Biomarkers for personalizing omega-3 fatty acid dosing

Cancer Prev Res (Phila). 2014 Oct;7(10):1011-22. doi: 10.1158/1940-6207.CAPR-14-0134. Epub 2014 Aug 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis*
  • Body Weight
  • Colon / metabolism
  • Dinoprostone / urine
  • Eicosanoids / metabolism
  • Fatty Acids / chemistry
  • Fatty Acids, Omega-3 / metabolism*
  • Fish Oils
  • Gas Chromatography-Mass Spectrometry
  • Hydroquinones / chemistry
  • Inflammation
  • Lipids / chemistry
  • Male
  • Models, Theoretical
  • Phospholipids / chemistry
  • Rats
  • Rats, Inbred F344
  • Tandem Mass Spectrometry
  • Temperature

Substances

  • Biomarkers, Tumor
  • Eicosanoids
  • Fatty Acids
  • Fatty Acids, Omega-3
  • Fish Oils
  • Hydroquinones
  • Lipids
  • Phospholipids
  • 2-tert-butylhydroquinone
  • Dinoprostone