 2,000-2,500kcal per day).

Placebo supplements:

  • Provided equal amount of fat as CLA supplements
  • 80% palm oil, 20% soybean oil.

Compliance with the intervention was assessed at each clinic visit (three and six months) where subjects returned leftover capsules. Compliance (percent) equal (number of capsules taken since last capsule count/number of capsules that should have been taken in same period) x 100.

Statistical Analysis

  • Power calculation: two-sided α of 0.05 and power of 80% showed that about 180 subjects per treatment arm were needed to detect a 8.2% difference in change in PWV. A dropout rate of 15% was assumed, raising the requirement to about 200 participants per arm.
  • Changes from baseline to six months across treatment arms were analyzed with intention-to-treat principle
  • Two-sided T-test or chi square test was used to test the differences in six-month changes between the two groups
  • Paired T-tests, Wilcoxon's tests or chi-square tests were used to test within-group changes.
Data Collection Summary:

Timing of Measurements

  • All variables were measured at baseline. Information on medication use, medical history, lifestyle factors, and physical activity was also obtained by baseline questionnaires.
  • Mean blood pressure, weight, waist and hip circumference were measured at both three and six months. These measurements were done earlier if the subjects dropped out of the study.
  • At six months, central vascular measurements, SCORE (see below), and changes in lifestyle (smoking, physical activity, alcohol consumption) were recorded
  • Biochemical analyses of plasma was performed at baseline and six months.

Dependent Variables

  • Aortic pulse wave velocity (PWV): Measured at baseline and six months with SphygmoCor system. Well-trained and certified technicians performed testing
  • Systolic and diastolic blood pressure: By oscillometric-automated device; conducted before 1,100; after overnight fast; performed in duplicate
  • Mean arterial pressure: Calculated from - mean arterial pressure = ( 2 x mean diastolic blood pressure + mean systolic blood pressure)/3
  • Pulse pressure: Systolic blood pressure minus diastolic blood pressure
  • Central aortic systolic pressure, central aortic diastolic pressure and central aortic pulse pressure: Measured by SphygomoCor Blood Pressure Analysis System
  • SCORE: 10-year absolute risk of fatal CVD was calculated from the European Systematic Coronary Risk Evaluation
  • Weight
  • BMI
  • Waist circumference: Measured midway between lower rib and crista iliaca
  • Hip circumference: Measured at the level of the greater trochanter
  • Waist-hip ratio.

Biochemical measurements: (all done in fasting blood samples; at baseline and six months)

  • Plasma total cholesterol
  • Plasma LDL cholesterol
  • Plasma HDL cholesterol
  • Plasma total/HDL cholesterol ratio
  • Plasma fasting triglycerides
  • Plasma fasting glucose
  • Plasma fasting insulin
  • High sensitivity CRP (hs-CRP)
  • Homeostasis model assessment of insulin resistance (HOMA-IR).

Independent Variables

  • Placebo vs. 80% c9t11, 20% t10c12 CLA groups
  • Changes from baseline to six months in each group were measured and between group differences were measured.

Control Variables

Description of Actual Data Sample:
  • Initial N: N=401
    • Placebo group: N=200
    • CLA group: N=201
  • Attrition (final N): 346 included in analysis  
    • Placebo group: N=173 (84 men-48.6%)
    • CLA group: N=173 (83 men-48.0%)
      • Seven subjects were excluded because they should not have been randomly assigned (met exclusion criteria)
      • 45 subjects (11%) had stopped consuming supplements at six months, so were excluded (similar in groups)
      • 48 subjects (23 placebo, 25 CLA) had missing PWV measurements for six-month follow-up
  • Age: Mean ages: 
    • Placebo group: 58.8±0.5 years
    • c9t11 CLA group: 58.0±0.4 years
  • Ethnicity: Live in the Netherlands
  • Other relevant demographics:
    • Mean compliance rate: Placebo (93%); c9t11 CLA (92%)
    • Current smoking (N): Placebo=14; c9t11=18
    • Baecke physical activity score: Placebo=7.9; c9t11=7.8
    • At baseline demographic characteristics and CVD risk markers were similar between the groups
  • Anthropometrics:
    • Median BMI: Placebo -27.7kg/m2; c9t11 CLA - 28.0kg/m2
    • Waist circumference: Placebo -99.2±0.7cm; c9t11 CLA -99.0±0.7cm
  • Location: Netherlands.

 

Summary of Results:

Key findings

No significant effects were observed from six months of c9t11 supplementation on aortic PWV, blood pressure, plasma lipids, insulin resistance, body composition or CRP in overweight and obese adults. 

 PWV

  • Mean (±SE) change in PWV from baseline to six months for placebo=0.09±0.06m/s; mean (±SE) change in PWV from baseline to six months for c9t11 CLA=0.00±0.07m/s. PWV did not change in the CLA group compared to the placebo group. 
  • Between group differences were not significant
  • No interaction was observed with sex SCORE, degree of obesity or pre-test PWV
  • Cardiovascular risk factors:
    • No significant differences in changes in mean systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure between the c9t11 CLA and placebo groups
    • There were no between-group differences in central aortic systolic and diastolic blood pressure or central aortic pulse pressure
    • Body weight, BMI, waist circumference and waist-hip ratio were not significantly different between the c9t11 CLA and placebo groups over six months of supplementation
    • Increases in the following were observed with six months of supplementation (change from baseline to six months):
      • Body weight in placebo: 0.65kg±0.16; P<0.05
      • BMI in placebo: 0.22±0.05kg/m2; P<0.05
      • Waist circumference in placebo: 0.79±0.25cm; P<0.05
      • Waist-hip ratio in placebo: 0.005±0.002; P<0.05
      • Waist circumference in c9t11 CLA: 0.84±0.31; P<0.05
  • Biochemical analyses:
    • When the c9t11 CLA group was compared with the placebo group significant differences were not observed in changes in triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, and total/HDL cholesterol ratio
    • No between group differences were observed for changes in plasma glucose, insulin, HOMA-IR or CRP.
    • Significant changes for baseline to six months were observed in the following:
      • Plasma HDL cholesterol in placebo: -0.04±0.02mmol/L; P<0.05
      • Plasma fasting glucose in placebo: -0.12±0.04mmol/L; P<0.05
      • Plasma fasting triglycerides in c9t11 CLA: 0.08±0.03mmol/L; P<0.05
  • Reported adverse events were deemed unrelated to use of the CLA supplement.
Author Conclusion:

No effects on PWV or CVD risk markers was seen as a result of six months of supplementation with c9t11 CLA. The results of the study do not support an anti-atherosclerotic role of c9t11 CLA supplements in obese and overweight adults.

Funding Source:
Government: Dutch Ministry of Economic Affairs
Industry:
Lipid Nutrition BV (Wormerveer, Netherlands)
Food Company:
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:

Participants were asked not to change diet over the intervention period. However, dietary intake at baseline and during the intervention was not assessed.

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.) 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? 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? 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? 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? 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)? 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? 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