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


Wigmore SJ, Ross JA, Falconer JS, Plester CE, Tisdale MJ, Carter DC, Fearon KC. The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition. 1996;12(1 Suppl):S27-30.

PubMed ID: 8850216
Study Design:
Time Study
C - Click here for explanation of classification scheme.
Quality Rating:
Negative NEGATIVE: See Quality Criteria Checklist below.
Research Purpose:
  1. To determine the effect of dietary fish oil supplementation on nutritional parameters and acute phase response in weight-losing pancreatic cancer patients.
  2. Compare results of fish oil supplementation trial with those observed in a previous study of intravenous (IV) and oral gammalinolenic acid (GLA) supplementation in a similar patient population.
Inclusion Criteria:

Eligible Subjects Must:

  • Have histologically confirmed, unresectable adenocarcinoma of the pancreas (Stages II, III, IV)
  • Eighteen consecutive patients were enrolled in study
Exclusion Criteria:
Not Described
Description of Study Protocol:


  • 18 Consecutive patients with histologically confirmed, unresectable adenocarcinoma of the pancreas
  • Palliative interventions were allowed and included surgical biliary bypass, endoscopic stenting, or no procedure


  • Time series with nutrition intervention
  • Measurements taken at baseline, 1 month after beginning supplementation, and 3 months after beginning supplementation (median = 3 months; interquartile range (IQR) = 3-5 months)

Blinding used (if applicable)

Not applicable

Intervention (if applicable)

  • Nutrition intervention with fish oil (MaxEPA®, Seven Seas Health Care, Hull, UK) containing 18% w/w eicosapentaenoic acid (EPA) and 12% w/w decosahexaenoic acid (DHA)
  • Initial dose = 2 grams/day (g/d) fish oil
  • Fish oil dose increased at weekly intervals by 2 g/week to maximum dose of 16 g/d, if tolerated
  • Each patient acted as his/her own control
  • To rule out placebo effect, weight loss data were compared with data observed during a previous study using a related polyunsaturated fatty acid (PUFA), gammalinolenic acid (GLA)
    • In the comparison (previous) study, 20 study patients received 10-day continuous IV infusion of GLA (median cumulative dose = 7.6 g/day; Scotia Pharmaceuticals, Callanish, UK)
    • After IV GLA administration, patients continued on oral GLA at initial dose of 3 g/d but increasing to maximum of 6 g/d, if tolerated

Statistical Analysis

  • Median and interquartile range
  • Analysis of paired data (CRP & Resting Energy Expenditure) performed using Student's 2 tailed t test
  • Weight loss data (before & after fish oil supplementation) expressed as weight change in kilogram per month (kg/month) and transformed using Oldham equations prior to regression analysis (Oldham PD. Interpretation of numerical data. London: English University Press;1968:110)
  • Weight change in kg/month transformed using Oldham equations prior to regression analysis
  • Comparisons between weight loss before and after GLA and fish oil supplementation made using Mann-Whitney U test
Data Collection Summary:

Timing of Measurements

  • Baseline, 1 month and 3 months after beginning supplementation
  • Median = 3 months
  • Interquartile range (IQR) = 3-5 months)

Dependent Variables

  • Body weight (kg)
    • measurement = spring balance scales (Seca, Germany); weighed without shoes and wearing light clothing
  • Total body water and total body water as percentage of body weight
    • measurement = Liters (L) and %; Determined by multiple frequency bioelectrical impedance analysis (MFBIA) (Xitron 4000 MFBIA Xitron Technologies, San Diego, USA) as previously described in: Hannan WJ, Cowen SJ, Fearon KC, Plester CE, Falconer JS, Richardson RA. Evaluation of multi-frequency bio-impedance analysis for the assessment of extracellular and total body water in surgical patients. Clin Sci. 1994;86(4):479-85.
  • Mid-arm muscle circumference (MAMC)
    • measurement = centimeters (cm) (no further description provided)
  • Triceps skinfold thickness (TSF)
    • measurement = millimeters (mm) (no further description provided)
  • Resting Energy Expenditure
    • measurement = indirect calorimetry with ventilated hood system (Delatrac, S&W Vickers, UK) as previously described in: Falconer JS, Fearon KC, Plester CE, Ross JA, Carter DC. Cytokines, the acute-phase response, and resting energy expenditure in cachectic patients with pancreatic cancer. Ann Surg. 1994;219(4):325-31.
  • C-reactive protein (CRP)
    • measurement = enzyme-linked immunosorbent assay (ELISA) to determine blood concentration

Independent Variables

  • Quantity of fish oil consumed

Additional Analysis

  • To rule out placebo effect, weight loss data were compared with data observed during a previous study using a related polyunsaturated fatty acid (PUFA), gammalinolenic acid (GLA)
    • In the comparison (previous) study, 20 study patients received 10-day continuous IV infusion of GLA (median cumulative dose = 7.6 g/day; Scotia Pharmaceuticals, Callanish, UK)
    • After IV GLA administration, patients continued on oral GLA at initial dose of 3 g/d but increasing to maximum of 6 g/d, if tolerated

