EAL

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 investigate whether one year of supplementation with conjugated linoleic acid (CLA) could decrease body weight and body fat mass regain in moderately obese persons after a low calorie diet-induced weight loss.
To assess the safety of the treatment and the influence of CLA on hormones that may influence growth or body fat metabolism.

Inclusion Criteria:

Healthy subjects
Between 18 and 65 years of age
Body mass index (BMI) 28 to 35kg/m²
Written informed consent
Stable body weight (±3kg in the past two months).

Exclusion Criteria:

Younger than 18 or older than 65 years of age
Body mass index less than 28 or greater than 35kg/m²
No written informed consent
Unstable weight (±3kg in the past two months)
Receiving drug therapy
Consuming a special diet
Taking dietary supplements for weight loss
Pregnant or lactating
Subjects with renal, liver, pancreatic or cardiac diseases, those with chronic inflammatory or infectious diseases and those with malignant tumors
Subjects who had active thyroid disease or who were receiving thyroid hormone treatment, and subjects taking adrenergic agonists, with known or suspected drug or alcohol problems or with any clinical condition rendering them unfit to participate.

Description of Study Protocol:

Recruitment

Recruited by two research centers in Denmark

Design

Randomized, double-blind, placebo controlled, parallel-group study with two treatment arms. Initially, all subjects followed a low calorie diet with an energy content of 330 to 4,200kJ per day for eight weeks. All subjects attended six group meetings with experienced dietitians to learn a weight loss regimen. Subjects that lost more than 8% of their initial weight during the LCD were randomly assigned to receive either either CLA or placebo. The two treatment groups received either six times 750mg CLA capsules or six placebo capsules (4.5g olive oil) per day for 52 weeks combined with a modest hypocaloric diet. CLA content of the capsules was approximately 80% of the total lipid content (approximately 3.4g CLA per day). Physical measurements, blood samples, urine samples, ECGs, DXA scans and measurements of blood pressure, waist circumference, hip circumference and pulse were taken four times total.

Blinding Used

Double blind.

Intervention

CLA supplementation of six 750mg CLA capsules or six placebo capsules of olive oil.

Statistical Analysis

Fisher's exact test was used for testing differences in sex distribution and dropout rates between treatment groups
Analysis of covariance used to compare the changes in body fat mass, fat free mass, percentage fat and body weight in the CLA and placebo groups with the use of the week zero value and body weight change as a covariate in addition to treatment center and sex as covariates
Repeated analyses of changes in FM, FFM, percentage fat and body weight performed
Paired T-test used to test changes from week zero to week 52 within treatment groups
Between-group analyses of changes in waist and hip circumferences, energy intake and all blood variables were analyzed with an unpaired T-test
An estimated 37 subjects per group were required for 90% statistical test power and 5% significance level.

Data Collection Summary:

Timing of Measurements

Subjects' characteristics and demographic data were recorded when the subjects entered the study
Body weight, adverse events and concomitant medication recorded at each visit with the dietitian for a total of 14 times during the 52-week treatment
Physical measurements, blood samples, urine samples, ECGs, DXA scans and measurements of blood pressure, waist circumference, hip circumference and pulse were taken four times total; before the LCD period, after the LCD period and after 26 and 52 weeks of treatment
Dietary supplements were returned by subjects at every bimonthly visit.

Dependent Variables

Body weight change measured by DXA scan and weight scale
Changes in fat mass and fat-free mass measured by DXA scan
Hip and waist circumferences
Adverse events as reported by subjects
Blood variables to measure treatment safety.

Independent Variables

Consumption of oral CLA supplement.

Control Variables

Gender
Ethnicity
Smoking habits
Alcohol intake
Body height
Medical conditions
Concomitant medications
Vital signs.

Description of Actual Data Sample:

Initial N: 122 subjects enrolled in the eight-week LCD period, 101 subjects were randomly assigned to one of two treatment groups (gender not discussed)
Attrition (final N): 83 subjects completed the 26-week treatment and 77 subjects completed the entire treatment period
Ethnicity: All subjects were white

Anthropometrics

Significant differences in body weight, BMI, body FM, and lean body mass were observed between the groups at week minus eight (before the LCD period) and week zero (baseline) (P<0.05)
Subjects in the placebo group had higher body weight and BMI than subjects in the CLA group
Percentage body FM was not significantly different between groups at weeks minus eight or zero (baseline)
Hip circumference measurements were slightly higher in the placebo group at baseline compared to the CLA group
No statistical difference between groups for waist circumferences and the ratio of waist to hip measurements.

Location

Two research centers in Copenhagen, Denmark.

Summary of Results:

Key Findings

Changes in body weight, body composition and dietary records:
- Both groups of subjects lost approximately 10kg body weight of which approximately 70% was fat mass
- Energy intake was lower in both groups at week 25 and week 52 than before the LCD with no significant difference observed between the groups
- Both groups regained approximately 3kg body weight when measured by DXA scan and approximately 4kg when assessed on a weight scale with no significant difference between groups
- Gains in FM and FFM were not significantly different between groups
Adverse events:
- Total of 563 adverse events were reported with no significant differences between groups
- 35 of the events were considered related to the treatment
- Of the subjects, 94.1% and 98% of the CLA and placebo groups, respectively, experienced AEs during the study with no significant difference between groups
- Five serious AEs were registered with four events in the placebo group; however, none were related to the treatment
Laboratory analyses:
- Several of the blood variables measured for the assessment of treatment safety changed during the LCD-induced weight loss but these variables recovered during the subsequent weight regain period with no significant difference between the groups
- Leukocyte concentration from week zero to week 52 was significantly different between the groups, with a greater increase in the CLA group than in the placebo group (P=0.03)
- CLA did not significantly affect fasting values of plasma glucose and insulin.

	Change (Week 52-week Zero)	Change (Week 52-week Zero)	P-value	P Between Groups
	CLA	Placebo
Weight (kg)	4.0±5.6	4.0±5.0	<0.001	0.51
Fat mass (kg)	2.13±4.99	2.73±4.92	<0.001	0.56
Fat free mass (kg)	0.94±1.74	0.51±1.77	<0.001	0.33
Percentage fat	1.1±4.0	1.4±3.9	0.002	0.47
Leukocytes (x10⁹per L)	0.81±1.21	0.19±1.14	0.001	0.03

Other Findings

Mean compliance was high in the CLA and placebo groups.

Author Conclusion:

CLA supplementation did not prevent regain of body FM and body weight after a major initial weight loss compared with a placebo. The absence of significant effect on FM and body weight corroborates the findings of other recent studies.

Funding Source:

Industry:

Cognis Corporation, Nutrition & Health Functional Ingredients

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

A perfect group match for body weight was not achieved at randomization.

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?	No
3.	Were study groups comparable?		No
	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?	No
	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?	Yes
	6.6.	Were extra or unplanned treatments described?	Yes
	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?	Yes
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