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Chromatin changes after long term vitamin D supplementation

ABSTRACT: In this study, we investigate the long-term in vivo modulation of the human epigenome following vitamin D₃ supplementation. Specifically, we analyse epigenetic changes in peripheral blood mononuclear cells (PBMCs) collected 84 days after administration of a single bolus dose of vitamin D₃ (1,000 IU/kg). Vitamin D is a well-known regulator of gene expression through the vitamin D receptor (VDR), which interacts with chromatin and modulates the epigenetic landscape of immune cells. However, the persistence and extent of these epigenomic effects in vivo remain insufficiently characterized.To address this question, we assess genome-wide epigenetic alterations in PBMCs to determine whether a single high dose of vitamin D₃ induces sustained modifications in regulatory regions associated with immune function and cellular signalling pathways. The study focuses on identifying changes in chromatin accessibility and regulatory element activity that may reflect long-lasting transcriptional priming of immune cells. This work represents a continuation of the VitDPAS study, which previously examined the immediate molecular responses to vitamin D₃ supplementation. By extending the analysis to the 84-day time point, the present study aims to determine whether the epigenetic effects of vitamin D₃ persist over the long term and contribute to prolonged immune modulation. Understanding these sustained epigenomic changes may provide new insights into the mechanisms through which vitamin D influences immune regulation and long-term health outcomes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE322656 | GEO | 2026/03/06

REPOSITORIES: GEO

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Project description:Background: In addition to its canonical functions, vitamin D has been proposed to be an important mediator of the immune system. Despite ample sunshine, vitamin D deficiency is prevalent (> 80%) in the Middle East, resulting in a high rate of supplementation. However, the underlying molecular mechanisms of the specific regimen and potential factors affecting an individual’s response to vitamin D are not well characterized. Objective: To characterize changes in blood transcriptomic and the potential mechanisms associated with vitamin D3 supplementation and response. Design: In this intervention study, one hundred vitamin D-deficient women were given a weekly oral dose (50,000 IU) of vitamin D3 for three months. A high-throughput targeted PCR, composed of 264 genes representing important blood transcriptomic fingerprints in health and disease states, was performed on pre- and post-supplementation blood samples to profile the molecular response to vitamin D3. Multivariate, network, gene ontology, and literature mining analyses were used for the interpretation of the transcriptomic profiling results. Results: We identified 54 differentially expressed genes that were strongly modulated by vitamin D3 supplementation. Network analyses showed significant changes in the immune-related pathways such as TLR4/CD14 and IFN receptors, and catabolic processes related to NFkB, which were subsequently confirmed by gene ontology enrichment analyses. We proposed a model for vitamin D3 response, using the reduced expression of the molecules involved and the receptor-mediated intra-cellular signaling leading to reduce cytokine production. Conclusions: Blood-transcriptomic profiles of vitamin D3 response were generated using a targeted blood gene panel. Vitamin D has a strong effect on the immune system, G-coupled protein receptor signaling, and the ubiquitin system. We highlighted the major molecular changes and biological processes induced by vitamin D3, which will help to further investigate the effectiveness of vitamin D supplementation among individuals in the Middle East.

Project description:Folate, and its synthetic form folic acid, function as donor of one-carbon units and have been, together with other B-vitamins, implicated in programming of epigenetic processes such as DNA methylation during early development. To what extent regulation of DNA methylation can be altered via B-vitamins later in life, and how this relates to health and disease, is not exactly known. The aim of this study was to identify effects of long-term supplementation with folic acid and vitamin B12 on genome-wide DNA methylation in elderly subjects. This project was part of a randomized, placebo-controlled trial on effects of supplemental intake of folic acid and vitamin B12 on bone fracture incidence (B-PROOF study). Participants with mildly elevated homocysteine levels, aged 65-75 years, were randomly assigned to take 400 µg folic acid and 500 µg vitamin B12 per day or a placebo during an intervention period of two years. DNA was isolated from buffy coats, collected before and after intervention, and genome-wide DNA methylation was determined in 87 participants (n=44 folic acid/vitamin B12, n=43 placebo) using the Infinium HumanMethylation450 BeadChip. After intervention with folic acid and vitamin B12, 162 (versus 14 in the placebo group) of the 431,312 positions were differentially methylated as compared to baseline. Comparisons of the DNA methylation changes in the participants receiving folic acid and vitamin B12 versus placebo, revealed one single differentially methylated position (cg19380919) with a borderline statistical significance. However, based on the analyses of differentially methylated regions (DMRs) consisting of multiple positions, we identified 6 regions that differed statistically significantly between the intervention and placebo group. Pronounced changes were found for regions in the DIRAS3, ARMC8 and NODAL genes, implicated in carcinogenesis and early embryonic development. Furthermore, serum levels of folate and vitamin B12 or plasma homocysteine were related to DNA methylation of 173, 425 and 11 regions, respectively. Interestingly, for several members of the developmental HOX genes, DNA methylation was related to serum levels of folate. Long-term supplementation with folic acid and vitamin B12 in elderly subjects resulted in effects on DNA methylation of several genes, among which genes implicated in developmental processes.

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Chromatin changes after long term vitamin D supplementation

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