n-3 fatty acids decrease colonic epithelial cell proliferation in high-risk bowel mucosa

Lipids. 1996 Mar;31 Suppl:S313-7. doi: 10.1007/BF02637099.

Abstract

The n-3 fatty acids (C20:5, eicosapentaenoic acid; c22:6, docosahexaenoic acid) may be important in the development, growth, and metastasis of colon cancer, a leading cause of death in North America. Patients who have had a bowel neoplasm have a high risk of developing a second neoplasm, and this risk is associated with a high percentage of cells correspond to the S phase of bromodeoxyuridine (BrdUrd) labeling in mucosal epithelial cells. To determine the effect of n-3 fatty acid supplementation on DNA synthesis of rectal mucosa, patients with stage 1 or stage 2 colon carcinoma or adenomatous polyps were randomized to consume either 9 g/d n-3 fatty acid capsules or 9 g/d placebo capsules. Plasma phospholipid fatty acid analysis and proctoscopic mucosal biopsies were performed at baseline, 3, and 6 mon. Colonic crypts were isolated from the mucosa, disassociated with enzymes, and incubated with BrdUrd, and %S phase was measured by flow cytometry. The plasma phospholipid n-6/n-3 ratio was determined by gas chromatography. Supplement compliance was assessed by plasma phospholipid n-6/n-3 ratio. Mean capsule consumption in these two group was 82%. Prior to supplementation, there were no significant differences in the %S phase and the plasma n-6/n-3 ratio between these groups. Patients whose colonic epithelial cells indicated hyperproliferation at baseline showed a strongly positive correlation to the %S phase of BrdUrd uptake and the n-6/n-3 ratio. There was no significant change after n-3 treatment in patients with low baseline. Those in the placebo group showed no significant difference in n-6/n-3 ratio, although there was an increase in the %S phase of BrdUrd uptake at 6 mon. The n-3 group did not have significant side effects, and polyps were not found after completing 12 mon of n-3 fatty acid supplementation. This study suggests that n-3 fatty acid may be a useful chemopreventive agent in some patients as reflected in a plasma biomarker of colon tumor growth and metastasis. A low plasma phospholipid n-6/n-3 fatty acid ratio may serve as a nutritional marker that is associated with colonic epithelial cell hyperproliferation in the n-3-supplemented group as compared with the placebo group. Characteristics of mucosal proliferation at baseline may be a crucial factor for the effect of n-3 fatty acid supplementation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Division / drug effects
  • Colonic Neoplasms / pathology*
  • Dietary Fats, Unsaturated / pharmacology*
  • Double-Blind Method
  • Fatty Acids, Omega-3 / pharmacology*
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated / pharmacology
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / drug effects*
  • Phospholipids / blood
  • Rectal Neoplasms / pathology*
  • Risk Factors

Substances

  • Dietary Fats, Unsaturated
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Fatty Acids, Unsaturated
  • Phospholipids