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


Taylor JS, et al. Conjugated linoleic acid impairs endothelial function. Arterioscler Thromb Vasc Biol. 2006; 26: 307-312.

PubMed ID: 16339498
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

The study examined the impact of supplementation with conjugated linoleic acid (CLA) on weight loss and cardiovascular risk factors. Body weight, body fat mass distribution, endothelial function, insulin sensitivity and markers of oxidative stress were examined after supplementing overweight middle-aged men.

Inclusion Criteria:
  • Non-smokers
  • White men
  • 35-60 years old
  • Without diabetes, hypertension or cardiovascular disease
  • Body mass index>27kg/m2
  • Informed consent from all participants.
Exclusion Criteria:
  • Smokers
  • Less than 35 years old or more than 60 years old
  • Diabetes, hypertension or cardiovascular disease
  • BMI<27kg/m2.
Description of Study Protocol:


Participants were recruited via media advertisements in the local community.


Random assignment was used to determine groups. An independent observer performed the randomization, also matching subjects by BMI and age. Participants received either CLA capsules or olive oil capsules for 12 weeks. The morning after an overnight fast, vascular measurements were recorded.  

Blinding used

Double-blind study


Participants received one of the following treatments for 12 weeks:

  • 4.5 grams per day CLA capsules (isomeric mixture; 60 calories per day); mixture was 35% 9c,11t CLA, 36% t10,c12 CLA, 1% to 2% 9c,11c and 10c,12c CLA, 1.5% 9t,11t and 10t,11t CLA, and <1% t8,c10 and c11,t13
  • Olive oil capsules (54 calories per day).

Natural Lipids supplied both types of capsules.

Statistical Analysis

  • Variables with skewed distribution were logarithmically transformed to achieve normal distribution prior to analysis
  • Student T test used for baseline comparison between CLA and olive oil groups
  • ANCOVA used to assess effects of treatment (CLA vs. olive oil). Baseline values were used as covariates
  • Post-hoc Bonferroni corrections were applied to groups of primary objective measurements (to avoid type I errors)
  • Two-tailed significance was as following for the measurements:
    • Blood pressure: P<0.025
    • Skin folds: P<0.005
    • Girths: P<0.001
    • FMD: P<0.025
    • Abdominal CT: P<0.008 
    • Weight, bioimpedance and exploratory blood analyses: P<0.05. 
Data Collection Summary:

Timing of Measurements

Measurements were made at baseline and then again after 12 weeks of supplementation. Measurements were made in the morning after an overnight fast.

Dependent Variables

  • Body weight
  • BMI.


  • Skinfold thicknesses: Measured at biceps, triceps, front mid-thigh, medical calf, subscapular, mid-axillary, and abdominal by standard guidelines
  • Abdominal, waist and hip girths
  • Body fat percent: Measured by bioelectrical impedence (tetrapolar method and Bodystat 1500 analyser)
  • Abdominal adipose tissue and liver fat: Measured using computed tomography (CT) images.

Endothelial function:

  • Changes in brachial artery diameter: Measured in response to reactive hyperemia with ultrasonic wall-tracking system
  • Brachial artery flow-mediated dilation (FMD): Calculated from the maximum change in brachial artery diameter from baseline. Baseline measurements were calculated after subjects rested 15 minutes. Then reactive hyperemia was produced using a sphygmomanometer after which internal brachial artery diameter was assessed each minute.

Blood measurements:

  • Glucose
  • Insulin
  • LDL cholesterol
  • HDL cholesterol
  • C-reactive protein
  • Leptin
  • Adiponectin
  • F2-isoprostanes: Measured as index of oxidative stress 
  • Tumor necrosis factor-α
  • Insumlin sensitivity (HOMA-IR).

Independent Variables

Olive oil group vs. control group: Change in each measurement as compared to baseline was reported for each group; the results of the ANCOVA analyses also showed the overall effect of supplementation with CLA.

