Modulation of Peripheral Immune Cells Following Vitamin D 3 Supplementation in Vitamin D-Insufficient Cancer Patients - Article

Sep 30, 2026

Uploaded by dhado

Low vitamin D3 levels are common in cancer patients, and vitamin D3 normalization may work alongside conventional oncology treatment. This study evaluated molecular effects of moderate-to-high dose vitamin D3 supplementation in vitamin D-deficient patients. Eight patients received 30,000 IU weekly for two months, with blood analysis before and after treatment. Improvements were observed in DNA integrity and mononuclear-cell telomere length, alongside immune and chromatin changes detected by ATAC-Seq. No significant shifts were found in cfDNA levels or global DNA methylation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Introduction

Background on vitamin D and immune regulation

Abstract and study overview

Article Modulation of Peripheral Immune Cells Following Vitamin D 3 Supplementation in Vitamin D-Insufficient Cancer Patients Alexandra Kalmar 1, Zsofia Brigitta Nagy 1, Liza Dalma Sumegi 1, Barbara Kinga Bartak 1, Csaba Kiss 2,3, Sandor Spisak 2, Bela Molnar 1 and Istvan Takacs 1, * Academic Editor: Carol Johnston Received: 14 November 2025 Revised: 20 December 2025 Accepted: 24 December 2025 Published: 29 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Internal Medicine and Oncology, Semmelweis University, 1083 Budapest, Hungary; [kalmar.sopkez.alexandra@semmelweis.hu](kalmar.sopkez.alexandra@semmelweis.hu) (A.K.); [nagy.zsofia@semmelweis.hu](nagy.zsofia@semmelweis.hu) (Z.B.N.); [sumegi.liza.dalma@semmelweis.hu](sumegi.liza.dalma@semmelweis.hu) (L.D.S.); [molnar.barbara.kinga@semmelweis.hu](molnar.barbara.kinga@semmelweis.hu) (B.K.B.); [molnar.bela@semmelweis.hu](molnar.bela@semmelweis.hu) (B.M.) 2 Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary; [kiss.csaba1173@gmail.com](kiss.csaba1173@gmail.com) (C.K.); [spisak.sandor@ttk.hu](spisak.sandor@ttk.hu) (S.S.) 3 Doctoral School of Biology, Eötvös Loránd University, 1117 Budapest, Hungary * Correspondence: [takacs.istvan@semmelweis.hu](takacs.istvan@semmelweis.hu) Abstract Background and aims: Low vitamin D3 levels are common in cancer patients, and these patients might benefit from vitamin D 3 level normalization in parallel with the conventional oncology treatment. This study aimed to examine the molecular effects of moderate–highdose vitamin D3 supplementation in vitamin D-deficient cancer patients. Methods: Eight patients under oncological treatment (5 lung cancer, 2 colorectal cancer, and 1 urothelial carcinoma) received 30,000 IU of vitamin D 3 per week for two months. Blood samples were collected before and after supplementation, and peripheral blood mononuclear cells (PBMCs) were isolated. With the aim of assessing further potential epigenetic alterations, global DNA methylation level was estimated on the basis of LINE-1 bisulfite-sequencing experiments on cfDNA and PBMC cells. In order to explore the chromatin accessibility alterations after the treatment in PBMCs, an assay for transposase-accessible chromatin with sequencing (ATAC-Seq) was performed using the (10x Genomics, Pleasanton, CA, USA) on a NextSeq 550 instrument using High Output Sequencing kit (Illumina, San Diego, CA, USA) . DNA integrity was assessed by the alkaline Comet-assay and telomere qPCR was also performed. Results: After serum 25-hydroxy-vitamin D levels were normalized, DNA integrity in mononuclear cells improved significantly (p = 0.01), while no significant changes were found in granulocytes. Vitamin D3 supplementation also led to significant changes in telomere length in mononuclear cells (p = 0.007) . No significant differences were observed incfDNA levels or DNA methylationin PBMCs and cfDNA after supplementation. ATAC-Seq revealed changes in PBMC composition, including an increased number of NK, pDC cells, and monocytes, especially in patients treated with Pembrolizumab in parallel with vitamin D supplementation. Conclusions: These exploratory findings suggest that the observed immune cell and chromatin changes after vitamin D 3 level normalization are compatible with immunomodulatory effects and warrant confirmation in larger, controlled cohorts. Keywords: vitamin D; cancer; ATAC-Seq; chromatin accessibility; Comet-assay; PBMC 1. Introduction Vitamin D is essential for normal immune function [1] . Upon exposure to UV-B radiation, vitamin D 3 is produced in a non-enzymatic reaction from 7-dehydrocholesterol in the skin [2] . Vitamin D must be converted into its active hormonal forms, 25-hydroxyvitamin D (25OHD) and

FAQs

What was the goal of this study in vitamin D-deficient cancer patients?

To examine molecular effects of moderate-to-high dose vitamin D3 supplementation alongside conventional cancer therapy.

How was vitamin D3 supplementation administered and for how long?

Eight patients received 30,000 IU of vitamin D3 per week for two months, with blood sampling before and after supplementation.

Which molecular or cellular outcomes changed after vitamin D3 normalization?

DNA integrity improved in mononuclear cells, telomere length changed in mononuclear cells, and ATAC-Seq showed immune composition changes in PBMCs.

Sep 30, 2026

Uploaded by dhado