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Vitamin D as a protective factor in multiple sclerosis
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.ORCID iD: 0000-0001-9581-3845
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
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2012 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, no 21, 2140-2145 p.Article in journal (Refereed) Published
Abstract [en]

Objective: To examine the association between 25-hydroxyvitamin D (25[OH]D) levels and the risk of multiple sclerosis (MS) in blood samples collected prospectively and during gestation.

Methods: In this nested case-control study, 2 population-based biobanks with 291,500 samples from164,000 persons collected since 1975 in the northern half of Sweden were used. We identified prospectively collected blood samples from MS cases (n = 192, controls matched 2:1) and gestational samples from pregnant mothers where the offspring had later developed MS (n = 37, control mothers matched 5:1). 25(OH)D levels were measured using an ELISA, and the risk of MS was analyzed using matched logistic regression.

Results: Levels of 25(OH)D ≥75 (vs <75) nmol/L in prospectively collected blood samples were associated with a decreased risk of MS (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.16- 0.98). No decrease in MS risk was found in the offspring exposed to gestational 25(OH)D levels ≥75 (vs <75) nmol/L (OR 1.8, 95%CI 0.53-5.8). The prevalence of 25(OH)D levels ≥75 nmol/L in female controls decreased gradually during 1976-2005 (p trend = 0.005).

Conclusion: This study supports the presence of an association between high 25(OH)D levels during the years preceding disease onset and a decreased risk of MS. In the very limited material with samples drawn in early pregnancy, where month-of-birth effects were controlled for, we found no association between gestational 25(OH)D levels and MS risk in the offspring. Decreasing 25(OH) D levels in the population may contribute to explain the increasing MS incidence that is suggested from epidemiologic studies.

Place, publisher, year, edition, pages
2012. Vol. 79, no 21, 2140-2145 p.
National Category
URN: urn:nbn:se:umu:diva-63632DOI: 10.1212/WNL.0b013e3182752ea8OAI: diva2:582447
Available from: 2013-01-08 Created: 2013-01-03 Last updated: 2015-04-22Bibliographically approved
In thesis
1. Environmental risk factors for multiple sclerosis
Open this publication in new window or tab >>Environmental risk factors for multiple sclerosis
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Miljöfaktorers betydelse för multipel skleros
Abstract [en]

Background Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. It usually strikes during young adulthood, and 2.5 million individuals are estimated to have the disease worldwide. The causes of MS are not known, but several factors have been shown to be associated with the risk of the disease, including certain genes, vitamin D, smoking and Epstein- Barr virus infection. Little is known about how/if these factors interact.

Methods Study I: The risk of MS by month of birth was investigated using MS cases from the Swedish MS registry and using general population controls. Studies II–V: We identified MS cases who had donated blood prior to disease onset, and MS cases whose mothers had donated blood during pregnancy, by cross-linking a database of MS cases, and a database of mothers of MS cases, to two local biobank cohorts. One of them consisted of blood samples collected during early pregnancy, and one with samples collected during health controls. Levels of 25(OH)D (25-hydroxyvitamin D), RBP (retinol binding protein, a surrogate marker for vitamin A), CRP (C- reactive protein), cotinine (a nicotine metabolite) and anti Epstein-Barr virus nuclear antigen-1 (EBNA-1) antibodies were measured in cases and matched controls. The risk of MS by categories of these exposures was estimated in bi- and multivariable matched logistic regression models.

Results Subjects born in spring had a higher risk of MS, but no influence of early gestational levels of the measured risk factors on the risk of MS in the offspring was observed. In prospective samples from MS cases and controls, 25(OH)D levels ≥75 nmol/l, intermediate RBP levels, and elevated CRP levels in young were associated with a decreased risk of MS. Elevated cotinine levels (suggestive of smoking) and high antibody reactivity against EBNA-1 were associated with an increased risk of MS. All factors but RBP were more clearly associated with MS in young subjects.

Conclusion All factors analyzed in prospectively collected samples were associated with the risk of MS, and taken together, the data indicate that the key etiopathological events that lead to MS occur before the age of 20–30. Study II provides support for trials exploring the primary preventive potential of oral vitamin D supplementation.

Place, publisher, year, edition, pages
Umeå: Umeå Universitet, 2013. 54 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1545
Multiple sclerosis, risk factors in epidemiology, prospective, month of birth, vitamin D, vitamin A, C-reactive protein, hygiene hypothesis, smoking, cotinine, Epstein-Barr virus
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Research subject
urn:nbn:se:umu:diva-64212 (URN)978-91-7459-545-1 (ISBN)
Public defence
2013-03-01, Hörsal E04, By 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Available from: 2013-02-08 Created: 2013-01-21 Last updated: 2013-02-08Bibliographically approved

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Salzer, JonatanHallmans, GöranNyström, MariaStenlund, HansWadell, GöranSundström, Peter
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