Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial

J Natl Cancer Inst. 2003 Dec 3;95(23):1765-71. doi: 10.1093/jnci/djg110.


Background: Calcium and vitamin D both appear to have antineoplastic effects in the large bowel. Although these nutrients are inter-related metabolically in bone and in the normal intestine, their potential interactions in large-bowel carcinogenesis are not well understood.

Methods: We assessed independent and joint effects of calcium supplementation and vitamin D status on adenoma recurrence in 803 subjects in a multi-center, placebo-controlled randomized clinical trial of calcium supplementation for the prevention of colorectal adenoma recurrence. Serum levels of 25-hydroxy [25-(OH)] vitamin D and 1,25-dihydroxy [1,25-(OH)2] vitamin D levels were determined, and the Taq I and Fok I polymorphisms in the vitamin D receptor (VDR) gene were analyzed by polymerase chain reaction. Risk ratios (RRs) for any adenoma recurrence were computed for calcium supplementation within groups defined by serum vitamin D levels and for serum vitamin D levels within treatment groups. Associations of VDR polymorphisms with recurrence risk were also evaluated. All statistical tests were two-sided.

Results: Among subjects with baseline 25-(OH) vitamin D levels at or below the median (29.1 ng/mL), calcium supplementation was not associated with adenoma recurrence, whereas among those with levels above the median, calcium supplementation was associated with a reduced risk (RR = 0.71, 95 % confidence interval [CI] = 0.57 to 0.89, P for interaction =.012). Conversely, serum 25-(OH) vitamin D levels were associated with a reduced risk only among subjects receiving calcium supplements (RR per 12 ng/mL increase of vitamin D = 0.88, 95% CI = 0.77 to 0.99, P for interaction =.006). VDR polymorphisms were not related to adenoma recurrence and did not modify the associations with vitamin D or calcium.

Conclusions: Calcium supplementation and vitamin D status appear to act largely together, not separately, to reduce the risk of colorectal adenoma recurrence. VDR genotype does not appear to be associated with risk.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoma / blood
  • Adenoma / genetics
  • Adenoma / prevention & control*
  • Aged
  • Anticarcinogenic Agents / blood
  • Anticarcinogenic Agents / therapeutic use*
  • Calcium Compounds / therapeutic use*
  • Colonoscopy
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / prevention & control*
  • Dietary Supplements
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Calcitriol / genetics*
  • Risk Assessment
  • Treatment Outcome
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood*
  • Vitamin D / therapeutic use*


  • Anticarcinogenic Agents
  • Calcium Compounds
  • Receptors, Calcitriol
  • Vitamin D
  • 25-hydroxyvitamin D