Control Variables

  • Regression analysis control variables = age, gender, type of palliation, pretreatment weight loss
Description of Actual Data Sample:


Initial N: 18 (gender of study subjects not provided)

Attrition (final N): 18 (gender of study subjects not provided)

Age: No information provided

Ethnicity: No information provided

Other relevant demographics:

Tumor Stage & Palliation Intervention in Fish Oil & GLA Groups


Fish Oil (n=18)

GLA (n=20)

UICC Tumor Stage II



UICC Tumor Stage III



UICC Tumor Stage IV



Surgical Biliary Bypass



Endoscopic Stenting



No Procedure




  • No difference between Fish Oil & GLA groups on age, gender, type of palliation, pretreatment weight loss
  • No information provided on other anthropometric or demographic variables


Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh, UK

Summary of Results:

Comparisons of Fish Oil Group Before and After Supplementation (n = 18)


Treatment Group
(Fish Oil)
Before Receiving Supplementation

Treatment Group
(Fish Oil) After Receiving Supplementation

Statistical Significance


Rate of Weight Loss

median = -2.9 kg/mo
IQR = -2 to -4.6 kg/mo

median = +0.3 kg/mo
IQR = 0 to +0.5



Baseline (Pretreatment)

1 month

3 months

Body Weight (kg)

62 (52-70)

63 (53-72) ns

62 (52-73) ns

Total Body Water (L)

37 (28-42)

36 (29-42) ns

34 (29-39) ns

Body water as % of body weight

56 (49-61)

55 (51-58) ns

55 (50-63) ns

MAMC (cm)

24 (21-26)

24 (21-26) ns

21 (20-24) ns

TSF (mm)

11 (7-15)

11 (7-14) ns

10 (6-13) ns

REE (kcal/kg/day)

25 (21-27)

24 (20-27) ns

26 (23-28) ns

CRP (mg/L)

15 (5-25)

10 (4-18) p<0.002

16 (10-26) ns

* values = median & interquartile range (IQR)
ns = not significant

Other Findings

  • In fish oil group:
    • 11/18 patients experienced weight gain
    • 3/18 were weight-stable
    • 4/18 continued to lose weight; rate of weight loss slowed from 5 kg/month pre-supplementation to 2 kg/month post-supplementation
  • In GLA group:
    • 1/20 experienced weight gain
    • 19/20 continued to lose weight; rate of weight loss slowed (data not provided) in 5/19
  • Data (numeric or tabular) on GLA intervention not provided. Further information on this study available in: Falconer JS, Ross JA, Fearon KCH. A phase II study of gamma-linolenic acid in pancreatic cancer and its effects on immune function and cytokine production. Horrobin DF, ed. New approaches to cancer treatment. Longman;1994:69.
  • Patients tolerated median dose of 12 grams fish oil/day (IQR = 8 - 15 g/day)
  • Some patients noted offensive tasting reuctations or transient diarrhea
Author Conclusion:
  • In the present study, fish oil supplementation slowed weight loss.
  • Further studies are required to confirm findings and determine active component of fish oil.

Further studies also should address whether or not fish-oil should be combined with additional nutritional support. 

Funding Source:
Scotia Pharmaceuticals (UK)
Pharmaceutical/Dietary Supplement Company:
University/Hospital: University of Edinburgh (UK)
Foundation associated with industry:
Reviewer Comments:
  • Study was small; n=18
  • No real comparison group; the comparison group was a previous study of IV and oral gamma-linolenic acid supplementation; not a true controlled study because comparison group study was conducted prior to fish oil study.
  • This is one of the early studies on fish oil and cachexia and did provide positive enough results to justify further study and future controlled trials.
  • Nearly all absolute value comparisons (exception is CRP at 1 month) were non-significant before and after fish oil supplementation. However, the rate of weight loss in the group decreased significantly from -2.9 kg/month to +0.3 kg/month. This demonstrates the group as a whole had positive outcome with intervention.
  • Advanced pancreatic cancer patients are a very difficult group in which to stablize, let alone improve, nutrition status. Even in those who continued to lose weight, the rate of loss slowed in a clinically (if not statistically) significant manner. This finding is positive.
  • Taking into account the limitations, this study demonstrates that fish oil supplementation is potentially beneficial in cachectic, advanced pancreatic cancer patients.
  • Study does not prove efficacy of fish oil intervention.
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) ???
  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? ???
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? No
  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? No
  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.) 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? N/A
  4.1. Were follow-up methods described and the same for all groups? No
  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.) No
  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? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? No
  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? No
  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? No
  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? No
  7.7. Were the measurements conducted consistently across groups? No
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)? 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? ???
  10.2. Was the study free from apparent conflict of interest? ???