Effects of vitamin D and calcium supplementation on markers of apoptosis in normal colon mucosa: a randomized, double-blind, placebo-controlled clinical trial.
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.
Fedirko
Veronika
V
Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA.
Bostick
Roberd M
RM
Flanders
W Dana
WD
Long
Qi
Q
Shaukat
Aasma
A
Rutherford
Robin E
RE
Daniel
Carrie R
CR
Cohen
Vaunita
V
Dash
Chiranjeev
C
D000236:Adenoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002118:Calcium / Q000627:therapeutic use*; D002762:Cholecalciferol / Q000378:metabolism; D003106:Colon / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D014807:Vitamin D / Q000627:therapeutic use*
D010919:Placebos; D014807:Vitamin D; D002762:Cholecalciferol; D002118:Calcium