Safety of vitamin D3 in adults with multiple sclerosis

Background: Vitamin D-3 may have therapeutic potential in several diseases, including multiple sclerosis. High doses of vitamin D-3 may be required for therapeutic efficacy, and yet tolerability-in the present context, defined as the serum concentration of 25-hydroxyvitamin D [25(OH)D] that does not cause hypercaleemia-remains poorly characterized. Objective: The objective of the study was to characterize the calcemic response to specific serum 25(OH)D concentrations. Design: In a 28-wk protocol, 12 patients in an active phase of multiple sclerosis were given 1200 mg elemental Ca/d along with progressively increasing doses of vitamin D-3: from 700 to 7000 mu g/wk (from 28 000 to 280 000 IU/wk). Results: Mean ( +/- SD) serum concentrations of 25(OH)D initially were 78 +/- 35 nmol/L and rose to 386 +/- 157 nmol/L (P < 0.001). Serum calcium concentrations and the urinary ratio of calcium to creatinine neither increased in mean values nor exceeded reference values for any participant (2.1-2.6 mmol/L and < 1.0, respectively). Liver enzymes, serum creatinine, electrolytes, serum protein, and parathyroid hormone did not change according to Bonferroni repeated-measures statistics, although parathyroid hormone did decline significantly according to the paired t test. Disease progression and activity were not affected, but the number of gadolinium-enhancing lesions per patient (assessed with a nuclear magnetic brain scan) decreased from the initial mean of 1.75 to the end-of study mean of 0.83 (P = 0.03). Conclusions: Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. The data support the feasibility of pharmacologic doses of vitamin D-3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.