SFEBES2016 Poster Presentations Clinical biochemistry (28 abstracts)
Changes in serum 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D in response to three vitamin D3 supplementation regimens
Jonathan Tang 1 , Holly Nicholls 1 , John Dutton 1 , Isabelle Piec 1 , Christopher Washbourne 1 , Lanja Saleh 2 , A Novak 2 , Graeme Close 3 , Helen Macdonald 4 & William Fraser 1
1University of East Anglia, Norwich, UK; 2University Hospital of Zurich, Zurich, Switzerland; 3Liverpool John Moores University, Liverpool, UK; 4University of Aberdeen, Aberdeen, UK
Background: 25-hydroxyvitamin D (25(OH)D) is metabolised into two forms of metabolites: 1,25-dihydroxyvitamin D (1,25(OH)2D) by the actions of 1α hydroxylase, and 24,25-dihydroxyvitamin D (24,25(OH)2D) by 24-hydroxylase. Studies suggest the production of 1,25(OH)2D is 24,25(OH)2D dependent. Genetic mutations of CYP24A1 gene resulting in reduced or total loss of 24-hydroxylase function are associated with hypercalcaemic conditions and increase renal stone formations.
Objective: To profile the changes in serum concentrations of 25(OH)D, 24,25(OH)2D and 1,25(OH)2D in three supplementation studies where subjects were given a single bolus, weekly or daily low dose of vitamin D3.
Method: Samples obtained from three studies were measured for 25(OH)D3/D2 and 24,25-(OH)2D3/D2 by liquid chromatography tandem mass spectrometry (LC-MS/MS) and 1,25-(OH)2D by enzyme immunoassay. In the first study, healthy volunteers (n=69) were given either a placebo or a single 100,000 IU bolus of vitamin D3. In the secondary study, two groups of athletes were given either 35,000 or 70,000 IU weekly dose of vitamin D3 over 12 weeks. In the third study, three groups of postmenopausal women (n=253) were given either placebo, 400 or 1,000 IU daily over a 12-month period.
Results: Subjects supplemented with single bolus and weekly high doses of vitamin D3 showed rapid increase in serum 25(OH)D and 24,25(OH)2D concentrations; a significant decrease (P>0.001) in 25(OH)D:24,25-(OH)2D ratio and a moderate increase in 1,25(OH)2D concentration. Daily low dose of vitamin D3 showed a moderate increase in 1,25(OH)2D concentration, and no significant change in 25(OH)D:24,25-d(OH)D ratio over the dosing period.
Conclusion: Increasing vitamin D3 supplementation results in an increase but relative difference in production of metabolites. Our findings showed the metabolism favors the production of 24,25(OH)2D rather than of 1,25(OH)2D when high dose of vitamin D3 is given, suggesting a mechanistic response to prevent toxicity. We advise low and regular dosing regimen may be most beneficial to the patients.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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