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Omega-3 fatty acids for cystic fibrosis

  1. Colleen Oliver1,*,
  2. Helen Watson2

Editorial Group: Cochrane Cystic Fibrosis and Genetic Disorders Group

Published Online: 27 NOV 2013

Assessed as up-to-date: 26 NOV 2013

DOI: 10.1002/14651858.CD002201.pub4


How to Cite

Oliver C, Watson H. Omega-3 fatty acids for cystic fibrosis. Cochrane Database of Systematic Reviews 2013, Issue 11. Art. No.: CD002201. DOI: 10.1002/14651858.CD002201.pub4.

Author Information

  1. 1

    The Royal Women's Hospital, Parkville, VIC, Australia

  2. 2

    Papworth Hospital NHS Foundation Trust, Cambridge Centre for Lung Infection, Cambridge, UK

*Colleen Oliver, The Royal Women's Hospital, Grattan St & Flemington Rd, Parkville, VIC, 3052, Australia. cmckarney@yahoo.com.au. colleen.oliver@thewomens.org.au.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 27 NOV 2013

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Characteristics of included studies [ordered by study ID]
Henderson 1994

Methods6-week, parallel design trial with 4 arms. Randomised using stratified randomised block design.


Participants12 children and young adults diagnosed with CF and pancreatic insufficiency (mean (SD) age 12.2 (5.4) years) on genotype or sweat test and able to complete the spirometric tests. Also pancreatic insufficient and plasma vitamin A and E levels within the normal range.

13 gender and age-matched people, without CF (mean (SD) age 13.4 (6.3) years), 7 male, 6 female.


Interventions8 x 1 g capsules fish oil (4 capsules twice daily) (3.19 g EPA and 2.21 g DHA) compared with olive oil placebo capsules flavoured to obtain a slight fish taste, over 6 weeks.


OutcomesOutcomes included in this review:
number of people experiencing adverse events;
number of deaths;
changes in haematological indices;
changes in plasma and erythrocyte levels of EPA and DHA and EPA/AA ratio.


NotesSignificantly lower plasma n-6 fatty acids (linoleic acid and arachidonic acid) noted at baseline in participants with CF compared with the group who did not have CF.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised using a stratified randomised block design.

Allocation concealment (selection bias)Unclear riskNot discussed in paper.

Blinding (performance bias and detection bias)
All outcomes
Low riskDescribed as double blind - while the capsules were not described as identical, it was stated that the placebo olive oil capsules were flavoured to obtain a slight fish taste which we agreed would be sufficient to blind participants.

Incomplete outcome data (attrition bias)
All outcomes
Low riskWithdrawals from the study were discussed with explanations (20 out of 25 randomised participants completed the study). Study included all participants in the data analysis, which was performed according to the intention-to-treat principle.

Selective reporting (reporting bias)Unclear riskProtocol not available for comparison, so unable to definitely eliminate selective reporting.

Other biasLow riskNo additional bias identified.

Keen 2010

Methods3-month, parallel design trial. Randomised using random number generator.


Participants43 children and adults with "severe" CF mutations (age range 7 to 41 years); 35 participants completed the study; 18 female, 17 males. 20 participants were chronically infected with Pseudomonas aeruginosa. 8 participants discontinued the study and the inclusion parameters of these patients did not differ from those who completed the study.


Interventions50 mg/kg per day of 1 of 3 fatty acid blend capsules over 3 months; group A capsules contained predominantly EPA and DHA, group C contained high proportion of linoleic acid and arachidonic acid and group B (placebo) contained predominantly saturated fatty acids. Participants increased their pancreatic enzymes by 10% to 20% to maintain normal stools.


OutcomesOutcomes included in this review:
changes in serum phospholipid essential fatty acid content;
changes in inflammatory markers;
adverse effects;
BMI and weight;
lung function;
medical treatment.


NotesActual dose of EPA and DHA administered not described.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomised using random number generator.

Allocation concealment (selection bias)Unclear riskNot discussed in paper.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskDescribed as double-blind; treatment was assumed to be administered as identical capsules; however, 2 participants complained of fish smell in group A.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk45 participants were initially randomised, but 2 were excluded due to acute exacerbations and therefore did not enter the study. Withdrawls from study were described: 35 participants completed the study; 8 discontinued because of low compliance (n = 4), stomach pains (n = 2) and weight gain (n = 2). Study did not include all participants in the data analysis, therefore data was not analysed as 'intention to treat'.

Selective reporting (reporting bias)Unclear riskProtocol not available for comparison, so unable to definitely eliminate selective reporting.

Other biasHigh riskThe lack of information on dosage is a potential risk of bias.

Lawrence 1993

Methods6-week cross-over study planned. However, significant carry-over effect of treatment noted at end of study, therefore analysis restricted to the first 6-week treatment period.


Participants19 adolescents and adults diagnosed with CF on genotype, sweat test, or clinically (median age 17 years, age range 12 years to 26 years), 11 male, 5 female.
3 participants excluded due to requiring a course of corticosteroids for asthma attacks.
All were recruited within 4 weeks of hospitalisation for acute respiratory infection and judged to be in optimum condition for disease stage. All were Pseudomonas aeruginosa colonised and produced at least 5 ml sputum daily.
Initial randomisation gave groups with comparable baseline characteristics except for age. The treatment group also had significantly greater weight, peripheral blood leucocyte and neutrophil counts.


