Vitamin D supplementation for patients with multiple sclerosis treated with interferon-beta: a randomized controlled trial assessing the effect on flu-like symptoms and immunomodulatory properties

Abstract

Background: Flu-like symptoms (FLS) are common side effects of interferon beta (IFN-β) treatment in patients with Multiple Sclerosis (PwMS) and are associated with post-injection cytokine surge. We hypothesized that vitamin D3 supplementation would ameliorate FLS by decreasing related serum cytokines' levels.

Methods: In a randomized, double blind study of 45 IFNβ-treated PwMS, 21 patients were assigned to 800 IU of vitamin D3 per day (low dose), while 24 patients received 4,370 IU per day (high dose) for one year. FLS were assessed monthly by telephonic interviews. Serum levels of 25-hydroxy-D (25-OH-D), calcium, PTH, IL-17, IL-10 and IFN-γ were measured periodically. EDSS, relapses, adverse events and quality of life (QoL) were documented.

Results: 25-OH-D levels increased to a significantly higher levels and PTH levels decreased in the high dose group. There was no significant change in FLS. IL-17 levels were significantly increased in the low dose group, while patients receiving high dose vitamin D had a heterogeneous IL-17 response. No significant differences in relapse rate, EDSS, QoL, serum IL-10 and IFNγ were found. Hypercalcemia or other potential major adverse events were not observed.

Conclusion: Vitamin D supplementation to IFN-β treated PwMS, at the doses used, seems safe and associated with dose-dependent changes in IL-17 serum levels, while not affecting IFN-β related FLS.

Trial registration: ClinicalTrials.gov ID: NCT01005095.

Figure 1

Study flow chart.

Figure 2

25-OH- vitamin D serum levels. Serum 25-OH-D (25-hydroxy-vitamin D) was measured at baseline, 3, 6 and 12 month using a chemiluminescent immunoassay. The high dose supplementation resulted in significantly higher serum 25-OH-D levels compared to low dose throughout the follow up (P < 0.001). With high dose, 25-OH-D levels were significantly above baseline at all time points (P ≤ 0.01), while low dose resulted in significantly increased 25-OH-D levels compared to baseline only at 3 months (P = 0.006) and at 6 months (P = 0.04).

Figure 3

Flu like symptoms score by time from enrollment to vitamin D supplementation. FLS were assessed by monthly phone interviews. Patients rated the extent of FLS on a Likert scale (a total FLS score ranging from 0 to 35). No significant change in FLS severity was noted in both dosage groups.

Figure 4

Flu like symptoms score and use of pain relieving medications. No statistically significant differences were found in FLS scores between patients who used analgesics and patients who did not use analgesics, regardless of vitamin D dose.

Figure 5

Changes in IL-17 serum levels after 3 months supplementation with vitamin D. A significant increase in serum IL-17 was detected at 3 month in the low dose vitamin D group (p = 0.037). Serum IL-17 response to high dose vitamin D was heterogeneous. 3 patients in each dosage group had IL-17 levels below the detection threshold of the ELISA kit at both time points (not shown in the figure).