ONC: EPA/Omega 3 Fatty Acids (2006)
To determine if a fish oil-enriched oral, liquid nutritional supplement (standardized to deliver 1.09 g eicosapentaenoic (EPA) per serving) can reverse weight-loss (produce weight gain) in advanced pancreatic cancer patients.
Eligible subjects must:
- Be a male or female between 18 to 80 years of age
- Have Histologically confirmed or unequivocal operative or radiological diagnosis of unresectable adenocarcinoma of pancreas
- Have a life expectancy > 2 months
- Have a WHO performance status < 2 at enrollment
- Written, informed consent
- Evidence of ongoing weight loss
Patients were ineligible to participate if they:
- Had received surgery or endoscopic stenting during the previous 4 weeks
- Had other active medical conditions
- Had another malignancy
- Were receiving medication that could profoundly modulate metabolism or weight
- Pregnancy or lactation
Recruitment
- 20 patients recruited to study
- None had received radiotherapy or chemotherapy
- On enrollment, none of the participants were jaundiced, pyrexial, ascitic, severely anemic, had evidence of infection or were taking steroids
- All patients had adequate pain control
- Pancreatic enzyme supplements were prescribed if patients had or developed clinically evident steatorrhea
Design
- Time series with nutrition intervention
- Study approved by Lothian Ethical Committee
- Each patient served as his/her own control with measures taken at baseline, 3 weeks, and 7 weeks until death, withdrawal from study, or deterioration of physical condition
Intervention
- Nutrition intervention of oral, liquid nutritional supplement enriched with fish oil, standardized to deliver 1.09 g eicosapentaenoic (EPA) per serving
- Subjects instructed to consume 2 servings (cans) per day of nutritional supplement in addition to regular intake (nutritional supplement provided by Ross Products)
- 2 servings per day provided 610 kcal, 32.2 g protein, 2.2 g EPA, and 0.96 decosahexaenoic acid (DHA)
- Compliance with nutrition intervention was measured by patient diary and return of labels of cans consumed as well as the plasma fatty acid analysis.
Statistical Analysis
- Median and interquartile range
- Analyzed on intention-to-treat basis
- Paired comparisons with baseline values using Wilcoxon signed rank test.
- p-value < 0.05 denotes significance
Timing of Measurements
- Baseline, 3 weeks, and 7 weeks
At initial visit:
- Assessment of height, pre-illness weight and duration of weight loss
Dependent Variables
*All variables measured at baseline, 3 weeks, and 7 weeks unless otherwise noted
- Weight
- Mid-arm muscle circumference (MAMC)
- Triceps skin-fold thickness (TSF) - 3 measures performed and mean value recorded
- Body composition - total body water values derived using validated equation (Hannan et al, 1995); lean body mass (LBM) calculated
- Dietary intake - baseline and 3 weeks; measured using 3-day food diary
- Energy expenditure - baseline and 3 weeks; resting energy expenditure (REE) measured (Falconer et al, 1994) after overnight fast using ventilated hood system
- C-reactive protein (CRP)
- Plasma phospholipid fatty acid analysis - baseline and 3 weeks
- Karnofsky performance status - baseline and 3 weeks and monthly thereafter
- Appetite - baseline and 3 weeks and monthly thereafter; measured on numerical scale of 0 to 10 where 0 = absolutely no appetite and 10 = extremely good appetite (Simons et al, 1996)
- Survival - recorded from time of diagnosis and study baseline to time of death
- Labs were drawn for LFTs, glucose, urea, electrolytes and CBC
- History and physical performed
Independent Variables
- Nutrition intervention with oral, liquid nutritional supplement which provided 610 kcal, 32.2 g protein, 2.2 g EPA, and 0.96 decosahexaenoic acid (DHA) per day
Control Variables
- N/A
Initial N:
- 20 participants; 10 males and 10 females
Attrition (final N):
- 18 available for analysis at 3 weeks (2 patients unavailable for analysis due to disease progression)
- 13 available for analysis at 7 weeks (5 additional patients unavailable for analysis due to disease progression)
- Reasons for stopping the supplement during the 7-week study period were:
- temporary interruption in supply of one patient (after 3 weeks)
- excessive weight gain in one patient (after 3 weeks)
- dislike of taste in two patients (after 3 weeks)
- progression of disease in remainder
- All 18 patients assessed at 3 weeks were consuming the supplement
- 12 of 13 patients assessed at 7 weeks were consuming the supplement
Age:
- Median = 62
- Range = 51-75
Ethnicity:
- Not provided
Other demographic variables:
- Tumor stages:
Stage | No. of pts. |
II | 8 |
III | 3 |
IV | 9 |
- Previous treatments
Treatment | No of pts. |
Chemotherapy | 0 |
Radiation | 0 |
Stenting | 8 |
Surgery | 8 |
- No clinical evidence of ascites or edema noted for the 7 week study period.
