ONC: EPA/Omega 3 Fatty Acids (2006)
Barber MD, Fearon KCH, Tisdale MJ, McMillan DC, Ross JA. Effect of a Fish Oil-Enriched Nturitional Supplement on Metabolic Mediators in Patients with Pancreatic Cancer Cachexia. Nutr Cancer 2001;40(2);118-124.PubMed ID: 11962246
To report the effects of a fish oil-enriched nutritional supplement on a variety of cytokine and hormonal mediators and other metabolic indicators in an attempt to explain the mechanisms whereby addition of fish oil to a conventional nutritional supplement may alter the metabolic milieu and allow the restoration of body composition toward normality.
Men and non-pregnant, non-lactating women, 18-80 years with
- histological confirmation or unequivocal opertive or radiological diagnosis of unresectable adenocarcinoma of the pancreas, and
- evidence of ongoing weight loss, and
- life expectancy > 2 months, and
- WHO performance status < 2 at enrollment, and
- written informed consent
- surgery or endoscopic stenting in previous 4 weeks
- receiving medications that could modulate metabolism or weight
- other active medical conditions
- other malignancies
Recruitment: Not described
Design: 20 patients were recruited for a 3 week study. They were asked to consume 2, 8-oz cans of a fish oil-enriched nutritional supplement daily. Study measurements were made at baseline and at 3 weeks.
Blinding used (if applicable): Not blinded
Intervention (if applicable): Patients were asked to consume 2, 8-oz cans of fish oil-enriched nutritional supplement daily during the 3 week study period (Total nutrient provision = 610 Cal, 32.2 g protein, 2.2 g EPA, 0.96 DHA.
The experimental product was provided by Ross Products Division.
Statistical Analysis: Data are presented as the median and interquartile range. Paired comparisons with baseline values were performed using Wilcoxon signed rank test or chi-square test for categorial data. P<0.05 denoted significance.
Timing of Measurements: At baseline and 3 weeks, the following measurements were made:
- Serum cytokine concentrations were measured using accepted methods
- soluble TNF receptors
- soluble IL-6 receptors
- Peripheral blood mononuclear cell (PBMC) cytokine production. PBMC were prepared using accepted methods then resuspended in culture medium with a) 10% fetal calf serum or b) autologuous plasma in the presence or absence of 10 micrograms E coli lipopolysaccharide (LPS)/mL .
- PBMC IL-1 Beta
- Serum hormone concentrations were measured after an overnight fast using accepted methods
- Urinary proteolysis inducing factor (PIF) was measured using a described method
- Body weight was measured using a beam scale.
Initial N: 20 patients (10 male; 10 female) were recruited. At enrollment none had
- fever (pyrexia)
- severe anemia
- clinical or radiological evidence of infection
- undergone chemotherapy or radio therapy at any time in their diseae
All had adequate pain control at time of study.
Pancreatic enzyme supplements were administered if patients had or developed clinical evidence of statorrhea.
Attrition: 2 patients were unavailable for assessment at week 3 due to deteriorating conditions (n=18 at week 3). Because of transport problems, urine samples of 2 patients were not availble for assessment at week 3 (n for PIF =15 at week 3).
Other relevant demographics:
- Sex = 10 men, 10 women (n=20)
- Median age = 62 (range 51-75 y)
- Cancer stage:
- Stage 2: 8 patients
- Stage 3: 3 patients
- Stage 4: 9 patients
- Stage 2: 8 patients
- Cancer location:
- Pancreas head: 17 patients
- Pancreas body: 3 patients
- Cancer diagnosis basis:
- 16 via histology
- 4 via unequivocal operative or radiologic findings
- Palliative surgery/stenting prior to study=8/8 respectively
Median nutritional supplement consumption = 1.9 cans/day assessed by food diaries and return of labels from empty cans (range 1.25-2).
Only significant results are included in the following table.
Measures and confidence intervals
Statistical Significance of Difference
|PBMC cytokine production||
Data provided in graph form only. Values not provided.
Data provided in graph form only. Values not provided
A significant decrease innumber of patients with detectable urine PIF
|P = 0.008|
|University/Hospital:||Royal Infirmary of Edinburgh NHS Trust|
|In-Kind support reported by Industry:||Yes|
Patients included in this study are a subset of patients described in Barber MD, et al. Br J Cancer 1999;81:80-86.
Sample size was extremely small. No description of power study results that would have established this as an appropriate sample size.
Ranges of data results are wide and many findings reported as median as opposed to mean.
There was no placebo control. Because of lack of placebo control these findings do not support authors' conclusions that fish oil was the component of the nutritional supplement as there was no comparison to a non-fish oil containing control product.
Study did not test the hypothesis.
On re-analysis to determine if this study helps elucidate if EPA helps to reduce the catabolic effects of cancer, the same comments hold. Because the study was not controlled, no conclusions can be drawn regarding the value of EPA.
Quality Criteria Checklist: Primary Research
|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|
|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?||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?||Yes|
|3.3.||Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)||No|
|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.)||???|
|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?||N/A|
|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%.)||N/A|
|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?||No|
|5.1.||In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?||No|
|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?||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?||Yes|
|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?||No|
|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)?||No|
|8.6.||Was clinical significance as well as statistical significance reported?||No|
|8.7.||If negative findings, was a power calculation reported to address type 2 error?||No|
|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|