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Old 03-11-2020, 12:36 PM
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Default High-dose vitamin D may be associated with MS worsening

This preliminary study (a poster session) found that in a mouse model, excessive vitamin D actually made the disease worse. “High-dose, long-term vitamin D supplementation lead to much worse disease in these mice,” said the lead author. Discuss with your neurologist the amount you should be taking. -D

High Dose Vitamin D Worsens Experimental CNS Autoimmune Disease By Raising T Cell-excitatory Calcium

S. Torke, D. Häusler, et al

Background: As low serum vitamin D has been associated with higher relapse rate and earlier disability in multiple sclerosis (MS), patients are commonly supplemented with the vitamin D precursor cholecalciferol. To model consequences of this practice, we tested long-term vitamin D supplementation at distinct doses in experimental autoimmune encephalomyelitis (EAE), the animal model of MS.

Objectives: The assess the effects of long-term high dose vitamin D supplementation on EAE severity and activation of the peripheral immune system.

Methods: Mice were fed continuously with a low, medium or high cholecalciferol diet to generate serum levels of 25-(OH) vitamin D representing vitamin D deficiency, normal ranges, or its excessive supplementation in MS followed by immunization with myelin oligodendrocyte glycoprotein (MOG) p35-55. Clinical symptoms were monitored, central nervous system (CNS) infiltration quantified and peripheral T cells / myeloid APCs phenotypically analyzed for expression of activation markers, co-stimulatory molecules and secretion of cytokines.

Results: Compared to vitamin D-deprived mice, its moderate supplementation reduced the severity of subsequent EAE, which was associated with an expansion of regulatory T cells. Direct exposure of murine or human T cells to vitamin D metabolites inhibited their activation. In contrast, mice with 25-(OH) vitamin D levels above 200 nmol/L developed fulminant EAE with massive CNS infiltration of activated myeloid cells, Th1 and Th17 cells. When dissecting this unexpected outcome, we observed that high, but not medium dose vitamin D had caused mild hypercalcemia associated with a T cell phenotype prone to pro-inflammatory activation. Raising murine serum calcium level by calcium gluconate injections resulted in increased expression of activation markers on CD4+ and CD8+ T cells confirming that this effect occurs in vivo independent of vitamin D. Exposing murine or human T cells to equivalent calcium concentrations in vitro enhanced its influx, triggering activation, upregulation of pro-inflammatory gene products and enhanced transmigration across a blood-brain barrier model.

Conclusions: These findings highlight excessive vitamin D supplementation and resulting hypercalcemia as novel risk factors promoting worsening of CNS demyelinating disease. Our data caution that in light of the currently limited information on a direct beneficial effect of vitamin D in MS, MS patients may be at danger of experiencing untoward immunological and/or clinical effects when vitamin D is supplemented excessively.

Here is a good article breaking this down in English:
https://multiplesclerosisnewstoday.c...ms-early-study
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