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A2491 - Eicosapentaenoic Acid (EPA)-Enriched Fish Oil Intervention in Severe Asthmatics with Low-Risk Versus High-Risk 5-Lipoxygenase (ALOX5) Gene Polymorphisms
Author Block: A. A. Zeki1, G. U. Schuster2, M. Rabowsky1, M. Cedeno1, C. Kivler3, L. Mu4, H. Allayee5, L. Qi4, C. B. Stephensen6, N. J. Kenyon7; 1Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of California, Davis, Davis, CA, United States, 2USDA-WHNRC, Univ of California at Davis, Davis, CA, United States, 3Respiratory Department, UC Davis Medical Center, University of California, Davis, Sacramento, CA, United States, 4Department of Biostatistics, University of California, Davis, Davis, CA, United States, 5Preventative Medicine, Keck School of Medicine of USC, Los Angeles, CA, United States, 6Department of Nutrition, University of California, Davis, Davis, CA, United States, 7Internal Medicine; Division of Pulmonary and Critical Care Medicine, University of California, Davis, Davis, CA, United States.
Rationale: Dietary intake of fish results in low incidence of asthma, yet data from clinical studies of various fish oil formulations for the treatment of asthma are inconclusive. This pilot clinical study was designed to 1) determine the prevalence of high- and low-risk arachidonate 5-lipoxygenase (ALOX5) gene polymorphisms in our asthma clinic population at U.C. Davis, and 2) study the effects of the dietary intake of eicosapentaenoic acid (EPA)-enriched omega-3 polyunsaturated fatty acids (n3-PUFA) in a subset of severe asthmatics. Our hypothesis was that EPA-enriched n3-PUFA supplements could ameliorate the production of inflammatory leukotrienes and decrease the number of acute exacerbations in patients with severe asthma, specifically in patients with “high-risk” ALOX5 gene polymorphisms.
Methods: Patients with low- vs. high-risk ALOX5 polymorphisms were randomized in a placebo-controlled, cross-over, intervention pilot study to receive orally ingested EPA-enriched omega-3 fatty acid capsules (5 g/day) or placebo capsules for 3 months. The primary endpoint was the number of acute asthma exacerbations per three-month period. The secondary clinical endpoints were FEV1 %predicted, FVC %predicted, morning peak expiratory flow rate (PEFR), and asthma control test (ACT) scores. We also conducted red blood cell (RBC) lipid membrane analyses, lipid assays, and measured cytokines.
Results: We found a high prevalence of the high-risk ALOX5 genotypes among 30 asthmatics who underwent genotyping. A total of N=15 subjects (8 low-risk, 7 high-risk) were successfully randomized. There was an average of 2.3±2.1 asthma exacerbations in the fish oil intervention arm compared to 3.5±1.8 exacerbations in the placebo control arm (p=NS). There was no significant difference in the change in FEV1 or FVC values during the intervention and control periods. However, there was a statistically significant increase in PEFRs in the fish oil intervention arm as compared to placebo. ACT scores also improved significantly from baseline (fish oil group: 15.1±5.1 to 18.4 ±3.7 vs. placebo: 16.4 ±3.4 to 17.1±4.8). RBC levels of EPA and docosahexaenoic acid (DHA) increased with the fish oil intervention, which led to a decrease in expected pro-inflammatory eicosanoid mediators. EPA-enriched fish oil treatment decreased plasma levels of osteopontin, IL-23, and IFN-gamma, as well as exhaled nitric oxide levels.
Conclusions: Fish oil intervention has a beneficial anti-inflammatory effect in a high-risk sub-group of severe asthma, however, it did not reduce exacerbations. Randomized clinical trials with larger sample sizes are warranted to further investigate whether fish oil supplementation in the high-risk ALOX5 genotype has any potential clinical benefits.