Effect of calcium supplementation on rectal epithelial hyperproliferation in intestinal bypass subjects

Fatty acids and bile acids are tumor promoters of experimental colon cancer in rats. Calcium can inhibit their effects. After intestinal bypass (IB), fecal bile acid and lipid levels increase markedly. In rats, IB increases colonic cell proliferation and carcinogen-induced colon tumor incidence. Whether fecal bile acids and lipids influence rectal epithelial proliferation in humans is uncertain. This study compared rectal epithelial proliferation in IB subjects and in controls matched for age, sex, and body mass index and investigated the effects of calcium carbonate supplementation (2400 or 3600 mg Ca2+/day for 12 weeks) on proliferation indices in IB subjects.Epithelial proliferation was studied by in vitro incubation of rectal biopsy specimens with [3H] thymidine. Twenty-four-hour stool collections were assayed for bile acids, lipids, and calcium.Whole crypt labeling index (LI) and upper crypt LI were increased in IB subjects compared with controls (P0.005). Calcium reduced whole crypt LI by 38% (P0.001) and upper crypt LI by 56% (P0.05). Levels of fecal bile acids (4.5 mmol/day) and lipids (131.9 g/day) were markedly elevated in IB subjects (P0.005).IB induces rectal hyperproliferation and expansion of the proliferative zone in association with excessive output of fecal bile acids and lipids. Oral calcium reverses the proliferative changes.