The article by Sotirchos et al. should not be misclassified as Level 1 evidence that high-dose cholcalciferol supplementation "is safe and well-tolerated...". [1]
In order to offer Class 1 evidence of safety/tolerability, a trial would need to be powered to demonstrate such an effect. This study was not designed to adequately address such endpoints; instead, the "[s]ample size was calculated based on in vitro data...". [1] There were safety signals, such as the statistically significant differences in end-study urine calcium:creatinine ratio between the groups. Additionally, 11% vs 5% reported nausea and 5% vs 0% had hypercalcemia. Although there was no difference in total number of relapses, one patient on high-dose relapsed within 5 weeks of initiation compared to 24 weeks of relapse-freedom for low-dose patients.
The unanswered question of high-dose safety is not insignificant, especially given a recent article which suggested that cholecalciferal increased falls in the elderly. [2] I encourage the authors to expand their work by testing a dose that more closely approximates those used in clinical practice and to exclude patients with baseline 25(OH)D levels <30 ng/mL as there is a need for higher doses in people with vitamin-D insufficiency. [3,4]
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. Bischoff-Ferrari H, Dawson-Hughes B, Orav E et al. Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial. JAMA Intern Med 2016;176:175-183.
3. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911- 1930.
4. Miller JW, Harvey DJ, Beckett LA, et al. Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults. JAMA Neurol 2015;72:1295-1303.
For disclosures, please contact the editorial office at journal@neurology.org.
The article by Sotirchos et al. should not be misclassified as Level 1 evidence that high-dose cholcalciferol supplementation "is safe and well-tolerated...". [1]
In order to offer Class 1 evidence of safety/tolerability, a trial would need to be powered to demonstrate such an effect. This study was not designed to adequately address such endpoints; instead, the "[s]ample size was calculated based on in vitro data...". [1] There were safety signals, such as the statistically significant differences in end-study urine calcium:creatinine ratio between the groups. Additionally, 11% vs 5% reported nausea and 5% vs 0% had hypercalcemia. Although there was no difference in total number of relapses, one patient on high-dose relapsed within 5 weeks of initiation compared to 24 weeks of relapse-freedom for low-dose patients.
The unanswered question of high-dose safety is not insignificant, especially given a recent article which suggested that cholecalciferal increased falls in the elderly. [2] I encourage the authors to expand their work by testing a dose that more closely approximates those used in clinical practice and to exclude patients with baseline 25(OH)D levels <30 ng/mL as there is a need for higher doses in people with vitamin-D insufficiency. [3,4]
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. Bischoff-Ferrari H, Dawson-Hughes B, Orav E et al. Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial. JAMA Intern Med 2016;176:175-183.
3. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011;96:1911- 1930.
4. Miller JW, Harvey DJ, Beckett LA, et al. Vitamin D Status and Rates of Cognitive Decline in a Multiethnic Cohort of Older Adults. JAMA Neurol 2015;72:1295-1303.
For disclosures, please contact the editorial office at journal@neurology.org.