Closer look: Researchers discover evidence for a new mechanism behind vitamin D’s role in treating multiple sclerosis

Posted on: October 15, 2014   by  Will Hunter

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A newly published study has found convincing evidence for the molecular mechanism underlying the effects of vitamin D on multiple sclerosis.

We covered this study last year when the findings were initially presented at the 5th Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC). However, the fully published paper provides some interesting additional information.

The cause of multiple sclerosis (MS) is not known, however the mechanism behind the disease is thought to be through destruction by the immune system of cells that produce myelin sheaths.

Research on the relationship between vitamin D and multiple sclerosis (MS) is an ever-expanding and exciting field.

There is a growing body of evidence that vitamin D is not only important in the development of multiple sclerosis but also in the activity of the disease and in its long term progression.

Multiple observational studies have shown that higher vitamin D levels are associated with fewer relapses.

The results of randomized controlled trials have been mixed, with some finding that vitamin D supplementation in patients with MS results in a decrease in the number of gadolinium-enhancing lesions (GELs).

GELs are lesions in the brain caused by MS that are highlighted by a chemical compound called gadolinium. Measuring GELs allow doctors to determine recent disease activity by seeing which lesions are active and which are inactive. However, it is important to note that many of these trials did not have enough power to detect an effect of vitamin D supplementation on disease activity.

Given this evidence, researchers from eight different countries, and led by Dr. Kassandra Munger, collaborated to determine if there was a possible mechanism underlying the relationship between vitamin D and MS activity.

To do this, they conducted a gene expression profile analysis at various time points among participants in the BENEFIT clinical trial. The BENEFIT clinical trial is an ongoing clinical trial initiated in 2005 that is looking at the long-term effects of early versus delayed treatment with the drug Betaseron in 468 patients with a first event suggestive of MS.

Gene expression profiling is the measurement of the activity (the expression) of genes at once in order to get a comprehensive picture of cellular functioning.

The research team wanted to identify genes or gene sets expressed in association with vitamin D levels and those expressed in association with MS activity to see if a relationship existed between the two. They looked at genes known to be related to vitamin D as well as genes not associated with vitamin D.

Vitamin D levels were measured at baseline and at 6, 12, and 24 months thereafter. The number of GELs from MRI scans performed at 3, 6, 9, 12, 18, and 24 months were measured to determine MS disease activity. Gene expression was measured at baseline, and at 3, 12, and 24 months.

After running statistical analyses on the above measurements, the team revealed the following results:

  • Vitamin D status was associated with a significantly lower GEL count, with every 20 ng/ml increase in vitamin D levels associated with a 55% decrease in GEL count.
  • As expected, vitamin D status was found to be associated with the gene expression of 63 genes known to be related to vitamin D.
  • More than 50% (34) of the genes associated with vitamin D were also associated with GEL count where lower GEL count was associated with increased expression of the 63 vitamin D-related genes.

The researchers interpreted the results by stating,

“In summary, by analyzing the gene expression, this study identified the first molecular evidence that immunological effects of 25(OH)D impact disease activity in patients with very early MS.”

They also added,

“The analysis of 25(OH)D gene set association with 25(OH)D levels showed strong gene set upregulation, this being suggestive of a context-dependent systemic role of 25 (OH)D in reducing GEL count by regulating whole gene sets to jointly influence and tune a variety of biological processes.”

This is the first study to examine the relationship between vitamin D-associated gene expression and MS activity (GEL count). The large overlap of the two gene sets hint that vitamin D’s possible effect of reducing disease activity of MS are mediated by vitamin D’s ability to upregulate certain genes that are involved in reducing GEL count.

Further evidence that this is one of the molecular mechanisms underlying vitamin’s D role with MS disease activity is the inverse association of vitamin D status with GEL count. Together these separate lines of evidence strongly point to upregulation of specific genes as one of the mediators by which vitamin D exerts beneficial effects on disease activity.

An important limitation to this study is that vitamin D levels were measured at fixed time points and not at the time of relapses. Analyses on the gene expression during relapses and relapse-free periods, times of increased or decreased activity, could give a better indicator of how vitamin D is affecting GELs during these disease states.

Further randomized controlled trials will be needed to confirm these findings, however studies like this provide additional support for the importance of vitamin D in MS disease activity.

Source

Munger, K. et al. Molecular mechanism underlying the impact of vitamin D on disease activity of MS. Annals of Clinical and Translational Neurology, 2014.

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