Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma

Wargovich, Michael J.; Isbell, Gerald M.; Shabot, Marc; Winn, Rodger J.; Lanza, Frank L.; Hochman, L G; E, Larson; Lynch, Patrick M.; Roubein, Leor D.; Levin, Bernard

doi:10.1016/0016-5085(92)91100-i

Cited by 81 publications

(24 citation statements)

References 25 publications

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“…The same may be true for the discrepancy between our data and those of others in regard to the epithelial proliferation rate. It is noteworthy in this respect that our patients probably had a much higher dietary calcium intake than the subjects studied by Lipkin et al (1985) and by Wargovich et al (1992). Whereas the latter ones had a daily intake of around 700 mg, our patients had a 24 h calcium excretion of about 1,600 mg.…”

Section: Patientsmentioning

confidence: 83%

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

Kleibeuker

Welberg²,

Mulder³

et al. 1993

Br J Cancer

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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 ...

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Section: Patientsmentioning

confidence: 83%

“…In the studies published so far biopsies were taken from the rectum (Lipkin & Newmark, 1985;Rozen et al, 1989;Gregoire et al, 1989;Stern et al, 1990;Barsoum et al, 1992;Wargovich et al, 1992), whereas we took them from the sigmoid. This may have had important implications for the effect of calcium.…”

Section: Patientsmentioning

confidence: 99%

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

Kleibeuker

Welberg²,

Mulder³

et al. 1993

Br J Cancer

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“…However, one cannot rule out the possibility that higher doses of calcium or vitamins are necessary to counteract an increased genetic tendency to polyp growth. 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].…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, calcium supplementation has reduced the pathological proliferative pattern of the colon crypts in patients with a high risk of CRC [17][18][19][20][21]. It has been postulated that the mechanism of action is an inactivation of the cocarcinogenic potential of secondary bile acids and fatty acids [22], and possibly a direct antitropism against hyperproliferative activity in the colonic mucosa [18,23].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 1998

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Background: Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer. This has been supported by animal experimental studies, case control and cohort studies. Materials and Methods: In a prospective intervention study of colorectal adenomas, and intermediary stage in colorectal carcinogenesis, 116 polyp-bearing patients received a placebo-controlled daily mixture of β-carotene 15 mg, vitamin C 150 mg, vitamin E 75 mg, selenium 101 µg, and calcium (1.6 g daily) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence. All polyps of <10 mm at enrolment or follow-up were left unresected until the end of the study. Results: 87–91% of the patients attended the annual endoscopic follow-up investigations, and 19% of the patients dropped out of the medical intervention. The rest consumed 85% of the total amount of tablets over the 3 years. The fecal calcium concentration was 2.3–2.7 times higher in patients taking active medication compared to the placebo group. Diet registration showed that, when adding the intake of antioxidants and calcium from diet and intervention, there was a significant difference between the intake of these substances in the active and the placebo group. No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period. Moreover, there was no effect on polyps of <5 or 5–9 mm, or on polyps in the different colonic segments analyzed separately. A reduced growth of adenomas was found in patients <60 years of age taking active medication (n = 8) compared to those taking placebo (n = 6; mean difference 2.3 mm; 95% CI 0.26–4.36). There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis (log-rank test p value 0.035). Subgroup analysis showed that only the group of patients with no family history of colorectal cancer, those with only one adenoma at inclusion, and those <65 years benefitted from the intervention medication. Conclusion: The study did not find an overall effect on polyp growth. Our data, however, may support a protective role of calcium and antioxidants on new adenoma formation.

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“…The results of five small uncontrolled clinical trials (Lipkin & Newmark, 1985;Buset et al, 1986;Lipkin et al, 1989;Rozen et al, 1989;O'Sullivan et al, 1993), nine small randomized placebo-controlled trials (Gregoire et al, 1989;Stern et al, 1990;Barsoum et al, 1992;Wargovich et al, 1992;Thomas et al, 1993;Bostick et al, 1993;Cats et al, 1995;Weisgerber et al, 1996;Bostick et al, 1997) and three full-scale randomized placebo-controlled trials (Armitage et al, 1995;Baron et al, 1995;Bostick et al, 1995) suggested that it is unlikely that calcium supplementation can substantially lower colorectal epithelial cell proliferation rates, but it may normalize the distribution of proliferating cells within colon crypts, as reviewed by Bostick, (1997). This is still consistent with the hypothesis that a higher consumption of calcium may reduce the risk of colorectal cancer.…”

Section: Calciummentioning

confidence: 99%

Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence

2003

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Objectives: This review provides an overview of the principal hypotheses and epidemiological evidence of the possible links between colorectal cancer and intake of milk and=or dairy products. Methods: The first section outlines the main hypotheses about the possible effect of calcium, vitamin D, fats and other milk components. The possible role of acid lactic bateria in fermented products is also discussed. The second section is a summary of the published epidemiological evidence. The results on milk, cheese and yoghurt are summarized using a meta-analytical approach. The results of studies on calcium and vitamin D are briefly described. Results: Case -control studies are heterogeneous and, on average, do not provide evidence of association between total intake of total dairy products, milk, cheese or yoghurt and colorectal cancer risk. The average result from cohort studies support the hypothesis of a protective effect of total dairy products (odds ratio (OR): 0.62; 95% confidence interval (CI): 0.52 -0.74; P heterogeneity test: 0.93) and for milk (OR: 0.80; 95% CI: 0.68 -0.95; P heterogeneity: 0.77). No association was found between cheese (OR: 1.10; 95% CI: 0.88 -1.36; P heterogeneity: 0.55) or yoghurt (OR: 1.03; 95% CI: 0.83 -1.28; P heterogeneity: 0.69) in cohort studies. Conclusions: Cohort studies consistently found a protective effect of total dairy products and milk intake, but the evidence is not supported by case -control studies. No relationship was found with cheese or yoghurt intake. As the number of cohort studies is still limited, their results need to be confirmed by other prospective studies.

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Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma

Cited by 81 publications

References 25 publications

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

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

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

Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence

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