Experimental Medications: Vitamin D3

Vitamin D is a type of hormone and a powerful mediator of immune function. The data documenting an association between low Vitamin D and high MS risk, relapses, disability, and CNS inflammation now appear to be strong, consistent, and reproducible. Data from a number of areas of investigation suggest that Vitamin D may be one underlying common factor that begins to make sense of the large amount of data on the geographic distribution of susceptibility to MS.

Genetically, a link appears to exist between changes in the genes involved in the synthesis of the Vitamin D hormone and the Vitamin D hormone receptor, and the risk of developing MS. The strongest genetic risk factor for MS is a specific gene (HLA DRB1*1501), whose activity appears to be influenced by Vitamin D.

A finding in animal models of MS that Vitamin D directly terminates production of disease-causing proteins may shed light on the mechanism of Vitamin D in MS. When Vitamin D is given to mice with EAE (an animal model of MS), it blocks the gene that encodes IL-17, stopping its production. IL-17 appears to be a major inflammatory component in MS. This study also demonstrates that Vitamin D increases suppressive T cells that combat inflammation.

An important longitudinal cohort study presented in 2012 by Mowry and colleagues37found that in people with MS, each 10 ng/ml higher Vitamin D level was associated with a 15-percent lower risk of a new T2 lesion, and a 32-percent lower risk of a gadolinium-enhancing lesion. Higher Vitamin D levels were associated with lower, but not statistically significant, relapse rates. While this was not a randomized treatment trial, it suggests that higher levels of Vitamin D may exert a protective role against MS disease activity. A number of new clinical trials, mostly using Vitamin D as an add-on to existing therapies in Phase IV studies, are ongoing to assess if supplemental Vitamin D can exert such disease-modifying effects. To follow is a sample of these investigations:

Mowry and colleagues at Johns Hopkins have initiated a multi-center clinical trial in which patients with relapsing-remitting MS will receive high-dose (5,000 IU/day) or low-dose (600 IU/day) oral Vitamin D in addition to Copaxone.38 Patients will be evaluated for two years, and the effect of high-dose Vitamin D supplementation on the rate of MS attacks as well as on the number of new lesions and change in brain volume on MRI will be determined. This trial is presently enrolling, with a goal of 172 participants, and is expected to run through December 2014.

Another study being run by the Johns Hopkins group is a small Phase I study39 in 40 individuals with MS, designed to determine the safety and immunologic effects of supplementation with low-dose (400 mg) and high-dose (10,000 mg) cholecalciferol (Vitamin D3), began in March 2010. The primary outcome measure is to determine the safety of high-dose Vitamin D3 and to assess the effects of this supplementation on serum immune markers; its clinical effects will also be assessed. Data are forthcoming.

A Phase II study that is currently recruiting40 participants is investigating whether Vigantol® oil, a form of Vitamin D hormone supplement (cholecalciferol), provides any added benefit when given in conjunction with Rebif. The study will have 348 participants; it began in February 2011 and is scheduled for completion in March 2014. Primary outcome measures are the mean change from baseline in the total volume of T2 lesions at week 48 and the proportion of relapse-free subjects at week 96. Secondary outcome measures include sustained disability progression, MRI measures of disease progression, the proportion of subjects free from disease activity at 96 weeks, and changes in cognitive function.

A Finnish Phase IV study with 70 participants is investigating cholecalciferol (Vitamin D3) as an add-on treatment to Betaseron in RRMS. Its primary outcome measure is biochemical; a secondary measure is the number of gadolinium-enhancing lesions and/or new enlarging lesions. It began in March 2008; data is still forthcoming.

The French CHOLINE Phase II study41 of 250 individuals with RRMS who are receiving ongoing treatment with Rebif began in January 2010 and is scheduled for completion in July 2014. Its primary outcome measure is a reduction in relapse rate; secondary outcome measures include the time to a first documented relapse, the mean number of relapses per subject per year, the number of relapse-free patients after two years of treatment, MRI measures of progression and lesion load, and change in quality of life.

Please note that no safety issues have been reported with these larger daily doses of Vitamin D3 (such as 5,000 to 10,000 IU/day). However, as with all medications and supplements, individuals should always consult their physician before making any changes to their treatment plan.

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