High dose vitamin D exacerbates central nervous system autoimmunity by raising T-cell excitatory calcium

Häusler, Darius; Torke, Sebastian; Peelen, Evelyn; Bertsch, Thomas; Djukic, Marija; Nau, Roland; Larochelle, Catherine; Zamvil, Scott S.; Brück, Wolfgang; Weber, Martin

doi:10.1093/brain/awz190

Cited by 45 publications

(39 citation statements)

References 74 publications

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“…Vitamin D is a neurosteroid hormone that affects various diseases, including stroke, cardiovascular disease, and multiple sclerosis. [8][9][10][11] Clinical studies show that low vitamin D levels are common in stroke patients due to reduced vitamin D intake, a lack of outdoor exercise, and decreased physiological synthesis. 8,[12][13][14] Furthermore, vitamin D has anti-inflammatory properties and low vitamin D levels may lead to increased inflammatory activity.…”

Section: Introductionmentioning

confidence: 99%

<p>Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke</p>

Huang

Cheng

et al. 2019

CIA

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Background and aim: Stroke-associated pneumonia (SAP) is a common complication in patients with acute ischemic stroke (AIS). This study explored the potential relationship between serum vitamin D levels and SAP. Methods: This study recruited 863 consecutive AIS patients. In-hospital SAP was defined as a complication that occurred after stroke, during hospitalization, that was confirmed radiographically. Serum vitamin D levels were measured within 24 hrs of admission and the patients were divided into vitamin D sufficient (>50 nmol/L), insufficient (25-50 nmol/L), and deficient (<25 nmol/L) groups. Results: In this study, 102 (11.8%) patients were diagnosed with SAP. Compared to the patients without SAP, patients with SAP had significantly lower vitamin D levels (P = 0.023). The incidence of SAP was significantly higher in patients with vitamin D deficiency than in those with vitamin D insufficiency or sufficiency (21.2% vs 16.2% & 9.5%, P = 0.006). After adjusting for confounders, vitamin D deficiency and insufficiency were independently associated with SAP (OR = 3.034, 95% CI = 1.207-7.625, P = 0.018; OR = 1.921, 95% CI = 1.204-3.066, P = 0.006, respectively). In multiple-adjusted spline regression, vitamin D levels showed a linear association with the risk of SAP (P < 0.001 for linearity). Conclusion: Reduced vitamin D is a potential risk factor of in-hospital SAP, which can help clinicians identify high-risk SAP patients.

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Section: Introductionmentioning

confidence: 99%

<p>Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke</p>

Huang

Cheng

et al. 2019

CIA

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“…A previous study could show a remarkable overlap of EBNA2 with VDR binding sites and thereby demonstrates a genetic argument for an interaction between genetic and environmental risk factors of MS [124]. A current study reports that long-term supplementation for several months with high doses of cholecalciferol results in a significantly promoted aggravation of clinical and histological EAE, but simultaneously they find a direct, anti-inflammatory, beneficial effect of vitamin D on lymphocytes of human and murine origin [125].…”

Section: Multiple Sclerosismentioning

confidence: 58%

The Effects of Vitamin D Deficiency on Neurodegenerative Diseases

Lauer¹,

Janitschke²,

Hartmann³

et al. 2020

Vitamin D Deficiency

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Approximately 90% of the elderly population in the western countries has at least a mild to moderate vitamin D hypovitaminosis. Besides the well-known function of vitamin D in calcium homeostasis, it has been recently found that several enzymes and receptors involved in its homeostasis are expressed in the nervous system and brain suggesting also an important role in the brain homeostasis. Interestingly, epidemiological and clinical studies found reduced vitamin D level associated with an increased risk of several neurodegenerative disorders. In this chapter, we focus on a potential link between vitamin D and Alzheimer's disease, Parkinson's disease, multiple sclerosis, prion disease, and motor neuron disease. Epidemiological studies were summarized, an overview of the known potential underlying pathomolecular mechanisms are given, and results from clinical studies dealing with vitamin D supplementation were presented. As an outlook, recent literature suggesting an impact of vitamin D on autism spectrum disease, depression, and schizophrenia are briefly discussed. In conclusion, the identification of an abundant vitamin D metabolism in the brain and the tight link between the increasing number of several neurological and mental disorders emphasize the need of further research making a clear recommendation of the intake and supplementation of vitamin D in a growing elderly population.

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“…The exposure of B cells to 1,25(OH) 2 D 3 inhibited their proliferation, plasma cell differentiation including immunoglobulin G and -M secretion, memory B cell generation and induced B cell apoptosis in proliferating B cells [26,27]. These findings, however, are challenged by a recent report which suggests that vitamin D at moderate levels may exert a direct immunoregulatory effect, while continuous high-dose vitamin D treatment might exacerbate clinical disease activity by raising levels of T-cell-excitatory calcium [28].…”

Section: Effects Of Vitamin D On the Immune Systemmentioning

confidence: 99%

Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats

et al. 2020

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Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in several clinical trials, since hypovitaminosis D was linked to higher disease activity and may even play a role in long-term outcome. Here, we review the current understanding of the molecular effects of vitamin D beyond calcium homeostasis, the potential beneficial action in MS and hazards including complications of chronic and high-dose therapy. In clinical trials, doses of up to 40,000 IU/day were tested and appeared safe as add-on therapy for short-term periods. A recent meta-analysis of a randomized, double-blind, placebo-controlled clinical trial investigating vitamin D as add-on therapy in MS, however, suggested that vitamin D had no therapeutic effect on disability or relapse rate. We recognize a knowledge gap for chronic and high-dose therapy, which can lead to life-threatening complications related to vitamin D toxicity including renal failure, cardiac arrythmia and status epilepticus. Moreover, vitamin D toxicity may manifest as fatigue, muscle weakness or urinary dysfunction, which may mimic the natural course of progressive MS. Given these limitations, vitamin D supplementation in MS is a sensitive task which needs to be supervised by physicians. While there is strong evidence for vitamin D deficiency and the development of MS, the risk-benefit profile of dosage and duration of add-on supplementation needs to be further clarified.

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High dose vitamin D exacerbates central nervous system autoimmunity by raising T-cell excitatory calcium

Cited by 45 publications

References 74 publications

<p>Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke</p>

<p>Reduced Vitamin D Levels are Associated with Stroke-Associated Pneumonia in Patients with Acute Ischemic Stroke</p>

The Effects of Vitamin D Deficiency on Neurodegenerative Diseases

Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats

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