@article{be5d99ff1c364765aa17d30abcad9f14,
title = "The anti-inflammatory effect of personalized omega-3 fatty acid dosing for reducing prostaglandin E2 in the colonic mucosa is attenuated in obesity",
abstract = "This clinical trial developed a personalized dosing model for reducing prostaglandin E2 (PGE2) in colonic mucosa using w-3 fatty acid supplementation. The model utilized serum eicosapentaenoic acid (EPA, w-3):arachidonic acid (AA, w-6) ratios as biomarkers of colonic mucosal PGE2 concentration. Normal human volunteers were given low and high w-3 fatty acid test doses for 2 weeks. This established a slope and intercept of the line for dose versus serum EPA:AA ratio in each individual. The slope and intercept was utilized to calculate a personalized target dose that was given for 12 weeks. This target dose was calculated on the basis of a model, initially derived from lean rodents, showing a log-linear relationship between serum EPA:AA ratios and colonic mucosal PGE2 reduction. Bayesian methods allowed addition of human data to the rodent model as the trial progressed. The dosing model aimed to achieve a serum EPA:AA ratio that is associated with a 50% reduction in colonic PGE2. Mean colonic mucosal PGE2 concentrations were 6.55 ng/mg protein (SD, 5.78) before any supplementation and 3.59 ng/mg protein (SD, 3.29) after 12 weeks of target dosing. In secondary analyses, the decreases in PGE2 were significantly attenuated in overweight and obese participants. This occurred despite a higher target dose for the obese versus normal weight participants, as generated by the pharmacodynamic predictive model. Large decreases also were observed in 12-hydroxyicosatetraenoic acids, and PGE3 increased substantially. Future biomarker-driven dosing models for cancer prevention therefore should consider energy balance as well as overall eicosanoid homeostasis in normal tissue.",
author = "Zora Djuric and Turgeon, {D. Kim} and Ananda Sen and Jianwei Ren and Kirk Herman and Devon Ramaswamy and Lili Zhao and Ruffin, {Mack T.} and Normolle, {Daniel P.} and Smith, {William L.} and Brenner, {Dean E.}",
note = "Funding Information: We thank all the individuals who volunteered for the Fish Oil Study. We also thank Melissa K. Tuck, Chelsea Crofoot, and Brian Kleiner for their roles in assisting with study coordination, participant recruitment, sample collection, and sample processing. We thank Megan Klatt for assistance with fatty acid dosing calculations, Arsh Patel for assisting with proliferation analyses, and Gillian Graifman for assisting with the dietary data. Nordic Naturals provided the EPA-Xtra in bulk for the research study. This work was supported by grants from the NIH: the Gastro-Intestinal SPORE P50 CA130810, the University of Michigan Comprehensive Cancer Center P30 CA046592, the University of Michigan Clinical Research Center UL1RR024986, the University of Pittsburgh Cancer Institute P30 CA047904, the University of Michigan Clinical Translational Resource Allocation Committee (CTRAC), the Kutsche Family Memorial Endowment (to Dean Brenner), and the Rose and Lawrence C. Page Foundation (to D. Kim Turgeon). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Funding Information: This work was supported by grants from the NIH: the Gastro-Intestinal SPORE P50 CA130810, the University of Michigan Comprehensive Cancer Center P30 CA046592, the University of Michigan Clinical Research Center UL1RR024986, the University of Pittsburgh Cancer Institute P30 CA047904, the University of Michigan Clinical Translational Resource Allocation Committee (CTRAC), the Kutsche Family Memorial Endowment (to Dean Brenner), and the Rose and Lawrence C. Page Foundation (to D. Kim Turgeon). Publisher Copyright: {\textcopyright}2017 AACR.",
year = "2017",
month = dec,
day = "1",
doi = "10.1158/1940-6207.CAPR-17-0091",
language = "English (US)",
volume = "10",
pages = "729--737",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "12",
}