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Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human plasma after a single dose of long-chain omega-3 PUFA

•A single dose of long-chain n-3 PUFAs induces changes in the ratio of downstream oxylipins.•EPA derived oxylipins were significantly elevated post treatment (6–24h) in plasma of healthy subjects.•No significant change in arachidonic acid and DHA oxylipin concentration was observed.•Even a single do...

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Published in:Prostaglandins & other lipid mediators 2014-06, Vol.109-111, p.23-31
Main Authors: Schuchardt, Jan Philipp, Schneider, Inga, Willenberg, Ina, Yang, Jun, Hammock, Bruce D., Hahn, Andreas, Schebb, Nils Helge
Format: Article
Language:English
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Summary:•A single dose of long-chain n-3 PUFAs induces changes in the ratio of downstream oxylipins.•EPA derived oxylipins were significantly elevated post treatment (6–24h) in plasma of healthy subjects.•No significant change in arachidonic acid and DHA oxylipin concentration was observed.•Even a single dose alters concentration of potent lipid mediators and might cause biological effects. Several supplementation studies with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion, we conducted a single dose treatment study with healthy subjects. In the present kinetic study, we compared patterns of hydroxy, epoxy and dihydroxy fatty acids in plasma of 6 healthy men before and after 6, 8, 24, and 48h of fish oil (1008mg EPA and 672mg DHA) ingestion. Levels of EPA- as well as other LC PUFA-derived hydroxy, epoxy and dihydroxy fatty acids were analyzed in plasma by LC–MS. Additionally, levels of these oxylipins were compared with their parent PUFA levels in plasma phospholipids. All EPA-derived oxylipin levels were significantly increased 6h after LC n-3 PUFA ingestion and gradually drop thereafter reaching the baseline levels about 48h after treatment. The relative increase in EPA plasma phospholipid levels highly correlated with the increase of plasma EPA-derived oxylipin levels at different time points. In contrast, plasma levels of arachidonic acid- and DHA-derived oxylipins as well as parent PUFA levels in plasma phospholipids were hardly changed. Our findings demonstrate that a single dose of LC n-3 PUFAs can rapidly induce a shift in the EPA oxylipin profile of healthy subjects within a few hours. Taking the high biological activity of the EPA-derived epoxy fatty acids into account, even short-term treatment with LC n-3 PUFAs may cause systemic effects, which warrant further investigation.
ISSN:1098-8823
DOI:10.1016/j.prostaglandins.2014.03.001