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      Timing of use of cod liver oil, a vitamin D source, and multiple sclerosis risk: The EnvIMS study

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          Abstract

          Background:

          Low vitamin D levels have been associated with an increased risk of multiple sclerosis (MS), although it remains unknown whether this relationship varies by age.

          Objective:

          The objective of this paper is to investigate the association between vitamin D 3 supplementation through cod liver oil at different postnatal ages and MS risk.

          Methods:

          In the Norwegian component of the multinational case-control study Environmental Factors In Multiple Sclerosis (EnvIMS), a total of 953 MS patients with maximum disease duration of 10 years and 1717 controls reported their cod liver oil use from childhood to adulthood.

          Results:

          Self-reported supplement use at ages 13–18 was associated with a reduced risk of MS (OR 0.67, 95% CI 0.52–0.86), whereas supplementation during childhood was not found to alter MS risk (OR 1.01, 95% CI 0.81–1.26), each compared to non-use during the respective period. An inverse association was found between MS risk and the dose of cod liver oil during adolescence, suggesting a dose-response relationship ( p trend = 0.001) with the strongest effect for an estimated vitamin D 3 intake of 600–800 IU/d (OR 0.46, 95% CI 0.31–0.70).

          Conclusions:

          These findings not only support the hypothesis relating to low vitamin D as a risk factor for MS, but further point to adolescence as an important susceptibility period for adult-onset MS.

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          Most cited references29

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          Use of the Danish Adoption Register for the study of obesity and thinness.

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            Immunomodulatory effects of Vitamin D in multiple sclerosis.

            Although Vitamin D is best known as a modulator of calcium homeostasis, it also has immune modulating potential. A protective effect of Vitamin D on multiple sclerosis is supported by the reduced risk associated with sun exposure and use of Vitamin D supplements. Moreover, high circulating levels of Vitamin D have been associated with lower risk of multiple sclerosis. In this study, we measured 1,25 (OH)(2) Vitamin D and 25 (OH) Vitamin D levels in multiple sclerosis patients separated into different clinical subgroups according to disease status. In addition, direct effects of 1,25 (OH)(2) Vitamin D on ex vivo CD4+ T cells and myelin-peptide specific T cell lines were investigated to gain more insight into putative regulatory mechanisms in the disease pathogenesis. One hundred and thirty-two Hispanic patients with clinically definite multiple sclerosis were studied, 58 with relapsing remitting multiple sclerosis during remission, 34 during relapse and 40 primary progressive multiple sclerosis cases. Sixty healthy individuals matched with respect to place of residence, race/ethnicity, age and gender served as controls. Levels of 25(OH)D(3) and 1,25(OH)(2)D(3), measured by ELISA were significantly lower in relapsing-remitting patients than in controls. In addition, levels in patients suffering relapse were lower than during remissions. In contrast, primary progressive patients showed similar values to controls. Proliferation of both freshly isolated CD4+ T cells and MBP-specific T cells was significantly inhibited by 1,25(OH)(2)D(3). Moreover, activated Vitamin D enhanced the development of IL-10 producing cells, and reduced the number of IL-6 and IL-17 secreting cells. Notably, Vitamin D receptor expression was induced by 1,25(OH)(2)D(3) in both activated and resting cells. Interestingly, T cells were able to metabolize 25(OH)D(3) into biologically active 1,25(OH)(2)D(3), since T cells express alpha1-hydroxylase constitutively. Finally, 1,25(OH)(2)D(3) also increased the expression and biological activity of indoleamine 2,3-dioxygenase, mediating significant increase in the number of CD4+CD25+ T regulatory cells. Collectively, these data suggest that 1,25(OH)(2)D(3) plays an important role in T cell homeostasis during the course of multiple sclerosis, thus making correction of its deficiency may be useful during treatment of the disease.
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              Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study.

              To examine whether past high sun exposure is associated with a reduced risk of multiple sclerosis. Population based case-control study. Tasmania, latitudes 41-3 degrees S. 136 cases with multiple sclerosis and 272 controls randomly drawn from the community and matched on sex and year of birth. Multiple sclerosis defined by both clinical and magnetic resonance imaging criteria. Higher sun exposure when aged 6-15 years (average 2-3 hours or more a day in summer during weekends and holidays) was associated with a decreased risk of multiple sclerosis (adjusted odds ratio 0.31, 95% confidence interval 0.16 to 0.59). Higher exposure in winter seemed more important than higher exposure in summer. Greater actinic damage was also independently associated with a decreased risk of multiple sclerosis (0.32, 0.11 to 0.88 for grades 4-6 disease). A dose-response relation was observed between multiple sclerosis and decreasing sun exposure when aged 6-15 years and with actinic damage. Higher sun exposure during childhood and early adolescence is associated with a reduced risk of multiple sclerosis. Insufficient ultraviolet radiation may therefore influence the development of multiple sclerosis.
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                Author and article information

                Contributors
                Journal
                Mult Scler
                Mult. Scler
                MSJ
                spmsj
                Multiple Sclerosis (Houndmills, Basingstoke, England)
                SAGE Publications (Sage UK: London, England )
                1352-4585
                1477-0970
                December 2015
                December 2015
                : 21
                : 14
                : 1856-1864
                Affiliations
                [1-1352458515578770]The KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Norway/Department of Global Public Health and Primary Care, University of Bergen, Norway/Department of Nutrition, Harvard T.H. Chan School of Public Health, USA
                [2-1352458515578770]Department of Global Public Health and Primary Care, University of Bergen, Norway/The Norwegian Multiple Sclerosis Competence Center, Department of Neurology, Haukeland University Hospital, Norway
                [3-1352458515578770]Department of Global Public Health and Primary Care, University of Bergen, Norway/Department of Nutrition, Harvard T.H. Chan School of Public Health, USA/The Norwegian Multiple Sclerosis Competence Center, Department of Neurology, Haukeland University Hospital, Norway
                [4-1352458515578770]Institute of Clinical Medicine, University of Oslo, Norway/Department of Neurology, Akershus University Hospital, Norway
                [5-1352458515578770]Department of Neurology, University Hospital of North Norway, Norway
                [6-1352458515578770]Department of Epidemiology and Biostatistics and Occupational Health, McGill University, Canada
                [7-1352458515578770]Department of Global Public Health and Primary Care, University of Bergen, Norway/Department of Clinical and Experimental Medicine, University of Sassari, Italy/Division of Medicine, McGill University, Canada
                [8-1352458515578770]Department of Epidemiology and Biostatistics and Occupational Health, McGill University, Canada/Research Institute of the McGill University Health Centre, Canada
                [9-1352458515578770]The KG Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen, Norway/The Norwegian Multiple Sclerosis Competence Center, Department of Neurology, Haukeland University Hospital, Norway
                Author notes
                [*]Department of Nutrition, Harvard T.H. Chan School of Public Health, 677 Huntington Ave., Boston, MA 02115, USA. Marianna.Cortese@ 123456igs.uib.no
                Article
                10.1177_1352458515578770
                10.1177/1352458515578770
                4657387
                25948625
                d15dd9db-b708-42a9-9703-b9e08047c5f6
                © The Author(s), 2015

                This article is distributed under the terms of the Creative Commons Attribution 3.0 License ( http://www.creativecommons.org/licenses/by/3.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( http://www.uk.sagepub.com/aboutus/openaccess.htm).

                History
                : 8 October 2014
                : 19 December 2014
                : 22 February 2015
                : 28 February 2015
                Categories
                Original Research Papers

                Immunology
                multiple sclerosis,vitamin d,timing,environmental risk factors,susceptibility,age,supplementation,cod liver oil

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