Balakrishnan, Neha, Raza Shaikh, Saame, Childs, Caroline, Miles, Elizabeth, Noakes, Paul S., Paras-Chavez, Carolina, Armstrong, Michael, Reisdroph, Nicole, Calder, Philip and Fisk, Helena (2025) Effects of EPA+DHA and corn oil supplementation on PUFA levels across plasma lipid pools and on downstream oxylipins: exploratory results from a randomized controlled trial in healthy humans. Nutrition Journal, 156 (2). (doi:10.1016/j.tjnut.2025.101274).
Abstract
Background: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may improve inflammatory conditions. We previously demonstrated that supplementation with EPA+DHA in adults elevates anti-inflammatory oxylipins in human plasma and adipose tissue. However, the localization of EPA/DHA in plasma lipid pools [phosphatidylcholines (PC), triglycerides (TAG), cholesteryl esters (CE), and nonesterified fatty acids (NEFA)] and how this relates to the downstream oxylipin levels remains unknown.
Objectives: this study aimed to identify the incorporation of supplemental EPA+DHA into plasma PC, TAG, CE, NEFA, and the impact on downstream oxylipins.
Methods: we conducted an exploratory analysis with available samples (n = 21, 20 female, 1 male, age 35–49 y) from a previous double-blind, placebo-controlled trial of participants randomly assigned to consume either 3 g of EPA+DHA concentrate (1.1 g EPA + 0.8 g DHA) or corn oil (CO) [1.65 g linoleic acid (LA) + 0.81 g oleic acid] daily for 12 wk. Plasma was analyzed using gas chromatography and mass spectrometry to quantify fatty acids and oxylipins, respectively.
Results: EPA+DHA supplementation increased EPA levels across PC, CE, NEFA, and TAG pools, and increased DHA levels in PC, CE, and TAG pools. Conversely, supplementation decreased LA levels in PC, CE, and NEFA pools, and decreased arachidonic acid (AA) levels in PC and NEFA pools. EPA+DHA supplementation also led to significant shifts in oxylipin concentrations compared with baseline, with predominant increases in anti-inflammatory and decreases in proinflammatory oxylipins. CO supplementation decreased TAG AA levels and modified concentrations of several AA-derived oxylipins. Levels of EPA+DHA and derived oxylipins were significantly higher across lipid pools following supplementation with EPA+DHA compared with CO.
Conclusions: these findings offer insights into supplemental EPA+DHA localization to different circulating lipid pools, which have implications for understanding how to mitigate systemic inflammation. Furthermore, studies are needed to evaluate relationships between the changes in polyunsaturated fatty acids, oxylipins, and markers of inflammation.
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