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Vitamin D and Its Derivatives in Pharmacology: Mechanisms and Therapeutic...
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Vitamin D and Its Derivatives in Pharmacology: Mechanisms and Therapeutic Applications

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 27 August 2026 | Viewed by 8248

Special Issue Editor

Dr. Agnieszka Sliwinska

E-Mail Website
Guest Editor
Department of Nucleic Acids Biochemistry, Medical University of Lodz, 251 Pomorska Str., 92-213 Lodz, Poland
Interests: hypoglycemic drugs; insulin resistance; type 2 diabetes; obesity; cancer; oxidative stress; vitamin D; DNA damage and repair
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The enormous progress made in understanding of the molecular actions of vitamin D in recent decades—including its genomic (VDR-dependent) and non-genomic interactions with numerous intracellular signaling proteins that regulate a wide range of biological processes in many tissues and cells—has revealed its broad spectrum of effects on the entire organism. At the same time, a growing number of reports indicate that vitamin D deficiency not only adversely affects the health of the musculoskeletal system but also constitutes a significant risk factor for various health outcomes, such as cardiovascular disease, inflammation, cancer, and disorders of the immune, nervous, respiratory and reproductive systems. These observations have attracted the attention of clinical researchers and health care professionals who are currently investigating vitamin D and its derivatives for their protective and therapeutic effects. The Special Issue aims to showcase outstanding review articles covering all aspects of vitamin D and its derivatives, including their discovery, testing, analysis, approval, delivery, manufacturing and clinical applications. Submissions to this Special Issue must include a cover letter stating the novelty of the review article in comparison to related reviews published in the literature.

Dr. Agnieszka Sliwinska
Guest Editor

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • vitamin D, synthesis and metabolism
  • vitamin D derivatives
  • vitamin D deficiency related diseases
  • clinical trials on vitamin D and/or its derivatives

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Published Papers (4 papers)

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Research

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13 pages, 5736 KB  
Article
Lactobacillus rhamnosus GG Administration Is Associated with Stimulation of Vitamin D/VDR Pathway and Mucosal Microbiota Modulation in Ulcerative Colitis Patients: A Pilot Study
by Cristiano Pagnini, Manuele Gori, Maria Carla Di Paolo, Riccardo Urgesi, Claudia Cicione, Maria Zingariello, Francesca Arciprete, Viola Velardi, Elisa Viciani, Antonella Padella, Andrea Castagnetti, Maria Giovanna Graziani and Gianfranco Delle Fave
Pharmaceuticals 2025, 18(11), 1651; https://doi.org/10.3390/ph18111651 - 1 Nov 2025
Cited by 6 | Viewed by 2495
Abstract
Background: The interaction between probiotics and the vitamin D/vitamin D receptor (VDR) pathway has been increasingly explored as a potential mechanism for immune modulation in inflammatory bowel disease (IBD). Lactobacillus rhamnosus GG (LGG) has shown promising results in ulcerative colitis (UC) patients, [...] Read more.
Background: The interaction between probiotics and the vitamin D/vitamin D receptor (VDR) pathway has been increasingly explored as a potential mechanism for immune modulation in inflammatory bowel disease (IBD). Lactobacillus rhamnosus GG (LGG) has shown promising results in ulcerative colitis (UC) patients, but its effect on the VDR pathway remains unexplored in humans. Aim: To test the hypothesis that LGG can stimulate the vitamin D/VDR pathway and modulate mucosal-adherent microbiota. Methods: In this study, we analyzed a subgroup of 13 patients from the LGGinUC trial, in which UC patients with mild-to-moderate disease activity received LGG monotherapy for four weeks. Colonic biopsy samples were collected before and after treatment to evaluate VDR expression via RT-qPCR and immunohistochemistry. Mucosal-adherent microbiota was also analyzed by DNA extraction and next-generation sequencing (NGS). Results: LGG administration significantly increased VDR mRNA expression in colonic mucosa (p < 0.05), with a corresponding rise in VDR protein levels in both epithelial and sub-epithelial compartments. Microbiota analysis revealed a reduction in α-diversity, primarily due to a decrease in commensal bacterial species, while β-diversity remained largely unchanged. Conclusions: Although the present results have to be considered preliminary, this is the first human study demonstrating that probiotic supplementation can upregulate VDR expression in colonic mucosa. We propose that LGG may exert its beneficial effects in UC by stimulating the VDR pathway, which in turn modulates mucosal immunity and microbiota composition. Further studies with larger sample sizes and longer treatment durations are needed to validate these findings and explore their therapeutic implications. Full article
(This article belongs to the Special Issue Vitamin D and Its Derivatives in Pharmacology: Mechanisms and Therapeutic Applications)
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Review

