High dietary intake of calcium has demonstrated a reasonably consistent risk reduction of between 15% and 40% for colorectal cancer. Clear parameters for dosing are not yet available, with some studies showing no further benefit above Calcium 155
700-800 mg/day of total calcium, while other studies suggest an ongoing inverse dose-dependent relationship without cut-off (Schatzkin & Peters 2004).
A 2005 Cochrane review examining the effect of supplementary calcium on the incidence of colorectal cancer and the incidence or recurrence of adenomatous polyps included two double-blind, placebo-controlled trials with a pooled population of 1346 subjects. The doses of supplementary elemental calcium used were 1200-2000 mg/day for 3-4 years. The reviewers concluded that while the evidence to date appears promising and suggests a moderate degree of prevention against colorectal adenomatous polyps, more research with similar findings is required before this can be translated into any preventative protocol (Weingarten et al 2005).
Not included in the Cochrane review was a multicentre, placebo-controlled randomised study assessing the independent and joint effects of calcium supplementation and vitamin D status on adenoma recurrence in 803 subjects. Interestingly only those subjects with baseline vitamin D levels above the median (29.1 mg/mL) experienced a risk reduction with calcium supplementation (RR 0.71). Similarly, high vitamin D status was not independently associated with risk reduction, but was protective in combination with calcium supplementation (Grau et al 2003). These findings are suggestive of a synergistic action between the nutrients. Earlier hypotheses regarding the action of calcium in this role focused on calcium's ability to bind bowel-irritating substances secreted into bile. This notion is further supported by a number of studies demonstrating enhanced chemoprotection when high doses of calcium have been combined with dietary factors such as reduced fat and increased carbohydrate, fibre and fluid intakes (Hyman et al 1998, Rozen et al 2001, Schatzkin & Peters 2004).
One significant development in our understanding has been the discovery of human parathyroid calcium-sensing receptors in the human colon epithelium, which function to regulate epithelial proliferation and differentiation. New in vitro studies suggest that expression of these receptors may be induced by the presence of extracelullar calcium and vitamin D, therefore promoting greater differentiation of the epithelial cells (Chakrabarty et al 2005) and inducing apoptosis (Miller et al 2005).
The emerging evidence to date for a combined role of calcium, either dietary or supplemental, and vitamin D is strong and further elucidation of the independent and combined effects of these nutrients will assist in the development of preventative protocols.
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