Editors' ChoiceCancer

The New Dish on Fish

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Science Translational Medicine  03 Nov 2010:
Vol. 2, Issue 56, pp. 56ec172
DOI: 10.1126/scitranslmed.3001855

Although fish oil has been widely recognized to provide health benefits for patients with heart disease, now there is something more worrisome than bad taste or mercury levels when it comes to fish oil capsules: an increased risk of colon cancer in patients with chronic colitis. Fish oil is rich in the long-chain omega-3 fatty acids docosahexaenoic acid (DHA) and ecosapentaenoic acid (EPA), which have been proposed to reduce colon cancer risk in patients with inflammatory bowel disease (IBD). IBD is characterized by chronic colitis and an increased risk of colon cancer caused, in part, by defects in transforming growth factor (TGF)–β signaling. A recent study by Woodworth et al. that examined Helicobacter hepaticus–induced colitis in SMAD3–/– mice, a model of defective TGF-β signaling, raises questions about the benefits of fish oil in patients with IBD. Mice treated with varying doses of fish oil showed a proportionate increase in colonic inflammation that was associated with a higher rate of dysplasia and postinfection mortality. The effects appeared to be mediated through alterations in inflammatory cell populations: Fish oil decreased CD8+ cells, reduced CD69 expression on CD4+ and CD8+ T cells, and increased FoxP3+ CD25+ CD4+ T regulatory cells that express L-selectin. The alteration in T regulatory cells is likely caused by dysregulated TGF-β signaling and may influence the migration of lymphocytes to Peyer’s patches, immune regulatory regions in the colon. Overall, fish oil decreased immune function in mice with TGF-β defects in the setting of infection and chronic colitis and increased the risk of neoplastic progression. As dietary supplementation with omega-3 fatty acids is becoming increasingly common in people, further evaluation of these findings is needed. Perhaps the adage “if it tastes bad, it must be good for you” is not necessarily true.

H. L. Woodworth et al., Dietary fish oil alters T lymphocyte cell populations and exacerbates disease in a mouse model of inflammatory colitis. Cancer Res. 70, 7960–7969 (2010). [Abstract]

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