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

• Published in: Lipids Vol. 31; no. 1Part2; pp. S313 - S317
• Main Authors: Huang, Yun‐Ching, Jessup, J. Milburn, Forse, R. Armour, Flickner, Stacy, Pleskow, Douglas, Anastopoulos, Harry T., Van Ritter, Blackburn, George L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer‐Verlag 01.01.1996
• Subjects: acide gras insature; acide gras polyinsature; acidos grasos insaturados; acidos grasos poliinsaturados; blood lipids; Cell Division - drug effects; cells; cellule; celulas; Colonic Neoplasms - pathology; complement alimentaire; control de enfermedades; controle de maladies; crecimiento; croissance; Dietary Fats, Unsaturated - pharmacology; disease control; Double-Blind Method; Fatty Acids, Omega-3 - pharmacology; Fatty Acids, Omega-6; Fatty Acids, Unsaturated - pharmacology; fosfolipidos; growth; hemolipidos; Humans; intestin; Intestinal Mucosa - cytology; Intestinal Mucosa - drug effects; intestines; intestinos; lipide sanguin; membrana mucosa; mucous membrane; muqueuse; neoplasmas; neoplasme; neoplasms; pathogenese; pathogenesis; patogenesis; phosphatide; phospholipids; Phospholipids - blood; polyunsaturated fatty acids; Rectal Neoplasms - pathology; replicacion; replication; Risk Factors; suplementos; supplements; unsaturated fatty acids; uridina; uridine
• ISSN: 0024-4201; 1558-9307
• DOI: 10.1007/bf02637099

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.