Randomized controlled trials of vitamin D and cancer incidence: A modeling study

PLoS One. 2017 May 1;12(5):e0176448. doi: 10.1371/journal.pone.0176448. eCollection 2017.


Although geographic ecological studies and observational studies find that ultraviolet B exposure and 25-hydroxyvitamin D [25(OH)D] concentrations are inversely correlated with 15-20 types of cancer, few randomized controlled trials (RCTs) of vitamin D support those findings. The poor design of some RCTs may account for that lack of support. Most vitamin D RCTs to date have considered the vitamin D dose, rather than initial, final, or changes in, serum 25(OH)D concentrations. Here a model is developed for use in designing and analyzing vitamin D RCTs with application to cancer incidence. The input variables of the model are vitamin D dose, baseline and achieved 25(OH)D concentrations, known rates of cancer for the population, and numbers of participants for the treatment and placebo arms is estimated-vitamin D dosage and numbers of participants are varied to achieve desired hazard ratio significance, using information from two vitamin D RCTs on cancer incidence conducted in Nebraska with good agreement between the model estimates and reported hazard ratios. Further improvements to the conduct of vitamin D RCTs would be to start the trial with a moderate bolus dose to achieve the desired 25(OH)D concentrations, and bloodspot 25(OH)D assay use in summer and winter annually to monitor seasonal and long-term changes in 25(OH)D concentration and compliance, and to allow dosage adjustment for achievement of desired vitamin D status.

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Humans
  • Incidence
  • Middle Aged
  • Models, Theoretical*
  • Nebraska / epidemiology
  • Neoplasms / blood*
  • Neoplasms / drug therapy
  • Neoplasms / epidemiology*
  • Odds Ratio
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic* / methods
  • Seasons
  • Vitamin D / administration & dosage
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood


  • Antineoplastic Agents
  • Vitamin D
  • 25-hydroxyvitamin D

Grants and funding

The authors received no specific funding for this work.