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

Citation:

 Finocchiaro C, Segre O, Fadda M, Monge T, Scigliano M, Schena M, Tinivella M, Tiozzo E, Catalano MG, Pugliese M, Fortunati N, Aragno M, Muzio G, Maggiora M, Oraldi M, Canuto RA. Effect of n-3 fatty acids on patients with advanced lung cancer: A double-blind, placebo-controlled study. Br J Nutr. 2012; 108: 327-333.

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

To examine the effect of a n-3 fatty acid supplement on nutritional, inflammatory and oxidative parameters in lung cancer patients.

Inclusion Criteria:
  • Advanced inoperable non-small cell lung cancer
  • Men and women
  • Age between 18 and 70 years
  • Weight loss 10% or less during the previous three months
  • Life expectancy two months or more
  • Karnofsky Performance Status 80 or more
  • Informed consent.
Exclusion Criteria:
  • Chemotherapy failure
  • Metastatic disease
  • Presence of diabetes or cardiovascular, infectious, inflammatory, neurological or psychiatric disease
  • Previous cancer diagnosis within the past five years or relapsed cancer
  • Taking n-3 fatty acid supplement.
Description of Study Protocol:

Recruitment

Conducted between May 2007 and May 2008. 

Design

  • Multi-center
  • Randomized
  • Double blind.

Blinding Used

n-3 fatty acid supplement and placebo were packaged identically and were indistinguishable from each other.

Intervention

  • Computer-generated random assignments presented in sequentially numbered sealed envelopes:
    • n-3 fatty acid supplement containing 510mg EPA and 340mg DHA (four capsules daily)
    • Placebo containing 850mg olive oil (four capsules daily).
  • All participants received three courses of chemotherapy with cisplatin and gemcitabine during the study
  • Inflammatory, oxidative and nutritional status was determined
  • Study duration: 66 days.

Statistical Analysis

  • Unpaired T-test evaluated differences between n-3 and placebo groups
  • Paired T-test assessed differences within groups.

 

Data Collection Summary:

Timing of Measurements

  Baseline Day 8 Day 22 Day 66
Weight x x x x
Height x      
Dietary record x x x x
Blood sampling                                x x x x

 

Dependent Variables

  • Nutritional status:
    • Percentage weight loss
    • Serum proteins including albumin, prealbumin and transferrin.
  • Dietary intake:
    • Three-day diet diary
  • n-3 fatty acid concentration:
    • Percent EPA, DHA and docosapentanoic acid (DPA) from plasma lipids
    • Percent EPA, DHA and DPA from phospholipids in erythrocyte membranes.
  • Inflammatory markers (plasma):
    • C-reactive protein
    • IL-6
    • TNFα
    • Prostaglandin E2 (PGE2).
  • Reactive oxygen species markers:
    • Plasma 2',7'-dichlorofluorescin diacetate
    • Plasma hydroxynonenal (HNE).
  • Supplement compliance:
    • Self-reported intake of capsules on food record.

Independent Variables

n-3 fatty acid supplement.

Description of Actual Data Sample:

Initial N

  • n-3 fatty acid: N=19
  • Placebo: N=14.

Attrition (Final N)

  • n-3 fatty acids: N=13 (eight males, five females):
    • Changed oncology departments: N=2
    • Treatment refusal: N=2
    • Diarrhea related to supplement: N=2.
  • Placebo: N=14 (11 males, three females).

Age (Mean±SD)

  • n-3 fatty acids: 55.56±7.35 years (range 46 to 66 years)
  • Placebo: 60.57±7.43 years (range 50 to 70 years).

Other Relevant Demographics

  • Karnofsky Performance Status similar between groups
  • Energy Intake (mean±SD):
    • n-3 fatty acids: 1,990.56±393.44kcal per day (29.22±6.38kcal per kg)
    • Placebo: 1,685.57±169.32kcal per day (26.42±5.65kcal per kg).
  • Protein Intake (mean±SD):
    • n-3 fatty acids: 68.56±15.03g per day (1.02±0.29g per kg)
    • Placebo: 60.00±8.50g per day (0.94±0.24g per kg).

Anthropometrics 

  • Percentage weight loss (mean±SD):
    • n-3 fatty acids: 3.0±3.5
    • Placebo: 2.0±3.3.
  • BMI (mean±SD):
    • n-3 fatty acids: 26.19±6.98
    • Placebo: 25.25±3.92.

Location

Multi-center study (estimated three sites per author affiliations) in Turin, Italy.

 

Summary of Results:

Mean Changes in Nutritional, Inflammatory and Oxidative Status from Baseline to End of Study

Nutrition Status n-3 Fatty Acid Group P-Value Placebo Group P-Value P-Value Between Group Differences
Weight (kg) 78.50±15.94 <0.05 68.92±13.44 NS NS *
BMI 27.65±7.02 NS 25.58±4.43 NS NS
Energy Intake (kcal per day) 2160.00±330.80 NS 1730.29±242.69 NS NS
Protein Intake (g per day) 74.88±17.33 NS 61.43±8.52 NS NS
Energy Intake (kcal per kg) 29.63±7.00 NS 26.11±4.08 NS NS
Protein Intake (g per kg) 1.04±0.32 NS 0.94±0.16 NS NS
Serum Proteins — NS — NS NS
EPA          
Plasma, percent ↑ <0.05 — NS <0.05
Erythrocyte membrane, percent ↑ <0.05 — NS <0.05
DHA          
Plasma, percent  ↑ <0.05  — NS  <0.05 
Erythrocyte Membrane, percent  — NS  — NS  NS 
Inflammatory Status          
CRP —  NS ↑ <0.05 <0.05
IL-6 ↓ NS ↑ NS <0.05
TNFα —  NS ↑ NS NS
PGE2 ↓ <0.05 — NS NS
Oxidative Status          
ROS ↓ —  ↑ NS <0.05
HNE ↓ <0.05 ↑ NS <0.05

 

* NS: Non-significant. 

Author Conclusion:

Patients with lung cancer consuming a n-3 fatty acid supplement while receiving chemotherapy experienced a significant reduction in inflammatory and oxidative markers as well as a significant increase in body weight.

Funding Source:
Industry:
Sigma-Tau S.p.a.
Pharmaceutical/Dietary Supplement Company:
University/Hospital: Piedmont Region grant; University of Italy, Turin
Reviewer Comments:
  • Short-term study (66 days) with a dropout rate of 32%; not intention to treat
  • No sample size calculation
  • Compliance with capsules was not reported. Plasma levels of EPA and DHA were used to confirm compliance with treatment.
  • Participants met with RD weekly but it wasn't clear whether counseling occurred in addition to diet diary review
  • Didn't measure changes in lean body mass
  • Did not specify the number of sites included in the study.
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? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  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.) 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")? 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? 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? 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? Yes
  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? 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)? 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? 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