VITAMIN D CAN INHIBIT AND PREVENT MULTIPLE SCLEROSIS Research strongly suggests that high dose vitamin D3 therapy can significantly inhibit the progression of multiple sclerosis, with no adverse side effects. Other research also strongly suggests that if children maintain an adequate 25(OH)D level through puberty, they will not develop MS. Clinicians treating patients with MS should be recommending high dose vitamin D therapy for those patients. Significant clinical benefits have been demonstrated, with no reported adverse side effects. 25(OH)D levels between 100-150 nmol/L are safe and effective, and even occur naturally in many individuals. Health care practitioners treating children should recommend that their young patients maintain a 25(OH)D level between 80-100 nmol/L through puberty to prevent MS from developing. I am neither a Physician nor a microbiologist. However, I suffer from Primary Progressive Multiple Sclerosis. I was able to stop the radiographic progression of my MS (for the past 3 years) through high dose vitamin D therapy.   The Research Mouse studies conducted over 10 years ago by Colleen Hayes, PhD at the University of Wisconsin-Madison revealed that vitamin D can stop immunodemyelinating disease. Since that time, multiple meta-analyses and clinical studies have shown that vitamin D decreases the incidence, and inhibits the progression, of Multiple Sclerosis. Let's discuss the existing research, and how it fits together, starting with the mouse studies. Dr. Hayes was inducing EAE (experimental autoimmune encephalomyelitis- the mouse model of MS) and discovered that pretreatment with calcitriol (the hormonal form of vitamin D) had astounding effects. Dr. Hayes reported that: "Moreover, 1a,25-(OH)2D3 pretreatment completely blocked EAE induction in MBP primed B10.PL mice (39). Further,1a25-(OH)2D3 treatment rapidly reversed the paralytic symptoms of mice with severe acute EAE (178)." (footnote 1) Vitamin D has an obvious immunomodulating effect that stops white blood cells from attacking native tissue. Vitamin D not only completely stopped EAE (mouse MS) from developing, but vitamin D also reversed the effects of EAE when utilized during the acute phase of the disease (i.e. early). Dr. Hayes explained, "Our laboratory has also studied the process by which 1a,25-(OH)2D3 reversed EAE(178). Mice with severe acute EAE (complete hind limb paralysis) were randomized to receive 1a,25-(OH)2D3 or placebo treatment. The hormone-treated animals began walking with a wobbly gate[sic] at 3 days post treatment, whereas placebo treated mice remained paralyzed. A histolopathological examination at 3 days post treatment showed the hormone-treated mice had a 50% decrease in white matter and meningeal inflammation" (footnote 2) The immunomodulating activity of vitamin D demonstrated in the mouse studies is also demonstrated in studies analyzing human populations. Two studies from the Harvard School of Public Health show that higher vitamin D levels decrease the incidence of MS in humans. The first study involved analysis of data gathered between 1980 and 1999 from dietary assessments of 238,000 nurses involved in the Nurses Health Study and Nurses Health Study II. The results were stunning: "We found a 40% reduction in risk of MS among women who use supplemental vitamin D, primarily in the form of multivitamins, compared with women who do not use supplements" (Footnote 3.) The second study by the Harvard School of Public Health involved analysis of blood samples obtained from the Department of Defense. More than seven million blood samples were available, and from those samples and other records 257 cases of MS were identified. Those cases were then matched to 2 controls by age, sex, race/ethnicity, and dates of blood collection. The 25(OH)D blood levels were analyzed, and (Footnote 4) In addition to the Harvard studies, other research has revealed a direct link between vitamin D and a gene suspected of causing MS, and Clinical trials have demonstrated that high dose vitamin D can reduce the frequency of MS attacks, and the number of active MS lesions, by 50% or more. In a study funded by the MS Society of Canada, the UK MS Society, the Wellcome Trust and the Medical Research Council, Dr. Julian C. Knight (University