Interventions2.7 g EPA daily compared with identical olive oil placebo capsules, over 6 weeks.


OutcomesOutcomes included in this review:
number of people experiencing adverse events;
number of deaths;
changes in haematological and growth indices;
changes in lung function;
changes in in-vitro neutrophil chemotaxis.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskDid not state the randomisation technique.

Allocation concealment (selection bias)Unclear riskNo details were provided in the primary paper.

Blinding (performance bias and detection bias)
All outcomes
Low riskDescribed as double blind, treatment was administered as 'identical olive oil capsules'.

Incomplete outcome data (attrition bias)
All outcomes
Low riskOf the 19 participants recruited, 3 participants were excluded from the study before analysis due to corticosteroid treatment during the first treatment period.

Selective reporting (reporting bias)Unclear riskProtocol not available for comparison, so unable to definitely eliminate selective reporting.

Other biasLow riskNo additional bias identified.

Panchaud 2006

Methods2 x 6-month period, cross-over trial with no washout period.


Participants17 children and young adults with CF and pancreatic insufficiency (mean (SD) age 18 (9) years)), 10 male and 7 female. 1 participant discontinued study after 8 months for personal convenience.


InterventionsLiquid dietary supplement containing PUFA mixture (EPA, DHA, GLA and STA) compared with liquid dietary supplement without PUFA mixture over 6 months. Volume of supplementation was determined according to participant's weight; intake ranged from 100 mg - 300 mg DHA and 200 mg - 600 mg EPA per day.


OutcomesOutcomes included in this review:
number of people experiencing adverse events;
number of deaths;
changes in peripheral blood neutrophil membrane composition;
in vitro neutrophilic response to inflammatory stimuli;
changes in in-vitro neutrophil chemotaxis.


NotesRelatively low daily dose EPA and DHA compared to previous clinical trials.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskDid not state the randomisation technique.

Allocation concealment (selection bias)Unclear riskNo details were provided in the primary paper.

Blinding (performance bias and detection bias)
All outcomes
Low riskDescribed as double blind, placebo treatment was not stated to be identical but it was described as the same liquid dietary supplement as the intervention but without the PUFA mixture.

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk17 participants were randomised; 16 completed the study and one discontinued after 8 months for personal convenience.
Due to technical reasons, data could not be analysed for several participants' samples at baseline (4 participants), after treatment with omega-3 supplements (1) and after placebo (2).
High possibility of attrition bias since the analysis of the final cohort differed from the original cohort.

Selective reporting (reporting bias)Unclear riskProtocol not available for comparison, so unable to definitely eliminate selective reporting.

Other biasLow riskNo additional bias identified.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Alicandro 2013Omega 3 supplementation compared with large omega-6 fatty acid source (germ oil) rather than a neutral placebo that contains relatively little omega-3 or omega-6 fatty acid (olive oil).

Christophe 1992Omega-3 supplementation compared with large omega-6 fatty acid source (borache oil) rather than a neutral placebo that contains relatively little omega-3 or omega-6 fatty acid (olive oil).

Katz 1996Parenteral (via blood stream), not enteral (oral) supplementation with omega-3 fatty acids.

Koletzko 2000Eligibility unclear, attempts made to contact author for further information, but no response received.

Kurlandsky 1994Omega-3 supplementation compared with large omega-6 fatty acid source (sunflower oil) rather than a neutral placebo that contains relatively little omega-3 or omega-6 fatty acid (olive oil).

Lloyd-Still 2006Omega-3 supplementation compared with large omega-6 fatty acid source (corn/soy) rather than a neutral placebo that contains relatively little omega-3 or omega-6 fatty acid (olive oil).

Romano 1997Eligibility unclear, attempts made to contact author for further information, but no response received.

Starling 1988Eligibility unclear, attempts made to contact author for further information, but no response received.

van Biervliet 2008Omega-3 supplementation compared with large omega-6 fatty acid source (sunflower oil) rather than a neutral placebo that contains relatively little omega-3 or omega-6 fatty acid (olive oil).

 
Characteristics of studies awaiting assessment [ordered by study ID]
O'Sullivan 2011

Methods12-month parallel trial.

Participants83 infants diagnosed with CF in the first 2 months of life who were exclusively bottle fed.

InterventionsInfant formula containing DHA and AA compared to standard infant formula containing no DHA or AA over 12 months.

OutcomesWeight and height at 1 year of age;

Serum DHA and AA levels, IRT and alpha feto-protein levels;

Brasfield CXR score.

NotesFecal elastase measured at screening and then monthly for the study duration.

 
Comparison 1. Omega-3 fatty acids versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Adverse events1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

    1.1 Diarrhoea and eructation
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 2 Lung function1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    2.1 FEV1 % predicted
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    2.2 FVC % predicted
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Clinical variables1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    3.1 Change in body mass index
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Biochemical markers of essential fatty acid status (EPA & DHA content)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    4.1 Change in EPA % content of neutrophil membrane
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    4.2 Change in DHA % content of neutrophil membrane
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 5 Biochemical markers of essential fatty acid status (B4/B5 ratio)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    5.1 Leukotriene B4 to leukotriene B5 ratio
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Biochemical markers of essential fatty acid status (EPA & DHA content)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    6.1 Change in EPA content of serum phospholipids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Change in DHA content of serum phospholipids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Biochemical markers of essential fatty acid status (n6/n3)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

    7.1 Change in n6/n3 ratio content of serum phospholipids
1Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]