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44 pages, 870 KB  
Review
Vitamin D-Related Signaling and Epigenetic Regulation: Evidence from Experimental, Observational, and Interventional Studies
by Hanna Kozłowska, Edyta Cichocka, Sylwia Barbara Górczyńska-Kosiorz and Janusz Gumprecht
Pharmaceuticals 2026, 19(6), 906; https://doi.org/10.3390/ph19060906 - 8 Jun 2026
Viewed by 327
Abstract
The active vitamin D metabolite, 1,25-dihydroxycholecalciferol [1,25(OH)2D], exerts its biological effects through binding to the vitamin D receptor (VDR), a ligand-activated transcription factor regulating the expression of genes involved in calcium and phosphate homeostasis, immune modulation, and cell proliferation and differentiation. [...] Read more.
The active vitamin D metabolite, 1,25-dihydroxycholecalciferol [1,25(OH)2D], exerts its biological effects through binding to the vitamin D receptor (VDR), a ligand-activated transcription factor regulating the expression of genes involved in calcium and phosphate homeostasis, immune modulation, and cell proliferation and differentiation. In addition to direct transcriptional regulation, 1,25(OH)2D signaling also involves epigenetic mechanisms. A total of 90 studies were included in this narrative review, comprising experimental studies (n = 45), observational studies (n = 17), population-based studies (n = 8), interventional studies (n = 15), and mixed-design studies (n = 5). Experimental studies in cell cultures and animal models demonstrate that 1,25(OH)2D may affect several major epigenetic regulatory pathways, including chromatin remodeling, DNA methylation, histone modifications, and the expression of non-coding RNAs, particularly microRNAs. Preclinical evidence suggests that the epigenetic actions of 1,25(OH)2D are involved in metabolic regulation, immune responses, bone development, fibrotic processes, carcinogenesis, ageing, and fetal programming. However, evidence from observational studies and randomized controlled trials remains limited and inconclusive. Some studies have reported alterations in miRNA expression, methylation of selected loci, and epigenetic age markers. The clinical relevance of 1,25(OH)2D–mediated epigenetic regulation has not yet been fully established. The interpretation of available findings is limited by substantial heterogeneity in study populations, exposure and intervention protocols, environmental factors, interindividual variability in response to vitamin D supplementation associated with genetic polymorphisms and methylation status, and the restricted range of analyzed cell types. This subject requires randomized controlled trials integrating molecular endpoints with clinically relevant outcomes. Full article
(This article belongs to the Special Issue Vitamin D and Its Derivatives in Pharmacology: Mechanisms and Therapeutic Applications)
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26 pages, 445 KB  
Review
Vitamin D in Endocrine Disorders: A Broad Overview of Evidence in Musculoskeletal, Thyroid, Parathyroid, and Reproductive Disorders
by Balazs Lengyel, Richard Armos, Bence Bojtor, Andras Kiss, Balint Tobias, Henriett Piko, Anett Illes, Eszter Horvath, Zsuzsanna Putz, Istvan Takacs, Janos P. Kosa and Peter Lakatos
Pharmaceuticals 2026, 19(1), 54; https://doi.org/10.3390/ph19010054 - 26 Dec 2025
Cited by 2 | Viewed by 2790
Abstract
Vitamin D is well established for its skeletal effects, being a cornerstone of several endocrine disorders. In recent years, it has come under investigation as a potential disease-modifying drug in several endocrine disorders through its immune modulatory and anti-tumorigenic action, particularly in thyroid [...] Read more.
