title: Modulation of blood oxylipin levels by long-chain omega-3 fatty acid supplementation in hyper- and normolipidemic men.
abstract: BACKGROUND
  Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) such as EPA and DHA have been shown to possess beneficial health effects, and it is believed that many of their effects are mediated by their oxygenated products (oxylipins). Recently, we have shown that serum levels of several hydroxy, epoxy, and dihydroxy FAs are dependent on the individual status of the parent FAs in a cohort of normo- and hyperlipidemic subjects. So far, the effect of an increased dietary LC n-3 PUFA intake on hydroxy, epoxy, and dihydroxy FA levels has not been investigated in subjects with mild combined hyperlipidemia.
  
  
  METHODS
  In the present study, we compared oxylipin patterns of 10 hyperlipidemic (cholesterol >200mg/dl; triglyceride >150mg/ml) and 10 normolipidemic men in response to twelve weeks of LC n-3 PUFA intake (1.14g DHA and 1.56g EPA). Levels of 44 free hydroxy, epoxy and dihydroxy FAs were analyzed in serum by LC-MS. Additionally, oxylipin levels were compared with their parent PUFA levels in erythrocyte membranes; a biomarker for the individual PUFA status.
  
  
  RESULTS
  Differences in the oxylipin pattern between normo- and hyperlipidemic subjects were minor before and after treatment. In all subjects, levels of EPA-derived oxylipins (170-4800pM) were considerably elevated after LC n-3 PUFA intake (150-1400%), the increase of DHA-derived oxylipins (360-3900pM) was less pronounced (30-130%). The relative change of EPA in erythrocyte membranes is strongly correlated (r≥0.5; p<0.05) with the relative change of corresponding epoxy and dihydroxy FA serum levels. The effect on arachidonic acid (AA)-derived oxylipin levels (140-27,100pM) was inconsistent.
  
  
  CONCLUSIONS
  The dietary LC PUFA composition has a direct influence on the endogenous oxylipin profile, including several highly biological active EPA- and DHA-derived lipid mediators. The shift in oxylipin pattern appears to be dependent on the initial LC PUFA status particularly for EPA. The finding that also levels of other oxylipins derived from ALA, LA or AA are modified by LC n-3 PUFA intake might suggest that at least some of the effects of EPA and DHA could be mediated by a shift in the entire oxylipin profile.
authors.affiliation: Institute of Food Science and Human Nutrition, Leibniz University Hannover, Germany. Electronic address: Schuchardt@nutrition.uni-hannover.de.
authors.forename: Jan Philipp
authors.initials: JP
authors.lastname: Schuchardt
authors.affiliation: Institute of Food Science and Human Nutrition, Leibniz University Hannover, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Schmidt
authors.affiliation: Institute of Food Science and Human Nutrition, Leibniz University Hannover, Germany.
authors.forename: Gaby
authors.initials: G
authors.lastname: Kressel
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Willenberg
authors.affiliation: Department of Entomology and Comprehensive Cancer Center, University of California Davis, CA, USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
authors.affiliation: Institute of Food Science and Human Nutrition, Leibniz University Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hahn
authors.affiliation: Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Germany.
authors.forename: Nils Helge
authors.initials: NH
authors.lastname: Schebb
mesh_terms: D000328:Adult; D019587:Dietary Supplements; D015118:Eicosapentaenoic Acid / Q000032:analysis / Q000097:blood; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects; D005227:Fatty Acids / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D008055:Lipids / Q000097:blood; D008875:Middle Aged; D054883:Oxylipins / Q000097:blood*; D055815:Young Adult
chemical_list: D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D008055:Lipids; D054883:Oxylipins; D015118:Eicosapentaenoic Acid
keywords: Arachidonic acid; DHA; Diols; EPA; Eicosanoids; Epoxides; Hyperlipidemia; Omega-3 fatty acids; PUFA