“Chicken or egg? The study below shows that MS disease activity on IFN-beta is linked to low vD levels and suggest the mechanism is via complex network of gene regulation. What this study does not address is whether the low vD levels are a consequence of MS disease activity; the so called consumptive hypovitaminosis D hypothesis. There is published data showing that proliferating T cell, which are the major players in autoimmunity, consume vD as part of their proliferative response. The only way to sort out association (consumptive hypovitaminosis) from causation (low vD levels cause MS disease activity) is to do a randomised double-blind placebo-controlled trial of vD supplementation in MS. The good news is that there are several clinical trials that are currently underway. The bad news is that I think all of these studies are underpowered and are unlikely to give a definitive answer.”
Munger et al. Molecular mechanism underlying the impact of vitamin D on disease activity of MS. Ann Clin Transl Neurol. 2014 1(8):605-17. d
OBJECTIVE: Some previous studies suggest modest to strong effects of 25-hydroxyvitamin D (25(OH)D) on multiple sclerosis (MS) activity. The objective of this study was to explore the mechanistic rationale that may explain potential clinical effects of 25(OH)D.
METHODS: This study measured serum 25(OH)D levels and global gene expression profiles over a course of up to 2 years in CISers starting treatment with interferon beta-1b (IFNB-1b) after a clinically isolated syndrome. MS disease activity was assessed by the number of gadolinium-enhancing lesions present on repeated magnetic resonance imaging (MRIs).
RESULTS: The number of gadolinium-enhancing lesions was highly significantly associated with 25(OH)D levels. Conducting various systems-level analyses on the molecular level, multiple lines of evidence indicated that 25(OH)D regulates expression dynamics of a large gene-gene interaction system which primarily regulates immune modulatory processes modulating MS activity. The vitamin D response element was significantly enriched in this system, indicating a direct regulation of this gene interaction network through the vitamin D receptor. With increasing 25(OH)D levels, resulting regulation of this system was associated with a decrease in MS activity. Within the complex network of genes that are regulated by 25(OH)D, well-described targets of IFNB-1b and a regulator of sphingosine-1-phosphate bioavailability were found. The 25(OH)D effects on MS activity were additively enhanced by IFNB-1b.
INTERPRETATION: Here, we provide mechanistic evidence that an unbalanced 25(OH)D gene expression system may affect MS activity. Our findings support a potential benefit of monitoring and managing vitamin D levels (e.g., through supplementation) in early MS patients treated with IFN-beta-1b.