Biomarkers for personalizing omega-3 fatty acid dosing
Title | Biomarkers for personalizing omega-3 fatty acid dosing |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Jiang Y, Djuric Z, Sen A, Ren J, Kuklev D, Waters I, Zhao L, Uhlson CL, Hong YH, Murphy RC, Normolle DP, Smith WL, Brenner DE |
Journal | Cancer Prev Res (Phila) |
Volume | 7 |
Issue | 10 |
Pagination | 1011-22 |
Date Published | 2014 Oct |
ISSN | 1940-6215 |
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. |
DOI | 10.1158/1940-6207.CAPR-14-0134 |
Alternate Journal | Cancer Prev Res (Phila) |
PubMed ID | 25139294 |
PubMed Central ID | PMC4185239 |
Grant List | AT002782 / AT / NCCAM NIH HHS / United States CA130810 / CA / NCI NIH HHS / United States GM068848 / GM / NIGMS NIH HHS / United States HL117798 / HL / NHLBI NIH HHS / United States M01 RR000042 / RR / NCRR NIH HHS / United States P30 CA046592 / CA / NCI NIH HHS / United States P50 CA130810 / CA / NCI NIH HHS / United States |