• Increase Font Size
  • Decrease Font Size
  • View as PDF

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:
  • To examine the long-term safety (over 24 months) of daily supplementation of conjugated linoeic acid (CLA) in overweight subjects. The present 12-month study is an extension of a previous 12-month study
  • Safety was evaluated with clinical chemistry analyses and reported adverse events and the impact of CLA on body fat mass, lean body mass, bone mineral mass, body weight and BMI was evaluated.
Inclusion Criteria:
  • Participated in a previous 12-month study
  • New informed consent forms were completed prior to enrollment
  • 18 to 65 years of age
  • BMI = 25 to 30kg/m2.
Exclusion Criteria:
  • Drug treatment
  • Special diets or diet substitution for weight loss
  • Pregnant or lactating
  • Diabetes mellitus
  • Renal, liver, pancreatic, chronic inflammatory disease, infectious disease
  • Cardiac failure
  • Cancer
  • Thyroid treatment
  • Alcohol or drug abuse.
Description of Study Protocol:

Recruitment

Volunteers from two research centers.

Design

  • This study is an extension of a previous 12-month study. The authors stated that the previous study was a randomized, double-blind, placebo controlled trial, although these details are not described in the current article. In the first study, daily supplementation with a 1:1 mixture of the conjugated linoleic acid (CLA) isomers cis-9, trans-11 and trans-10, cis-12 was tested. Three groups were monitored:
    • CLA-FFA received the free fatty acid form of CLA
    • CLA-TG received the triglyceride form of CLA
    • PLAC received olive oil as the placebo
  • Participants completing this initial study were included another 12-month study in which all subjects (all three groups) received 3.4g CLA each day in the triglyceride form. Subjects remained in their original groups (CLA-FFA, CLA-TG and PLAC).

Blinding Used

Double-blind.

Intervention

  • All three groups (CLA-FFA, CLA-TG, and PLAC) were given daily six soft gel capsules of CLA-TG 4.5g (3.4g CLA isomers, Natural Lipids) over the 12-month extension
  • Food consumption was ad libitum without energy restriction or lifestyle changes
  • No changes in exercise habits.

Statistical Analysis

  • Test power of 80% was planned
  • ANOVA (treatment and center as factors) was done to test comparability among the three groups at month zero
  • Analysis of covariance was used to test comparisons among treatment groups for change from month zero in DXA and weight (treatment, center and gender were factors; month zero value, total energy intake, exercise, drug x energy intake and drug x training score were covariates)
  • Tukey's studentized T-test was used for pairwise comparisons of all three groups
  • Fisher's exact test used to analyze categorical variables
  • All tests were two-tailed
  • Significance was considered as P<0.05.
Data Collection Summary:

Timing of Measurements

  • The extension study immediately followed the original study with no gap in supplementation
  • Month zero was used as baseline for groups CLA-FFA and CLA-TG and month 12 was used as baseline for the PLAC group so changes could be observed over the 12- to 24-month study period.

Dependent Variables

  • Body weight was measured every three months
  • BMI was recorded every three months
  • Vital signs (blood pressure and heart rates) were recorded every three months
  • Adverse events (AE) were recorded every three months and serious adverse events (SAEs) were monitored continuously
  • Body composition was measured at 12, 18 and 24 months
  • Blood samples were analyzed for:
    • Alanine amino transferase (ALAT)
    • Asparate amino transferase (ASAT)
    • Hemoglobin
    • Bilirubin
    • Chloride
    • Creatininephosphokinase (CPK)
    • Creatinine
    • Erythrocytes
    • Y-glutamyl transferase (y-GT)
    • Leukocytes
    • Potassium
    • Sodium
    • Thyroid-stimulating hormone (TSH)
    • Thrombocytes
    • Thyroxin
    • HbA1c
    • Glucose
    • HDL-cholesterol
    • LDL-cholesterol
    • Total cholesterol
    • Triglycerides
    • Insulin-like growth factor-1 (IGF-1)
    • Insulin
    • Insulin c-peptide
    • Leptin
    • Lp(a) 
  • Body composition was measured by dual-energy X-ray absorption. 

Independent Variables

  • CLAFFA
  • CLATG
  • PLAC

Control Variables

  • Diet and exercise was measured by 14-day diet and exercise records at 12, 18 and 24 months
  • Compliance was recorded every three months. The number of capsules delivered was compared with the number returned and a participant was compliant if 75% of CLA capsules were taken.
Description of Actual Data Sample:

Initial N

  • 134 (24 males, 110 females) 
  • The extension study participants were from the original 157 subjects that completed the previous 12-month placebo controlled study
  • For the three groups:
    • CLA-FFA: N=46
    • CLA-TG: N=47
    • PLAC: N=41.

Attrition (final N)

  • 125 (93% completed the study).
  • The three groups had similar withdrawal rates. Withdrawal rates for the groups were:
    • CLA-FFA: N=2
    • CLA-TG: N=3
    • Group PLAC: N=4.

Age

  • Mean years ± SD:
    • CLA-FFA: 45.1±10.5
    • CLA-TG: 48.6±10.6
    • PLAC: 45.1±8.8
  • There were no statistical differences reported in age between the groups. 

Other Relevant Demographics

Compliance in taking supplements was similar across groups: 95% in group CLA-FFA and 94% in groups CLA-TG and PLAC.

Anthropometrics

BMI was 25 to 30kg/m2.

Location

Norway. 

