Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas

Int J Colorectal Dis. 2007 Jul;22(7):765-76. doi: 10.1007/s00384-006-0240-4. Epub 2007 Jan 10.


Background and aims: Omega-3 fatty acids in fish oil exert a protective effect on the development of colorectal cancer in animal models. Patients with colorectal adenomas have been shown to have increased crypt cell proliferation and decreased apoptosis in macroscopically normal appearing colonic mucosa. We investigated whether dietary supplementation with eicosapentaenoic acid (EPA) could alter crypt cell proliferation and apoptosis in such patients.

Patients/methods: Thirty subjects were randomised to either 3 months of highly purified EPA in free fatty acid form (2 g/day) or to no treatment. Colonic biopsies were taken at the initial colonoscopy and repeated 3 months later, and analysed for cell proliferation and apoptosis (immunohistochemistry) and mucosal fatty acid content.

Results/findings: Crypt cell proliferation was significantly reduced whilst apoptosis was significantly increased after EPA supplementation. Neither crypt cell proliferation nor apoptosis were altered in the control group. EPA in the mucosa increased significantly after EPA supplementation, whereas there was no significant change in controls.

Conclusions: Dietary supplementation with EPA significantly increases levels of this fatty acid in colonic mucosa, associated with significantly reduced proliferation and increased mucosal apoptosis. Further studies are needed to assess the potential efficacy of EPA supplementation in preventing polyps in the chemoprevention of colorectal cancer.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adenoma / pathology
  • Adenoma / prevention & control*
  • Adenoma / surgery
  • Administration, Oral
  • Apoptosis / drug effects*
  • Biopsy
  • Cell Proliferation / drug effects*
  • Colon / cytology*
  • Colon / drug effects
  • Colon / metabolism
  • Colonoscopy
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / prevention & control*
  • Colorectal Neoplasms / surgery
  • Eicosapentaenoic Acid / administration & dosage
  • Eicosapentaenoic Acid / therapeutic use*
  • Fatty Acids / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / cytology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome


  • Fatty Acids
  • Eicosapentaenoic Acid