Control Variables

 ANCOVA was used with baseline values as covariates.

Description of Actual Data Sample:
  • Initial N: 40 males
    • Olive oil: N=19
    • CLA: N=21
  • Attrition (final N): Final  N=40; all subjects completed the study
  • AgeMean age:
    • Olive oil=47±8 years
    • CLA=45±6 years
  • Ethnicity: White
  • Anthropometrics:
    • Mass (kg): Olive oil=97±13; CLA=101±9
    • BMI: Olive oil =33±3; CLA=33±3kg/m2
    • Fat percent: Olive oil 29±3; CLA=28±4
    • Systolic blood pressure, mm Hg: Olive oil=128±13; CLA=122±10
    • Diastolic blood pressure, mm Hg: Olive oil=85±7; CLA=80±8
    • Baseline anthropometrics were not significantly different between the groups
  • Location: Not described.


Summary of Results:

Key Findings

  • CLA supplementation did not lead to weight loss (a trend to weight loss was observed -1.1kg, P=0.06, but was not significant) or decrease in total body fat
  • Limb fat was reduced by CLA, but CLA did not impact abdominal or liver fat
  • CLA impaired brachial artery endothelial function and increased F2-isoprostanes
  • Insulin sensitivity and plasma lipid profiles were not impacted by CLA supplementation.

Other Findings

  • Baseline: CLA and olive oil groups did not differ in baseline measurements of age, mass, BMI, fat percent, blood pressure, anthropometrics (skin folds and girths), endothelial function, abdominal CT measurements or blood analyses
  • Changes after supplementation:
    • Olive oil group: The only significant change observed was a decrease in tumor necrosis factor-α (-61pg/mL [95% CI, -3 to -120]; P=0.04)
    • CLA group:
      • Body mass did not change significantly (-1.1kg [95% CI, -2.3 to 0.04]; P=0.06)
      • BMI did not change significantly (-0.4kg/m2 [95% CI, -0.8 to 0.03]; P=0.07)
      • Total body fat did not change significantly (-1% [95% CI, -2.5 to 0.5]; P=0.18)
      • Limb skin-folds decreased significantly (-7.8mm [95% CI, -11.1 to -4.5] P<0.001)
      • Torso skin-folds did not decrease significantly (-4.0mm [95% CI, 11.5 to 3.5], P=0.29)
      • Total torso-to-limb skin-folds ratio increased significantly (+0.13 [95% CI, 0.03 to 0.24]; P=0.017) 
      • Abdominal, waist, and hip girths did not change significantly
      • Abdominal fat and liver fat as measured by CT did not change significantly
      • Brachial artery FMD decreased significantly (-1.3 % [95% CI, -2.4 to -0.3]; P=0.013)
      • F2-isoprostanes increased significantly (+91pg/mL [95% CI, 3 to 178]; P=0.042)
      • Insulin sensitivity, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, CRP, glucose, leptin, adiponectin and tumor necrosis factor-α did not change significantly
      • Entire group (CLA + olive oil)
        • Loss of skin-fold thickness was associated with an increase in F2-isoprostanes, P=0.012 (significant negative correlation between change in F2-isoprostanes and change in total limb skin-folds)
        • Correlations were not observed when each group was examined separately
        • Significant correlations were not observed between change in endothelial function and change in F2-isoprostanes or change in limb skin-fold thicknesses.
Author Conclusion:

Supplementation for 12 weeks with an isomeric CLA mixture had no significant effect on BMI and at most modest effects on adiposity. The observed pattern of fat loss was peripheral instead of central. The cardiovascular safety of CLA supplementation is questionable because of impairment in endothelial function and increased markers of oxidative stress. The authors do not recommend CLA as a supplement for weight loss until further studies can demonstrate its safety.

Funding Source:
Other: British Heart Foundation Project Grant
Reviewer Comments:

Participants' compliance with supplementation was not reported.

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%.) N/A
  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
  4.5. 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? No
  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)? 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