TABLE II.

Clinical trials of fatty acid supplementation and asthma

Study design	Study population	Treatment	Outcomes	Results
Randomized, double-blind, placebo-controlled trial, Portugal44	20 female patients with stable persistent asthma	DHA and EPA combination plus 10 mg of vitamin E or placebo twice daily for 2 wk	FENO was determined, with ACQ scores and FEV1 as secondary outcomes.	Short-term dietary supplementation with n-3 PUFAs was not associated with changes in exhaled NO levels, asthma control, or lung function in women with stable asthma.
Observational cohort analysis of randomized controlled trials, Australia43	516 children (age 18 mo-5 y) with a family history of asthma	Fish oil supplement (500 mg of tuna fish oil) or placebo (500 mg of Sunola oil)	Symptoms or diagnoses of asthma and allergic disease were determined at 18 mo, 3y,and 5y.	There was no association between plasma levels of n-3 or n-6 at 18 mo, 3 y, and 5 y and the prevalence of asthma or wheezing, eczema, or atopy at 5 y.
Double-blind, randomized controlled trial, Australia45	39 asthmatic children (age 8–12 y) with a history of wheeze in the last 12 mo and AHR to histamine	Fish oil (n-3 group, n = 20) or safflower/palm/olive oil (n-6 group, n = 19) supplements for 6 mo	Lung function and bronchial hyperresponsiveness were determined by using FEV1, FVC, and histamine inhalation. LPS stimulated PBMC TNF-α production.	TNF level decrease in the n-3 group trended toward significance. Diet had no effect on the severity of asthma in children or other outcome measures.
Parallel double-blind, randomized trial, Germany40	23 asthmatic patients with dust mite allergy (age 22–29 y)	PUFA-enriched blend (450 mg of EPA, 180 mg of, 60 mg of γ-LA, and 60 mg of stearidonic acid) or placebo	Three weeks of dietary supplementation and then daily challenge with low dose mite allergen was done for 2 wk after which subjects. Lung function was measured based on FEV1 and exhaled NO levels. Sputum and plasma eosinophil counts and CysLT levels were measured after allergen exposure.	Exhaled NO levels were lower in the n-3 PUFA group before and after allergen challenge compared with the placebo group. Serum eosinophil counts, eosinophilic cationic protein levels, and in vitro CysLT release are decreased in the n-3 PUFA group.
Randomized controlled trial, Australia46	616 pregnant women whose unborn children were at high risk of asthma based on family history	HDM avoidance intervention; dietary supplementation with daily n-3–rich tuna fish oil (500 mg), margarines, and cooking oils or placebo (Sunola oil) starting at 6 mo	Asthma symptoms or diagnosis or treatment were assessed by using a parental questionnaire, atopic status was determined by using skin prick testing, and serum IgE levels in offspring were measured at 18 mo.	There was a lower prevalence of wheeze in the diet intervention group, but physician-diagnosed asthma was not reduced. HDM reduction reduced use of oral steroids but did not affect outcomes.
Randomized, double-blind, placebo-controlled trial, Denver, Colorado47	43 children (age 6–14 y) with mild-to-moderate persistent asthma	Enriched n-3 fatty acid and antioxidant (3 g of EPA, 1.6 g of DHA, 3.0 g of GLA; vitamins E and C, β-carotene, taurine, zinc, copper, selenium, molybdenum, and calcium) formula vs control (same caloric amount blended with 100% high-oleic safflower oil) formula for 12-wk trial as between meal snack or at mealtime	Numbers of asthma-free days were determined, and assessment of fatty acid levels and safety outcomes was performed. Measurement of asthmatic symptoms, skin prick test responses, serum eosinophilic cationic protein levels, eosinophil counts, serum IgE levels, exhaled NO levels, and methacholine challenge test results were determined.	There were no differences in asthma-free days between the 2 groups. Higher exhaled NO levels were seen in the control group compared with the treatment group at 4, 8, and 12 wk. Higher EPA levels were found in serum and PBMC phospholipids in the treatment group. No differences were found in adverse events.
Randomized, double-blind crossover study, United Kingdom41	20 subjects, including 10 with clinically diagnosed EIB and 10 healthy control subjects recruited from university and sporting teams	Supplemental fish oil (3.2 g of EPA and 2.2 g of DHA) or placebo (olive oil) for 3 wk, washout period (normal diet) for 2 wk, and then alternative supplement for 3 wk	At all 3 phases, plasma LTB4, TNF-α, IL-1β, and urinary LTE4 and 9α levels, as well as 11β-PGF2 levels, were measured before and after exercise. Lung function was measured by using FEV1 after exercise and sputum inflammatory mediators.	There was less of a decrement in lung function after exercise and decreased inflammatory mediator levels in the n-3 PUFA diet group.
Double-blind crossover study, Sweden48	25 patients with mild-to-moderate asthma (20–54 y)	3 wk n-3 fatty acid supplement (daily dose: 4 g of EPA and 2 g of DHA) or placebo (50:50 mix of soybean and corn oil), followed by washout period (normal diet) for 3 wk and then switch to alternative therapy for 3 wk	Fatty acid composition of serum phospholipids at baseline and after each period of treatment was measured.	n-3 diet supplementation alters PUFA ratio and the ratio of downstream oxylipins.
Randomized, double-blind, crossover study, United Kingdom42	16 patients with mild-to-moderate persistent asthma with EIB	n-3 PUFAs (3.2 g of EPA and 2.0 g of DHA) or placebo (olive oil) over 8 wk (1 wk on normal diet, 3 wk on treatment diet or placebo, 2-wk washout period, and then switched to alternative diet for 2 wk)	Pre-exercise and postexercise measurements of pulmonary function, induced sputum cell count differential, proinflammatory eicosanoid metabolite and cytokine concentrations, and eicosanoid metabolites LTB4 and LTB5 were measured from activated PMNLs.	Fish oil diet improved pulmonary function and reduced sputum proinflammatory mediators compared with placebo and normal diets.
Randomized, double-blind, placebo-controlled trial, Russia49	46 patients with mild-to-moderate atopic asthma (age 18–56 y)	Four capsules of lipid extract (50 mg of n-3 PUFAs, including DHA and EPA, and 100 mg of olive oil) or placebo (150 mg of olive oil) for 8 wk	Patient-recorded symptoms and medication use before study medication doses were determined. FEV1 was measured by using spirometry and concentration of exhaled H2O2.	Decreased daytime wheeze and exhaled H2O2 levels and increased morning PEF were seen in the lipid extract group.
Cross-sectional study, Denmark50	528 children (age 16 y) identified in registries from previous study in 1990 whose mothers had fish oil supplementation or placebo during the last 6 wk of pregnancy	Fish oil supplementation with four 1-g gelatin capsules (32% EPA, 23% DHA, and 2 mg of tocopherol) or four 1-g capsules of olive oil (control 1) or no supplement (control 2) from week 30 of pregnancy until delivery	Asthma diagnosis was determined in offspring at 16 y of age. Follow-up was extracted from the national patient registry.	Supplementation with n-3 PUFAs during late pregnancy reduced the risk of asthma and allergic asthma in offspring.

ACQ, Asthma Control Questionnaire; CysLT, cysteinyl leukotriene; EIB, exercise-induced bronchospasm; FENO, fraction of exhaled nitric oxide; FFQ, food frequency questionnaire; FVC, forced vital capacity; HDM, house dust mite; NO, nitric oxide; PEF, peak expiratory flow; PMNL, peripheral mononuclear lymphocytes.