In a moderately sized study from Finland, investigators wanted to know whether the addition of vitamin D to interferon-beta-1b (a first line disease modifying treatment) had a favourable outcome on disease activity. In order to assess this they measured serum (blood) neurofilament levels a protein found in neurones as a marker of MS disease activity.
What they found was that the addition of vitamin D had no effect on neurofilament levels compared to those not supplementing. It would be easy then to conclude that vitamin D has no impact on disease activity in MS over and above that of the disease modifying treatment.
Am I correct?
Let’s just say, I wouldn’t rush to flush all your vitamin D tablets down the toilet because of these findings.
My reservations of this study are two fold. Not being disparaging to the investigators, but their test measure (serum neurofilament) is reading at the bottom range of assay detection and the chances of random performance characteristics influencing the final outcome increase as a result (see Figure below – note that the majority of readings are below 20pg/ml). This means that you would probably have to inflate the sample size by a x100-fold to demonstrate a group difference. Secondly, they found no correlation with EDSS (disability measure for MS) or timed-25 foot walk, and only 5 out of the 32 participants at the start of the study had enhancing lesions on their scans suggesting that the study population were not diverse enough in disease activity or highly active entering into the study, respectively. Again, you would have to inflate the sample size to compensate.
The crux of this study therefore is not the intervention in question i.e. vitamin D, but the test, i.e. serum (blood) neurofilament levels. In subjects who are already on a disease modifying treatment that reduces neurofilament levels you need to have a population that are active despite being on treatment to assess the added benefit of add-on strategies or use a much larger population.
Vitamin D supplementation and serum neurofilament light chain in interferon‐beta‐1b‐treated MS patients
Serum neurofilament light chain (sNfL) is a promising biomarker of MS activity, progression, and treatment response. The aim of the present study was to address whether sNfL concentrations are affected by supplementation of vitamin D and correlate with disease activity in interferon‐beta‐1b (IFNb‐1b)‐treated Finnish MS.
Materials and Methods
Serum samples were available of 32 participants of the Finnish vitamin D randomized controlled trial (17 vitamin D/15 placebo). Serum 25 hydroxyvitamin D was measured using radioimmunoassay and sNfL using single‐molecule array (Simoa). Correlation of sNfL with brain magnetic resonance imaging (MRI) activity, burden of disease (BOD, mm3), and disability was assessed at the study baseline and at 52 weeks.
Serum NfL concentrations were similar in the patients randomized to high‐dose vitamin D and placebo at the study baseline and at month 12 follow‐up (p‐value). Concentrations of sNfL were higher in patients with Gadolinium‐enhancing lesions in brain MRI: median (95% CI) sNfL was 14.84 (9.9–42.5) pg/ml and 11.39 (8.9–13.2) pg/ml in patients without Gd+ lesions (p = .0144) and correlated with enhancing lesion volume (Pearson r = .36, p = .037) at the study baseline but not at week 52. Serum NfL did not correlate with the MRI BOD or disability measured by expanded disability status scale and 25‐foot walk test.
In this small cohort of clinically stable IFN‐treated Finnish MS patients, sNfL levels were similarly low in patients supplemented with high‐dose vitamin D or placebo. Subclinical disease activity in MRI was associated with higher sNfL levels.