The Anti-inflammatory Effect of Personalized Omega-3 Fatty Acid Dosing for Reducing Prostaglandin E2 in the Colonic Mucosa Is Attenuated in Obesity

This clinical trial developed a personalized dosing model for reducing prostaglandin E₂ (PGE₂) in colonic mucosa using -3 fatty acid supplementation. The model utilized serum eicosapentaenoic acid (EPA, -3):arachidonic acid (AA, -6) ratios as biomarkers of colonic mucosal PGE₂ concentration. Normal human volunteers were given low and high -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. Cancer Prev Res; 1–9. ©2017 AACR.

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