Vitamin d as a protective factor in multiple sclerosis pdf

This complex is capable of binding to genomic vitamin D response elements, modulating the expression of a variety of genes. Vitamin D receptor expression has been reported in most immune cells, 14 as well as in CNS tissues. These cells are therefore, able to synthesize and secrete active vitamin D in both an autocrine and paracrine fashion, 16 indicating that vitamin D plays a role in the immune system. The in vitro addition of 1,dihydroxyvitamin D3 1,25 OH 2D3 to antigen-presenting cells namely, monocytes, macrophages, and dendritic cells inhibits the surface expression of major histocompatibility complex II-complexed antigens, and of costimulatory molecules, leading to reduced T cell stimulatory capacity.

Additionally, 1,25 OH 2D3 directly exerts its immunomodulatory effects on T lymphocytes by inhibiting the production of Type 1 helper T cell cytokines considered to be the key mediators in graft rejection and autoimmune diseases and stimulating the production of Type 2 helper T cell cytokines, which have immunoregulatory functions. This compound also affects T cell maturation, inducing a shift away from the inflammatory T-helper 17 cells phenotype and facilitating the production of regulatory T cells.

However, experimental studies have reported that the observed immunomodulatory effects of vitamin D only occur at hyper-physiologic concentrations, which causes hypercalcemia in humans. Many clinical trials have been, or are currently being conducted to test the therapeutic application of vitamin D or its analogs in inflammatory processes. It is well known that MS is more prevalent in higher latitudes, where sunlight is of lower intensity than in lower latitudes.

Recent meta-analyses 20 supported a latitude gradient in MS prevalence. Several recent studies found that increased body exposure to sunlight, and hence a decreased susceptibility to vitamin D deficiency, is also associated with a decreased risk of MS, 21 - 26 especially if the sun exposure occurred during childhood and adolescence.

Studies have also shown that the birth month is correlated with MS risk; individuals born in the fall namely, whose mothers were exposed to summer sunlight have a low MS risk, whereas individuals born in the spring have a higher risk of MS. This observation indicates the presence of an association among maternal sunlight exposure during pregnancy, vitamin D status, and the risk of MS.

In , a systematic review 27 analyzed published data on the effects of birth month for , MS patients born in the Northern Hemisphere. The results of this analysis demonstrated a significant increase of MS risk among individuals who were born in April and a reduction in risk in people who were born in October and November.

However, sunlight also has an immunosuppressive effect, 28 and UVR was recently found to suppress experimental autoimmune encephalomyelitis. Studies that evaluate either serum vitamin D levels or vitamin D intake, are needed to determine whether vitamin D deficiency is a risk factor for MS independent of sun exposure.

The strongest evidence in this regard came from a large prospective case-control study 31 of more than 7 million US military personnel from whom serum samples were obtained before any appearance of MS symptoms. A recent study concluded that sun exposure and vitamin D status independently affect the risk of MS.

The study showed that the relative risk of MS was significantly lower in women whose mothers had high milk or vitamin D intake during pregnancy than in women born to low-intake mothers. Several studies have shown that vitamin D levels are lower in MS patients than in controls. The association of disease activity with vitamin D levels in MS patients has been evaluated in multiple studies that demonstrated a lower MS relapse rate in patients with higher levels of vitamin D.

The EDSS is a commonly used index of clinical disability in MS, with scores ranging from 0 corresponding to a normal examination and function to 10 for death due to MS. Two recent studies conducted in support this association. In the first study, 53 patients were prospectively followed, and EDSS scores were correlated with plasma vitamin D levels. Serum 25 OH D concentrations were measured at baseline and at 6, 12, and 24 months. Patients were followed for 5 years with clinical assessments and MRI.

Even MS patients who are fully mobile are theoretically more susceptible to vitamin D deficiency because they avoid sun exposure, worsening their symptoms. Therefore, establishing the effects of vitamin D on disease activity and severity in MS patients requires randomized controlled trials RCTs. Table 1 summarizes interventional studies in which MS patients received vitamin D supplementation. In one RCT, a significant decrease in T1-enhancing lesions was seen in the treatment group.

Multiple studies have demonstrated favorable immunological changes in the serum of MS patients in the treatment group. However, none of the RCTs listed in Table 1 were sufficiently powered to observe a treatment effect. Therefore, we cannot conclude that vitamin D is a clinically effective treatment for MS patients; however, we can conclude that a high dose of vitamin D is safe in the short term.

Approximately 6 large RCTs are ongoing; the results of these analyses will provide solid evidence regarding the benefits of vitamin D supplementation. Summary of vitamin D interventional studies that have been carried out in multiple sclerosis patients.

The increase in the concordance ratio for MS risk between mono- and dizygotic twins with increasing latitude suggests that genetic effects may be stronger for individuals with low concentrations of vitamin D. It is likely that these genes contribute to MS risk by decreasing the levels of active vitamin D. Furthermore, vitamin D receptor-binding elements have been identified in the majority of MS-associated genes, indicating that the expression of many of these genes may be regulated by vitamin D.

