title: Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway.
abstract: Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA) contribute to the regulation of cardiovascular function. CYP enzymes also accept EPA and DHA to yield more potent vasodilatory and potentially anti-arrhythmic metabolites, suggesting that the endogenous CYP-eicosanoid profile can be favorably shifted by dietary omega-3 fatty acids. To test this hypothesis, 20 healthy volunteers were treated with an EPA/DHA supplement and analyzed for concomitant changes in the circulatory and urinary levels of AA-, EPA-, and DHA-derived metabolites produced by the cyclooxygenase-, lipoxygenase (LOX)-, and CYP-dependent pathways. Raising the Omega-3 Index from about four to eight primarily resulted in a large increase of EPA-derived CYP-dependent epoxy-metabolites followed by increases of EPA- and DHA-derived LOX-dependent monohydroxy-metabolites including the precursors of the resolvin E and D families; resolvins themselves were not detected. The metabolite/precursor fatty acid ratios indicated that CYP epoxygenases metabolized EPA with an 8.6-fold higher efficiency and DHA with a 2.2-fold higher efficiency than AA. Effects on leukotriene, prostaglandin E, prostacyclin, and thromboxane formation remained rather weak. We propose that CYP-dependent epoxy-metabolites of EPA and DHA may function as mediators of the vasodilatory and cardioprotective effects of omega-3 fatty acids and could serve as biomarkers in clinical studies investigating the cardiovascular effects of EPA/DHA supplementation.
authors.affiliation: Max Delbrueck Center for Molecular Medicine, Berlin, Germany Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Fischer
authors.affiliation: Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Konkel
authors.affiliation: Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Mehling
authors.affiliation: Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Blossey
authors.affiliation: Humboldt University of Berlin, Berlin, Germany.
authors.forename: Andrej
authors.initials: A
authors.lastname: Gapelyuk
authors.affiliation: Humboldt University of Berlin, Berlin, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Wessel
authors.affiliation: Omegametrix GmbH, Martinsried, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: von Schacky
authors.affiliation: Experimental and Clinical Research Center (ECRC), Berlin, Germany HELIOS Klinikum Berlin-Buch, Berlin, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Dechend
authors.affiliation: Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Muller
authors.affiliation: Lipidomix GmbH, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rothe
authors.affiliation: Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Friedrich C
authors.initials: FC
authors.lastname: Luft
authors.affiliation: Experimental and Clinical Research Center (ECRC), Berlin, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Weylandt
authors.affiliation: Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Wolf-Hagen
authors.initials: WH
authors.lastname: Schunck
mesh_terms: D000293:Adolescent; D000328:Adult; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D019587:Dietary Supplements; D004537:Eicosanoic Acids / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D004537:Eicosanoic Acids; D015525:Fatty Acids, Omega-3; D003577:Cytochrome P-450 Enzyme System
keywords: cytochrome P450; lipidomics; nutrition