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


Syvertsen C, Halse J, Hoivik HO, Gaullier J-M, Nurminiemi M, Kristiansen K, Einerhand A, O'Shea M, Gudmundsen O. The effect of six months supplementation with conjugated linoleic acid on insulin resistance in overweight and obese. Int J Obes. 2007; 31: 1,148-1,154.

PubMed ID: 17031391
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To evaluate if CLA as a mixture of the main isomers trans-10 cis-12 and cis-9 trans-11 affects the insulin resistance in healthy overweight and obese male and female adults.

Inclusion Criteria:
  • Healthy male and females
  • Age range 18 to 65 years
  • Body mass index between 28 and 32kg/m2.
Exclusion Criteria:
  • Drug therapy
  • Special diet taking dietary substitutes for weight loss two weeks before study start
  • CLA consumption during the last three months before the study
  • Pregnant and lactating women
  • Type 1 diabetes or those with untreated type 2 diabetes
  • History of hypertension; renal, liver, pancreatic, chronic inflammatory or infectious diseases, cardiac failure or malignant tumors
  • Active thyroid disease or receiving thyroid hormone substitution
  • Adrenergic agonist use
  • Known or suspected drug or alcohol abuse
  • Any clinical condition rendering a person unfit to participate.
Description of Study Protocol:


  • Recruited at two research centers
  • Subjects for the euglycemic hyperinsulinemic clamp study were recruited from the overall initial group.


  • Randomized, double-blind, placebo-controlled parallel study
  • Subjects were randomized to CLA or placebo in blocks of six.

Blinding used

Double blind.


  • Placebo: 4.5g per day olive oil in six opaque soft capsules
  • CLA: 3.4g per day (4.5g Clarinol G80; Lipid Nutrition, Loders Croklaan); 37.5% cis-9 trans-11 and 38% trans-10 cis-12, remaining mixture was made of other fatty acids (containing less than 2% of trans-trans, less than 7% of saturated fatty acids and less than 1% free fatty acids)
  • No co-interventions of in lifestyle or nutrition were implemented.

Statistical Analysis

  • Results are presented as medians and 95% confidence interval
  • Comparison within treatment groups regarding change from baseline was performed using paired Wilcoxon's signed rank test
  • Test for differences between groups was performed by Wilcoxon's rank sum test on the differences between six months and baseline
  • The differences were also analyzed by analysis of covariance (baseline as covariate) and repeated measure analysis of variance (ANOVA) to look for significant treatment, center or time effects
  • Correlation analysis was performed using Spearman rank test.
  • A significance level of 5% was used in tests, and all tests were two-tailed.
Data Collection Summary:

Timing of Measurements

  • Baseline and six months
  • Weight, BMI, vital signs and adverse events were recorded every three months
  • Body composition was measured at baseline, three and six months.

Dependent Variables

  • Weight, height, BMI, waist, body fat mass percentage (DXA) 
  • HbA1c percentage, c-peptide, adiponectin, leptin in accredited laboratories
  • Euglycemic insulin clamp test: Two fasting blood samples for glucose and insulin; insulin was mixed with 0.9% NaCl to a concentration of 300U per L and infused at a constant rate of 1mU per kg per minute; plasma glucose concentration was checked every five to 10 minutes using the glucose dehydrogenase method (HemoCue AB) and held constant at 5mmol per L by a variable glucose infusion (200g per L); blood for insulin measurements was drawn during the last 30 minutes of the clamp procedure; mean duration of test procedure was two hours, 57 minutes and the glucose uptake (M) (mg per minute) was calculated from the amount of glucose (mg) infused over the last 30 minutes under euglycemic conditions; body weight and lean body mass determined by DXA were used to correct the values of M
  • Homeostasis model assessment (HOMA) was calculated from fasting insulin and fasting glucose data using the following formula: (fasting insulin uU per ml) x (fasting glucose mmol per L ) over 22.5
  • Quantitative insulin sensitivity check index (QUICKI) was calculated as 1/log(fasting insulin uU per ml) + log(fasting glucose mg per dL). Insulin was determined by RIA.
  • Vital signs
  • Adverse events.

Independent Variables

  • Placebo
  • CLA
  • Six months trial duration.

Control Variables

Baseline values served as covariates.

Description of Actual Data Sample:

Initial N

118 (percentage of male and female was not stated).

Attrition (final N)

  • 12 subjects in the CLA and 13 in the placebo group dropped out
  • Another 10 subjects had less than 70% compliance
  • Final total of 83 subjects with valid values at baseline and six months; 18 male, 65 female
  • Subpopulation of 49 subjects entered euglycemic hyperinsulinemic study at baseline and 41 completed a second study after six months; 15 male, 34 female.


  • Overall study: Mean age was 48 years
  • Euglycemic clamp study: Mean age was 49 years.


