Am J Clin Nutr. 2026 Jun 25:101419. doi: 10.1016/j.ajcnut.2026.101419. Online ahead of print.
ABSTRACT
BACKGROUND: Icosapent ethyl (IPE), an ethyl ester of eicosapentaenoic acid (EPA, C20:5n-3), is thought to have immunomodulatory properties and may protect against colorectal cancer (CRC).
OBJECTIVES: This study aimed to assess the effect of IPE on changing total marine omega-3 polyunsaturated fatty acid (PUFA) and individual fatty acid composition in colorectal tissue.
METHODS: We conducted a prospective, single-arm clinical trial of 4g/d IPE (VASCEPA®) treatment for 8-12 weeks among patients with a recent history of adenoma. We collected pre- and post-treatment colorectal biopsies through flexible sigmoidoscopy, and participants’ diet and lifestyle via questionnaires. The primary outcome was the change in total marine omega-3 PUFA in colorectal tissue measured by gas-liquid chromatography. We examined changes in individual fatty acids exploratorily.
RESULTS: Among a total of 81 patients enrolled, 72 had paired pre- and post-treatment tissue fatty acid data. After intervention, the tissue composition (median [interquartile range]) of total marine omega-3 PUFA increased from 2.10% (0.96%) to 5.21% (1.97%), with a fold change of 2.40 (0.82). With a slight decrease in omega-6 PUFA (fold change = 0.96 [0.27]), the ratio of marine omega-3 to omega-6 PUFA increased (fold change = 2.58 [0.81]). Among individual fatty acids, EPA increased the most (fold change: 5.88 [3.63]). The cumulative amount of IPE treatment, rather than daily dosage, showed a positive correlation with changes in tissue EPA composition (Spearman’s ρ=0.23, P=0.051). The treatment effect on tissue EPA changes appeared to be stronger for participants with lower than higher dietary EPA intake at baseline, although the interaction tests did not reach statistical significance (P for interaction=0.26).
CONCLUSIONS: IPE treatment substantially increased incorporation of marine omega-3 PUFA, particularly EPA, into the colorectal tissue while reducing tissue omega-6 PUFA composition.
TRIAL REGISTRATION: The PREvention using EPA against coloREctal cancer (PREPARE) trial was registered as ClinicalTrials.gov identifier: NCT04216251.
PMID:42349681 | DOI:10.1016/j.ajcnut.2026.101419