EAL

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

Citation:

Barber MD, McMillan DC, Preston T, Ross JA, Fearon KC. Metabolic response to feeding in weight-losing pancreatic cancer patients and its modulation by a fish-oil-enriched nutritional supplement. Clin Sci (Lond). 2000 Apr; 98(4): 389-399.

PubMed ID: 10731472

Study Design:

Non-Randomized Controlled Trial

Class:

C - Click here for explanation of classification scheme.

Quality Rating:

NEUTRAL: See Quality Criteria Checklist below.

Research Purpose:

To examine the metabolic response to feeding in cachectic cancer patients compared with healthy controls
To examine the effects of an eicosapentaenoic acid (EPA) enriched oral food supplement on this response.

Inclusion Criteria:

Patients with pancreatic cancer who were losing weight but with no clinical evidence of ascites, peripheral edema, diabetes mellitus or malabsorption and weight-stable healthy controls.

Exclusion Criteria:

Receiving chemotherapy or radiotherapy
Surgery in the preceding four weeks
Clinical or radiological evidence of infection
Jaundiced or severely anemic
Receiving steroids.

Description of Study Protocol:

Design

Non-randomized controlled trial.

Intervention

Cancer patients were studied at baseline and after three weeks of consuming an EPA-enriched oral food supplement.

Statistical Analysis

Data presented as median (interquartile range)
Significance tested using Mann-Whitney U test, Wilcoxon signed rank test or Chi-squared test, P<0.05 significance
Software Statview; Abacus Concepts, Berkeley, CA, USA.

Data Collection Summary:

Timing of Measurements

Baseline days one (fasting) and two (fed) for both cancer patients and healthy controls
After three weeks of supplementation for cancer patients only day one (fasting) and two (fed).

Dependent Variables

Weight (kg), weight loss (percentage), fat mass (percentage)
Protein oxidation (mg per kg per minute)
Carbohydrate oxidation (mg per kg per minute)
Fat oxidation (mg per kg per minute)
Resting energy expenditure (kJ per day)
Serum insulin concentration (m units per L)
Serum glucose (mmol per L)
Cortisol concentration (mmol per L).

Independent Variables

Age
Sex
Time.

Control Variables

Healthy weight stable controls were used to assess normal response to fasting and fed states at baseline only.

Description of Actual Data Sample:

Initial N:
- Cancer patients: 10 male, nine female (Note, heading on table indicates N=16 and no other area of the article indicates dropout; therefore, indication of 10 male and nine female may be a typographical error)
- Healthy controls: 6 (three male, three female)
Attrition (final N):
- N=16 cancer patients
- N=6 healthy controls
Age: Cancer patients were significantly (P<0.05) older at median 63 years (range 56 to 66 years) than controls median 54 years (range 50 to 62 years)
Anthropometrics: Controls were significantly (P<0.01) heavier (median 77.2kg) than cancer patients (median 55.2kg) and had significantly (P<0.05) higher fat mass (median 33.4%) than cancer patients (28.1%). Per design, controls were weight stable but cancer patients reflected a median weight loss of 17.1% (P<0.001).
Location: Scotland, UK.

Summary of Results:

Key Findings

There was no difference in overall resting energy expenditure between the cancer and control groups, but the energy expenditure expressed per kg was much higher in the cancer patients due to their decreased weight
The initial fasting serum insulin concentration was significantly lower in cancer patients than controls but rose significantly (P<0.01) over the three-week supplementation period
In the fasting state there was little change in metabolic measurements over a four-hour period for either group
In the fed state, healthy controls showed prompt and substantial increase in insulin concentration but cancer patients had slower increase, which improved after supplementation period.

Fasting Metabolic Features of Weight-losing Cancer Patients and Healthy Controls at Baseline, and of Patients After Three Weeks Consumption of Fish-oil-enriched Supplement

	Cancer Patient Baseline	Controls	Patient V Control P-value	Cancer Patient After Supplement	Patient V Baseline P-value	Patient V Controls P-value
Resting energy expenditure (kJ per day)	5,690	6,170	>0.01	5,440	>0.1	<0.05
REE (kJ per day per kg)	100.4	78.7	<0.005	98.7	<0.05	<0.05
Insulin (m-units per L)	3.3	6.2	<0.05	5.0	<0.01	>0.1
Glucose (mmol per L)	5.5	5.1	>0.4	5.7	>0.2	>0.2
Cortisol (mmol per L)	552	520	>0.3	551	>0.05	>0.6

Other Findings

Protein oxidation was similar in both groups during the fasting state. Carbohydrate oxidation doubled in controls and tripled in cancer patients during feeding. Fat oxidation was greater in cancer patient fasting state than in controls but fell more dramatically upon feeding.
Patients consumed a median of 1.9 cans per day of the supplement (range 1.25 to 2.0)
After supplementation, there were no significant differences between the percentage nutrient utilization of patients after supplementation and control subjects at baseline.

Author Conclusion:

Cancer patients had a lower serum insulin concentration, an elevated resting energy expenditure per unit weight and an increased rate of fat oxidation in the fasting state. When fed, cancer patient exhibited relative glucose intolerance with a reduction in the metabolic cost of feeding compared with controls. After three weeks of supplemental consumption of a fish-oil-enriched (EPA) oral drink, cancer patients exhibited weight gain and an increase in fasting insulin concentration with decreased resting energy expenditure and normalization of substrate utilization.
The results suggest that an EPA-enriched nutritional supplement can reduce the previously elevated resting component of energy expenditure in cancer patients.

Funding Source:

Industry:

Ross Products Division, Abbott Laboratories, Columbus, OH, USA

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

This study was financially supported by Ross Products Division, Abbott Laboratories, Columbus, OH, USA
The subjects were selected with unknown protocols and sample size was small
Some of the significant findings were due to inclusion of weight-related calculations; therefore, weight gain alone may have had impact on the noted improvements, regardless of the supplement components.

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?		???
	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?		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?	No
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	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")?	Yes
4.	Was method of handling withdrawals described?		No
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	4.4.	Were reasons for withdrawals similar across groups?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	Yes
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?	No
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?	No
	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?	No
	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?	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)?	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?	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