In a study involving 12 patients in an active phase of multiple sclerosis (MS), results indicate that serum concentrations of 25(OH)D [25-hydroxyvitamin D] in the range of 400 nmol/L can be attained with high doses of vitamin D(3) without causing hypercalcemia or hypercalcuria, or adverse clinical or paraclinical effects. The patients were given 1,200 mg elemental calcium/d for 28 weeks along with progressively increasing doses of vitamin D(3): from 700 to 7000 mug/week (from 28,000 to 280,000 IU/week). Mean serum concentrations rose from 78 nmol/L, at baseline, to 386 nmol/L, at intervention end. However, the mean values of serum calcium concentrations and the urinary ratio of calcium to creatinine did not increase nor exceed reference values for any participant. Additionally, 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. Furthermore, a decrease in the mean number of gadolinium-enhancing lesions per patient was observed. Thus, the authors of this study conclude, “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.”