Summary of Results:
  • Adverse events: 
    • 50% of subjects reported AEs for a total of 124 single events. Frequencies were similar in groups (P=0.26).
    • Seven AEs were deemed related to supplementation (all were mild)
    • Gastrointestinal complaints were the most reported drug-related AE
    • Serious adverse events: During the trial, SAEs were reported by eight subjects, but they were deemed unrelated to the supplementation
  • Blood analyses: 
    • Hemoglobin, bilirubin, chloride, CPK, creatinine, erythrocytes, y-GT, potassium, sodium, TSH, thyroxin and IGF-1 did not change with supplementation
    • Total cholesterol:
      • Lower in group CLA-FFA at month 24 than month zero; Δ24-0 = -0.23±0.73mmol per L, P<0.05
      • Not significantly lower in CLA-TG at month 24 compared with month zero
    • HDL-cholesterol:
      • CLA-FFA did not change between month zero and 24
      • CLA-TG decreased between month zero and 24; Δ24-0 = -0.09±0.26mmol per L; P=0.026
      • PLAC did not change significantly between month 12 and 24
    • LDL-cholesterol and triglycerides did not change significantly in any of the groups
    • Lp(a):
      • CLA-FFA increased between month zero and 24; Δ24-0 = 54±122mg; P<0.05   
      • CLA-TG increased between month zero and 24; Δ24-0 = 58±138mg; P<0.05
      • PLAC increased between month 12 and 24; Δ24-12 = 47±106mg; P<0.05
    • Blood glucose:
      • CLA-FFA and CLA-TG: No significant changes between month zero and 24
      • PLAC did not change significantly between month 12 and 24
    • Insulin:
      • CLA-FFA did not change significantly between zero and 24 months
      • CLA-TG increased slightly between months zero and 24; Δ24-0 = 14.9±39.2pmol per L; P=0.01
      • PLAC: No significant change
    •   Leptin:
      • CLA-FFA decreased between month zero and 24; Δ24-0 = -221±431pmol per L; P<0.001
      • CLA-TG decreased between month zero and 24; Δ24-0 = -347±448pmol per L; P<0.001  
      • PLAC decreased between month 12 and 24; Δ24-12 = -383±460pmol per L; P<0.001
    • ALAT: No significant changes observed for any groups
    • ASAT: 
      • CLA-FFA increased between month zero and 24; Δ24-0 = 3.07±6.28U per L; P<0.002 
      • CLA-TG increased between month zero and 24; Δ24-0 = 2.25±5.44U per L; P<0.009
      • PLAC: No significant change
    • Leukocytes:
      • CLA-FFA increased between month zero and 24; Δ24-0 = 0.60±1.76 10g per L; P=0.028
      • CLA-TG increased between month zero and 24; Δ24-0 = 0.92±1.21 10g per L; P<0.001
      • PLAC: No significant change
    • Thrombocytes:
      • CLA-FFA increased between month zero and 24; Δ24-0 = 31.8±37.1 10g per L;  P<0.001
      • CLA-TG increased between month zero and 24; Δ24-0 = 35.8±48.3 10g per L; P<0.001
      • PLAC increased between month 12 and 24; Δ24-12 = 24.1±30.8 10g per L; P<0.001
  • Vital signs: Blood pressures and heart rates were within normal ranges; no differences between or within groups over the 24-month study
  • BMI and body weight:
    • Reductions in BMI and body weight were observed at month 24 as compared to month zero in CLA-FFA (change of -1.5±4.1kg, P=0.013) and CLA-TG (change of -2.4±3.4, P<0.001)
    • In PLAC, body weight was reduced by -1.6±3.2 (P=0.003) between 12 and 24 months
    • Decreases in body weight and BMI were observed during the initial six months of supplementation in groups CLA-FFA and CLA-TG and between months 12 to 18 in PLAC. Following, there was no further reductions in weight or BMI.
  • Body composition:
    • BFM:
      • CLA-FFA: Reduced at 24 months compared to zero months; Δ24-0 = -1.8±3.7kg; P<0.001 
      • CLA-TG: Reduced at 24 months compared to zero months; Δ24-0 = -2.7±3.4kg; P<0.001 
      • For both CLA-FFA and CLA-TG groups, the greatest fat loss was in first six months of supplementation. In months 12 to 24, no further loss of fat mass was observed.
      • PLAC: Reduced at 24 months compared to 12 months; Δ24-12 = -1.7±2.8kg; P<0.00; most fat loss occurred during the first six months of supplementation
    • LBM: No significant changes observed in any groups
    • Bone mineral mass: No significant changes observed in any groups
  • Diet and exercise:
    •  Energy intake:
      • CLA-FFA: Significant reduction in energy intake at month 24 compared to month zero; Δ24 -0 =-870±1,510kJ per day; P<0.05
      • CLA-TG: Significant reduction in energy intake at month 24 compared to month zero; Δ24 -0 = -1,289±2,159kJ per day; P<0.05
      • PLAC: No changes observed between 12 and 24 months
    • Exercise: No significant changes observed in any of the groups
    • No correlations were observed between changes in body weight and body composition with changes in diet or exercise.

 

Author Conclusion:
  • Supplementation with CLA for 24 months led to a significant reduction in body fat mass (6% to 8%). Lean body mass was maintained.
  • CLA was well tolerated. Changes in safety parameters were within normal ranges.
  • Authors conclude that CLA supplementation is safe and could be helpful as a weight loss supplement.
Funding Source:
Other: Cognis Nutrition and Health Ltd.
Reviewer Comments:
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? N/A
  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? N/A
  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