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.
Balakrishnan N, Shaikh S, et al. • The Journal of nutrition • 2026
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
Results
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).
Results
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.
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.
Results
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.
Results
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.
Results
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.
Methods
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.
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