The association between vitamin D status and risk for multiple sclerosis (MS) prevention and/or disease modification has been the centre of considerable research and public discussion over the last decade. Studies ranging from mechanistic (cell and animal models) to population health to clinical trials have explored how low vitamin D status influences MS risk and whether vitamin D can be used as a standalone or add-on treatment for MS. To date, varying study approaches and inconsistencies in findings have limited the capacity to develop evidence-informed, clear recommendations on vitamin D for people affected by MS. Despite the lack of definitive recommendations, people living with MS are vocal regarding their interest in vitamin D and its relationship to the disease. They want to know whether they should test their vitamin D status, whether supplementation is necessary, and if so how much supplementation is required and what the best sources of vitamin D are. They access various sources to obtain this information such as their healthcare team, organizations like the MS Society of Canada, friends and family, the internet and social media. It is therefore imperative that they are provided with clear, accurate information to make the best decisions for them regarding vitamin D.In early 2016, the MS Society of Canada convened a panel of scientific and clinical experts, staff from other national MS patient organizations, and a person affected by MS to discuss the available evidence on the link between vitamin D and MS. The purpose of the meeting was to begin the process of developing evidence-driven statements that can help guide people affected by MS in making informed decisions about their health. The recommendations will also support healthcare professionals and policy makers by providing them with a detailed assessment of the evidence on vitamin D and MS that will guide clinical practice and public health policy. Discussions at the in-person meeting led to the creation of key statements on vitamin D and MS that would provide guidance in four areas: prevention, disease modification, comorbidities (presence of more than one condition), and toxicity. Following the meeting, email exchanges and teleconferences were held during which members of the panel identified and graded scientific publications relevant to each statement (see grading system in Appendix). The relatively small number of relevant published studies, particularly randomized clinical trials, limited the panel's ability to conduct a formal systematic review and meta-analysis. The statements were then discussed and revised in a follow-up teleconference, and final grades were assigned based on thoughtful assessment of the level of evidence supporting each statement and expert consensus.# INTRODUCTION Vitamin D for General Health
Vitamin D plays an essential role in human health, primarily in calcium and phosphate regulation to support bone health. Before vitamin D can act at the tissue level it must first be converted to 25hydroxyvitamin D in the liver and then to 1,25-dihydroxyvitamin D -the active hormone that is the main functioning unit. An individual's vitamin D status can be measured in two ways -vitamin D dietary intake and vitamin D levels in the blood. The latter gives a true picture of vitamin D status, and is determined by measuring the amount of 25-hydroxyvitamin D in in the blood 1 .
In addition to the well documented role in bone health, evidence is emerging from ecological and observational studies that the active form of vitamin D -1,25-dihydroxyvitamin D -also has functions in immune, cardiovascular, and neurological systems, as well as glucose regulation and placental function. This is supported by knowledge that the active vitamin D hormone is synthesized not only in the liver but in cells in the placenta, pancreas, prostate, breast, and in immune cells such as macrophages. Such information has been the basis of observations of the association of vitamin D status in humans and certain cancers, immune disorders, cardiovascular disease, abnormal glucose metabolism, and neurodegenerative diseases.
Health Canada has published recommendations for daily consumption of vitamin D which are based on a 2010 report from the U.S. Institute of Medicine: Infants 0-1 year -400 IU (10 g)/day; children and adults 1-70 years -600 IU (15 g)/day; adults over 70 years -800 IU (20 g)/day. The recommended intake is the same for males and females. For pregnant and lactating women, the recommendation is the same as for adults. For adults over 50 years, Health Canada recommends a daily vitamin D supplement of 400 IU since aging may reduce the efficiency of vitamin D synthesis in the skin. Too much vitamin D can be harmful, so Health Canada also recommends an upper intake limit of 4000 IU (100 g)/day unless there is a medical reason such a malabsorption or bone disease that requires higher intakes as directed by a physician.
Vitamin D can be obtained from food and supplements, and humans are able to synthesize vitamin D in the skin when exposed to ultraviolet radiation from the sun in the summer months. Black pigment in skin reduces the production of vitamin D, therefore people with pigmented skin are more at risk of low vitamin D status and may need supplements to acquire adequate vitamin D, especially during Canadian winters. While skin exposure to the sun can result in obtaining sufficient vitamin D, excessive exposure has been associated with risk of skin cancer, therefore one should follow Health Canada 1 Provinces and territories do not cover the cost of vitamin D tests for the general public. Certain health conditions are exempt from the cost, though multiple sclerosis is not currently one of them.

# Recommended Vitamin D Intake

# Sources of Vitamin D
recommendations for safe sun exposure. Coverage of the skin with low SPF (<30) sunscreen will allow some vitamin D to be produced in the skin.
Food sources of vitamin D are primarily fatty fish (e.g. salmon and mackerel), egg yolks and vitamin D fortified foods. In Canada, cow's milk and margarine have mandatory regulations for vitamin D fortification. Voluntary fortification is also done for some orange juice and plant milk products.
In Canada, vitamin D supplements are primarily found in pill form as vitamin D3 (cholecalciferol) -the form that is made in the skin. Vitamin D2 (ergocalciferol) is derived from plant sources and is used in foods and supplements but primarily in the United States. It is thought that vitamin D3 is the most biologically active form but this is debated. Of note, the Food and Drug Administration does not regulate Vitamin D supplements, hence the potency of supplements may vary between preparations. To absorb the largest amount of vitamin D from a supplement or vitamin D fortified food source, it should be taken with the meal that contains the highest amount of fat since vitamin D is soluble in fat. The time of day of vitamin D supplementation does not appear to affect the absorption of vitamin D. Vitamin D can also be taken as an emulsion and obtained from cod liver oil, however it's important to discuss these applications with a healthcare professional to understand dosing, benefits and safety.
As new research evidence emerges, experts are assessing the role vitamin D plays in the development and course of MS. The recommendations in this report are based on assessment of the available evidence, and are intended for those who are at risk -as defined in the following section -of developing MS and those who live with MS.

# Vitamin D and Multiple Sclerosis

# VITAMIN D AND MS RECOMMENDATION STATEMENTS

# Multiple Sclerosis prevention for at-risk populations
1-1 Adults deemed to be at risk 2 of developing multiple sclerosis (MS) are advised to achieve and maintain a normal vitamin D status defined as serum 25-hydroxyvitamin D in the target range of 50-125 nmol/L (20-50 ng/ml). Once this level has been achieved, they are encouraged to consult with their primary care physician about the frequency of monitoring on the basis of changes in health status. Vitamin D testing is advisable but not essential.
(Level 3 evidence, Grade C recommendation)
Additional considerations  Additional evidence provided by genetic studies (e.g. Mendelian Randomization) supports the epidemiological evidence that there is an association between higher vitamin D status and reduced MS risk.  Although these genetic studies are unable to prescribe target vitamin D status for at risk populations, they eliminate confounding factors and strengthen the epidemiological observations.  Careful language is needed to avoid the term "genetic risk" which may mislead the public to think that they can be genetically screened for MS risk based on vitamin D alleles. 2 "at risk" population defined as first-degree relatives (parents, children, and siblings) of a family member with MS. Children with a first degree relative with MS (i.e. parent or sibling) have a 3-5% absolute risk of developing MS, which is higher than the general population. Individuals should bear in mind other lifestyle factors that could modify one's risk of developing MS, including past exposure to Epstein -Barr virus, smoking and second-hand tobacco exposure, and obesity. Also, of note, obesity may result in lower vitamin D levels, hence, obese people may need higher doses of vitamin D to achieve the same serum level as those with normal weight.