folder

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway

Authors

  • R. Fischer
  • A. Konkel
  • H. Mehling
  • K. Blossey
  • A. Gapelyuk
  • N. Wessel
  • C. von Schacky
  • R. Dechend
  • D.N. Muller
  • M. Rothe
  • F.C. Luft
  • K. Weylandt
  • W.H. Schunck

Journal

  • Journal of Lipid Research

Citation

  • J Lipid Res 55 (6): 1150-1164

Abstract

  • Cytochrome P450 (CYP)-dependent metabolites of arachidonic acid (AA) contribute to the regulation of cardiovascular function. CYP enzymes also accept eicosapentaenoic acid (EPA) and docosahexaenoic acid (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- and CYP-dependent pathways. Raising the Omega-3 Index from about 4 to 8 primarily resulted in a large increase of EPA-derived CYP-dependent epoxy-metabolites followed by increases of EPA- and DHA-derived lipoxygenase-dependent monohydroxy-metabolites including the precursors of 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 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.


DOI

doi:10.1194/jlr.M047357