DFA: Linoleic Acid (LA) and Intermediate Health Outcomes (2011)

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

To define and study fatty acid (FA) factors as measures of dietary fat quality and endogenous FA metabolism in relation to metabolic syndrome (MetS).

Inclusion Criteria:
  • Subjects in this study were taking part in a population-based cohort study, the Uppsala Longitudinal Study of Adult Men (ULSAM)
  • This study started in Uppsala, Sweden, in 1970 and all men born between 1920 and 1924 and living in Uppsala were invited to take part
  • The subjects were examined at baseline at age 50 years of age, and were reinvestigated at the ages of 60, 70, 77 and 82 years
  • The ULSAM cohort analyzed data collected at age 50 (N=2,322) and age 70 (N=1,221)
  • In this cross-sectional study, complete FA data on subjects at age 50: N=2,009
  • A randomly selected sub-sample of subjects at age 70 and who had complete FA data for this cross-sectional study: N=576.  
Exclusion Criteria:

Not defined.

Description of Study Protocol:


  • Subjects in this study were taking part in a population-based cohort study, the Uppsala Longitudinal Study of Adult Men (ULSAM)
  • This study started in Uppsala, Sweden, in 1970 and all men born between 1920 and 1924 and living in Uppsala were invited to take part.


Prospective cohort study.

Statistical Analysis

  • The normal distribution of the continuous variables was examined with Shapiro-Wilk’s test, and skewed variables were log transformed
  • Descriptive results are presented
  • Differences in means were explored by analysis of variance
  • Tests for trend between the numbers of MetS criteria in relation to the factor one score were carried out by using linear regression analysis
  • Cross-sectional and prospective univariate and multivariate logistic regression analysis was performed with the different factor scorings as independent variables at age 50 y and were adjusted for BMI, smoking habit and physical activity
  • P<0.05 were considered significant.
Data Collection Summary:

Timing of Measurements

At 50 and 70 years of age in the population-based cohort.

Dependent Variables

Metabolic syndrome.

Independent Variables 

Fatty acids in serum lipids as a measure of dietary fat quality. 

Description of Actual Data Sample:
  • Initial N: 
    • Subjects at age 50: N=2,009
    • Subjects at age 70: N=576  
  • Attrition (final N): As above
  • Age: 50 years; 70 years
  • Other relevant demographics: The prevalence of MetS among those with complete FA data were 14% (281 of 2,009) at age 50 years and 26% (147 of 576) at age 70 years, which suggests that the sub-samples with complete FA data were representative.
  • Location: Uppsala, Sweden.
Summary of Results:

 Key Findings

  • The factor analysis generated three major FA factors:
    • A low–linoleic acid (LA) factor
    • A dietary saturated FA factor
    • An n-3 polyunsaturated FA (PUFA) factor
  • All factors differed between those subjects with MetS 14% (N=281 of  2,009) and those without MetS at age 50 years
  • Only the low-LA factor differed at age 70 years, which suggests an association between MetS and fat quality
  • The low-LA factor (odds ratio: 1.51; 95%CI: 1.28, 1.79; P<0.0001) and the n-3 PUFA factor (0.76; 0.64, 0.90; P<0.001) predicted MetS development over 20 years, independent of smoking habits, physical activity and BMI.

 Other Findings

  • The mean score for the low-LA factor increased with 0.23 and 0.20 for each added MetS risk factor at ages 50 and 70 years, respectively (P <0.0001)
  • A high factor one (low-LA) and a low factor three (n-3 PUFA) significantly predicted the development of MetS over 20 years, independent of lifestyle factors, suggesting that changes in FA composition and desaturase activities appear long before the onset of MetS
  • Some differences concerning the relations between the FA factors and MetS at ages 50 and 70 years may reflect differences in fat intake, differences in enzyme activity or limited power in the analyses, especially at age 70 years.
Author Conclusion:

The authors support the current dietary recommendations to increase PUFA intakes and restrict saturated FA intakes based on their assumption that the generated FA factors represented dietary fat quality and endogenous FA metabolism which may be important in the development of MetS.

Funding Source:
Foundation for Geriatric Research, Swedish Diabetes Association, Swedish Heart-Lung Association
Reviewer Comments:
  • Some of the population-based cohort protocol was published elsewhere, so the inclusion and exclusion criteria information were limited and somewhat unclear
  • It was unclear exactly which lab(s) or where the subjects went for their testing on each occasion. The location was not disclosed, nor was it clear if the same staff completed the FA analyses. It was noted that the FA composition was analyzed with different equipment and the protocols were published elsewhere.
  • It was unclear why only a random sample of the 70-year-olds was used as a sub-sample
  • The random sampling method was not disclosed
  • It was unclear if the measures were conducted consistently since the specific protocol information was published elsewhere and this was a 20-year prospective study. It was unclear if the setting had changed in the 20 years and whether there was more than one location where the measures were conducted.
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) N/A
  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) N/A
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? ???
  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? No
  2.2. Were criteria applied equally to all study groups? ???
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  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? N/A
  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? 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? N/A
  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? Yes
  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? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  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? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  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? N/A
  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? ???
  7.7. Were the measurements conducted consistently across groups? N/A
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? 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