New Evidence Strengthens the Connection of Vitamin D to Multiple Sclerosis
While the cause of MS has not yet been identified, everyone agrees that the interactions of both genetic and environmental factors are very important. Exciting new research is beginning to identify both genetic and environmental circumstances involving vitamin D that could increase one’s risk for developing MS and also target Vitamin D as a potential therapy that could both prevent and treat MS.
Perhaps the most prominent example of the importance of the environment in developing MS is the long-standing observation that population rates of MS increase with increasing distance from the equator in both the northern and southern hemispheres. This “latitude effect” correlates with the decrease in sun exposure as one moves away from the equator. Since it is already known that exposure to the ultraviolet radiation of the sun is the major source of Vitamin D in humans, scientists have been testing the hypothesis that vitamin D has an effect on the risk of developing MS. Work is also being done to identify gene mutations in families with multiple individuals have MS to identify potential genetic variants that increase the risk of developing MS. These two research approaches have resulted in new information that potentially links both environmental exposure to vitamin D and genetic factors related to vitamin D activation.
Observational research is strongly pointing to a reduced level of vitamin D in the blood as a risk factor for developing MS. Studies of who gets MS have confirmed that higher levels of sun exposure and higher blood levels of vitamin D were both associated with decreased risk of a first de-myelinating event which is often the first indicator of developing MS. In addition, there is evidence that high levels of vitamin D in utero and during adolescence and adulthood also have a positive effect on reducing the risk of developing MS. Recent research also suggests that vitamin D may have an important effect on the immune system that reduces inflammatory processes which occur during MS flares.
In addition, genetic research is pointing to the identification of at least one genetic variant that implicates vitamin D in MS. In December, researchers at Oxford University published the results of a study that set out to look for rare genetic changes that could explain strong clusters of MS in some families within an existing Canadian study. They sequenced all the gene-coding regions in the genomes of 43 individuals selected from families with four or more members with MS. The team compared the DNA changes they found against existing databases, and identified a change in the gene CYP27B1 as being of interest. The CYP27B1 gene plays an important role in converting Vitamin D, which is a biologically inactive molecule, to its biologically active form. The researchers then looked for the same rare gene variant in over 3,000 families of unaffected parents with a child with MS. They found 35 parents who carried one copy of this variant along with one normal copy. In every one of these 35 cases, the child with MS had inherited the mutated version of the gene.
The exact nature of the relationship between Vitamin D and MS is still unclear. However, further research now underway will determine if vitamin D may have preventative as well as disease-modifying effects. In the animal model of MS, vitamin D supplementation prevents and slows the progression of the disease while vitamin D deficiency worsens the disease. We also know that the risk of developing MS appears to be lower in people with relatively high intakes or relatively high blood levels of vitamin D. In those with MS, high vitamin D levels have been associated with decreased risk for attacks and less severe disability.
Whether vitamin D can influence the course of MS once someone's been diagnosed is also still unclear. Both genetic and environmental research shows that vitamin D could have possible effects on the risk for developing MS as well as on those diagnosed with MS. Further research is being planned to clearly define the role of vitamin D in the prevention, progression, and treatment of MS. What is clear is that vitamin D deficiency is extremely common in this part of the country and our northern latitude limits the times of year when we are likely to get adequate exposure to sunshine. In addition, much of the ultraviolet rays of the sun are absorbed at the New England latitudes making sunlight a lesser source of Vitamin D. The optimal approaches for vitamin D supplementation in the general population and in those with MS have not been established, yet it is important that everyone take a minimum daily amount of Vitamin D supplement. I recommend at least 2000 international units and no more than 4000 international units per day for my patients with MS. Due to the inherited risk of MS and the possible preventative effect of vitamin D supplementation, you may also want to discuss with your physician the possible implications of vitamin D deficiency and supplementation for your children.
Seventy percent of people with MS who have difficulty walking see that as the most challenging aspect of managing their disease, according to a recent survey sponsored by the National MS Society and Acorda Therapeutics, maker of Ampyra, a drug intended to improve walking.
Respondents to the survey reported that problems with mobility restrict their daily activities and affect their emotional and financial well-being. Some 60% of adults with MS who experience difficulty walking have fallen; for a third of them, a fall resulted in an injury.
While 65% of those surveyed reported walking difficulties or trouble with balance, 40% “rarely or never” discussed the issues with their doctor.
“Clearly we need to encourage and empower people with MS to discuss walking impairment with their doctor, including newly diagnosed patients who may be experiencing only mild problems with walking or balance difficulties,” said Nicholas LaRocca, PhD, vice president for Health Care Delivery and Policy Research at the Society.
- In a two-year Phase III trial, the oral MS therapy BG-12 significantly reduced—by up to 51%—the average number of annual MS relapses. More than 1,400 people with relapsing-remitting MS participated in the study. BG-12 is thought to inhibit the immune cells and molecules that are involved in MS attacks on the brain and spinal cord. This study should help to define further the safety and promise of BG-12 as a potential therapy for relapsing MS.
- The experimental intravenous MS therapy alemtuzumab significantly reduced relapse rates and the worsening of disability in a two-year Phase III study that compared alemtuzumab to Rebif. The study, called CARE-MS II, involved 840 people with relapsing-remitting MS. The FDA has fast-tracked alemtuzumab, which should speed up future review.
- A study of 324 patients comparing the MS oral therapy teriflunomide with Rebif found no significant difference in the numbers of participants in each group who experienced events defined as treatment failure. Teriflunomide is thought to prevent damage to the nervous system by immune cells. A previous phase III trial was more successful and three others are ongoing. The FDA is reviewing an application for marketing approval of teriflunomide.
To stay current on MS therapies in the pipeline for FDA approval, sign up for MS eNEWS at www.nationalMSsociety.org/signup.