Effects of EPA and DHA Supplementation on Plasma Specialized Pro-resolving Lipid Mediators and Blood Monocyte Inflammatory Response in Subjects with Chronic Inflammation (OR29-01-19)

Abstract

ObjectivesThe role of n-3 fatty acid-derived specialized pro-resolving mediators (SPMs), including the novel docosapentaenoic acid (DPA) products, in reducing inflammation in humans has not been determined. We evaluated the differential effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on plasma SPMs and the resulting impact on the inflammatory response of peripheral blood monocytes. MethodsIn a randomized, controlled, crossover trial, 21 subjects (9 men and 12 women, 50–75 y) with chronic inflammation (C-reactive protein > 2 μg/mL) entered a 4-week lead-in control phase (high oleic sunflower oil, 3 g/d) and then two sequential 10-week supplementation phases with pure EPA or DHA (3 g/d each), separated by a 10-week washout phase. Plasma phospholipid (PL) fatty acid composition and SPMs, including their precursors, were measured at the end of each phase. Following lipopolysaccharides (LPS) stimulation, the inflammatory response of blood monocytes was assessed by inflammatory gene expression. ResultsEPA increased PL EPA (P < 0.001) and plasma concentrations of 18-HEPE, the precursor of the E-series resolvins (RvEs) (P < 0.001). The increase in plasma 18-HEPE concentrations, was associated with the increase in PL EPA (β = 14.9 pg/ml, P < 0.01). However, RvEs were undetectable. EPA increased PL DPA (P < 0.001) but not DPA-derived SPMs. DHA increased PL DHA and plasma concentrations of 17-HDHA and 14-HDHA, the precursors of DHA-derived SPMs (P < 0.001). DHA also significantly increased PL EPA and 18-HEPE (P < 0.001), suggesting some DHA retroconversion to EPA. Interestingly, DHA lowered PL DPA (P < 0.001) but increased the DPA-derived SPMs RvD5n-3 DPA and MaR1n-3 DPA (P < 0.001). In monocytes, while both EPA and DHA lowered the LPS-induced expression of TNFA(P < 0.03 and P < 0.001, respectively), TNFA expression was inversely correlated with plasma concentrations of MaR1n-3 DPA (ρ = –0.32, P < 0.04). ConclusionsRelative to EPA, DHA supplementation increases a broader range of SPMs, with EPA and DHA differentially affecting PL DPA and DPA-derived SPMs. Plasma concentrations of MaR1n-3 DPA following EPA and DHA supplementation are associated with an attenuated inflammatory response in blood monocytes, suggesting a potential role of this SPM in reducing inflammation in humans. Funding SourcesFunded by USDA/NIFA and Cohn Student Award. Supporting Tables, Images and/or Graphs▪