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

Arch Biochem Biophys 505(2):226-30 (2011)
Hector F Deluca, Jean M Prahl and Lori A Plum
Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, United States.

Vitamin D intoxication was produced with oral doses of either vitamin D(3) or 25-hydroxyvitamin D(3) in CYP27B1 -/- (1?-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 400-700ng/ml or 1000-1750nM in the serum of both groups of mice. Toxicity was evidenced by severe hypercalcemia and weight loss. Measurement of 1,25-dihydroxyvitamin D(3) in serum confirmed its absence from serum of the CYP27B1 -/- mice given 25-hydroxyvitamin D(3). 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. Copyright © 2010 Elsevier Inc. All rights reserved. DOI: 10.1016/j.abb.2010.10.012 * PMID: 20965147
- - - - - -

400 ng/ml is 1.5X more than seen for humans and is 10X higher than the Toxic level stated by the Instutute of Medicine

See also VitaminDWiki

• Toxic level of vitamin D may be 300 ng - 2008
• Toxicity of vitamin D 300 ng but selected 100 ng to be prudent – Aug 2008