Vitamin D supplementation and neurofilament light chain in multiple sclerosis

Abstract

Objectives The effect of vitamin D supplementation on the disease course of multiple sclerosis (MS) is not established. Neurofilament light chain (NFL) is a sensitive marker of axonal degeneration. The aim of this study was to establish whether high‐dose vitamin D supplementation reduces serum levels of NFL. Materials and Methods We have performed a 96 weeks placebo‐controlled randomized study of weekly supplementation with 20 000 IU vitamin D3 in 71 patients with relapsing remitting MS (RRMS). Serum levels of NFL were measured at baseline, week 48 and week 96 with a single molecule (Simoa) assay in 69 of these patients. Results Serum levels of 25‐hydroxyvitamin D more than doubled in the vitamin D group. Compared to placebo, vitamin D supplementation had no overall effect on the change in serum levels of NFL from baseline (P = 0.93 at week 48 and P = 0.56 at week 96). In the subgroup of patients not receiving disease‐modifying therapy, NFL decreased by 30.9% to week 48% and 32.6% to week 96 from baseline in the vitamin D group as compared to the placebo group (P = 0.06 for both time points). Conclusion With a possible exception for patients not treated with disease‐modifying drugs, weekly supplementation with 20 000 IU vitamin D3 did not affect NFL levels in these RRMS patients.

Natural Variation of Vitamin D and Neurofilament Light Chain in Relapsing-Remitting Multiple Sclerosis

“…However, our results do not support an effect of rising 25(OH)D levels driven mainly by seasonal alterations in UVR exposure on axonal degeneration in RRMS, as measured by serum NfL levels. This is in line with the finding of no effect of high-dose oral vitamin D 3 supplementation on serum NfL levels in RCTs among RRMS patients with DMT (10,11).…”

“…Due to the northern location of Norway, vitamin D status varies substantially between winter (November to March) and summer (May to September). We have earlier seen a trend for a reduction in serum NfL levels among RRMS patients without DMTs on vitamin D supplementation (10). Moreover, we have shown that introduction of IFN-β therapy reduces NfL levels in the current patient cohort (5).…”

“…We have previously reported results from a two-year observational study of 85 RRMS patients with rather high disease activity showing an inverse association between naturally increasing 25(OH)D levels and inflammatory MRI disease activity before introduction of interferon beta-1a (IFN-β) treatment (6), while NfL levels were positively correlated with inflammatory MRI disease activity and inversely with IFN-β initiation (5). However, in a two-year double-blinded RCT of high-dose oral vitamin D 3 supplementation (20,000 IU/week) in another cohort of 68 patients with RRMS with lower disease activity we found only a strong trend for a reduction among patients without DMTs and no overall effect of increasing serum 25(OH)D levels on serum levels of NfL (10). The aim of the current study was therefore to clarify the potential relationship between natural variations in 25(OH)D serum concentrations and change in serum NfL levels both prior to and during IFN-β therapy in our observational RRMS cohort.…”

“…Results from randomized placebo-controlled trials (RCTs) have indicated a relationship between increasing serum levels of 25(OH)D after vitamin D supplementation and reduced inflammatory MRI disease activity in RRMS (9). However, the effect of vitamin D treatment on serum levels of NfL is uncertain, as it has only been investigated in RCTs with a limited number of rather clinically stable patients (10,11).…”

Vitamin D, smoking, EBV, and long-term cognitive performance in MS

“…Cortical lesions and gray matter loss are more strongly associated with cognitive decline than white matter lesions, 4 but ultimately, we cannot evaluate from NfL elevations only which pathology was driving the results. Intriguingly, vitamin D supplementation was associated with decreased NfL levels in a 2-year randomized clinical trial among untreated patients with MS. 45 In another study, smoking was linked to brain atrophy, 19 which is, in turn, related to neuroaxonal injury and cognitive impairment. 5 Our findings add to the evidence that NfL may be a promising biomarker for clinical MS research.…”