Dietary Supplements

Effects of EPA+DHA and Corn Oil Supplementation on PUFA Concentrations across Plasma Lipid Pools and on Downstream Oxylipins: Exploratory Results from a Randomized Controlled Trial in Healthy Humans.

TL;DR

EPA+DHA supplementation increased EPA and DHA levels across multiple plasma lipid pools and led to significant shifts in oxylipin concentrations with predominant increases in anti-inflammatory and decreases in proinflammatory oxylipins compared with corn oil supplementation.

Key Findings

EPA+DHA supplementation increased EPA levels across all four major plasma lipid pools measured.

  • EPA levels were elevated in phosphatidylcholines (PC), cholesteryl esters (CE), nonesterified fatty acids (NEFA), and triglycerides (TAG) following supplementation.
  • The supplementation dose was 3 g of EPA+DHA concentrate daily (1.1 g EPA + 0.8 g DHA) for 12 weeks.
  • The exploratory analysis included n=21 participants (20 female, 1 male, age 35-49 years).
  • This was a double-blind, placebo-controlled randomized trial (ISRCTN96712688).

EPA+DHA supplementation increased DHA levels in three of the four plasma lipid pools examined.

  • DHA levels were significantly increased in PC, CE, and TAG pools following EPA+DHA supplementation.
  • DHA incorporation was not reported as significantly increased in the NEFA pool.
  • Plasma was analyzed using gas chromatography to quantify fatty acids.

EPA+DHA supplementation decreased linoleic acid (LA) levels in multiple plasma lipid pools.

  • LA levels were decreased in PC, CE, and NEFA pools following EPA+DHA supplementation.
  • The corn oil comparator provided 1.65 g LA + 0.81 g oleic acid daily.
  • LA displacement from plasma lipid pools may reflect competitive incorporation dynamics between n-6 and n-3 fatty acids.

EPA+DHA supplementation decreased arachidonic acid (AA) levels in plasma PC and NEFA pools.

  • AA reductions were observed specifically in the PC and NEFA fractions.
  • AA is an n-6 precursor to proinflammatory oxylipins, and its reduction in key lipid pools may have downstream anti-inflammatory implications.
  • The supplementation period was 12 weeks.

EPA+DHA supplementation produced significant shifts in plasma oxylipin concentrations compared with baseline, with predominant increases in anti-inflammatory and decreases in proinflammatory oxylipins.

  • Oxylipins were quantified using mass spectrometry.
  • The shifts in oxylipin profile were observed in comparison to both baseline values and the corn oil control group.
  • Levels of EPA+DHA-derived oxylipins were significantly higher across lipid pools following EPA+DHA supplementation compared with corn oil.

Corn oil supplementation decreased AA levels in the TAG pool and modified concentrations of several AA-derived oxylipins.

  • The corn oil group received 1.65 g linoleic acid + 0.81 g oleic acid daily for 12 weeks.
  • Corn oil supplementation had its own distinct effect on AA-derived oxylipin concentrations.
  • The specific direction and identity of affected AA-derived oxylipins were noted as changes from baseline in the corn oil group.

The study population for this exploratory analysis was predominantly female and middle-aged.

  • The exploratory analysis used available samples of n=21 participants.
  • Demographics were 20 female and 1 male, aged 35-49 years.
  • Participants were described as healthy adults from a previously conducted randomized controlled trial.
  • The original trial was registered at www.isrctn.com as ISRCTN96712688.

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Citation

Balakrishnan N, Shaikh S, Childs C, Miles E, Noakes P, Paras-Chavez C, et al.. (2026). Effects of EPA+DHA and Corn Oil Supplementation on PUFA Concentrations across Plasma Lipid Pools and on Downstream Oxylipins: Exploratory Results from a Randomized Controlled Trial in Healthy Humans.. The Journal of nutrition. https://doi.org/10.1016/j.tjnut.2025.101274