ONC: Dietary Supplements and Medical Food Supplements Containing Fish Oil (2013)


Murphy RA, Mourtzakis M, Chu QS, Baracos VE, Reiman T, Mazurak VC. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer. 2011 Apr 15; 117(8): 1,775-1,782. Epub 2011 Feb 28.

PubMed ID: 21360698
Study Design:
Non-Randomized Controlled Trial
C - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:

To examine the effect of nutritional intervention with fish oil (FO) on weight and body composition against standard of care (SOC) during the course of chemotherapy.

Inclusion Criteria:
  • A histologically confirmed diagnosis of non-small cell lung cancer
  • Naive to chemotherapy
  • A CT image ±45 days from the initiation of chemotherapy (mean, 25±3 days) and a second CT image ±45 days after receiving chemotherapy (mean, 21±5 days) were included in the analyses.
Exclusion Criteria:
  • Patients without histologically confirmed diagnosis on non-small cell lung cancer
  • Patients who were not naive to chemotherapy
  • Patients who had not received two CT images during the six weeks.
Description of Study Protocol:


All newly referred patients with lung cancer at Cross Cancer Institute in Edmonton, Alberta, Canada.


Randomized: To avoid the challenges of previous studies, the current study was designed as an open-label study with a contemporaneous control group.

Blinding Used

Patients meeting eligibility criteria consented to either nutritional intervention with fish oil or standard of care (no intervention). Blood draws and anthropometric measurements were taken at the same time points for both groups.


Patients were instructed to achieve a minimum intake of 2g of EPA per day beginning on the first day of chemotherapy and continuing for the duration of their chemotherapy.

Statistical Analysis

  • Mean ±SE and significance was determined at P<0.05
  • All tests were two-sided
  • Two-sample student T-test and chi-square test were used to determine differences between the fish oil group and standard-of-care group
  • Data for the reference group are provided as a frame of reference and were not compared statistically with the two groups
  • Repeated-measures analysis of variance with Bonferonni comparisons was used to analyze changes in tissue mass from baseline to the end of chemotherapy in the two groups
  • Simple linear regression was used to examine the relation between muscle rate of change and plasma PL EPA
  • Used SPSS statistical software, version 17.0.
Data Collection Summary:

Timing of Measurements

Skeletal muscle and adipose tissue were measured from beginning to completion of first-line chemotherapy.

Dependent Variables

  • Weight: Weight was measured using a medical balance beam scale at baseline and each time point
  • Body mass index: WHO categories were used to classify 
  • Body composition: Skeletal muscle and adipose tissue was analyzed using electronically stored CT images that had been obtained for diagnostic purposes
  • Fish oil supplement compliance: Amount of supplement taken per day was recorded by subjects and any unused capsules or liquid were returned at the time of patient visits. A compliance rate less than 80% resulted in withdrawal from the study
  • Plasma phospholipid fatty acid analysis: Composition was determined by automated gas liquid chromatography.

Independent Variables

2.2g of EPA fish oil supplements per day.

Control Variables

Included a reference group to detail typical baseline characteristics of patients receiving first-line chemotherapy to provide information concerning the expected changes in body composition during chemotherapy.

Description of Actual Data Sample:
  • Initial N: 104 patients met the inclusion criteria
  • Attrition (final N): 40 patients completed the study
    • Fish oil group: 16
    • Standard of care (no intervention) group: 24
    • Reference group: 104.
  • Age (mean ±SD):
    • Fish oil group: 63±2.1 years
    • Standard of care group: 64±1.8 years
    • Reference group: 62±1.0 years.
  • Anthropometrics: There were no significant differences with regard to baseline characteristics and anthropometric measures noted between the fish oil group and standard of care group
  • Location: Cross Cancer Institute in Edmonton, Alberta, Canada.
Summary of Results:
  • Weight: Patients in the standard of care group lost significantly more weight than patients in the fish oil group 
  • Muscle: Approximately 69% of patients in the fish oil group maintained or gained muscle compared with 29% of patients in the standard of care group
  • Estimated whole-body skeletal and fat mass: Loss of skeletal mass was evident in patients in the standard of care group, with some patients losing up to 5.3kg of muscle from baseline to the end of treatment. Loss of skeletal muscle occurred concurrently with increased muscle fat content in the standard of care group.
  • Tumor progression and fish oil supplementation: No significant difference in treatment response was observed
  • Plasma Phospholipid Fatty Acid Analysis: Mean plasma phospholipid EPA in the standard of care group at baseline was comparable to EPA concentrations at the end of the study period. The mean plasma phospholipid EPA in the fish oil group was increased more than two-fold from baseline. There was a positive linear relation noted between change in plasma EPA concentration and rate of muscle change from baseline to the end of the study (R2=0.55; P=0.01).



Author Conclusion:
  • The results indicate that supplementation with fish oil ameliorates muscle and adipose tissue wasting in lung cancer patients and provides a benefit over patients treated with standard of care receiving first-line chemotherapy
  • Patients receiving fish oil maintained weight, muscle mass and adipose tissue throughout approximately 10 weeks of chemotherapy despite presenting with mean weight loss of 6.3% over the previous six months
  • Maintenance of weight and muscle mass reported herein cannot be solely attributed to fish oil intervention
  • Early intervention with fish oil during chemotherapy resulted in maintenance of weight, muscle mass and muscle quality compared with patients receiving standard of care
  • The results of the current study require verification in larger randomized trials.
Funding Source:
Ocean Nutrition Canada and Ascenta Health
Pharmaceutical/Dietary Supplement Company:
University/Hospital: Cross Cancer Institute
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? 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) N/A
  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? Yes
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? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? Yes
  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? 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)? 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