This Article Full Text Full Text (PDF) Perspective on this Article All Versions of this Article: 1940-6207.CAPR-08-0157v1 2/3/213    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fedirko, V. Articles by Dash, C. Search for Related Content PubMed PubMed Citation Articles by Fedirko, V. Articles by Dash, C. Related Collections Clinical Intervention Clinical Intervention: Diet and Diet-related Factors Related Article

Effects of Vitamin D and Calcium Supplementation on Markers of Apoptosis in Normal Colon Mucosa: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Authors' Affiliations: Departments of ¹ Epidemiology and ² Biostatistics and Bioinformatics, Rollins School of Public Health, ³ Winship Cancer Institute, and ⁴ Nutrition and Health Sciences Program, Graduate Division of Biological and Biomedical Sciences, Emory University; ⁵ Division of Digestive Diseases, Emory University School of Medicine, Atlanta, Georgia and ⁶ Department of Medicine, GI Division University of Minnesota, Minneapolis, Minnesota

Requests for reprints: Roberd M. Bostick, Department of Epidemiology, Rollins School of Public Health, Emory University, 1518 Clifton Road Northeast, Atlanta, GA 30322. Phone: 404-727-2671; Fax: 404-727-8737; E-mail: rmbosti{at}sph.emory.edu.

To further clarify and/or develop calcium and vitamin D as chemopreventive agents against colorectal cancer in humans, understand the mechanisms by which these agents reduce risk for the disease, and develop "treatable" biomarkers of risk for colorectal cancer, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D₃, alone and in combination on markers of apoptosis, in the normal colorectal mucosa. Ninety-two men and women with at least one pathology-confirmed colorectal adenoma were treated with 2.0 g/d calcium or 800 IU/d vitamin D₃, alone or in combination, versus placebo over 6 months. Overall expression and colorectal crypt distributions of Bcl-2 (an apoptosis inhibitor) and Bax (an apoptosis promoter) in biopsies of normal-appearing rectal mucosa were detected by automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, Bax expression along the full lengths of crypts increased 56% (P = 0.02) in the vitamin D group and 33% in both the calcium (P = 0.31) and calcium plus vitamin D (P = 0.36) groups relative to the placebo group. The vitamin D treatment effect was more pronounced in the upper 40%, or differentiation zone, of crypts (80%; P = 0.01). There were no statistically significant treatment effects on Bcl-2 expression. Overall, these preliminary results suggest that calcium and vitamin D, individually or together, may enhance apoptosis in the normal human colorectal epithelium, and the strongest treatment effects may be vitamin D related and in the upper sections of the colorectal crypts.

Key Words: vitamin D • calcium • apoptosis • randomized controlled trial • normal colorectal mucosa

Related Article

Vitamin D, Calcium, and Colorectal Neoplasia: New Insights on Mechanisms of Action

Elizabeth T. Jacobs, Peter W. Jurutka, María Elena Martínez,, and David S. Alberts
Cancer Prevention Research 2009 2: 197-199. [Full Text] [PDF]

This article has been cited by other articles:

				E. T. Jacobs, P. W. Jurutka, M. E. Martinez,, and D. S. Alberts Vitamin D, Calcium, and Colorectal Neoplasia: New Insights on Mechanisms of Action Cancer Prevention Research, March 1, 2009; 2(3): 197 - 199. [Full Text] [PDF]