Vitamin D is well established for its skeletal effects, being a cornerstone of several endocrine disorders. In recent years, it has come under investigation as a potential disease-modifying drug in several endocrine disorders through its immune modulatory and anti-tumorigenic action, particularly in thyroid disease, gynecologic disorders, and general fertility. Vitamin D supplementation is well established in the treatment of osteoporosis, osteomalacia, hypoparathyroidism, and primary hyperparathyroidism. In autoimmune thyroid disease, there is a negative correlation between 25(OH)D3 levels and prevalence. Currently available data are inconclusive on supplementation as a disease-modifying treatment. In Hashimoto’s thyroiditis, while some found improved thyroid function, a decline in progression, and antibody titers, these findings were not consistent, and some found no improvements. Painless postpartum thyroiditis severely lacks evidence. Interventional studies failed to demonstrate benefits in Graves’ disease. The literature consistently reports lower vitamin D levels in infertility, polycystic ovarian syndrome (PCOS), and endometriosis. In PCOS, data suggest that vitamin D supplementation is beneficial; however, results in exact benefits vary and there is no consensus on dosing. Current guidelines support supplementation as part of preconception nutritional care. In general, for female infertility and endometriosis, the results are conflicting, with a lack of high-quality evidence. The literature suggests there is a possible benefit regarding sperm motility, but not in testosterone levels for males. In conclusion, while in vitro studies and animal models are promising, the available evidence is often contradictory, with high heterogeneity in study designs and populations. Our paper highlights the need for further high-quality research to resolve current controversies. Full article
(This article belongs to the Special Issue Vitamin D and Its Derivatives in Pharmacology: Mechanisms and Therapeutic Applications)
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34 pages, 2199 KB  
Review
Vitamins A and D and Their Combinations for Breast and Colorectal Cancers: Analysis of the Clinical, Epidemiological, Preclinical and Transcriptomic Data
by Temitope O. Lawal, Bolanle A. Adeniyi and Gail B. Mahady
Pharmaceuticals 2025, 18(11), 1684; https://doi.org/10.3390/ph18111684 - 6 Nov 2025
Viewed by 2112
Abstract
Background and Objectives: Vitamins A and D have been reported to improve cancer outcomes. In this work, we reviewed recent meta-analyses, preclinical, and transcriptomics data for these vitamins and combinations for breast and colon cancers. Methods: Searches for meta-analyses, preclinical, and [...] Read more.
Background and Objectives: Vitamins A and D have been reported to improve cancer outcomes. In this work, we reviewed recent meta-analyses, preclinical, and transcriptomics data for these vitamins and combinations for breast and colon cancers. Methods: Searches for meta-analyses, preclinical, and transcriptomic data for vitamins A and D in breast and colorectal cancers were conducted using electronic databases from June 2012 to May 2025. Studies describing the effects of vitamin A and D levels (through diet, supplementation, and serum concentrations) on the risk, prognosis, metastasis, and survival rates of breast and colon cancer patients, and the doses needed to achieve these endpoints, were included. Preclinical and transcriptomics studies investigating combinations of vitamins A and D were also reviewed. Results: The reviewed studies showed an inverse correlation between vitamin A intake and the risk and survival rates of breast cancers. Sufficient vitamin D3 levels were associated with improved survival outcomes, lower tumor grades, and less ER- or triple-negative breast cancers. For colorectal cancers, meta-analyses showed conflicting results for vitamin A, but clear evidence that vitamin D reduced both risk and mortality. Preclinical and transcriptomics studies provide compelling evidence that vitamins A and D combinations may be more effective for the prevention and treatment of breast and colon cancers, due to their significant synergistic effects and the larger number of cancer-signaling pathways impacted. Conclusions: Vitamins A and D reduce breast and colorectal cancer incidence, risk and mortality through multiple mechanisms of action, and offer significant potential as therapeutic and chemopreventative agents. Full article
(This article belongs to the Special Issue Vitamin D and Its Derivatives in Pharmacology: Mechanisms and Therapeutic Applications)
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