RANDOMIZED, DOUBLE-BLINDED, PLACEBO-CONTROLLED STUDY OF EFFECT OF WHEAT BRAN FIBER AND CALCIUM ON FECAL BILE-ACIDS IN PATIENTS WITH RESECTED ADENOMATOUS COLON POLYPS

Background: Ongoing epidemiologic and nutritional studies suggest that colorectal carcinogenesis is consistent with complex interactions bet ween genetic susceptibility and environmental and dietary factors. Amo ng the dietary components found to reduce colon cancer risk are high i ntakes of dietary fiber and calcium. Purpose: We designed and conducte d a randomized, double-blinded, placebo-controlled trial involving sup plementation of the customary dietary intake with fiber and calcium an d measurements of fecal bile acids to examine the potential mechanisms by which added dietary interventions might reduce colorectal cancer r isk, Methods: In a randomized, double-blinded, phase II study, we used a factorial. design to measure the effects of dietary wheat bran fibe r (2.0 or 13.5 g/day) in the form of cereal and supplemental calcium c arbonate (250 or 1500 mg/day elemental calcium) taken as a tablet on f ecal bile acid concentrations and excretion rates, Measurements were m ade at base-line randomization (i.e., after a 3-month placebo run-in p eriod using 2.0 g wheat bran fiber plus 250 mg calcium carbonate) and after 3 and 9 months on treatment in a randomly selected 52-patient su bsample of the 95 fully assessable study participants who had a histor y of colon adenoma resection. Concentrations of fecal bile acids, tota l, primary (i.e., chenodeoxycholic and cholic), and secondary (i.e., d eoxycholic, lithocholic, and ursodeoxycholic), were measured in 72-hou r stool samples by gas-liquid chromatography, All P values resulted fr om two-sided tests, Results: All geometric mean fecal bile acid concen trations and excretion rates were lower at 9 months than at 0 months o r 3 months on treatment in the high-dose fiber, high-dose calcium, and high-dose fiber/high-dose calcium treatment groups, The high-dose fib er effect at 9 months of supplementation was statistically significant with respect to virtually all geometric mean fecal bile acid concentr ations and excretion rates. For example at 9 months versus 0 months, h igh-dose fiber supplementation caused a reduction in fecal concentrati ons of total bile acids (52% reduction; P = .001) and deoxycholic acid (48% reduction; P = .003), High-dose calcium supplementation also had a significant, but lower, effect at 9 months versus 0 months on the g eometric mean total bile acid (35% reduction; P = .044) and deoxycholi c fecal bile acid (36% reduction; P = .052) concentrations. Conclusion s: High-dose wheat bran fiber and calcium carbonate supplements given for 9 months are associated with statistically significant reductions in both total and secondary fecal bile acid concentrations and excreti on rates in patients with resected colon adenomas. This study supports the hypothesis that one of the important ways in which a high intake of wheat bran fiber and calcium may reduce the risk of colorectal neop lasia and cancer is by reduction of the concentrations of fecal bile a cids. Implication: Phase III studies of these agents in the prevention of adenoma recurrence are necessary to confirm this hypothesis and ha ve now been initiated at multiple institutions.