No abstract

Calcium reduces colorectal cell turnover and might therefore protect against neoplasia. The inhibitory effects of dietary calcium were tested in a double-blind controlled trial in patients with familial adenomatous polyposis who had undergone previous abdominal colectomy and ileorectal anastomosis. Patients received supplemental calcium carbonate (1500 mg/day) or placebo tablets for 6 months; sigmoidoscopy was performed before and after treatment. Rectal biopsies were maintained in short-term organ culture, and crypt cell production rate (CCPR) was measured stathmokinetically. A total of 25 patients completed the trial; polyp counts were obtained before and after treatment in all and CCPR values in 16. Calcium treatment reduced the mean (s.e.m.) CCPR from 4.72 (0.48) to 2.42 (0.48) cells per crypt per h (P < 0.05), while values for placebo were unchanged (5.46 (1.21) versus 5.08 (1.17) cells per crypt per h). Calcium had no demonstrable effect on the number, size or distribution of rectal polyps. The ability of oral calcium supplementation to suppress rectal epithelial proliferation supports its potential to prevent development of colorectal carcinoma in high-risk individuals.

No abstract

1. The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3, controls calcium absorption in the human duodenum, an effect that is mediated by mucosal vitamin D receptor expression. Functional vitamin D receptor signalling in the human colon is suggested by the reduced colonic mucosal cell proliferation seen in response to 1,25-dihydroxyvitamin D3. Thus 1,25-dihydroxyvitamin D3 might be expected to reduce cell proliferation in the small-bowel epithelium. 2. We have used an organ-culture system combined with the metaphase arrest technique to study the effects of 1,25-dihydroxyvitamin D3 on human duodenal mucosal proliferation. To validate our technique, multiple human mucosal explants were established in organ culture and vincristine (0.6 micrograms/ml) was added at 10 h. Explants were removed sequentially from 10 to 15 h and metaphase arrest figures were demonstrated by using the Feulgen reaction. The mean number of metaphase arrest figures was plotted against time in culture to show a linear accumulation of metaphases between 11 and 15 h (correlation coefficient = 0.93, r2 = 0.87, P < 0.0001). The mean crypt cell production rate was 2.01 (0.27) cells/h per crypt. 3. Paired normal duodenal mucosal biopsies from six patients were then established in organ culture with or without 10(-10) mol/l (100 pmol/l) 1,25-dihydroxyvitamin D3. The crypt cell production rate was determined between 12 and 15 h after vincristine-induced metaphase arrest. 1,25-Dihydroxyvitamin D3 reduced the median crypt cell production rate from 2.42 (1.15-4.82) to 1.41 (0.03-2.05) cells/h per crypt (P < 0.05). Thus, vitamin D3 reduces human duodenal epithelial cell proliferation.

The preservation of colonic mucosal mass requires the presence of feces; thus, colonic hypoplasia develops with enteral feeding. Fermentable soy fiber may maintain fecal bulk and prevent mucosal atrophy. We therefore compared the effects of Enrich (containing soy fiber) with Ensure (fiber-free) on mucosal mass, fecal bile acids, and cell proliferation in the rat. Sprague-Dawley rats (n = 20) were randomized into groups receiving either standard rat food, Enrich, or Ensure. After 4 weeks, rats were weighed and killed at intervals after administration of vincristine sulfate (1 mg/kg intraperitoneally), which was given to induce metaphase arrest within the intestinal crypts and to allow calculation of crypt cell production rate. Fecal free bile acids and neutral steroids were analyzed using gas-liquid chromatography and gas-liquid chromatography mass spectrometry. Nucleic acid concentrations in the small and large intestine and crypt cell production rate in the small bowel were unaffected by diet. In the proximal large bowel, both enteral diets produced a marked reduction in crypt cell production rate to values only 5% to 7.5% of control values (p < .001). In the midcolon of rats fed Ensure, there was a similar reduction, but this hypoplastic effect was completely prevented by Enrich. Without an elevation in the lithocolic acid to deoxycholic acid ratio, secondary bile acid concentrations were increased in rats receiving Enrich (p < .05 to .01) but not in those receiving Ensure. Thus, fermentable soy fiber diets may prevent the midcolonic mucosal hypoplasia induced by enteral feeding.