Calcium carbonate suppresses haem toxicity markers without calcium phosphate side effects on colon carcinogenesis

Red meat intake is associated with increased risk of colorectal cancer. We have previously shownthat haemin, haemoglobin and red meat promote carcinogen-induced preneoplastic lesions,aberrant crypt foci, in the colon of rats. We have also shown that dietary calcium phosphateinhibits haemin-induced promotion, and normalizes faecal lipoperoxides and cytotoxicity.Unexpectedly, high-calcium phosphate control diet-fed rats had more preneoplastic lesions in thecolon than low-calcium control diet-fed rats. The present study was designed to find a calciumsupplementation with no adverse effect, by testing several doses and types of calcium salts. One invitro study and two short-term studies in rats identified calcium carbonate as the most effectivecalcium salt to bind haem in vitro and to decrease faecal biomarkers previously associated withincreased carcinogenesis: faecal water cytotoxicity, thiobarbituric acid reactive substances. A longterm carcinogenesis study in dimethylhydrazine-injected rats demonstrated that a diet containing100 μmol/g calcium carbonate did not promote aberrant crypt foci, in contrast with previouslytested calcium phosphate diet. The results suggest that calcium carbonate, and not calciumphosphate, should be used to reduce haem-associated colorectal cancer risk in meat-eaters. Theysupport the concept that the nature of the associated anion to a protective metal ion is importantfor chemoprevention