title: n-3 fatty acids decrease colonic epithelial cell proliferation in high-risk bowel mucosa.
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.
authors.affiliation: Cancer Research Institute, Deaconess Pathway Health Network, Department of Surgery, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Huang
authors.forename: J M
authors.initials: JM
authors.lastname: Jessup
authors.forename: R A
authors.initials: RA
authors.lastname: Forse
authors.forename: S
authors.initials: S
authors.lastname: Flickner
authors.forename: D
authors.initials: D
authors.lastname: Pleskow
authors.forename: H T
authors.initials: HT
authors.lastname: Anastopoulos
authors.forename: V
authors.initials: V
authors.lastname: Ritter
authors.forename: G L
authors.initials: GL
authors.lastname: Blackburn
mesh_terms: D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects*; D010743:Phospholipids / Q000097:blood; D012004:Rectal Neoplasms / Q000473:pathology*; D012307:Risk Factors
chemical_list: D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D010743:Phospholipids