HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jones, G. Search for Related Content PubMed PubMed Citation Articles by Jones, G. Agricola Articles by Jones, G.

Pharmacokinetics of vitamin D toxicity^1,2,3,4

¹ From the Departments of Biochemistry and Medicine, Queen's University, Kingston, Ontario, Canada

ABSTRACT

Although researchers first identified the fat-soluble vitamin cholecalciferol almost a century ago and studies have now largely elucidated the transcriptional mechanism of action of its hormonal form, 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃], we know surprisingly little about mechanisms of vitamin D toxicity. The lipophilic nature of vitamin D explains its adipose tissue distribution and its slow turnover in the body (half-life 2 mo). Its main transported metabolite, 25-hydroxyvitamin D₃ [25(OH)D₃], shows a half-life of 15 d and circulates at a concentration of 25–200 nmol/L, whereas the hormone 1,25(OH)₂D₃ has a half-life of 15 h. Animal experiments involving vitamin D₃ intoxication have established that 25(OH)D₃ can reach concentrations up to 2.5 µmol/L, at which it is accompanied by hypercalcemia and other pathological sequelae resulting from a high Ca/PO₄ product. The rise in 25(OH)D₃ is accompanied by elevations of its precursor, vitamin D₃, as well as by rises in many of its dihydroxy- metabolites [24,25(OH)₂D₃; 25,26(OH)₂D₃; and 25(OH)D₃-26,23-lactone] but not 1,25(OH)₂D₃. Early assumptions that 1,25(OH)₂D₃ might cause hypercalcemia in vitamin D toxicity have been replaced by the theories that 25(OH)D₃ at pharmacologic concentrations can overcome vitamin D receptor affinity disadvantages to directly stimulate transcription or that total vitamin D metabolite concentrations displace 1,25(OH)₂D from vitamin D binding, increasing its free concentration and thus increasing gene transcription. Occasional anecdotal reports from humans intoxicated with vitamin D appear to support the latter mechanism. Although current data support the viewpoint that the biomarker plasma 25(OH)D concentration must rise above 750 nmol/L to produce vitamin D toxicity, the more prudent upper limit of 250 nmol/L might be retained to ensure a wide safety margin.

This article has been cited by other articles:

				R. Joshi Hypercalcemia due to Hypervitaminosis D: Report of Seven Patients J Trop Pediatr, April 1, 2009; (2009) fmp020v1. [Abstract] [Full Text] [PDF]

				P. M Brannon, E. A Yetley, R. L Bailey, and M. F. Picciano Overview of the conference "Vitamin D and Health in the 21st Century: an Update" Am. J. Clinical Nutrition, August 1, 2008; 88(2): 483S - 490S. [Abstract] [Full Text] [PDF]