Safety of vitamin D3 in adults with multiple sclerosis.

Background: Vitamin D3 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 hypercalcemia--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 D3: from 700 to 7000 microg/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 D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin.