Low 25‐hydroxyvitamin D, but not the bioavailable fraction of 25‐hydroxyvitamin D, is a risk factor for multiple sclerosis

Behrens, Janina; Rasche, Ludwig; Gieß, René M.; Pfuhl, Catherina; Wakonig, Katharina; Freitag, Erik; Deuschle, Katrin; Bellmann‐Strobl, Judith; Paul, Friedemann; Ruprecht, Klemens; Dörr, Jan

doi:10.1111/ene.12788

Cited by 55 publications

(30 citation statements)

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“…In this cohort, VD deficiency showed an inverse association with measures of disability and was furthermore linked to a higher T2w lesion count but was not associated with T2 lesion volume, total brain volume as well as gray and white matter volumes. A high prevalence of VD deficiency in MS patients has been demonstrated in other studies: In an earlier study on a different patient cohort, we reported VD deficiency already in very early phases of MS (5). A cross-sectional study of 50 RRMS patients revealed a VD deficiency with a mean of 22.3 ng/ml /ml (42).…”

Section: Discussionsupporting

confidence: 71%

“…The exact cause of multiple sclerosis (MS), a chronic inflammatory and neurodegenerative autoimmune disease of the central nervous system (1) is unknown. However, several environmental and genetic factors have been associated with MS pathogenesis, among them are vitamin D (VD) serum levels (2)(3)(4)(5), vitamin D receptor polymorphisms (VDP) (6)(7)(8)(9)(10), and sunlight exposure (11,12). In fact, increasing evidence suggests that VD deficiency may affect disease progression and outcome in MS.…”

Section: Introductionmentioning

confidence: 99%

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Vitamin D and Disease Severity in Multiple Sclerosis—Baseline Data From the Randomized Controlled Trial (EVIDIMS)

et al. 2020

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Objective: To investigate the associations between hypovitaminosis D and disease activity in a cohort of relapsing remitting multiple sclerosis (RRMS) and clinically isolated syndrome (CIS) patients. Methods: In 51 RRMS and 2 CIS patients on stable interferon-β-1b (IFN-β-1b) treatment recruited to the EVIDIMS study (Efficacy of Vitamin D Supplementation in Multiple Sclerosis (NCT01440062) baseline serum vitamin D levels were evaluated. Patients were dichotomized based on the definition of vitamin D deficiency which is reflected by a < 30 vs. ≥ 30 ng/ml level of 25-hydroxyvitamin D (25(OH)D). Possible associations between vitamin D deficiency and both clinical and MRI features of the disease were analyzed. Results: Median (25, 75% quartiles, Q) 25(OH)D level was 18 ng/ml (12, 24). Forty eight out of 53 (91%) patients had 25(OH)D levels < 30 ng/ml (p < 0.001). Patients with 25(OH)D ≥ 30 ng/ml had lower median (25, 75% Q) T2-weighted lesion counts [25 (24, 33)] compared to patients with 25(OH)D < 30 ng/ml [60 (36, 84), p = 0.03; adjusted for age, gender and disease duration: p < 0.001]. Expanded disability status scale (EDSS) score was negatively associated with serum 25(OH)D levels in a multiple linear regression, including age, sex, and disease duration (adjusted: p < 0.001). Interpretation: Most patients recruited in the EVIDIMS study were vitamin D deficient. Higher 25(OH)D levels were associated with reduced T2 weighted lesion count and lower EDSS scores.

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Section: Discussionsupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Vitamin D and Disease Severity in Multiple Sclerosis—Baseline Data From the Randomized Controlled Trial (EVIDIMS)

et al. 2020

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“…Low 25(OH)D serum levels have been associated with high risk of multiple sclerosis [26]. Free and bioavailable vitamin D did not differ between multiple sclerosis patients and their healthy controls [27]. In pediatric patients with chronic kidney disease, both free and bioavailable vitamin D were significantly lower than in healthy controls [28].…”

Section: Discussionmentioning

confidence: 99%

25-Hydroxivitamin D Serum Concentration, Not Free and Bioavailable Vitamin D, Is Associated with Disease Activity in Systemic Lupus Erythematosus Patients