Anthropometrics
- Baseline Weight = 55.2 kg (48.8-61.2)
- Baseline BMI = 19.8 kg/m2 (17.8-21.8)
- Rate of weight change per month pre-intervention = -2.9 kg (-4.4 - -2.2)
- Percent weight loss from usual body weight (UBW) = 17.9% (15.9-22.8)
- MAMC = 20.8 cm (18.4-22.4)
- TSF = 11.1 mm (7.8-15.9)
- Percent Total body water = 52.9% (51.2-56.1)
- LBM = 41.5 kg (38.1-44.8)
- Fat mass = 14.5 kg (12.8-16.7)
Other Clinical Variables
*Values reported are median (interquartile range)
- CRP = 10 mg l-1 (<10-27)
- Karnofsky performance status = 85 (80-90); Score ranges from 10 (moribund) to 100 (normal)
- Appetite = 5 (3-7); Score ranges from 0 (no appetite) to 10 (excellent appetite)
Location:
- University Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH8 9JA, UK
Variables |
Three Weeks1 |
Seven Weeks1 |
Weight Change (kg) |
+1.0 (-0.1 + 2.0) |
+2.0 (-0.4 + 4.6) |
MAMC Change (cm) |
0 (-0.2 + 0.5) |
+0.4 (-0.7 + 1.1) |
TSF Change (mm) |
0 (-0.2 + 0.4) |
-0.2 (-0.5 + 0.5) |
% Total body water Change |
+0.1 (-0.3 + 1.9) |
-0.1 (-0.4 + 1.5) |
LBM Change (kg) |
+1.0 (+0.6 + 1.4) |
+1.9 (+1.0 + 3.0) |
Fat mass Change (kg) |
-0.2 (-0.8 + 0.9) |
+0.2 (-0.6 + 2.0) |
CRP Change (mg/l) |
0 (0 + 3) |
0 (-5 + 22) |
Karnofsky performance status Change3 |
+10 (0 + 10) |
+10 (0 + 10) |
Appetite Change4 |
+1 (0 + 1) |
+1 (0 + 1) |
Caloric Intake (kcal/d) |
1798 (1355-2474)5 |
N/A |
REE (kcal/d) |
1303 (1188-1470)6 |
N/A |
REE/kg body weight (kcal/kg/d) |
24.0 (20.2-25.8)7 |
N/A |
REE/kg LBM (kcal/kg/d) |
31.8 (27.7-33.9)8 |
N/A |
1 Values are median (interquartile range)
2 p-value for paired comparison with baseline value using Wilcoxon signed rank test
3 Score ranges from 10 (moribund) to 100 (normal)
4 Score ranges from 0 (no appetite) to 10 (excellent appetite)
5 Baseline = 1450 kcal (1048-2043)
6 Baseline = 1339 kcal/kg/day (1159-1448)
7 Baseline = 24.2 kcal/kg/day (23.1-27.7)
8 Baseline = 34.0 kcal/kg/day (29.6-35.6)
Consumption of nutritional supplement
- median 1.9 cans (range 1.2-2 cans/day)
No significant changes in lab values of course of study.
- This small pilot study suggests that a fish oil-enriched oral, liquid nutritional supplement has the potential to be a safe, effective, anti-cachectic agent vs. conventional nutritional supplements.
- A randomized, controlled trial is required to confirm the observed anti-cachectic effect, evaluate effect on survival, or any as yet undetected side-effects.
- Pancreatic cancer patients who were previously losing weight were able to gain weight in this study due to the consumption of a fish oil-containing nutritional supplement
- Pancreatic cancer patients who continued to lose weight on the study did so at a slower rate than prior to the study
- Hydration remained stable in this study population (reported as TBW as % of BW)
- Patients in this study appeared to be gaining lean body mass versus just water weight in terms of weight gain.
- The increase in Karnofsky performance status could be related to improvements in LBM.
- TSF and MAMC levels did not change and reflect evidence that protein and fat stores were preserved by the administration of omega-3 fatty acid supplement.
- Caloric intake improved by 500 kcal/day
- Appetite improved in the initial stages of the study
- No toxicities were noted from the supplement
- Fish-oil supplement may have prevented an increase in C-reactive protein levels
- This is a good preliminary pilot study.
- This study suggests an EPA-enriched oral, liquid nutritional may halt and/or reverse cancer cachexia.
- There was no control group so cannot rule out that effects were due to simple increases in intake of calories & protein.
- A controlled trial is required to confirm these findings.
- It should be noted that one of the authors, AC Voss, is an employee of Ross Products who supplied the nutritional supplement used in this study
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) | 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? | ??? | |
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? | N/A | |
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? | ??? | |
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.) | 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? | 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? | 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? | 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? | ??? | |
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? | 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? | 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)? | ??? | |
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? | No | |
10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
10.2. | Was the study free from apparent conflict of interest? | No | |