1,25-Dihydroxyvitamin D is not responsible for toxicity caused by vitamin D or 25-hydroxyvitamin D

Arch Biochem Biophys. 2011 Jan 15;505(2):226-30. doi: 10.1016/j.abb.2010.10.012. Epub 2010 Oct 18.


Vitamin D intoxication was produced with oral doses of either vitamin D₃ or 25-hydroxyvitamin D₃ in CYP27B1 -/- (1α-hydroxylase knockout) and wild-type mice. These compounds were equally toxic in wild-type and the mutant mice. Since the null mutant mice are unable to produce 1,25-dihydroxyvitamin D, it is clear 1,25-dihydroxyvitamin D is not responsible for vitamin D intoxication. On the other hand, 25-hydroxyvitamin D rises to levels of 400-700 ng/ml or 1000-1750 nM in the serum of both groups of mice. Toxicity was evidenced by severe hypercalcemia and weight loss. Measurement of 1,25-dihydroxyvitamin D₃ in serum confirmed its absence from serum of the CYP27B1 -/- mice given 25-hydroxyvitamin D₃. Since high concentrations of 25-hydroxyvitamin D can bind the vitamin D receptor and can induce transcription, 25-hydroxyvitamin D is likely responsible for toxicity of vitamin D excess.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / deficiency
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • Animals
  • Body Weight / drug effects
  • Calcifediol / blood
  • Calcifediol / metabolism
  • Calcifediol / toxicity*
  • Calcitriol / blood
  • Calcitriol / metabolism
  • Calcitriol / toxicity
  • Gene Knockout Techniques
  • Male
  • Mice
  • Transcription, Genetic / drug effects
  • Vitamin D / blood
  • Vitamin D / metabolism
  • Vitamin D / toxicity*


  • Vitamin D
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol
  • Calcifediol