EAL

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 assess whether the addition of oral calories and protein in conjunction with fish oil could reverse weight-loss in patients with advanced pancreatic cancer.

Inclusion Criteria:

Men or non-pregnant, non-lactating women between 18 and 80 years with

histological confirmation or
unequivocal operative or
radiological diagnosis of unresectable adenocarcinoma of the pancreas with evidence of ongoing weight loss plus
life expectancy greater than 2 months,
World Health Organization (WHO) performance status < 2 at enrollment and
Written informed consent

The Lothian Ethical Committee approved the study protocol.

Exclusion Criteria:

Surgery or endoscopic stenting during the previous four weeks
Other active medical conditions
Another malignancy
Receiving medication that could profoundly modulate metabolism or weight

Special note:

No patients had received radiotherapy or chemotherapy

Description of Study Protocol:

Recruitment

A total of 20 patients were recruited for the study. Confirmation of unresectable pancreatic adenocarcinoma was by histology (16/20) or unequivocal operative or radiological findings (4/20).

Design

Timeseries (7 weeks) of twenty patients consented to consume two cans per day of an omega 3 FA supplemented liquid nutritional supplement.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Patients were asked to consume two cans of fish oil-enriched nutritional supplement per day. Each 237 ml can of supplement contained:

310 calories
16.1 grams protein
6.5 grams fat
49.7 grams carbohydrate

Each can of supplement also contained 1.09 grams of eicosapentaenoic acid (EPA), 0.46 grams of docosahexaenoic acid (DHA), 1320 IU vitamin A, 72 IU vitamin E, and 156 mg vitamin C. Patients were instructed to store the supplement in the refrigerator.

Supplement provided by Ross Products Division, ABbott Laboratories, Columbus, OH, USA.

Statistical Analysis

Data are presented as the median and interquartile range.
Paired comparisons with baseline values were performed using Wilcoxon signed rank test.
A P-value of less than 0.05 was taken to denote significance.

Special notes:

Study was analyzed on an intention-to-treat basis.
Due to the inevitable deterioration of patients in this study with a palliative intervention, of the 20 patients initially enrolled, data were available on 18 patients at 3 weeks and 13 patients at 7 weeks.

Data Collection Summary:

Timing of Measurements

Measurements were performed at baseline and 3 and 7 weeks. However, patients continued to be assessed until death, withdrawal from the study or until their condition deteriorated such that further assessment was not possible. Trial results were monitored independently.

Dependent Variables

Toxicity assessment: Blood was measured for full blood count, electrolytes, urea, glucose and liver function tests using standard automated techniques. Toxicity reported to physicians or observed on clinical examination was documented.
Anthropometry: At the initial assessment, height, pre-illness stable weight and duration of weight loss were recorded. Current weight was obtained from patients without shoes and wearing light clothing using a spring balance scales. Mid-arm muscle circumference (MAMC) was calculated using Jelliffe's equation. Triceps skinfold thickness (TSF) was measured using Harpenden calipers.
Body composition analysis: Total body composition and total body water were measured using a multiple frequency bioelectrical impedence analyzer. Lean body mass was calculated assuming that lean tissue contains 73% water.
Nutritional intake: Daily caloric intake was measured at baseline and after 3 weeks of supplement administration. Values were based on the mean intake recorded in a 3-day food diary calculated using CompEat 4 software (Nutrition Systems, London, United Kingdom).
Energy expenditure: At baseline and after 3 weeks resting energy expenditure (REE) was measured after an overnight fast using indirect calorimetry (Deltatrac II, Datex, Helsinki, Finland).
Acute phase protein response (APPR): The APPR was documented by assaying serum C-reactive protein (CRP).
Fatty acid analysis: At baseline and after 3 weeks, plasma phospholipid fatty acid analysis was performed by gas chromatography.
Performance status and appetite: At baseline, 3 weeks, and at monthly intervals thereafter, Karnofsky Performance Status (KPS) was measured. Appetite was measured on a numerical rating scale between 0 and 10, with 0 indicating absolutely no appetite adn 10 indicating extremely good appetite.
Survival: Survival was recorded from the time of diagnosis (date of confirmation of adenocarcinoma of the pancreas) and study baseline to the time of death.

Independent Variables

The fish oil-enriched nutritional supplement, as described above, was assessed by the median number of cans consumed by each patient.

Description of Actual Data Sample:

Initial N: 20 (10 females, 10 males)

Attrition (final N): 13 (number of females and males not provided)

Of the 20 patients enrolled, 18 were available for analysis at week 3 and 13 patients at week 7

Age: Median age 62 years (range 51-75)

Ethnicity: Not provided.

Other relevant demographics: Not provided.

Anthropometrics: Not applicable.