et al. 2017

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We aim to evaluate the prevalence of vitamin D deficiency in patients with systemic lupus erythematosus (SLE) and investigate the association between total, free and bioavailable vitamin D serum concentrations and disease activity. Patients with SLE (ACR 1997) consecutively seen at UNIFESP’s outpatient’s clinics had disease activity measured after clinical and laboratory evaluation using SLEDAI (Systemic Lupus Erythematosus Disease Activity Index). 25-hydroxyvitamin D (25(OH)D) serum concentrations measured by chemiluminescence and vitamin D binding protein (DBP) measured by ELISA were used to calculate free and bioavailable vitamin D. Healthy blood donors were used as controls. A total of 142 patients (71.4%) had 25(OH)D serum concentrations below 30 ng/mL. Total 25(OH)D serum concentration was associated with disease activity categorized in 5 continuous groups of SLEDAI. 25(OH)D serum concentrations were higher among patients with SLEDAI 1–5 and lower in those with severe activity (SLEDAI≥20) (p <0.05). On the other hand, no statistically significant difference was observed for DBP, free and bioavailable vitamin D measurements in the disease activity subgroups evaluated. Vitamin D deficiency is highly prevalent among patients with SLE and was associated with higher disease activity. DBP serum level and calculation of free and bioavailable vitamin D were not associated with SLE disease activity.

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“…However, its contribution to MS susceptibility is yet to be established, as studies inspecting this contribution have reported inconsistent results. The serum levels of DBP and calcitriol do not differ between patients and healthy controls, thus denying serum levels of bioavailable metabolite of vitamin D as a risk factor for MS. 19 Another study, denied the association between DBP serum levels and MS susceptibility/activity, as no differences were observed in DBP concentrations among subjects (RRMS patients in relapse/remission phase) and healthy controls. 20 Yet another study has reported DBP in MS patients to be of a higher serum level compared with healthy controls.…”

Section: Cyp24a1 Cyp27b1 Dbp and Vdr Genesmentioning

confidence: 99%

Protective and Risk Factors in Multiple Sclerosis

et al. 2019

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Introduction Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system (CNS). Damage to myelin proteins occurs during MS progression and relapse. Over 2 million people suffer from the consequences of pathological mechanisms which MS involves, monocular visual loss, limb weakness/sensory loss, diplopia (double vision) and ataxia resulting from optic neuritis, transverse myelitis, brainstem dysfunction, and cerebellar lesions being among them. 1 Based on the disease course, MS patients can be divided into four main types: I) Relapsing-remitting MS (RRMS), which is by far the most common type, affecting about 85% of MS patients; II) Secondary progressive MS (SPMS), which may progress in patients with relapsingremitting MS; III) Primary progressive MS (PPMS); and IV) Progressive-relapsing MS (PRMS). 2 A recently detected subtype of the disease described as "myelocortical MS" argues against the idea that neural degeneration necessarily occurs following demyelination. In patients with myelocortical MS, demyelinated lesions in cerebral white matter were not observed. Similar to typical MS courses, however, the mean cortical neuronal densities were significantly lower than those of the healthy controls. 3 These new findings will further improve the diagnoses and treatments utilized in MS patients. Genetic Factors Human Leukocyte Antigen and microRNAs Genes The human leukocyte antigen (HLA)-DRB1 gene explains up to 10.5% of the genetic variance underlying risk. 4 HLA-DRB1*15:01 allele has the strongest association with increased MS risk among genetic risk factors and has been consistently associated with MS susceptibility in approximately all populations studied, pointing to a specific antigen presentation as the pathogenic mechanism. Based on previous studies, the association between MS and the HLA-DR15 haplotype (HLA-DRB1*15:01 allele and the alleles in linkage disequilibrium with it; HLA-DQB1*0602 and HLA-DQA1*0102) has been shown throughout both European and non-European populations, 5 except in Sardinian individuals, among whom MS susceptibility has been reported to be associated with HLA-DR4 (DRB1*0405, DQA1*0301, DQB1*0302) instead of HLA-DR15. 5-7 The association between HLA-DR2 and MS has been observed mostly among northern European populations. 8 A single vitamin D response element was identified in the HLA-DRB1 promoter region, advancing the idea of an interaction between vitamin D and HLA-DRB1. The role of this interaction in disease etiology has not been elucidated yet, but it can be hypothesized that a lack of vitamin D in early childhood can alter the expression levels of HLA

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Low 25‐hydroxyvitamin D, but not the bioavailable fraction of 25‐hydroxyvitamin D, is a risk factor for multiple sclerosis

Cited by 55 publications

References 33 publications

Vitamin D and Disease Severity in Multiple Sclerosis—Baseline Data From the Randomized Controlled Trial (EVIDIMS)

Vitamin D and Disease Severity in Multiple Sclerosis—Baseline Data From the Randomized Controlled Trial (EVIDIMS)

25-Hydroxivitamin D Serum Concentration, Not Free and Bioavailable Vitamin D, Is Associated with Disease Activity in Systemic Lupus Erythematosus Patients

Protective and Risk Factors in Multiple Sclerosis

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