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Does the Vitamin D Emperor Have Clothes?

Vitamin D levels may not correlate with disease activity in MS, despite statistically significant findings in this study.

The aim of this study was to examine whether low vitamin D levels correlate with disease activity in multiple sclerosis (MS). Subjects were participants from Turku, Finland, in the PRISMS Study of interferon beta-1a; 15 patients had received either of the two drug dosages, and 8 had received placebo. From serum specimens that had been drawn every 3 months and at time of relapse, up to 64 weeks, the authors measured serum 25-hydroxyvitamin D (S-25[OH]D), parathyroid hormone, and calcium levels and performed several other clinical chemistry assays in the 23 patients with MS and in 23 healthy laboratory workers (controls).

The authors state that half of all participants had S-25(OH)D levels at or below 37 nmol/L (considered deficient) at some point during the year. Levels of 25(OH)D were lower and levels of intact parathyroid hormone (iPTH) were higher during relapses than during remissions. The abstract also states, "All 21 relapses during the study occurred at serum iPTH levels >20 ng/L. . .whereas 38% of patients in remission had iPTH levels 20 ng/L. . .There is an inverse relationship between serum vitamin D level and MS clinical activity. . .."

Comment: This simple clinician had some difficulty following the authors’ presentation. The supplementary figure published online plotted vitamin D levels and relapses over a 1-year interval for 12 patients. Relapses did not occur any more often during the presumed high-risk months (8 in December through May, when vitamin D levels are lowest) than during the other months (11 relapses).

Figure 2 of the article is a scatter plot of S-25(OH)D and iPTH levels from patient specimens drawn during relapse (21) or remission (122). All values for the relapses fit well within calculable confidence intervals for the remission values: Mean vitamin D levels and standard deviations (SDs) were 47.4±14.4 nmol/L during relapses and 60.0±21.8 nmol/L during remissions, giving 95% confidence intervals of 19.2 to 75.6 in relapse and 17.3 to 102.7 in remission. For iPTH levels, respective means and standard errors were 33.1 (2.6) ng/L and 26.4 (1.1) ng/L, giving SDs of 11.91 and 12.15 respectively, for 95% CIs of 9.8 to 56.5 for relapses and 2.6 to 50.2 for remissions.

Looking at the authors’ data on measurements by season, the groups did not differ in vitamin D levels. The iPTH peaks, in winter, did differ (41 ng/L in controls, 29 ng/L in patients), but both were well within the cited normal range (15–65 ng/L). Calcium in winter was also within the normal range (2.15–2.51 mmol/L): about 2.35 mmol/L in controls and 2.23 mmol/L in patients.

For all of these comparisons, the finding of statistical significance seems to rely on comparing individual test values rather than patients, and even then by relying on differences in means rather than, say, 95% confidence intervals of the means. Biologic significance could also be questioned, because all of these differences, regardless of assessment method, apparently fall within normal ranges. The conclusion of an association between vitamin D levels and MS relapses does not seem well substantiated. I am beginning to wonder how well-clothed the vitamin D emperor is in MS.

— John F. Kurtzke, MD, FACP, FAAN

Dr. Kurtzke is Professor Emeritus of Neurology, Georgetown University, and Consultant in Neurology and Neuroepidemiology, VAMC, Washington, DC.

Published in Journal Watch Neurology May 27, 2008

Citation(s):

Soilu-Hänninen M et al. A longitudinal study of serum 25-hydroxyvitamin D and intact parathyroid hormone levels indicate the importance of vitamin D and calcium homeostasis regulation in multiple sclerosis. J Neurol Neurosurg Psychiatry 2008 Feb; 79:152.

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• Medline abstract (Free)