title: Biomarkers for personalizing omega-3 fatty acid dosing.
abstract: Prostaglandin E2 (PGE2) has been linked to a higher risk of colorectal cancer. PGE2 in colon tissue can be reduced by increasing dietary eicosapentaenoic acid (EPA). The dose-dependent relationships between dietary EPA, serum EPA:arachidonate (AA) ratio, urinary PGE2 metabolites, and colonic eicosanoids were evaluated to develop biomarkers for prediction of colonic PGE2. Male rats were fed diets containing EPA:ω6 fatty acid ratios of 0, 0.1, 0.2, 0.4, or 0.6 for 5 weeks. Increasing the dietary EPA:ω6 fatty acid ratio increased EPA:AA ratios in serum and in the proximal, transverse, and distal colon (P < 0.001). The urinary PGE2 metabolite was reduced (P = 0.006). EPA-rich diets reduced colonic tissue PGE2 concentrations by 58% to 66% and increased PGE3 by 19- to 28-fold. Other AA-derived eicosanoids were reduced by 35% to 83%. The changes were not linear, with the largest changes in eicosanoids observed with the lower doses. A mathematical model predicts colonic tissue eicosanoids from the EPA:AA ratio in serum and the EPA dose. Every 10% increase in serum EPA:AA was associated with a 2% decrease in the (geometric) mean of PGE2 in the distal colon. These mathematical relationships can now be applied to individualized EPA dosing in clinical trials.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Family Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Zora
authors.initials: Z
authors.lastname: Djuric
authors.affiliation: Department of Family Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Ananda
authors.initials: A
authors.lastname: Sen
authors.affiliation: Department of Family Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Ren
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Kuklev
authors.affiliation: Department of Family Medicine, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Ian
authors.initials: I
authors.lastname: Waters
authors.affiliation: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, University of Colorado Denver, Aurora, Colorado.
authors.forename: Charis L
authors.initials: CL
authors.lastname: Uhlson
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: Yu H
authors.initials: YH
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, University of Colorado Denver, Aurora, Colorado.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Murphy
authors.affiliation: Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Normolle
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan.
authors.forename: William L
authors.initials: WL
authors.lastname: Smith
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan. Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan. VA Medical Center, Ann Arbor, Michigan. dbrenner@med.umich.edu.
authors.forename: Dean E
authors.initials: DE
authors.lastname: Brenner
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D001835:Body Weight; D003106:Colon / Q000378:metabolism; D015232:Dinoprostone / Q000652:urine; D015777:Eicosanoids / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D005395:Fish Oils; D008401:Gas Chromatography-Mass Spectrometry; D006873:Hydroquinones / Q000737:chemistry; D007249:Inflammation; D008055:Lipids / Q000737:chemistry; D008297:Male; D008962:Models, Theoretical; D010743:Phospholipids / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D053719:Tandem Mass Spectrometry; D013696:Temperature
chemical_list: D014408:Biomarkers, Tumor; D015777:Eicosanoids; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D006873:Hydroquinones; D008055:Lipids; D010743:Phospholipids; C018855:2-tert-butylhydroquinone; D015232:Dinoprostone