The effect of omega-3 fatty acids on bronchial hyperresponsiveness, sputum eosinophilia, and mast cell mediators in asthma

Abstract

Background: Omega-3 fatty acid supplements have been reported to inhibit exercise-induced bronchoconstriction (EIB). It has not been determined whether omega-3 supplements inhibit airway sensitivity to inhaled mannitol, a test for bronchial hyperresponsiveness (BHR) and model for EIB in people with mild to moderate asthma.

Methods: In a double-blind, crossover trial, subjects with asthma who had BHR to inhaled mannitol (n = 23; 14 men; mean age, 28 years; one-half taking regular inhaled corticosteroids) were randomized to omega-3 supplements (4.0 g/d eicosapentaenoic acid and 2.0 g/d docosahexaenoic acid) or matching placebo for 3 weeks separated by a 3-week washout. The primary outcome was the provoking dose of mannitol (mg) to cause a 15% fall in FEV1 (PD15). Secondary outcomes were sputum eosinophil count, spirometry, Asthma Control Questionnaire (ACQ) score, serum triacylglyceride level, and lipid mediator profile in urine and serum.

Results: PD15 (geometric mean, 95% CI) to mannitol following supplementation with omega-3s (78 mg, 51-119 mg) was not different from placebo (88 mg, 56-139 mg, P = .5). There were no changes in sputum eosinophils (mean ± SD) in a subgroup of 11 subjects (omega-3, 8.4% ± 8.2%; placebo, 7.8% ± 11.8%; P = .9). At the end of each treatment period, there were no differences in FEV1 % predicted (omega-3, 85% ± 13%; placebo, 84% ± 11%; P = .9) or ACQ score (omega-3, 1.1% ± 0.5%; placebo, 1.1% ± 0.5%; P = .9) (n = 23). Omega-3s caused significant lowering of blood triglyceride levels and expected shifts in serum fatty acids and eicosanoid metabolites, confirming adherence to the supplements; however, no changes were observed in urinary mast cell mediators.

Conclusions: Three weeks of omega-3 supplements does not improve BHR to mannitol, decrease sputum eosinophil counts, or inhibit urinary excretion of mast cell mediators in people with mild to moderate asthma, indicating that dietary omega-3 supplementation is not useful in the short-term treatment of asthma.

Trial registry: ClinicalTrials.gov; No.: NCT00526357; URL: www.clinicaltrials.gov.

Figures

Figure 1 –

Participant flow diagram. BHR = bronchial hyperresponsiveness; ICS = inhaled corticosteroid; PD15 = provoking dose of mannitol (mg) to cause a 15% fall in FEV1; p.r.n = as needed; Rx = supplement.

Figure 2 –

The individual data and geometric mean (95% CI) for PD15 in subjects with asthma following 3 wk of daily omega-3 fatty acid supplementation compared with placebo, demonstrating no change in PD15. (n = 23, P = .5). ● = inhaled corticosteroid group; ○ = β2-agonist group; + = two subjects who did not have a PD15 value. See Figure 1 legend for expansion of abbreviation.

Figure 3 –

The individual data and mean (SE) for the percentage of eosinophils in sputum in a subgroup of subjects with asthma following 3 wk of daily omega-3 fatty acid supplementation compared with placebo, demonstrating no change in percent eosinophils (n = 11, P = .9). ● = inhaled corticosteroid group; ○ = β2-agonist group.

Figure 4 –

The individual data and mean (SE) for serum triglyceride levels in subjects with asthma following 3 wk of daily omega-3 fatty acid supplementation compared with placebo, demonstrating a significant decrease in serum triglyceride concentration following omega-3 fatty acid supplementation (n = 23, P = .0011). *P < .0011. ● = inhaled corticosteroid group; ○ = β2-agonist group.

Figure 5 –

The individual data and mean (SE) for combined omega-3 fatty acids in serum (weight [wt] as a percentage of total phospholipid) in subjects with asthma following 3 weeks of daily omega-3 fatty acid supplementation compared with placebo, demonstrating a significant increase in omega-3 fatty acid levels in serum following omega-3 fatty acid supplementation (n = 23, P < .001). *P < .001. ● = inhaled corticosteroid group; ○ = β2-agonist group.