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

Citation:

Taylor LA, Pletschen L, Arends J, Unger C, Massing U. Marine phospholipids: A promising new dietary approach to tumor associated weight loss. Support Care Cancer. 2010; 18: 159-170.

PubMed ID: 19404684
 
Study Design:
Time Study
Class:
C - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:

To investigate the effect of a new formulation of marine fatty acids, marine phospholipids (MPL), on weight loss in cancer patients. 

Inclusion Criteria:
  • More than 18 years of age
  • Diagnosis of solid tumor
  • Written informed consent
  • Tumor-associated weight loss.
Exclusion Criteria:
  • Allergy against food from marine sources
  • Current radiotherapy or chemotherapy for at least four weeks previous to dietary intervention
  • Stable weight
  • Less than 18 years of age.
Description of Study Protocol:

Recruitment

Subjects recruited as inpatients from the Department of Medical Oncology at Tumor Biology Center Freiburg between June 2007 and October 2008.

Design

  • Patients were asked to take marine phospholipids as softgel capsule preparation of 500mg three times a day with meals for six weeks.
  • Patients recorded capsule intake, weight, appetite and pain score daily in provided diary.
  • Patients were examined at three points:
    • Before intervention
    • After three weeks
    • After six weeks.
  • Examination included:
    • Blood sampling for routine analysis and determination of lyso-PC and fatty acid profiles in plasma phospholipids
    • Red blood cells (RBC) and  mononuclear lymphocytes (MNL)
    • Physical exam
    • Bioelectrical impedance analysis (BIA)
    • Completion of EORTC QLQ-C30 quality of life questionnaire.

Intervention

  • MPL as softgel capsule preparation of 500mg three times a day with meals for a six-week period 
  • MPL capsules with lipid composition of 67.72g per 100g neutral lipids and 32.75g per 100g polar lipids with 87.5% phosphatidylcholine. Fatty acid profile of 18.8g per 100g eicosapentaneoic acid (EPA) and 22.8 g/100 g docosahexaenoic acid (DHA) bound in neutral lipids and 16.5g per 100g EPA and 33.7g per 100g DHA bound in phospholipids
  • MPL preparation encapsulated into softgel capsules, 500mg per capsule by pharmagel.

Statistical Analysis

Statistical analysis (T-tests, Mann-Whitney and correlation as well as quartile analyses) performed with SigmaState 3.1 and XLStatistics: Excel Workbooks for Statistical Data Analysis.

Data Collection Summary:

Timing of Measurements

  • Capsule intake, weight, appetite and pain scores recorded by patient daily for six-week study period
  • Patient examined before intervention, after three weeks and after six weeks
    • Blood sampling
    • Physical exam
    • Bioelectrical impedance analysis
    • Completion of EORTC QLQ-C30 quality of life questionnaire.

Dependent Variables

  • BMI
  • Body weight
  • Weight change
  • Appetite
  • Global health measured by EORTC QLQ-C30
  • BIA results
  • Laboratory parameters.

Independent Variables

MPL supplementation of 500mg three times daily.

Control Variables

  • Compliance with MPL capsule intake
  • Tumor entity
  • Age
  • Gender.
Description of Actual Data Sample:
  • Initial N: 38 subjects eligible for study, 31 subjects (16 females, 15 males) enrolled in study
  • Attrition (final N): 17 subjects (10 females, seven males)
  • Age: 59.2±13.4 years for all enrolled subjects, 62.2±8.9 years for analyzed patients.

Other relevant demographics: 

  • Tumor entity (number of patients):
    • Urogenital: Three patients
    • Gynecological: Eight patients
    • Gastrointestinal: 12 patients
    • Other: Eight patients

Anthropometrics

Baseline BMI, body weight and weight loss since first diagnosis the same between all subjects and analyzed subjects.

Location

Freiburg, Germany.

