Cholecalciferol or 25-Hydroxycholecalciferol Neither Prevents Nor Treats Adenomas in a Rat Model of Familial Colon Cancer

卷:145

Irving, Amy A. ; Plum, Lori A. ; Blaser, William J. ; Ford, Madeline R. ; Weng, Chao ; Clipson, Linda ; DeLuca, Hector F. ; Dove, William F.

Univ Wisconsin

关键词: chemoprevention;    nutritional supplementation;    animal models;    endoscopy;    colorectal cancer;   

DOI  :  10.3945/jn.114.204396

学科分类：食品科学和技术

【 摘 要 】

Background: Epidemiologic studies in humans have shown associations between greater sunlight exposure, higher serum 25-hydroxycholecalciferol [25(OH)D-3] concentrations, and reduced colon cancer risk. However, results from a limited number of vitamin D supplementation trials in humans have not shown a protective effect. Objective: We sought to determine whether adding to the diet increasing amounts of either 25(OH)D-3, the stable metabolite measured in serum and associated with cancer risk, or cholecalciferol (vitamin D-3), the compound commonly used for supplementation in humans, could reduce emergent adenomas (chemoprevention) or decrease the growth of existing adenomas (treatment) in the colons of vitamin D sufficient rats carrying a truncation mutation of adenomatous polyposis coli (Apc), a model of early intestinal cancer. Methods: Apc(Pirc/+) rats were supplemented with either vitamin D-3 over a range of 4 doses [6-1500 mu g/(kg body weight cl)] or with 25(OH)D-3 over a range of 6 doses [60-4500 mu g/(kg body weight . d)] beginning after weaning. Rats underwent colonoscopy every other week to assess effects on adenoma number and size. At termination (140 d of age), the number of tumors in the small intestine and colon and the size of tumors in the colon were determined, and serum calcium and 25(OH) D-3 measurements were obtained. Results: At lower doses (those that did not affect body weight), neither of the vitamin D compounds reduced the number of existing or emergent colonic tumors (P-trend > 0.24). By contrast, supplementation at higher doses (those that caused a suppression in body weight gain) with either 25(OH)D-3 or vitamin D-3 caused a dose-dependent increase in colonic tumor number in both males and females (P-trend < 0.003). Conclusions: No evidence for protection against colon tumor development was seen with lower dose supplementation with either cholecalciferol or 25-hydroxycholecalciferol. Thus, the association between sunlight exposure and the incidence of colon cancer may involve factors other than vitamin D concentrations. Alternative hypotheses warrant investigation. Furthermore, this study provides preliminary evidence for the need for caution regarding vitamin D supplementation of humans at higher doses, especially in individuals with sufficient serum 25(OH)D-3 concentrations.