The anti-inflammatory effect of personalized omega-3 fatty acid dosing for reducing prostaglandin E2 in the colonic mucosa is attenuated in obesity

Zora Djuric, D. Kim Turgeon, Ananda Sen, Jianwei Ren, Kirk Herman, Devon Ramaswamy, Lili Zhao, Mack T. Ruffin, Daniel P. Normolle, William L. Smith, Dean E. Brenner

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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.

Original languageEnglish (US)
Pages (from-to)729-737
Number of pages9
JournalCancer Prevention Research
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2017

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Djuric, Z., Turgeon, D. K., Sen, A., Ren, J., Herman, K., Ramaswamy, D., Zhao, L., Ruffin, M. T., Normolle, D. P., Smith, W. L., & Brenner, D. E. (2017). The anti-inflammatory effect of personalized omega-3 fatty acid dosing for reducing prostaglandin E2 in the colonic mucosa is attenuated in obesity. Cancer Prevention Research, 10(12), 729-737. https://doi.org/10.1158/1940-6207.CAPR-17-0091