Effects of supplemental vitamin D and calcium on oxidative DNA damage marker in normal colorectal mucosa: a randomized clinical trial

Cancer Epidemiol Biomarkers Prev. 2010 Jan;19(1):280-91. doi: 10.1158/1055-9965.EPI-09-0448.


The exact antineoplastic effects of calcium and vitamin D(3) in the human colon are unclear. Animal and in vitro studies show that these two agents reduce oxidative stress; however, these findings have never been investigated in humans. To address this, we conducted a pilot, randomized, double-blind, placebo-controlled, 2 x 2 factorial clinical trial to test the effects of calcium and vitamin D(3) on a marker of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OH-dG), in the normal colorectal mucosa. Patients (N = 92) with at least one pathology-confirmed colorectal adenoma were treated with 2 g/d calcium and/or 800 IU/d vitamin D(3) versus placebo over 6 months. Overall labeling and colorectal crypt distribution of 8-OH-dG in biopsies of normal-appearing rectal mucosa were detected by standardized automated immunohistochemistry and quantified by image analysis. After 6 months of treatment, 8-OH-dG labeling along the full lengths of colorectal crypts decreased by 22% (P = 0.15) and 25% (P = 0.10) in the calcium and vitamin D(3) groups, respectively, but not in the calcium plus vitamin D(3) group. The estimated treatment effects were strongest among participants with higher baseline colon crypt vitamin D receptor expression (P = 0.05). Overall, these preliminary results indicate that calcium and vitamin D(3) may decrease oxidative DNA damage in the normal human colorectal mucosa, support the hypothesis that 8-OH-dG labeling in colorectal crypts is a treatable oxidative DNA damage biomarker of risk for colorectal neoplasms, and provide support for further investigation of calcium and vitamin D(3) as chemopreventive agents against colorectal neoplasms.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adenoma / pathology
  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Calcium Carbonate / therapeutic use*
  • Calcium, Dietary / therapeutic use
  • Cholecalciferol / therapeutic use*
  • DNA Damage / drug effects*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / analysis
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Intestinal Mucosa / drug effects*
  • Intestinal Neoplasms / prevention & control*
  • Male
  • Middle Aged
  • Oxidative Stress / drug effects
  • Pilot Projects
  • Precancerous Conditions / pathology


  • Biomarkers, Tumor
  • Calcium, Dietary
  • Cholecalciferol
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Calcium Carbonate