Rationale: Specialized pro-resolving mediators (SPM - lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid (DHA) and docosapentaenoic acid (n-3 DPA). These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood. Objective: Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses. Methods and Results: Healthy volunteers were enrolled in a double blinded, placebo controlled, crossover study and peripheral blood was collected at baseline, 2, 4, 6 and 24h post administration of placebo or one of three doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria, and a decrease in the diurnal activation of leukocytes and platelets, as measured by a decreased adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24h post-supplementation when compared with placebo. Conclusions: Together these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement.Clinical Trial Registration: NCT03347006.
RCT Entities:
Rationale: Specialized pro-resolving mediators (SPM - lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acidsdocosahexaenoic acid (DHA) and docosapentaenoic acid (n-3 DPA). These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood. Objective: Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses. Methods and Results: Healthy volunteers were enrolled in a double blinded, placebo controlled, crossover study and peripheral blood was collected at baseline, 2, 4, 6 and 24h post administration of placebo or one of three doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria, and a decrease in the diurnal activation of leukocytes and platelets, as measured by a decreased adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24h post-supplementation when compared with placebo. Conclusions: Together these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement.Clinical Trial Registration: NCT03347006.
Authors: Wolfgang Marx; Nicola Veronese; Jaimon T Kelly; Lee Smith; Meghan Hockey; Sam Collins; Gina L Trakman; Erin Hoare; Scott B Teasdale; Alexandra Wade; Melissa Lane; Hajara Aslam; Jessica A Davis; Adrienne O'Neil; Nitin Shivappa; James R Hebert; Lauren C Blekkenhorst; Michael Berk; Toby Segasby; Felice Jacka Journal: Adv Nutr Date: 2021-10-01 Impact factor: 8.701
Authors: Stefania Lamon-Fava; Jisun So; David Mischoulon; Thomas R Ziegler; Boadie W Dunlop; Becky Kinkead; Pamela J Schettler; Andrew A Nierenberg; Jennifer C Felger; Krishna Rao Maddipati; Maurizio Fava; Mark Hyman Rapaport Journal: Prostaglandins Leukot Essent Fatty Acids Date: 2020-12-05 Impact factor: 4.006