Multiple Sclerosis not helped with half a microgram of calcitriol – 2012

Effects of Adjunct Low-Dose Vitamin D on Relapsing-Remitting Multiple Sclerosis Progression: !!Preliminary Findings of a Randomized Placebo-Controlled Trial

Multiple Sclerosis International, Volume 2012 (2012), Article ID 452541, 7 pages
Vahid Shaygannejad,1 Mohsen Janghorbani,2 Fereshteh Ashtari,1 and Hamed Dehghan1
1 Department of Neurology, Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan 8144503500, Iran
2 Department of Epidemiology and Biostatistics, School of Public Health, Isfahan University of Medical Sciences, Isfahan 8144503500, Iran
Received 16 November 2011; Accepted 13 February 2012

The aim of this preliminary study was to evaluate the effect of low-dose oral vitamin D in combination with current disease-modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis (RRMS). A phase II double-blind placebo-controlled randomized clinical trial conducted between October 2007 and October 2008 included 50 patients with confirmed RRMS aged 25 to 57 years and normal serum 25-hydroxyvitamin D. They were randomly allocated to receive 12 months of treatment with either escalating doses up to 0.5??g/day or placebo combined with disease-modifying therapy. Response to treatment was assessed at eight-week intervals. In both groups, the mean relapse rate decreased significantly ( p < 0 . 0 0 1 ). In the 25 patients treated with placebo, the mean (SD) Expanded Disability Status Scale (EDSS) increased from 1.70 (1.21) at baseline to 1.94 (1.41) at the end of study period ( p < 0 . 0 1 ). Average EDSS and relapse rate at the end of trial did not differ between groups. Adding low-dose vitamin D to routine disease-modifying therapy had no significant effect on the EDSS score or relapse rate. A larger phase III multicenter study of vitamin D in RRMS is warranted to more assess the efficacy of this intervention.

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Letter to the editor about this publication

“Calcitriol” Is Not Synonymous with “Vitamin D”
Samantha M. Kimball1 and Heather E. Hanwell2
1Department of Chemistry and Chemical Engineering, Royal Military College of Canada and Department of Nutritional Sciences, University of Toronto, Toronto, ON, M5S 3E2, Canada
2Neurosciences and Mental Health, Hospital for Sick Children, University of Toronto, Toronto, ON, M5G 1X8, Canada

Regarding the recent article by Shaygannejad et al. [1], we are writing to express serious concerns about the portrayal of the intervention and the authors’ interpretation and discussion of the findings. Of predominate concern is that the authors utilized a calcitriol intervention in their study but referred to it as “vitamin D”. The erroneous use of the term “vitamin D” is of concern for several reasons.

Firstly, vitamin D is the biologically inactive form that can be synthesized in the skin when exposed to ultraviolet B radiation and is found in foods. In order to produce the active metabolite, calcitriol (or 1,25-dihydroxyvitamin D; 1,25(OH)2D), vitamin D must be hydroxylated in two subsequent reactions by two separate hydroxylases. The second hydroxylation step—conversion of 25-hydroxyvitamin D [25(OH)D] to 1,25(OH)2D via 1?-hydroxylase—is under tight regulatory control. By providing adequate substrate (i.e., vitamin D), circulating 25(OH)D concentrations increase and cells are able to locally produce and use 1,25(OH)2D in a self-regulated manner without affecting circulating levels of calcitriol. In contrast, supplying calcitriol directly produces a systemic increase in calcitriol, thus bypassing the key regulatory steps and increases risk of hypercalcemia. On the other hand, supplementation with vitamin D is quite safe at levels up to 10,000?IU/d [2, 3]. Wingerchuk et al. 4 have previously demonstrated the risk of hypercalcemia with calcitriol treatment in patients with MS. With this sole exception [4], none of the published vitamin D-related trials in patients with MS have administered calcitriol; the authors failed to note this or compare the findings of their calcitriol intervention to the only other published calcitriol intervention in MS. The differences in the safety profile and activity of vitamin D versus calcitriol alone are significant and necessitate accurate nomenclature.

Next, the authors indicate “no unusual or unexpected safety risks found with vitamin D therapy in our study population with RRMS”; however, not only did they administer calcitriol rather than vitamin D, but also no characterization of the dosage {nope: it was 1/2 microgram – VitaminDWiki} nor description of the rationale for the selected dosage was present. Furthermore, since there is neither mention of serum calcium, urine calcium nor 1,25(OH)2D levels in response to therapy dose, we cannot assess the effect of oral calcitriol [1,25(OH)2D] supplementation on biochemical outcomes in these patients.

Overall, the authors’ naivety regarding metabolism of vitamin D is evidenced in that they (i) neglected to monitor calcium or calcitriol levels when treating with calcitriol, (ii) monitored 25(OH)D levels—which are the biomarker of vitamin D status in the normal situation but are not relevant during calcitriol therapy, and (iii) directly compare studies of supplementation with vitamin D, calcitriol, and alphacalcidiol (a synthetic analogue of calcitriol) without distinguishing the various forms and their inherently different activity.

In conclusion, the work presented here “a calcitriol intervention in adults with MS” cannot be directly compared with the majority of the previous vitamin D-related MS interventions in the literature. Barring instances of genetic mutations causing dysfunction of the 1-alpha hydroxylase, at present, there is no rationale to support the use of calcitriol over vitamin D.

References

• V. Shaygannejad, M. Janghorbani, F. Ashtari, and H. Dehghan, “Effects of adjunct low-dose vitamin d on relapsing-remitting multiple sclerosis progression: preliminary findings of a randomized placebo-controlled trial,” Neurological Research, vol. 2012, Article ID 452541, 7 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
• R. Vieth, “Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety,” American Journal of Clinical Nutrition, vol. 69, no. 5, pp. 842–856, 1999. View at Scopus
• J. N. Hathcock, A. Shao, R. Vieth, and R. Heaney, “Risk assessment for vitamin D,” American Journal of Clinical Nutrition, vol. 85, no. 1, pp. 6–18, 2007. View at Scopus
• D. M. Wingerchuk, J. Lesaux, G. P. A. Rice, M. Kremenchutzky, and G. C. Ebers, “A pilot study of oral calcitriol (1,25-dihydroxyvitamin D3) for relapsing-remitting multiple sclerosis,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 76, no. 9, pp. 1294–1296, 2005. View at Publisher · View at Google Scholar · View at Scopus

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See also VitaminDWiki

• Neurology J. had 4 items on Multiple Sclerosis and Vitamin D – review by MS Soc Aug 2012
• Overview MS and vitamin D
• All items in category MS and vitamin D 404 items