of Oxford, UK) and collaborators at Oxford and the University of British Columbia have established a direct relationship between a gene believed to play a role in MS and vitamin D. (footnote 5) According to a February 6, 2008 article entitled "Study Shows link Between vitamin D and an MS Gene", appearing on the National Multiple Sclerosis Society website:"The researchers found that proteins activated by vitamin D in the body bind to a particular DNA sequence lying next to the DRB1*1501 variant, in effect switching the gene on. The authors believe that vitamin D deficiency may lead to lowered expression of this gene, in turn altering immune processes that ultimately trigger the immune attack on brain and spinal cord tissues in MS." The gene study again demonstrates the link between adequate levels of vitamin D and preventing MS."Our study implies that taking vitamin D supplementsduring pregnancy and the early years may reduce the risk of child developing MS in later life," lead author Dr. Sreeram Ramagopalan said in the news release. "Vitamin D is a safe and relatively cheap supplement with substantial potential health benefits. There is accumulating evidence that it can reduce the risk of developing cancer and offer protection from other autoimmune diseases." ("Vitamin D Deficit May Trigger MS Risk Gene", U.S. News and World Report (Health), February 5, 2009.) In a presentation at the 2008 annual meeting of the American Academy of Neurology on April 28, 2008, a group of Canadian researchers presented the results of a study sponsored by the Canadian MS Society. The study involved a group of 25 MS patients who took an average of 14,000 IU of vitamin D3/day for 1 year (high dose group), and a group of 24 MS patients who took an average of 1000 IU/day for 1 year. The contrasting results were astounding. The group taking 14,000 IU/day suffered 41% fewer relapses that they did in the year before the study began, and only 16% suffered any relapses in the year of the study. By contrast, in the group taking 1000 IU/day, there were only 17% fewer relapses, and 40% suffered relapses during the year of the study. The high dose D3 group was also given 1200 mg/day of calcium. Even though the high dose group reached a maximum mean 25(OH)D level of 413 nmol/L, there were no adverse side effects reported, including calcium abnormalities. High dose vitamin D therapy cut the relapse rate by over 50% (Footnote 6)   Dosage/Side Effects A 2007 study from the University of Wisconsin -Madison revealed that MS patients could take fairly large amounts of vitamin D3, with no side effects. The 28 week study involved only 12 patients with RRMS that were given increasing doses of vitamin D3, escalating from 28,000 t0 280,000 IU/week. The searchers found that "Patients' serum 25(OH)D concentrations reached twice the top of the physiologic range without eliciting hypercalcemia or hypercalciuria. Thedata support the feasibility of pharmacologic doses of vitamin D3 for clinical research, and they provide objective evidence that vitamin D intake beyond the current upper limit is safe by a large margin." Kimball, Ursell, O'Connor and Vieth; "Safety of Vitamin D3 In Adults With Multiple Sclerosis"; The AmericanJournal of Clinical Nutrition; Vol. 86, pp.645-651, at 645 (2007) An ancillary finding was that over the short course of the study, the number of gadolinium enhancing lesions(by MRI) among the study participants decreased by 50%. (Footnote 7) The Wisconsin Study and the Canadian Study (discussed above) both provide good evidence that high dose vitamin D therapy is safe. Since it has been reported that 14,000 IU/day is safe, and given the results of the Canadian Study, 14,000 IU/day of vitamin D3 appears to be a therapeutic dose. Dr. Hayes stresses the importance of 25(OH)D level over any oral dosage of vitamin D. Dr. Hayes noted; "Adults living or working in sunny environments easily generate >10,000 IU/day of vitamin D through sun exposure without adverse effects., so the safe upper limit for total vitamin D nutrition is at least 10,000 IU/day (Vieth 1999)"(footnote 7)., and that "Adults living or working in sunny environments, where MS prevalence is lowest, have circulating 25-hydroxyvitamin D3 levels between 105 and 163 nmol/L (Vieth 