Table 1.
Summary of published studies and proposed trials of omega-3 fatty acid supplementation in chronic obstructive pulmonary disease (COPD)
| 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 |
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.
*Statistically significant P <0.05 a odds ratio <1, bodds ratio ≥1.0, codds ratio ≥1.5.
PUFA refers to both omega-3 and omega-6 fatty acid intake.
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.
eWeighted mean.