ONC: Dietary Supplements and Medical Food Supplements Containing Fish Oil (2013)
Citation:
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
- To determine the effect of dietary fish oil supplementation on nutritional parameters and acute phase response in weight-losing pancreatic cancer patients.
- 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:
Recruitment
- 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
Design
- 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 |
2 |
5 |
| UICC Tumor Stage III |
7 |
7 |
| UICC Tumor Stage IV |
9 |
8 |
|
Surgical Biliary Bypass |
6 |
7 |
| Endoscopic Stenting |
7 |
10 |
|
No Procedure |
5 |
3 |
Anthropometrics
- 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
Location
Royal Infirmary of Edinburgh, Lauriston Place, Edinburgh, UK
Summary of Results:
Comparisons of Fish Oil Group Before and After Supplementation (n = 18)
|
|
Treatment Group |
Treatment Group |
Statistical Significance p-value |
|
Rate of Weight Loss |
median = -2.9 kg/mo |
median = +0.3 kg/mo |
p=0.002 |
|
|
|
|
|
|
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 |
|
|
|
| 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:
| Industry: |
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| University/Hospital: | University of Edinburgh (UK) | ||
| Not-for-profit |
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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.
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Quality Criteria Checklist: Primary Research
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| 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? | ??? | |