1999). Thus a serum 25-hydroxyvitamin D > 100 nmol/L may be optimal to prevent MS." (Footnote 8). Personal Anecdotal Experience I was diagnosed with PPMS in February, 2004, and was advised that there was nothing available that could stop the progression of the disease. I had active MS lesions by gadolinium MRI at the time of my diagnosis. My research revealed the mouse studies by Dr. Hayes and the Harvard School of Public Health analysis of the Nurses Health Studies. I raised my 25(OH)D level to 100nmol/L, and have maintained that level for the past 3 years. I have obtained serial 25(OH)D and blood calcium levels and, although my 25(OH)D level has been as high as 234 nmol/L, I have never experienced an elevated blood calcium level. Ten months after my diagnosis I had a second gadolinium enhanced MRI, and displayed no active MS lesions. I have undergone annual gadolinium enhanced MRIs, and have had no active MS lesions for 3 years (3 consecutive MRIs). High dose vitamin D3 therapy has stopped the radiographic progression of my MS, and reversed significant bowel symptoms I experienced prior to institution of the therapy (although it has not reversed motor symptoms in arms, trunk and legs). Prevention of Multiple Sclerosis Both the Harvard School of Public Health, and Dr. Hayes, discuss the important findings of immigration studies that strongly suggest that if children maintain an adequate level of vitamin D through puberty, they do not develop MS (footnote 1, at p , and footnote 4, at. p. ). The Harvard School of Public Health suggests that: "according to a recent review, the best serum 25-hydroxy vitamin D concentrations are between 80-100 nmol/L (42)" (Footnote 5, citing ). The recent gene research suggests that pregnant women and young children should take supplemental vitamin d to prevent Ms, and suggests 200 IU/day. Conclusions Studies to date have found that high dose vitamin D therapy will significantly reduce the frequency of MS attacks in individuals with RRMS. After extensive research, no contrary studies were located. Neurologists (or others) who treat patients with Multiple Sclerosis should be recommending to those patients that they increase their 25(OH)D blood levels to 100-150 nmol/L. Patients can safely take an average of 14,000 IU/day with no adverse side effects.No author has suggested any adverse side effects at this level, and the collateral benefits are significant. All physicians should be recommending that children maintain a 25(OH)D level of 80-100 nml/L through puberty to prevent MS. Again, there are no known adverse side effects, and there are significant collateral benefits. Epilogue: Guillian-Barre Syndrome It appears that the induction of EAE in mice mimics the onset of Guillian-Barre syndrome. Perhaps high dose vitamin D3 should be administered, in addition to undertaking appropriate diagnostic procedures, at the first sign of unexplained neurologic symptoms. There are no reported side effects of high dose vitamin D therapy, and all of the studies, particularly the mouse studies, indicate that high dose vitamin D therapy is likely to stop the demyelinating process and rapidly reverse the symptoms, if instituted early in the diagnostic process. Footnotes:1." Hayes, et.al., "The Immunological Functions of the Vitamin D Endocrine System", Cellular and Molecular Biology, (at page 11) 49(2), 03-34 Mar, 2003, ISSN 0145-5680/03, citing2. Id, at p. 12)3. Munger, et.al., "Vitamin D intake and the incidence of multiple sclerosis", NEUROLOGY, pp.60-65, at 64,January (1 of 2) 2004.4. Serum 25-Hydroxyvitamin D Levels and Risk of Multiple SclerosisKassandra L. Munger, Lynn I. Levin, Bruce W. Hollis, Noel S. Howard, and Alberto Ascherio; JAMA. Vol.296, No.23, pp.2832-2838 (Deccember., 2006) 5. Expression of the Multiple Sclerosis associated MHC class II allele HLA-DRB1*1501 is Regulated by Vitamin D is published in PLoS Genetics.6." Immunological Analysis of a Phase I/II Dose-Escalation Trial of Oral Vitamin D3 with Calcium Supplementation in Patients with Multiple Sclerosis' presented April 28, 2009 at the annual meeting of the American Academy of Neurology. 7. Hayes,"Vitamin D: a Natural Inhibitor of Multiple Sclerosis", Proceedings of the Nutrition Society, 2000, v.59, p531-535, at p.533.8. Ibid.