 

Summary of Results:

 Key Findings

  • Tumor progression during MPL intake:
    • Nine out of 17 patients had no measurable tumor progression during MPL intake
    • Only one patient suffered progression that had been classified as stable disease in the period of time before intervention and all other patient experiencing progression during MPL intake were experiencing progressive disease in period before intervention.
  • Laboratory parameters:
    • Results of routine blood analysis show no changes in all routine blood parameters documented
    • Only high-density lipoprotein (HDL) fraction significantly increased 30% on average after six weeks of MPL intake (P=0.029).
  • BIA: Results showed no changes in all determined parameters
  • Influence of MPL intake on fatty acid profiles of blood cells and plasma: Intake of capsules over a six-week period induced a significant change in fatty acid profiles of blood cells and plasma PL regarding PUFA (AA, EPA, DHA) content
  • Influence of MPL intake on body weight:
    • Body weight was measured and documented every day by the subjects
    • Compared to baseline, median body weight is stable throughout the six weeks of MPL intake (+0.6% body weight)
    • Media weight loss in the group of analyzed patients during the six weeks before MPL intake was -2.0% body weight
    • Median change of weight before MPL intake is clearly of negative value while the median change during MPL intake is slightly positive
      • The difference would be significant (P=0.037)  but necessary to consider that mathematical comparison is problematic as the weight values six weeks before intervention were only single values that were not documented in the same fashion as weight values during MPL intake.
    • Five out of 17 patients (29%) already experienced some weight gain during the six weeks previous to MPL intake while 10 of 17 gained weight during MPL intervention.
  • Correlation between body weight change and fatty acids: Observed effects of MPL intake on fatty acid profiles in the plasma PL and the patients' weight positively correlate (R=0.64, P=0.006) and similar relationship observed between percentage of EPA in total RBC fatty acids and median weight change (R=0.64; P=0.005) but not in MNL or with DHA percentages
  • Quality of life:
    • Comparison of individual scores before and after MPL intake resulted in positive changes
    • Translating the changes of median scores in our investigation, improvement of functional scores was moderate (social score) to very much (physical and role score), improvement of appetite was moderate while pain reduction and improvement of global health was perceived as very much.  
Parameter Week Zero Week Six Statistical Significance of Group Difference
Triglycerides (mg per dL) 139±72 136±68  
Total cholesterol (mg per dL) 177±59 170±42  
VLDL (mg per dL) 13±9 10±6  
LDL (mg per dL) 133±58 118±45  
HDL (mg per dL) 43±13 56±18 P=0.029
Lyso-PC (umol) 187±103 182±131  
CRP (mg per dL) 1.7 (median) 1.8 (median)  
IL-1 (pg per ml) ND (<3/9) ND (<3/9)  
IL-6 (pg per ml) 27.9±37.2 38.9±53  
TNFα (pg per ml) 2.3±3.1 2.9±4.1  
BMI (kg/m2) 20.2+3.7 20.2+3.4  
Phase angle (at 50 kHz) 4.9±0.9 4.7±1.1  
Lean body mass (kg) 39±8.6 39.6±7.7  
Fat mass (kg) 21.2±7.2 20.1±7  
Intracellular water (liter) 15.2±3.3 14.4±3  
Extracellular water (liter) 15.7±3.4 16.3±4.4  

 

Other Findings

 Compliance with MPL formulation:

  • Very satisfactory with preparation highly accepted with very few side effects recorded.
Author Conclusion:
  • A dosage of 1.5g per day MPL is highly accepted and a compliant formulation of marine fatty acids.
  • Low-dose supplementation induces a significant change in fatty acid profiles in plasma PL, RBC and MNL in tumor patients suffering from excessive weight loss and advanced disease.  
  • MPL led to weight stabilization compared to baseline throughout a six-week period while quality of life improved.
  • Further investigation of new η-3 fatty acid formulation in patients at earlier stage of cancer disease and with dosage adjusted to BMI or fat mass is expected to confirm these results.
Funding Source:
Industry:
Dietmar Hopp Stftungs GmbH and Kirstins Weg e.V.
Pharmaceutical/Dietary Supplement Company:
Reviewer Comments:
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) 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.) 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? 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? 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? 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? 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? Yes
  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)? 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? 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