Effects of postnatal omega-3 fatty acid supplementation on offspring pro-resolving mediators of inflammation at 6 months and 5 years of age: A double blind, randomized controlled clinical trial.

BACKGROUND: Resolution of inflammation is an active process involving specialised pro-resolving mediators (SPMs) generated from the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Omega-3 fatty acid supplementation during infancy may provide an intervention strategy to modify SPMs and reduce oxidative stress. This study evaluates the effect of omega-3 fatty acid supplementation in infancy on SPMs and F2-isoprostanes from 6 months to 5 years of age. METHODS: In a double-blind, placebo-controlled, parallel-group study design, 420 infants were randomized to a daily supplement of omega-3 fatty acids (280mg DHA and 110mg EPA) or olive oil (control), from birth to age 6 months. Blood was collected at birth (cord blood), 6 months, 12 months and 5 years. Plasma SPMs included 18-HEPE, E-series resolvins, 17-HDHA, D-series resolvins, 14-HDHA, 10S,17S-DiHDoHE, MaR1 and PD1. F2-isoprostanes were measured in plasma and urine, as markers of oxidative stress in vivo. RESULTS: The change in the concentration of 18-HEPE from birth to 6 months was greater in the omega-3 fatty acid group (Ptimepoint*group=0.04) with levels at 6 months significantly higher than controls (P=0.02). Other SPMs were not different between the groups at any time point. Plasma 18-HEPE concentration were associated with erythrocyte EPA concentrations after age and group adjustments (P<0.001), but not with allergic outcomes at 12 months. There were no between-group differences in plasma and urinary F2-isoprostanes at any time point. CONCLUSION: Omega-3 fatty acid supplementation from birth to 6 months of age increased SPM at 6 months but the effects were not sustained after supplementation ceased. Given that 18-HEPE is a biologically active metabolite, future studies should examine how the increase in 18-HEPE relates to potential health benefits of omega-3 fatty acid supplementation in infancy.