Fish Oil Supplementation in Overweight/Obese Patients with Uncontrolled Asthma. A Randomized Trial

Abstract

Rationale: Omega-3 fatty acid (n3PUFA) supplementation has been proposed as a promising antiasthma strategy. The rs59439148 ALOX5 polymorphism affects leukotriene production and possibly inflammatory responses to n3PUFA. Objectives: Assess the effects of n3PUFA supplementation and ALOX5 genotype on asthma control in patients with obesity and uncontrolled asthma. Methods: This multicenter trial among 12- to 25-year-olds with overweight/obesity and uncontrolled asthma randomized subjects in a 3:1 allotment to n3PUFA (4 g/d) or soy oil control for 24 weeks. Asthma Control Questionnaire was the primary outcome; secondary outcomes included blood leukocyte n3PUFA levels, urinary leukotriene-E4, spirometry, and asthma-related events. The number of SP1 tandem repeats in rs59439148 determined ALOX5 genotype status. Simple and multivariable generalized linear models assessed effects on outcomes. Results: Ninety-eight participants were randomized (77 to PUFA, 21 to control), and more than 86% completed all visits. Asthma and demographic characteristics were similar among treatment groups. n3PUFA treatment increased the n3-to-n6 PUFA ratio in circulating granulocytes (P = 0.029) and monocytes (P = 0.004) but did not affect mean Asthma Control Questionnaire change at 6 months (n3PUFA: mean, -0.09; 95% confidence interval [CI], 0.09 to 0.10; vs. control: mean, -0.18; 95% CI, -0.42 to 0.06; P = 0.58). Changes in urinary leukotriene-E4 (P = 0.24), forced expiratory volume in 1 second % predicted (P = 0.88), and exacerbations (relative risk [RR], 0.92; 95% CI, 0.30-2.89) at 6 months were similar in both groups. n3PUFA treatment was associated with reduced asthma-related phone contacts (RR, 0.34; 95% CI, 0.13-0.86; P = 0.02). ALOX5 genotype did not affect n3PUFA treatment responses. Conclusions: We did not find evidence that n3PUFA use improves most asthma-related outcomes and cannot recommend it as a prevention strategy for overweight/obese patients with asthma. Clinical trial registered with www.clinicaltrials.gov (NCT01027143).

Keywords: EPA; asthma; fish oil; obesity; omega-3 fatty acids.

Figure 1.

Study diagram and procedures. Screening included informed consent and medical history collection; eligibility and inclusion/exclusion criteria were assessed for run-in and randomization. Phone visits occurred 2, 6, 10, 16, and 20 weeks after visit 3. + indicates procedure was performed. *Urinary leukotriene E4, exhaled nitric oxide, blood for n3/n6 ratio. ACQ = Asthma Control Questionnaire; IND = Investigational New Drug number; PUFA = polyunsaturated fatty acid.

Figure 2.

CONSORT Diagram of the study screening, randomization, and follow-up for overweight and obese adolescents with poorly controlled asthma. BMI = body mass index; PUFA = polyunsaturated fatty acid.

Figure 3.

Total n3 and n6 polyunsaturated fatty acid (PUFA) concentration and n3/n6 ratios within peripheral blood (A) granulocytes and (B) monocytes and by treatment group at baseline and 3 and 6 months of the intervention period. *P < 0.05 and **P < 0.01 for the comparisons of 3-month and 6-month values adjusting for baseline values. CI = confidence interval.