25-Hydroxyvitamin D response to graded vitamin D₃ supplementation among obese adults

Context: Guidelines have suggested that obese adults need 2 to 3 times more vitamin D than lean adults to treat vitamin D deficiency, but few studies have evaluated the vitamin D dose response in obese subjects. Objective: The purpose of this study was to characterize the pharmacokinetics of 25-hydroxyvitamin D [25(OH)D] response to 3 different doses of vitamin D₃ (cholecalciferol) in a group of obese subjects and to quantify the 25(OH)D dose-response relationship. Design, Setting, Intervention, Patients: This was a randomized, single-blind study of 3 doses of oral vitaminD3 (1000, 5000, or 10,000 IU) given daily to 67 obese subjects for 21 weeks during the winter months. Main Outcome Measures: Serum 25(OH)D levels were measured at baseline and after vitamin D replacement, and 25(OH)D pharmacokinetic parameters were determined, fitting the 25(OH)D concentrations to an exponential model. Results: Mean measured increments in 25(OH)D at week 21 were 12.4 ± 9.7 ng/mL in the 1000 IU/d group, 27.8 ± 10.2 ng/mL in the 5000 IU/d group, and 48.1 ± 19.6 ng/mL in the 10,000 IU/d group. Steady-state increments computed from the model were 20.6 ± 17.1, 35.2 ± 14.6, and 51.3 ± 22.0 ng/mL, respectively. There were no hypercalcuria or hypercalcemia events during the study. Conclusion: Our data show that in obese people, the 25(OH)D response to vitamin D₃ is directly related to dose and body size with ~2.5 IU/kg required for every unit increment in 25(OH)D (nanograms per milliliter).