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Effect of n–3 polyunsaturated fatty acids on Barrett's epithelium in the human lower esophagus ^1,2,3

¹ From the Department of Upper Gastrointestinal Surgery (SPM, APB, JC, and MR) and the Department of Histopathology (VS), Norfolk and Norwich University Hospital, Norwich, United Kingdom, and the Institute of Food Research, Norwich, United Kingdom (SPM, APB, EKL, and ITJ)

Background: Epidemiologic studies suggest a reduced risk of esophageal adenocarcinoma in populations with a high consumption of fish, and n–3 fatty acids inhibit experimental carcinogenesis. One possible explanation is the suppression of eicosanoid production through inhibition of cyclooxygenase 2 (COX-2).

Objective: The objective was to determine the effects of dietary supplementation with the n–3 fatty acid eicosapentaenoic acid (EPA) on a number of biological endpoints in Barrett's esophagus.

Design: Fifty-two participants with known Barrett's esophagus underwent endoscopy. Biopsy samples were obtained from a recorded level within the area of Barrett's esophagus, and then 27 patients were randomly assigned to consume EPA capsules (1.5 g/d) for 6 mo or no supplement (controls). At the end of this period, patients again underwent endoscopy, and biopsy samples were collected at the same level. Tissue samples were analyzed for mucosal lipid, prostaglandin E₂, leukotriene B_4, COX-2 protein, and RNA concentrations. Cellular proliferation was also measured, by Ki-67 immunohistochemistry.

Results: The EPA content of esophageal mucosa increased over the study period in the n–3–supplemented subjects and was significantly different from the content in the controls (P < 0.01). There was also a significant decline in COX-2 protein concentrations (measured by immunoblotting) in the n–3 group, and the difference was significant from that in the controls (P < 0.05); no difference in COX-2 RNA concentrations was observed between groups. This change in COX-2 protein was inversely related to the change in EPA content (P < 0.05). There was no significant difference in the change in prostaglandin E₂, leukotriene B₄, or cellular proliferation between the 2 groups.

Conclusion: Supplementation with EPA significantly changed n–3 fatty acid concentrations and reduced COX-2 concentrations in Barrett's tissue.

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