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

Citation:

Ryan AM, Reynolds JV, Healy L, Byrne M, Moore J, Brannelly N, McHugh A, McCormack D, Flood P. Enteral nutrition enriched with eicosapentaenoic acid (EPA) preserves lean body mass following esophageal cancer surgery: Results of a double-blinded randomized controlled trial. Ann Surg. 2009 Mar; 249(3): 355-363.

 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To investigate the potential anticatabolic properties of EPA in a complex major surgery treatment model.

Inclusion Criteria:

All adult patients presenting to the Esophageal and Gastric Center at St. James's Hospital from July 2005 to July 2007 with resectable esophageal cancer.

Exclusion Criteria:
  • Patients with:
    • Metastatic disease
    • Immunologic disorder
    • Cardiac, liver or renal failure
    • Active small intestinal disease (e.g., Crohn's disease)
    • Known allergies to any of the ingredients within the treatment formulas
    • Poorly controlled diabetes
    • Existing use of fish oil and n-3 fatty acids supplements.
  • Emergency esophagectomy cases
  • Patients who could not receive five days of supplementation prior to surgery and patients who had the feeding regimen interrupted for greater than three days in the post-operative period.
Description of Study Protocol:

Recruitment

Patients of St. James's Hospital in Dublin, Ireland.

Design

Randomized trial.

Blinding Used

Double blind.

Intervention

  • EPA treatment arm
  • Pre- and post-operative interventions.

Statistical Analysis

  • Student T-test
  • One-way ANOVA
  • Chi-squared or Fisher exact test for categorical variables
  • Mann Whitney U and Wilcoxon signed rank tests for non-normal distribution
  • Friedman test for changes over time.
Data Collection Summary:

Timing of Measurements

  • Baseline:
    • Nutritional/Body Composition
    • Biochemical
    • Immunological.
  • POD (one, three, seven, 14, 21):
    • Biochemical
    • Immunological.
  • Clinical data and post-operative complications were continuously collected throughout the study and entered into an electronic database.

Dependent Variables

  • Post-operative complications
  • Plasma and cell membrane fatty acid composition
  • SIRS and maximum body temperature 
  • Body composition
  • Acute phase response, cytokines and coagulation markers

Independent Variables

EPA supplementation.

Control Variables

  • Patient characteristics, clinical and nutritional matching
  • Clinical management parameters.
Description of Actual Data Sample:
  • Initial N: 70
  • Attrition (final N): 75.7%; 17 were excluded.

Patient Demographics

  • Male to female ratio was greater (P=0.036) in the EPA group
  • Multi-modal therapy was greater in the EPA group (P=0.496)
  • No difference between groups for age, anthropometrics and albumin.

Location

 St. James's Hospital, Dublin, Ireland.

Summary of Results:

 Key Findings

 
EPA Group
Standard EN Group
Statistical Significance of Group Difference
Change
P-value
Change
P-value
95% CI
Weight loss

Loss 1.2kg fat mass
0.9
 Loss 1.8kg±3.3kg
0.03

0.17, 3.1

  
Lost more than 5% body weight in one month 8% (N=2)
 
 39% (N=10)
 
 
 P=0.03
Lean mass

Gain 0.3kg
0.8
 Loss 1.9kg±3.7kg
0.03

0.17, 3.6

  
Lean mass in legs  
 
 Loss 0.3kg±0.6kg
0.05

-0.01, 0.57

  
Lean mass in arms  
 
 Loss 0.17kg±0.3kg
0.01

0.04 to 0.3

  
Lean mass in trunk  
 
 Loss 1.44kg±2.7kg
0.03

0.12 to 2.76

  

 

 
EPA Group
Standard EN Group
Statistically Significant Difference
X2
P-value
Change
X2
P-value
IL-8 Changes over time
6.5
0.263
  
10.9

0.05

 Higher on POD 7 and 14 for EN Group

P=0.05
IL-10 Changes over time
 
 
  
 
 
 None  
TNF-α concentration
 
 
  
 
 
 None  
Maximum body temperature
 
 
 Increased on POD 1, 3, 4, 5, 6 and 7
 
 
   P<0.01


 

Author Conclusion:

Peri-operative enteral nutrition enriched with 2.2g EPA per day prevents loss of lean body mass in the first three weeks after esophagectomy. The study suggests that EPA at this does has significant anticatabolic effects that may merit evaluation in larger cohorts of patients undergoing complex surgery.

Funding Source:
University/Hospital: St. James Hospital
Reviewer Comments:
  • Analysis of variance between groups was not fully disclosed; rather, within-group statistical significance was reported for a majority of anthropometric and cytokine marker data
  • Data was not controlled for confounding factors nor was it mentioned that statistical controls were utilized for demonstrating between group significance
  • Body temperature data was demonstrated as a table with statistical significance but the data was not discussed in the literature.
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? No
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  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? No
  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? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  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? Yes
  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? No
  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? ???
  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? ???
  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? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? No
  8.1. Were statistical analyses adequately described and the results reported appropriately? No
  8.2. Were correct statistical tests used and assumptions of test not violated? No
  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? 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? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes