Researchers and clinicians from around the globe gathered recently in Chicago to develop strategies for testing whether vitamin D supplements can prevent the development of MS. Participants discussed the latest findings relevant to vitamin D and MS and potential clinical trial designs, taking the first steps to making these exciting studies a reality. “Vitamin D and MS Prevention: An International Workshop,” was chaired by Colleen E. Hayes, PhD (University of Wisconsin-Madison) and Anne-Louise Ponsonby, PhD (Murdoch Children’s Research Institute, Canberra Australia), and was funded by the National MS Society.
Background: Research is increasingly pointing to a reduced level of vitamin D in the blood as a risk factor for developing MS. Years ago, MS researchers wondered why MS occurs less often in regions of the world where exposure to sunlight is high. Dr. Hayes – a professor of biochemistry and microbiology – and colleagues suggested that vitamin D, which is made by cells in the skin in response to sunlight, may suppress the immune response involved in MS. She and others have since shown that in lab mice, vitamin D can reduce the effects of EAE, an MS-like disease.
Epidemiologic studies (studies of who gets MS) have backed up laboratory studies. Dr. Ponsonby – an epidemiologist and public health physician – was a co-author of the Ausimmune Study, a comprehensive Australian study that showed that higher levels of sun exposure and higher blood levels of vitamin D were both associated with decreased risk of having a first demyelinating event, often the first indicator of subsequent MS.
The National MS Society has led the way in pursuing this avenue of MS research, funding much of Dr. Hayes’ work, first funding the Ausimmune study, and now, a new clinical trial testing whether vitamin D can reduce disease activity in people who have MS. Read more on clinicaltrials.gov.
The Meeting: Participants included experts in vitamin D studies, immunology, statistics, epidemiology, clinical MS research, pediatric MS, and MS biomarkers. The group began by bringing its vast experience to bear in discussing the promise and potential pitfalls of conducting “primary prevention studies” using vitamin D to potentially prevent MS before it occurs.
“We are people from all over the world and we have one common purpose – to stop this disease,” noted Dr. Hayes. “The research that has been done by the people in this room and others provides us with strong evidence that vitamin D may help.”
Alberto Ascherio, MD, DrPH (Harvard School of Public Health) and colleagues have published pivotal studies relating to several MS risk factors. His 2006 study (link to Dec 19, 2006 news article) – supported by the Society – compared levels of vitamin D in blood serum stored from military personnel during their service, and found that those with higher levels of vitamin D were at lower risk for later developing multiple sclerosis. Dr. Ascherio noted a major concern about designing vitamin D studies, based on his research. “Compliance is likely to be a major obstacle,” he said. “You have to worry about people in the placebo group that might take vitamin D anyway, and make the study powerful enough to account for that.”
George Ebers, MD, FRCP(C) (University of Oxford) reported on findings “hot off the press” – his team recently confirmed an association between MS and a gene linked to vitamin D. Dr. Ebers cautioned that before beginning a study, “You absolutely need to know what the rate of MS is in your country,” noting that the reported rates of MS is increasing in some areas.
Dr. Hayes reviewed basic research that could have a strong impact on planned studies. For example, female mice treated with vitamin D are protected from MS-like disease, but not male mice. “Normal estrogen may be essential for vitamin D benefits,” she said. Also, her research points to the immune messenger protein interleukin-10 as being essential for vitamin D protection from MS-like disease in mice. “Anything that destroys that pathway may undermine a treatment trial,” said Dr. Hayes.
Jorge Correale, MD (Raul Carrea Institute for Neurological Research Argentina) discussed his research on the immune response and vitamin D. “Vitamin D is particularly reduced during relapses in people with MS,” he said, noting that administering vitamin D to cells isolated from people with MS resulted in modulation of immune “T cells” which have been previously implicated in MS activity. He noted that cells that reduce inflammation are activated by vitamin D and those that promote inflammation are suppressed.
Reinhold Vieth, PhD, FCACB (University of Toronto) has been studying vitamin D for decades. His team’s findings show that this vitamin is associated with decreased PSA (a marker for prostate cancer), and a decreased risk of breast cancer. His experience provided numerous important considerations for conducting vitamin D prevention trials in MS. “Vitamin D binding protein [a protein that helps to transport the vitamin within the body] acts as a safety buffer to prevent toxicity,” he said. “It protects the body from having too much vitamin D.” Dr. Vieth works with the team that found vitamin D supplements to be safe in small, early study of people with MS (Neurology 2010;75(5):480).
Co-chair Dr. Ponsonby encouraged participants with her review of similar efforts undertaken to combat other diseases such as folate supplementation to mothers in pregnancy to prevent spina bifida. “I remember being at a primary prevention meeting in the early 1990’s ,like this one, to talk about sudden infant death syndrome prevention, which was taking one in 250 children in Tasmania at that time,” she said. “I thought, ‘How are we going to get this done?’ Five years later, it felt so good to be at another meeting, talking about how, after changes in health recommendation, the rate of SIDS had decreased by up to 70% in several countries.”
Future Steps: After reviewing data and hearing from statisticians and clinicians about the feasibility and expense of primary prevention studies, participants agreed to look at three study designs. The next steps are to submit a report based on the summit to a peer reviewed journal, and to begin the process of designing and seeking funding for the proposed prevention trials.
Timothy Coetzee, PhD, chief research officer of the National MS Society, complimented Drs. Hayes, Ponsonby, and colleagues on the “audaciousness” of their efforts. “Can we end MS by something as simple as vitamin D supplementation? This goal is as big as they come, but it fits right into the Society’s bold commitment to do everything possible to free the world of MS.”
Read more about research to end MS.