Epithelial cell proliferation in the sigmoid colon of patients with adenomatous polyps increases during oral calcium supplementation

Abstract

Summary To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5gCa2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementation for 9 months without dietary restrictions. Epithelial proliferation rate in colonic biopsies, expressed as labelling index (%), was determined with 5-bromodeoxyuridine and immunohistochemistry. Biopsies were taken from the midsigmoid at time of polyp excision and at the end of the intervention period. Median labelling index increased from 6.1% before to 8.7% after 12 weeks calcium (n = 17, P <0.02). This was due to increased labelling in the basal third of the crypts (11.9 vs 16%), whereas labelling in mid and luminal compartments was not affected. Labelling index remained increased after I year calcium supplementation at 8.8%. Crypt length was not affected by calcium. These results are in contrast to those of others, who have shown a decrease of rectal epithelial proliferation during similar doses of calcium. Therefore, the effect of nutritional intervention on colonic epithelial proliferation should be studied in biopsies taken not only from the rectum, but also from more proximal parts of the colon. Caution with respect to large scale intervention studies with calcium in high risk groups is mandatory.Nutritional factors are of major importance in the etiology of colon cancer (Weisburger & Wynder, 1987). Therefore attention has been focused recently on possible ways to reduce cancer risk by dietary modifications. In this respect calcium. has been suggested to be a promising nutritional component (Newmark et al., 1984). Several investigators have found that supplemental dietary calcium reduces the epithelial proliferation rate in rectal mucosa in subjects at an increased risk for colon cancer (Lipkin & Newmark, 1985; Rozen et al., 1989). Hyperproliferation of colonic epithelium has repeatedly been shown to be associated with an increased cancer risk (Terpstra et al., 1987;Scalmati et al., 1990;Risio et al., 1991) and reduction of the proliferation rate may thus indicate a beneficial effect with respect to tumorigenesis. However, in the studies on the effect of calcium so far reported, proliferation was measured in rectal epithelium, whereas epidemiological surveys have shown that nutritional risk factors for rectal and colonic cancer are not the same (Ziegler et al., 1986). The favourable effect of calcium on rectal epithelium may therefore not be extrapolated automatically to the colonic epithelium. Another point is that patients enrolled in previous studies were not given dietary guidelines to keep dietary calcium intake constant during calcium supplementation and thus it could not be excluded that the effects of calcium supplementation were modified by unforeseen changes in the intake of dietary calcium. Therefore, we performed an intervention study with oral calcium supplementation in patients with an ...

Effects of Supplemental Dietary Calcium on Quantitative and Qualitative Fecal Fat Excretion in Man

“…Whether the increase of fecal fat excretion might be harmful for the colonic epithelial cells and might thus induce in creased cell proliferation was not evaluated in this study, but this cannot be fully excluded. In this respect it is worth mentioning that although several investigators have found that oral calcium supplementation caused a lower ing of epithelial cell proliferation in the rec tum [23][24][25], this has not been confirmed in other studies [26,27] and we even found an increase of proliferative activity of the epithe lium in the sigmoid during calcium supple mentation [28], Whether these discrepancies are related to the effects of calcium on fatty acid excretion is only speculative.…”

Calcium supplements interact significantly with long-term diet while suppressing rectal epithelial proliferation of adenoma patients

“…[21][22][23][24][25][26][27][28][29][30] However, results of a number of international ecological and analytic epidemiologic studies did not support the hypothesis that calcium-deficient diet is a risk for colorectal cancer and did not find a cancer preventive value for calcium supplementation in humans. 11,13,14,16,22,26,31,32 These findings were in contrast to the findings of experimental studies in animals, where a calcium deficient or supplemented diet had a marked protective effect on large bowel epithelial proliferation and also on the process of carcinogenisis. 6,23,28 -30,33 Suppression of large bowel epithelial proliferation by calcium has been explained by intraluminal binding of bile and fatty acids to calcium that thereby reduces the damaging effects of bile and fatty acids on colonic epithelial cells and/or by the strengthening their intercellular bonds by calcium and/or by systemic strengthening through calcium and vitamin D metabolism.…”

Growth and Recurrence of Colorectal Polyps: A Double-Blind 3-Year Intervention with Calcium and Antioxidants

“…An inhibitory effect of 2.0 g of calcium daily has been demonstrated on the hyperproliferating epithelial cytokinetics, with no effect of 1.5 g [21]. Also, the stabilizing effect of calcium has mostly been observed in hyperproliferative rectal mucosa [18], whereas an increased labelling index was found in the sigmoid mucosa [66]. No difference in segmental polyp growth pattern or new polyp formation related to calcium and antioxidants was found in the present study.…”