{ "abstract": "Vitamin D–Vitamin D receptor (VDR) signaling extends beyond calcium-phosphate homeostasis and regulates immune tolerance, inflammation, cellular differentiation, oxidative stress, and endocrine physiology. This systematic review evaluated the relationship between vitamin D–VDR signaling and thyroid disorders, including hypothyroidism, hyperthyroidism, Hashimoto’s thyroiditis, Graves’ disease, thyroid autoimmunity, genetic susceptibility, experimental mechanisms, and therapeutic implications. This study was conducted and reported in accordance with the PRISMA 2020 statement. PubMed/MEDLINE and Scopus were searched for studies published from January 2005 through June 2026, supplemented by backward and forward citation screening of relevant studies and reviews. Eligible evidence included human observational and interventional studies, genetic investigations, and relevant animal and in vitro studies addressing vitamin D status, vitamin D exposure or supplementation, VDR variation, vitamin D metabolism, or vitamin D–VDR mechanisms in relation to thyroid function, thyroid disease, thyroid autoantibodies, or related biological outcomes. A total of 13,623 records were identified, of which 11,730 unique records underwent title and abstract screening, 449 reports were assessed at the full-text stage, and 118 primary studies were included in the final synthesis. Because of substantial heterogeneity in populations, study designs, vitamin D exposures, outcomes, genetic backgrounds, and experimental models, findings were synthesized narratively rather than by quantitative meta-analysis. Lower circulating 25-hydroxyvitamin D [25(OH)D] concentrations were frequently associated with thyroid disease, particularly autoimmune phenotypes, and increased thyroid peroxidase and thyroglobulin antibodies in Hashimoto’s thyroiditis. Interventional evidence suggests that vitamin D supplementation may reduce thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) concentrations in some patients with autoimmune thyroid disease. However, these laboratory changes represent immunological surrogate outcomes and should not be interpreted as evidence of restored thyroid function, prevention of progression to overt hypothyroidism, reduced dependence on thyroid hormone replacement, or sustained clinical remission. Randomized evidence does not establish a general preventive effect of vitamin D supplementation on incident hypothyroidism. Associations between VDR polymorphisms, including FokI/rs2228570, rs1544410, rs731236, and rs7975232, and thyroid autoimmunity were inconsistent across populations. Experimental evidence implicates immune regulation, Th17/Treg balance, inflammatory signaling, vitamin D metabolism, and calcium-phosphate homeostasis. The evidence was limited by substantial clinical, methodological, and biological heterogeneity, frequent reliance on observational studies, population-specific genetic findings, and differences between experimental models and human thyroid physiology. Overall, vitamin D–VDR signaling represents a biologically plausible modifier of thyroid disease, but current evidence does not establish universal causality or therapeutic efficacy.", "abstract_shown": true, "affiliations": [ "Department of Pharmacology, RAK College of Medical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates", "A. J. Hospital and Research Centre, A. J. Institute of Hospital Management, Mangalore 575004, India", "Department of Pathological Sciences, College of Medicine, Ajman University, Ajman 346, United Arab Emirates", "Faculty of Medicine, Manipal University College Malaysia, Melaka 75150, Malaysia", "Manipal College of Health Professions, Manipal Academy of Higher Education, Manipal 576104, India", "RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates", "Department of Pharmacology, Alva’s Institute of Medical Science and Research Centre, Moodbidri 574227, India" ], "article_type": "review article", "arxiv": null, "author_total": 16, "authors": [ { "affs": [ 0 ], "name": "Shakta Mani Satyam", "orcid": "0000-0001-5761-2073" }, { "affs": [ 0 ], "name": "Murk Jai Pal Paryani", "orcid": "0009-0008-8562-4096" }, { "affs": [ 0 ], "name": "Ilmia Shameer", "orcid": "0009-0002-2078-3308" }, { "affs": [ 0 ], "name": "Shams Al-dawoodi", "orcid": "0009-0006-6083-2193" }, { "affs": [ 0 ], "name": "Ebrahim Safaii", "orcid": "0009-0005-9945-1307" }, { "affs": [ 1 ], "name": "Rashmi Kumari", "orcid": "0009-0009-4564-3388" }, { "affs": [ 2 ], "name": "Abdul Rehman" }, { "affs": [ 0 ], "name": "Hussein Saleh" }, { "affs": [ 3 ], "name": "Prakashchandra Shetty", "orcid": "0000-0001-9277-4414" }, { "affs": [ 4 ], "name": "Sainath Prabhakar", "orcid": "0000-0002-9919-4444" }, { "affs": [ 5 ], "name": "Bhoomendra Bhongade", "orcid": "0000-0002-4057-7125" }, { "affs": [ 6 ], "name": "Laxminarayana Kurady Bairy", "orcid": "0000-0002-1828-6946" }, { "affs": [ 0 ], "name": "Afnan Afroz" }, { "affs": [ 0 ], "name": "Manasvi Udaya Kumar", "orcid": "0009-0001-2092-9576" }, { "affs": [ 0 ], "name": "Karthik Nair" }, { "affs": [ 0 ], "name": "Anuradha Asokan Nair", "orcid": "0009-0008-6049-5080" } ], "bibtex": "https://research.draconitic.com/paper/2amh4yft785vr.bib", "cited_by": 0, "doi": "10.3390/biom16101532", "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702144/?tool=EBI", "id": "2amh4yft785vr", "issns": [ "2218-273X" ], "landing_url": "https://www.mdpi.com/2218-273X/16/10/1532", "language": "eng", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2734|Vitamin D Research Studies" ] ], "openalex": "W7223037519", "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702144/pdf/?tool=EBI", "pmcid": "PMC13702144", "pmid": null, "published": "2026-10-01", "publisher": "MDPI AG", "ris": "https://research.draconitic.com/paper/2amh4yft785vr.ris", "sources": [ { "first_seen": "2026-10-30T12:18:59Z", "native_id": "10.3390/biom16101532", "source": "crossref", "url": "https://www.mdpi.com/2218-273X/16/10/1532" }, { "first_seen": "2026-10-30T12:21:45Z", "native_id": "PMC:PMC13702144", "source": "europepmc", "url": "https://europepmc.org/article/PMC/PMC13702144" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2734|Vitamin D Research Studies", "subfield": "general" } ], "title": "Vitamin D–VDR Signaling Across Thyroid Disorders: A Systematic Review of Molecular Mechanisms, Autoimmunity, Genetic Susceptibility, Experimental Evidence and Therapeutic Translation", "title_text": "Vitamin D–VDR Signaling Across Thyroid Disorders: A Systematic Review of Molecular Mechanisms, Autoimmunity, Genetic Susceptibility, Experimental Evidence and Therapeutic Translation", "type": "peer-reviewed", "updated_at": "2026-10-30T12:21:45Z", "url": "https://research.draconitic.com/paper/2amh4yft785vr", "venue": "Biomolecules", "versions": [] }