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Table 1 Summary of published studies and proposed trials of omega-3 fatty acid supplementation in chronic obstructive pulmonary disease (COPD)

From: Feasibility of omega-3 fatty acid supplementation as an adjunct therapy for people with chronic obstructive pulmonary disease: study protocol for a randomized controlled trial

Author Broekhuizen et al. Shahar et al. McKeever et al. de Batlle et al. Hirayama et al. Barr (Investigator) protocol Engelen (Investigator) protocol Proposed study
Year 2005 1994 2008 2011 2010 2012 (recruiting) 2012 (recruiting) 2012
Country Netherlands United States Netherlands Spain Japan United States United States Australia
Study type Randomized controlled trial Cross sectional Cross sectional Cross sectional Case controlled Interventional pilot Randomized controlled trial Interventional feasibility
Retrospective/prospective Prospective Retrospective Retrospective Retrospective Retrospective Prospective Prospective Prospective
Sample size (n) 102 7,902 13,820 250 618 40-45 77 40
n with COPD 102 (100%) 197 (2.5%) 553 (4%) 250 (100%) 278 (45%) 40-45 (100%) Unclear 40 (100%)
Definition of COPD PBD, ≥ GOLD stage 2 (at least 50%≤FEV1 <80% predicted) FEV1 ≤65% ≥ GOLD stage 2 (at least 50%≤FEV1 <80% predicted) Not PBD PBD FEV1/FVC <0.70 PBD FEV1/FVC <0.70 PBD FEV1/FVC <0.70 and PBDFEV1 <65% predicted PBD FEV1 <70% predicted PBD FEV1/FVC <0.70
Mean Age (SD) A- 64 (10) 54 (6)e 42.2 (11.2) 68 (8) 65.8 (6)e N/A N/A N/A
P- 62 (8)
Mean PBD FEV1 % (SD) A- 38.2 (13.1) 90 (18)e Not reported 53 (16) Not reported N/A N/A N/A
P- 35.8 (15.1)
Intervention PUFA blendd No No No No Fish oil Fish oil Fish oil
Placebo Palm oil (80%) & sunflower oil (20%) No No No No Corn oil Olive oil Corn oil
Control group Yes No No No Yes Yes Yes Yes
Supplementation duration 8 weeks N/A N/A N/A N/A 6 months (2g EPA/ 0.5g DHA per day) 4 weeks (3.5g or 2.0g omega-3 per day) 4 months (3.4g omega-3 per day)
Six-minute walk test No No No No No Yes No Yes
Bicycle ergometry Yes No No No No No No No
Pulmonary function Yes Yes Yes Yes Yes Yes No Yes
Blood biomarkers Yes No No Yes No Yes Yes Yes
HADS No No No No No No No Yes
Dyspnea questionnaire No No No No Yes No No Yes
QOL questionnaire No No No No No Yes No Yes
FFQ No Yes (61-item, intake past year) Yes (178 item, past years intake) Yes (122 item, past 2 years intake) Yes (138 item, past 5 years intake) No No Yes (74 item, past years intake)
Endothelial function No No No No No Yes No No
Muscle strength(skeletal & respiratory) Yes No No No No No Yes No
Muscle protein synthesis & breakdown No No No No No No Yes No
Oxidative capacity No No No No No No Yes No
Duel-Energy X-ray absorptiometry No No No No No No Yes No
Statistical test Linear regression Logistic regression Nonlinear regression Logistic regression Logistic regression Association between n-3 intake and endothelial function Association between
n-3 intake and protein synthesis
ANOVA
Comparison PUFA and placebo group after 8 week intervention. Association between n-3 intake and COPD Association between n-6 intake and COPD Association between PUFA and biomarkers Association between PUFA intake and COPD  
Results Greater ↑ exercise capacity in PUFA compared to placebo group*. COPD strongly and inversely associated with intake of n-3 fatty acids*b No association between COPD and n-3 intake. ↑ ALA associated with↓ TNF-α *a ↑ prevalence COPD associated with, ↓ PUFA intake *b, ↓ n-6 intake *b, ↓ n-3 intake *b N/A N/A N/A
↑ intake of four of the n-6 fatty acids associated with ↑ risk of COPD*c. ↑ LA and AA associated with ↑ CRP *c
PUFA no effect on FEV1 or muscle strength.
  No change in blood biomarkers in either group.    ↑ AA associated with ↑ IL-6 *c     
  1. A, active; ALA, alpha linoleic acid; ANOVA, analysis of variance; AA, arachidonic acid; CRP, C-reactive protein; DHA, Docosahexaeneoic acid; EPA, eicosapentaenoic acid; FEV1, forced expiratory volume in 1 second; FFQ, food frequency questionnaire; GOLD, Global initiative for chronic obstructive lung disease; HADS, Hospital anxiety and depression scale; IL-6, interleukin-6; LA, linoleic acid; n-3, omega-3 fatty acid; P, placebo; PBD, Post bronchodilator; PUFA, Polyunsaturated fatty acid; QOL, quality of life; 6MWD, six-minute walk distance; TNF-α, tumor necrosis factor-alpha.
  2. *Statistically significant P <0.05 a odds ratio <1, bodds ratio ≥1.0, codds ratio ≥1.5.
  3. PUFA refers to both omega-3 and omega-6 fatty acid intake.
  4. d PUFA blend consists of 400 mg stearidonic acid, 760 mg gamma-linolenic acid, 1,200 mg alpha-linolenic acid, 700 mg eicosapentaenoic acid and 340 mg docosahexaenoic acid.
  5. eWeighted mean.