People with Multiple Sclerosis have blunted responses to Vitamin D supplementation - Jan 2024

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Transcriptomics identifies blunted immunomodulatory effects of vitamin D in people with multiple sclerosis

Scientific Reports Vol 14, Article number: 1436 (2024) https://doi.org/10.1038/s41598-024-51779-0
Wei Z. Yeh, Rodney Lea, Jim Stankovich, Sandeep Sampangi, Louise Laverick, Anneke Van der Walt, Vilija Jokubaitis, Melissa Gresle & Helmut Butzkueven

Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). However, the immune effects of vitamin D in people with MS are not well understood. We analyzed transcriptomic datasets generated by RNA sequencing of immune cell subsets (CD4+, CD8+ T cells, B cells, monocytes) from 33 healthy controls and 33 untreated MS cases. We utilized a traditional bioinformatic pipeline and weighted gene co-expression network analysis (WGCNA) to determine genes and pathways correlated with endogenous vitamin D. In controls, CD4+ and CD8+ T cells had 1079 and 1188 genes, respectively, whose expressions were correlated with plasma 25-hydroxyvitamin D level (P < 0.05). Functional enrichment analysis identified association with TNF-alpha and MAPK signaling. In CD4+ T cells of controls, vitamin D level was associated with expression levels of several genes proximal to multiple sclerosis risk loci (P = 0.01). Genes differentially associated with endogenous vitamin D by case–control status were enriched in TNF-alpha signaling via NF-κB. WGCNA suggested a blunted response to vitamin D in cases relative to controls. Collectively, our findings provide further evidence for the immune effects of vitamin D, and demonstrate a differential immune response to vitamin D in cases relative to controls, highlighting a possible mechanism contributing to MS pathophysiology.
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Strange that studies have not tried activating the VDR in people with MS

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VitaminDWiki - Vitamin D Receptor activation can be increased in many ways

Resveratrol,  Omega-3,  Magnesium,  Zinc,   Quercetin,   non-daily Vit D,  Curcumin,   Berberine,  intense exercise, Butyrate   Sulforaphane   Ginger,   Essential oils, etc  Note: The founder of VitaminDWiki uses 10 of the 16 known VDR activators