  • For study population that completed two euglycemic clamps (N=41): Baseline
  • Weight: CLA, 89.0kg; Placebo, 86.0kg
  • BMI (kg/m2): CLA, 30.8; Placebo, 30.8
  • Body fat mass (percentage): CLA, 43.3; Placebo, 41.1 


Research centers: Diabetes and Overweight Medical Center, Oslo, Norway; Hedmark Medical Center, Hamar, Norway.

Summary of Results:

Key Findings

  • Compliance was 95% in the placebo and CLA clamp study groups (N=39), except for one with 65% and one with 17%, both in placebo group. These two latter subjects were included in all analyses.
  • There was a decrease in waist circumference in the CLA group (P=0.02) and a decrease in HbA1c in the placebo group (P=0.014) from the baseline values
  • There was a trend toward larger reduction in percent body fat and waist circumference after six months of supplementation in the CLA group compared to placebo (P=0.10 and 0.09, respectively).

Selected Characteristics of Study Population that Completed Two Euglycemic Clamps (N=41) 





Six Months


Change (CI)




Six Months


Change (CI)

BMI (kg/m2)



-0.06 (-1.1, 0.5)



0 (-0.5, 0.5) 
Body fat mass (percentage)  43.3 


 -0.65 (-2.5, 0.8) 41.1  41.8  -0.40 (-1.2, 1.5)  
Waist (cm 100  99  -2 (-1, -6)  99  98  -1.5 (-2, 3) 

HbA1c (percentage)

5.40  5.40  0 (-0.2, 0.1)  5.50  5.40  -0.2 (-0.3, 0.0) 
c-Peptide (pmol per L 759  777  51 (-89, 140)   663   772   19 (-105, 141) 


  • There was no statistical difference in either glucose uptake, uptake corrected for body weight (BW) or uptake corrected for lean body mass (LBM) between the treatment groups at baseline
  • Compared to baseline, none of the treatment groups had significant changes in glucose uptake (relative to BW or LBM) after six months. Also, no significant difference was found between treatment groups (P=0.93) when comparing the change from baseline to six months. 
  • When using published criteria regarding insulin resistance for glucose uptake corrected for LBM (by DXA), two subjects at baseline and one subject in each treatment group at six months were categorized as insulin resistant
  • There was no significant change for the glucose uptake insulin concentration ratio adjusted for LBM either within or between treatment groups in the sample that completed two clamps (N=35) 
  • Using published suggestions for insulin resistance based on glucose uptake insulin concentration ratio adjusted for LBM, four subjects at baseline and three subjects receiving CLA and two receiving placebo at six months were categorized as insulin resistant
  • Repeated measure ANOVA of insulin data showed a significant effect of time (P=0.03), but not for treatment or center
  • There was no significant difference within or between groups for either fasting insulin or fasting glucose concentration. Repeated measure ANOVA of fasting glucose data showed a significant effect of time (P=0.02) and the interaction factor of center x time (P<0.0001)
  • After six months of supplementation, there was no significant difference either within or between groups for HOMA values
  • Using a criterion for insulin resistance based on HOMA, nine subjects at baseline and four subjects (three subjects receiving CLA) after six months were categorized as insulin resistant
  • After six months of supplementation, there was no significant difference either within or between groups for QUICKI
  • For the whole population (per protocol, N=83), after six months of supplementation there was no significant difference either within or between groups for either HOMA or QUICKI
  • Using the cutoff value of 4.65 for HOMA, 13 subjects (seven subjects receiving CLA, five subjects placebo) (16%) were categorized as insulin resistant both at baseline and after six months.

 Other Findings

  • For clamp study participants, significant gender differences in median body weight at baseline [98.0kg (male) vs. 84.2 (female), P<0.001], median percent body fat [31.9% (male) vs. 44.6% (female), P<0.0001] and median leptin concentration [555pmol per L (male) vs. 1,575pmol per L (female), P=0.001]
  • Differences between six months data and baseline for these parameters were not significantly related to gender
  • Baseline fasting glucose at center one was lower than at center two (median value 5.08mmol per L (N=24) vs. 5.35mmol per L (N=25), P=0.014), although no other parameters differed significantly between centers
  • After six months, no significant difference between centers for any of the parameters listed in Table 2 of the article was found
  • There was a good correlation between fasting insulin and insulin during clamp at baseline (R=0.57, P=0.00004)
  • The prevalence of insulin resistance was not consistent between the different methods used and no single subject was categorized as being insulin resistant by all three methods either at baseline or at study completion.
Author Conclusion:

The present long-term study using the euglycemic hyperinsulinemic clamp method suggests that CLA as a commercial preparation containing a mixture of cis-9, trans-11 and trans-10, cis-12 isomers has no deleterious effect on either glucose metabolism or insulin resistance in healthy overweight and obese subjects.

Funding Source:
Lipid Nutrition a division of Loders Croklaan
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:

I did not include results on the correlation analysis, as this was performed on combined (CLA and placebo together) variables.

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? ???
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)? 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? 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