Re:Vitamin-D supplementation: Is the MS community studying too high a dose?
Elias S.Sotirchos, Johns Hopkins University School of Medicineess@jhmi.edu
Peter A. Calabresi, Baltimore, MD
Submitted April 26, 2016
We thank Dr. Kantor for the comments, but respectfully disagree regarding the interpretation of our results. [1] The sample size calculations were performed for immunological outcomes, however, it is not possible to perform power calculations for adverse effects with unknown frequency.
We have reservations that the safety signals identified by Dr. Kantor can be identified as such. The absolute value of urine calcium: Creatinine ratios was higher in the high-dose group, but abnormally elevated urine calcium: Creatinine ratios did not differ, making this finding unlikely to be of clinical importance. Furthermore, baseline urine calcium: Creatinine ratios were not obtained which limits the interpretation. Borderline hypercalcemia was noted in only one case and not associated with increased urine calcium: Creatinine ratio or clinical manifestations. In clinical practice, this would be unlikely to lead to complete discontinuation of supplementation. Relapses occurred in the same frequency. Attempts to interpret the time to relapse as indicative of an exacerbating effect of cholecalciferol are clearly problematic in this context. Our study's data regarding the safety of cholecalciferol are supported by other studies employing similar dosages. [2, 3]
Based on observational studies, 25(OH) D levels of 40-60 ng/mL may be the optimal target for MS patients. [4] High-dose cholecalciferol in our study achieved the desired levels, whereas supplementation with the daily recommended allowance of vitamin D was inadequate.
1. Sotirchos ES, Bhargava P, Eckstein C, et al. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology 2016;86: 382-390.
.
2. Kimball S, Vieth R, Dosch HM, et al. Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. J Clin Endocrinol Metab 2011;96: 2826-2834.
3. Smolders J, Peelen E, Thewissen M, et al. Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One 2010;5: e15235.
4. Bhargava P, Cassard S, Steele SU, et al. The vitamin D to ameliorate multiple sclerosis (VIDAMS) trial: study design for a multicenter, randomized, double-blind controlled trial of vitamin D in multiple sclerosis. Contemp Clin Trials 2014;39: 288-293.
For disclosures, please contact the editorial office at journal@neurology.org.
We thank Dr. Kantor for the comments, but respectfully disagree regarding the interpretation of our results. [1] The sample size calculations were performed for immunological outcomes, however, it is not possible to perform power calculations for adverse effects with unknown frequency.
We have reservations that the safety signals identified by Dr. Kantor can be identified as such. The absolute value of urine calcium: Creatinine ratios was higher in the high-dose group, but abnormally elevated urine calcium: Creatinine ratios did not differ, making this finding unlikely to be of clinical importance. Furthermore, baseline urine calcium: Creatinine ratios were not obtained which limits the interpretation. Borderline hypercalcemia was noted in only one case and not associated with increased urine calcium: Creatinine ratio or clinical manifestations. In clinical practice, this would be unlikely to lead to complete discontinuation of supplementation. Relapses occurred in the same frequency. Attempts to interpret the time to relapse as indicative of an exacerbating effect of cholecalciferol are clearly problematic in this context. Our study's data regarding the safety of cholecalciferol are supported by other studies employing similar dosages. [2, 3]
Based on observational studies, 25(OH) D levels of 40-60 ng/mL may be the optimal target for MS patients. [4] High-dose cholecalciferol in our study achieved the desired levels, whereas supplementation with the daily recommended allowance of vitamin D was inadequate.
1. Sotirchos ES, Bhargava P, Eckstein C, et al. Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis. Neurology 2016;86: 382-390. .
2. Kimball S, Vieth R, Dosch HM, et al. Cholecalciferol plus calcium suppresses abnormal PBMC reactivity in patients with multiple sclerosis. J Clin Endocrinol Metab 2011;96: 2826-2834.
3. Smolders J, Peelen E, Thewissen M, et al. Safety and T cell modulating effects of high dose vitamin D3 supplementation in multiple sclerosis. PLoS One 2010;5: e15235.
4. Bhargava P, Cassard S, Steele SU, et al. The vitamin D to ameliorate multiple sclerosis (VIDAMS) trial: study design for a multicenter, randomized, double-blind controlled trial of vitamin D in multiple sclerosis. Contemp Clin Trials 2014;39: 288-293.
For disclosures, please contact the editorial office at journal@neurology.org.