ECTS2016 Poster Presentations Biochemical testing (10 abstracts)
Profiles of 25 hydroxyvitamin D and its metabolites 24, 25-dihydroxyvitamin D and 1, 25-dihydroxyvitamin D in vitamin D3 supplementation studies
Jonathan Tang 1 , Holly Nicholls 1 , John Dutton 1 , Isabelle Piec 1 , Christopher Washbourne 1 , L Saleh 2 , A Novak 2 , G Close 3 , H Macdonald 4 , S Jackson 5 , J Greeves 5 & William Fraser 1
1University of East Anglia, Norfolk, UK; 2University Hospital of Zurich, Zurich, Germany; 3Liverpool John Moores University, Liverpool, UK; 4School of Medicine and Dentistry, Aberdeen, UK; 5HQ Army Recruiting and Training Division, Upavon, UK.
Background: Vitamin D plays an important role in calcium and phosphate homeostasis. Circulating 25 hydroxyvitamin D [25(OH)D] is metabolised into its biologically active form 1,25-dihydroxyvitamin D [1,25-d(OH)D] by the actions of 1α hydroxylase, and into inactive 2metabolite 24,25-dihydroxyvitamin D [24,25-d(OH)D] by 24-hydroxylase. Recent studies suggest the production of 1,25-d(OH)D) from 25(OH)D is 24,25-d(OH)D dependent. Genetic mutations of CYP24A1 gene resulting in reduced or total loss of 24-hydroxylase function are associated with hypercalcaemic conditions.
Objective: To establish the profiles of 25(OH)D, 24,25-d(OH)D and 1,25-d(OH)D in non-supplemented healthy individuals and investigate changes in three vitamin D3 supplementation studies.
Method: Samples obtained from a group of non-supplemented individuals and three vitamin D3 supplement studies (Table 1) were measured for 25(OH)D3/D2 and 24,25-d(OH)D3/D2 and total 1,25-d(OH)D.
Results: Mean 25(OH)D:24,25-d(OH)D ratio was established from non-supplemented subjects (Table 1). Subjects supplemented with daily vitamin D3 showed rapid increase in 25(OH)D and 24,25-d(OH)D concentrations, whereas only a moderate increase in 1,25-d(OH)D concentration. No significant changes were observed in 25(OH)D:24,25-d(OH)D ratio in subjects given more than 5000 IU, a decrease in ratio was found in subject given 1000 IU/day or less.
Conclusion: Increasing vitamin D3 supplementation results in an increase in metabolites but relative difference in production of 1,25-d(OH)D. Our results indicate that the metabolism favors the production of 24,25-d(OH)D than of 1,25-d(OH)D in the presence of high supplementation of vitamin D3 in contrast to regular low dosage in order to prevent toxicity. We advise caution when using extremely high supplementation levels may not be beneficial to the patients.
| Vitamin D | Mean±S.D. 25(OH)D nmol/l | Mean±S.D. 24,25-d(OH)D nmol/l | Mean±S.D. 1,25–d(OH)D pmol/l | Mean±S.D. 25(OH)D:24,25-d(OH) D ratio | Mean±S.D. 1,25-d(OH)D:24,25-d(OH)D ratios | ||||||
| n | dose (IU) | Baseline | Peak | Baseline | Peak | Baseline | Peak | Baseline | Peak | Baseline | Peak |
| 474 | None | 63.1±24.2 | – | 5.6±2.9 | – | – | – | 13±4 | – | – | – |
| 69 | Single 100,000 | 33.4±11.7 | 80.2±20.8 | 2.4±1.0 | 6.8±2.0 | 99.1±27.4 | 125.1±42.2 | 15±3 | 14±4 | 50±24 | 20±8 |
| 43 | 5000 and 10,000 daily | 86.3±19.3 | 176±58.8 | 7.9±2.2 | 14.7±4.5 | 104.8±44.2 | 135.3±56.2 | 12±3 | 13±4 | 15±6 | 10±4 |
| 253 | 400 and 1000 daily | 44.5±18.2 | 75±24.2 | 2.8±1.6 | 6.2±2.8 | – | – | 16±4 | 13±3 | – | – |
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