A randomized, double-blinded, parallel study to evaluate the dose-response of a monthly supplementation of 25 000, 50 000 or 100 000 IU of vitamin D3 in subjects with deficiency in vitamin D
Cavalier E (1), Jandrain B (2), Da Silva S (3), De Niet S (3), Vander-bistF(3), ScheenA(4).
1. Department of Clinical Chemistry, University of Liege, CHU Sart-Tilman, Liege Belgium.
2. Department of Clinical Pharmacology, ATC SA, Liege Belgium.
3. Clinical Department, Laboratoires SMB SA, Brussels Belgium.
4. Division of Diabetes, Nutrition and Metabolic Disorders, CHU SartTilman, University of Liege, Liege, Belgium.
Background: Approximately one billion people worldwide have low serum levels of vitamin D. The aim of this study was to evaluate the dose-response effect in order to determine the level of supplementation of vitamin D required in patients with deficiency in vitamin D concentration (< 20 ng/ml).
Methods: A randomized, parallel and double-blinded study was performed according to Good Clinical Practice in Belgium between December 2012 and May 2013 0ne hundred and fifty individuals (65 men and 85 female) aged over 18 years with a body mass index between 18 and 30 kg/m2 were selected because their vitamin D concentrations were between 5 ng/mL and 20 ng/mL at inclusion, consistent with vitamin D deficiency. The DiaSorin Liaison was used to measure serum levels of 25(OH)D (Stillwater, MN). The selected subjects were randomized into 3 groups of 50, each to receive a low, moderate or high dose of D-CURE® once a month. D-CURE® consists of an ampoule containing an oily solution of 25 000 IU vitamin D for oral use. Three dosing schedules were compared: subjects received a loading dose of 50 000,100 000 or 200 000 IU of vitamin D according to their group at Week 0, followed by 25 000, 50 000 or 100 000 at Week 4 and Week 8. The total study duration was 12 weeks. A total dose of 100 000, 200 000 and 400 000 IU, respectively, was therefore administered over 12 weeks. . Drug administration was supervised by the study staff allowing a 100% patient's compliance. Main endpoints were serum level of 25(OH), percentage of patients and time to reach the levels of 20 and 30 ng/ml over 12 weeks.
Results: Baseline levels of 25(OH)D were similar in the three groups (13.94 ± 3.75 ng/mL, 12.98 ± 3.85 ng/mL, 13.66 ± 3.57 ng/mL; p=0.42). A rather linear dose-response relationship was observed between the 3 groups, with increases in 25(OH)D levels proportionate to the dose administered. Mean increases in 25(0H)D levels were
- 7.92±0.87 ng/mL,
- 13.04±0.87 ng/mL and
- 20.18±0.86 ng/mL,
respectively, for 100 000 IU, 200 000 IU and 400 000 IU after 12 weeks of supplementation.
Overall, 98% of the subjects supplemented with 400 000 IU of vitamin D had their level of 25(0H)D above 20 ng/mL at Week 8, while 84% and 52% of patients receiving 200 000 IU or 100 000 IU reached that level after 12 weeks of treatment. Likewise, at week 12, 64% of individuals attained the target of 30 ng/mL in the 400 000 IU group compared to the lower dosage supplementation groups (24% and 4% for the 200 000 IU and 100 000 IU, respectively). No clinically relevant adverse events were observed after 3 months of supplementation, even with the higher doses. The individual maximum serum 25(OH)D concentration observed was 64 ng/ml which is far below 150 ng/ml, considered as the potentially "toxic" limit.
Conclusions: This study demonstrated a dose-response between vitamin D administration and plasma levels after monthly administrations of 25 000, 50 000 or 100 000 IU of vitamin D (D-CURE® ampoule). Serum concentration of 25(0H)D >20 ng/ml was obtained for all subjects (98%) in the group receiving the high dose of vitamin D only (100 000 IU per month). Starting the treatment with a high loading dose allows faster correction of the vitamin D deficiency.
Poster presented at Vitamin D conference in England - April 23-25 2014
- One pill every two weeks gives you all the vitamin D most adults need = 50,000 once every 2 weeks. Once a month is too infrequent
- How often should I take 50000 IU (1.25 mg) of vitamin D
- Take vitamin D3 daily or weekly shows that monthly dosing results in less benefit
Notional of Vitamin D benefit vs dosing frequency for vitamin D level < 30 nanograms