Location: Edinburgh, Scotland, United Kingdom and Birmingham, United Kingdom

Summary of Results:

Table 1. Baseline characteristics of patients with advanced pancreatic cancer and changes in characteristics after 3 and 7 weeks' administration of a fish oil-enriched nutritional supplement

Variables	Baseline n=20	Supplement administration-3 wk n=18 P	Supplement administration-7 wk n=13 P
Weight change, kg	-2.9 (-4.4-2.2)	+1.0 (-0.1+2.0) 0.024	+2.0 (-0.4+4.6) 0.033
MAMC, cm	20.8 (18.4-22.4)	0 (-0.2+0.5) NS	+0.4 (-0.7+1.1) NS
TSF, mm	11.1 (7.8-15.9)	0 (-0.2+0.4) NS	+0.2 (-0.5+0.6) NS
% total body water	52.9 (51.2-56.1)	+0.1 (-0.3+1.9) NS	-0.1 (-0.4+1.5) NS
Lean body mass, kg	41.5 (38.1-44.8)	+1.0 (+0.6+1.4) 0.0064	+1.9 (+1.0+3.0) 0.0047
Fat mass, kg	14.5 (12.3-16.7)	-0.2 (-0.8+0.9) NS	+0.2 (-0.8+2) NS
CRP, mg/L	10 (<10-27)	0 (0 + 3) NS	0 (-5+22) NS
KPS	85 (80-90)	+10 (0 + 10) 0.0047	+10 (0 + 10) 0.046
Appetite	5 (3-7)	+ 1 (0 + 1) 0.001	+1 (0 + 1) NS
Caloric intake/day	1450 (1048-2043)	1798 (1355-2474) 0.0016	No data
REE	1339 (1159-1448)	1303 (1186-1470) 0.18	No data

Abbreviations: MAMC, mid-arm muscle circumference; TSF, triceps skinfold thickness; CRP, C-reactive protein; KPS, Karnofsky Performance Status; and REE, Resting Energy Expenditure

Special notes about data presented in the table: Figures are presented as median values with interquartile ranges in parentheses. KPS is from a score of 10 (moribund) to 100 (normal). Appetite is a score from 0 (none) to 10 (excellent).

Other Findings

Patients consumed a median of 1.9 cans of the fish oil-enriched supplement per day (range 1.2-2).
Full blood count, urea, glucose, and liver function tests did not change significantly during the study (data not presented in article).
Median increase in caloric intake among patients after 3 weeks was 372 kcal/day.
A statistically significant increase in both EPA (P = 0.0003) and DHA (P = 0.0086) in plasma phospholipids occured after 3 weeks of supplementation administration.
A statistically significant improvement in appetite occurred at 3 weeks (P = 0.0095).
Survival: Nineteen of the patients have died. Once patient remains alive at 14 months from the time of diagnosis. The median survival from the time of diagnosis for all patients was 254 days (124-311). The median survival from the time of starting the supplement was 170 days (90-270).

Author Conclusion:

Conclusion

The administration of a nutritional supplement enriched with a fish oil resulted in weight gain in a group of patients with advanced pancreatic cancer who had previously been losing weight at a median rate of 2.9 kg/month.
EPA-enriched supplement may reverse cachexia in advanced pancreatic cancer and be a safe, effective alternative in contrast to conventional nutritional supplements.

Limitations

Not all of the patients who entered the present study completed the 7-week study period. This reflects the advanced stage of the disease and subsequent poor survival of patients with pancreatic cancer. By observing weight change in those survivors who remained in the study at 3 weeks (n=18) and 7 weeks (n=13), there might be a bias to overestimate the efficacy of EPA as an anticachetic agent.
Some patients continued to lose weight after taking the supplement. The reasons for this outcome are not clear because there was no relationship between weight change and disease stage, previous surgery, or the acute phase response.
A randomized, clinical controled trial would be required to confirm the observed anticachetic effect, evaluate any effect on survival and reveal any side effect.

Funding Source:

Industry:

Ross Products Division, Abbott Laboratories

Food Company:

University/Hospital:

Royal Infirmary of Edinburgh NHS Trust

In-Kind support reported by Industry:

Yes

Reviewer Comments:

A suggestive, small pilot study which needs further corroboration by a larger, controlled trial.

Strengths

Excellent compilance from patients. Would like to know how this was achieved, especially when other studies report lower total consumption of fish oil-enriched nutritional supplements.
Supplement consumption resulted in weight gain as well as improved performance status and appetite for patients with advanced pancreatic cancer.
Appropriate and useful outcome measurements.

Limitations

Non-randomized non-controlled timeseries
Small sample size
No information about the the races of patients
Assessment of EPA sources from food not recorded.
Need caloric intake data for 7 weeks of supplement administration.

Project support

Ross Products Division, Abbott Laboratories, Columbus, OH, USA
Royal Infirmary of Edinburgh NHS Trust, Edinburgh, Scotland, UK

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?		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.)	N/A
	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?	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?	N/A
	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.)	N/A
	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?	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?	No
	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?	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