Efficacy and safety of single or consecutive double high-dose oral cholecalciferol supplementation in adult patients with vitamin D deficiency

Background and Aim: Enhancing vitamin D levels as a crucial modifiable risk factor may provide a critical contribution to prevent susceptibility to various diseases, including musculoskeletal, autoimmune, and inflammatory rheumatic diseases as well as promoting overall health. However, adherence to daily vitamin D supplementation is generally poor, and there are some concerns regarding the high-dose vitamin D supplementation's safety. We aimed to investigate whether a single oral dose of 300,000 IU or consecutive twoday dosing of 300,000 IU each day of cholecalciferol could sufficiently and safely elevate vitamin D levels. Methods: This cross-sectional study was conducted on 160 inpatients with vitamin D deficiency and various musculoskeletal diseases. Subjects with serum 25(OH)D levels between 10 and 20 ng/mL (mild to moderate deficiency) received a single oral dose of 300,000 IU cholecalciferol, while those with severe vitamin D deficiency (<10 ng/mL) were supplemented with consecutive two-day doses of 300,000 IU cholecalciferol (a total of 600,000 IU). Results: After one week of replacement therapy, the 25(OH)D levels increased from 6.3 (4.0-9.9) ng/mL to 53.3 (8.3-84.4) ng/mL and from 15.0 (10.1-19.6) ng/mL to 38.4 (16.3-67.7) in the group with severe and those with the mild-to-moderate vitamin D deficiency, respectively. Except for three patients, nearly all patients (98%) achieved levels above 20 ng/mL. No signs of toxicity were observed in any of the patients. During the 6-month follow-up, falls were observed in 3 patients (2.8%), but no fractures were reported. Conclusion: A single dose of 300,000 IU of oral cholecalciferol or two consecutive doses with a total dose of 600,000 IU cholecalciferol can effectively and reliably increase the 25(OH)D serum levels within one week in nearly all patients. The results may contribute to optimizing treatment strategies for vitamin D deficiency and reevaluating the potential negative impact of high-dose vitamin D supplementation.