In conclusion, it is clear from observational studies that vitamin D deficiency is a modifiable risk factor for MS. Therefore, persons who are at risk for MS for example, first-degree relatives of MS patients, or patients with a single episode demyelinating attack should be screened for vitamin D deficiency.

As stated previously, evidence for the effect of vitamin D on disease progression is lacking, but it is known that MS patients have an increased prevalence for vitamin D deficiency due to for example, immobility, sun avoidance, corticosteroids, and anti-epileptic use. These patients are also susceptible to osteoporosis. The optimal serum vitamin D levels for exerting immunomodulatory effects have not been clinically established.

However, the long-term effects of such high levels are unknown. The author declares no affiliation or financial involvement with organizations or entities with a direct financial interest in the subject matter or materials discussed in the manuscript. No funding was received for this work from any organization. National Center for Biotechnology Information , U. Journal List Neurosciences Riyadh v. Neurosciences Riyadh. Fatimah M.

Author information Copyright and License information Disclaimer. Address correspondence and reprint request to: Dr. E-mail: as. Readers may copy, distribute, and display the work for non-commercial purposes with the proper citation of the original work. This article has been cited by other articles in PMC. Abstract Multiple sclerosis MS is a common neurological disease, and its etiology remains unknown. Vitamin D metabolism Vitamin D is a fat-soluble vitamin; its 2 main forms are ergocalciferol vitamin D2 , which is of plant origin, and cholecalciferol vitamin D3 , which is of animal origin.

Vitamin D as an immunomodulator Vitamin D receptor expression has been reported in most immune cells, 14 as well as in CNS tissues. Vitamin D and MS risk It is well known that MS is more prevalent in higher latitudes, where sunlight is of lower intensity than in lower latitudes. Table 1 Summary of vitamin D interventional studies that have been carried out in multiple sclerosis patients.

Two patients withdrew because of symptomatic hypercalcemia upon discontinuation of calcitriol at 12 months.

The EDSS increased to 3. Open in a separate window. Vitamin D, genetics, and MS The increase in the concordance ratio for MS risk between mono- and dizygotic twins with increasing latitude suggests that genetic effects may be stronger for individuals with low concentrations of vitamin D. Footnotes Disclosure. References 1. Immunopathogenesis of multiple sclerosis: new insights and therapeutic implications.

Continuum Minneap Minn ; 16 — Atlas of Multiple Sclerosis A growing global problem with widespread inequity. Kurtzke JF. A reassessment of the distribution of multiple sclerosis. Acta Neurol Scand. However, many interactions between these different factors occur more particularly between conception and the end of adolescence, which corresponds to the period of maturation of the immune system and thymus and may be related to the dysimmune nature of the disease.

The main mechanisms of action of vitamin D in MS appear to be immunomodulatory, involving the various categories of T and B lymphocytes in the general immune system, but neuroprotector and neurotrophic mechanisms could also be exerted at the central nervous system level.

Furthermore, several controlled immunological studies performed in MS patients have recently confirmed that vitamin D supplementation has multiple beneficial immunomodulatory effects. However, there is still an enduring absence of major conclusive randomized clinical trials testing vitamin D supplementation in MS patients because of the quasi-insurmountable practical difficulties that exist nowadays in conducting and completing over several years such studies involving the use of a vitamin.

Outdoor activities and diet in child- of life of MS patients, many of whom suffer MS in order to develop pharmaceuticals and hood and adolescence relate to MS risk above the Arctic Circle. J Neurol. Vitamin D in- take and incidence of multiple sclerosis.

Dietary intake of vitamin D during ado- improve sleeping patterns. While VD is known to increase during lescence and risk of multiple sclerosis. Bridger H. Why MS symptoms may improve as days get shorter [Internet]. However, research has not yet Harvard Gazette. As such, future research Norouzi R.

International Jour- nal of Preventive Medicine [Internet]. Melatonin dysregulation, past 50 years and the correlation of its symptoms sleep disturbances and fatigue in mul- tiple sclerosis. Journal of the Neurologi- or incidence with seasonal changes has shifted cal Sciences. Expression of the Mel1a- factors. Through epidemiological observation, melatonin receptor mRNA in T and B subsets of lymphocytes from rat a relationship between sunlight exposure thymus and spleen.

Se- is able to alleviate MS symptoms during the rum levels of melatonin and cyto- kines in multiple sclerosis. Biomed J. Based on experimental and clinical ;37 2 Corthay A.

Scandinavian Journal of Immu- nology. Front Immun. His research focuses on the role of mucosal innate and T cells in multiple sclerosis and experimental autoim- immunology and virology courses. Clin Exp Im- munol. Edited by avrilynn ding and arlinda deng Melatonin Contributes to the Seasonal- 1. Nylander A, Hafler DA. Multiple sclerosis. Predicting 5. Mehta BK. New hypotheses on sunlight and ity of Multiple Sclerosis Relapses.

Invest [Internet]. Available progression in primary progressive multiple the geographic variability of multiple sclerosis ; 6