title: The effect of wheat bran fiber and calcium supplementation on rectal mucosal proliferation rates in patients with resected adenomatous colorectal polyps.
abstract: Colorectal cancers continue as the second most common cause of death from cancer in the United States. Only a few prospective, randomized clinical trials have been performed to evaluate the potential preventive effects of dietary fiber or calcium in patients with an increased risk for the development or recurrence of colorectal cancer. We designed and conducted a double-blinded, placebo-controlled randomized trial involving supplementation of fiber and calcium intake and measurements of [3H]thymidine labeling index (LI) percentages in rectal mucosal biopsies obtained from patients with resected colorectal adenomas to examine the potential mechanisms by which dietary interventions might reduce colorectal cancer risk. We performed a randomized, double-blinded, Phase II study, using a factorial design to measure the effects of supplemental dietary wheat bran fiber (2.0 or 13.5 g/day) and calcium carbonate (250 or 1500 mg/day elemental calcium) supplementation on [3H]thymidine LI percentages in rectal mucosal crypts and 24-h in vitro outgrowth cultures. Measurements were made at baseline randomization (i.e., after a 3-month placebo run-in period using 2.0 g of wheat bran fiber plus 250 mg of calcium carbonate) and after 3 and 9 months on treatment in 100 randomized participants who had a history of colon adenoma resection. Neither the wheat bran fiber nor the calcium carbonate supplements significantly reduced [3H]thymidine LI percentages in rectal mucosal crypts (total or compartmental analysis) or 24-h in vitro outgrowth cultures at either 3 or 9 months of daily supplementation in the 93 evaluable participants. We conclude that 9 months of high-dose wheat bran fiber and calcium carbonate supplementation in study participants with a history of recently resected colorectal adenomas does not have a significant effect on cellular proliferation rates in rectal mucosal biopsies, comparing 3- and 9-month results to baseline results. Ultimately, there is great need for the evaluation of these two different nutrient interventions in the setting of Phase III studies wherein adenomatous polyp recurrence, rather than a rectal mucosal biomarker, serves as the primary end point.
authors.affiliation: Department of Medicine, University of Arizona, Tucson 85724, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Alberts
authors.forename: J
authors.initials: J
authors.lastname: Einspahr
authors.forename: C
authors.initials: C
authors.lastname: Ritenbaugh
authors.forename: M
authors.initials: M
authors.lastname: Aickin
authors.forename: S
authors.initials: S
authors.lastname: Rees-McGee
authors.forename: J
authors.initials: J
authors.lastname: Atwood
authors.forename: S
authors.initials: S
authors.lastname: Emerson
authors.forename: N
authors.initials: N
authors.lastname: Mason-Liddil
authors.forename: L
authors.initials: L
authors.lastname: Bettinger
authors.forename: J
authors.initials: J
authors.lastname: Patel
authors.forename: S
authors.initials: S
authors.lastname: Bellapravalu
authors.forename: P S
authors.initials: PS
authors.lastname: Ramanujam
authors.forename: J
authors.initials: J
authors.lastname: Phelps
authors.forename: L
authors.initials: L
authors.lastname: Clark
mesh_terms: D018256:Adenomatous Polyps / Q000473:pathology / Q000517:prevention & control / Q000601:surgery*; D000368:Aged; D002119:Calcium Carbonate / Q000008:administration & dosage / Q000627:therapeutic use*; D002136:Calcium, Dietary / Q000008:administration & dosage / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003111:Colonic Polyps / Q000473:pathology / Q000517:prevention & control / Q000601:surgery*; D004043:Dietary Fiber / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D010919:Placebos; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000601:surgery*; D012007:Rectum / Q000473:pathology*; D012307:Risk Factors; D013936:Thymidine; D014316:Tritium
chemical_list: D002136:Calcium, Dietary; D004043:Dietary Fiber; D010919:Placebos; D014316:Tritium; D002119:Calcium Carbonate; D013936:Thymidine