Research Papers: Gastrointestinal CancerEffects of fish oil supplementation on eicosanoid production in patients at higher risk for colorectal cancerWhite, Maya N.a; Shrubsole, Martha J.a,b,c,e; Cai, Qiuyina,b,c; Su, Timothya,b,c; Hardee, Jenningsh; Coppola, John-Anthonyi; Cai, Sunny S.j; Martin, Stephanie M.a,d; Motley, Sandraa,b; Swift, Larry L.f; Milne, Ginger L.g; Zheng, Weia,b,c,e; Dai, Qia,b,c; Murff, Harvey J.a,d,eAuthor Information aDepartment of Medicine bDivision of Epidemiology cVanderbilt Ingram Cancer Center dDivision of General Internal Medicine and Public Health, Vanderbilt University Medical Center eGRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System fDepartment of Pathology, Microbiology and Immunology, Vanderbilt University gDivision of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville hUniversity of Tennessee, Knoxville, Tennessee iUniversity of Florida College of Medicine, Gainesville, Florida jTulane University School of Medicine, New Orleans, Louisiana, USA Correspondence to Harvey J. Murff, MD, MPH, Division of General Internal Medicine and Public Health, Vanderbilt University, 6012 Medical Center East, 1215 21st Avenue South, Nashville, Tennessee 37232, USA Tel: +1 372 328 300; fax: +1 615 936 1269; e-mail: [email protected] European Journal of Cancer Prevention: May 2019 - Volume 28 - Issue 3 - p 188-195 doi: 10.1097/CEJ.0000000000000455 Buy Metrics Abstract Fish oil supplementation may represent a potential chemopreventive agent for reducing colorectal cancer risk. The mechanism of action of fish oil is unknown but presumed to be related to eicosanoid modification. The purpose of this study was to evaluate the effects of fish oil supplementation on the levels of urinary and rectal eicosanoids. We conducted a randomized, double-blind, controlled trial of 2.5 g of fish oil per day compared with olive oil supplementation over a 6-month period. Study participants had a history of colorectal adenomas. Randomization was stratified based on the gene variant rs174535 in the fatty acid desaturase 1 enzyme (FADS1), which affects tissue levels of arachidonic acid. A total of 141 participants were randomized. Urinary prostaglandin E2 metabolite (PGE-M) was measured at baseline, 3, and 6 months and rectal prostaglandin E2 (PGE2) at baseline and 6 months. Repeated-measures linear regression was used to determine the effect of the intervention on each outcome measure. Overall, fish oil supplementation was found to reduce urinary PGE-M production compared with olive oil (P=0.03). Fish oil did not reduce rectal PGE2 overall; however, it did significantly reduce PGE2 in the subgroup of participants not using aspirin or NSAIDs (P=0.04). FADS1 genotype did not seem to modify effects of fish oil on PGE2 production. We conclude that fish oil supplementation has a modest but beneficial effect on eicosanoids associated with colorectal carcinogenesis, particularly in those not taking aspirin or NSAIDs. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.