Effects of Vitamin D on Epigenetics, Seasonality, and Management of Rheumatoid Arthritis
Abstract
Background and Objectives: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which persistent synovial inflammation and joint damage are influenced not only by immune dysregulation but also by environmental, genetic, and epigenetic factors. Vitamin D is a secosteroid hormone and has emerged as a key immunomodulatory hormone, with reported effects on innate and adaptive immune responses, with potential relevance to RA clinical activity and treatment. This narrative review synthesizes mechanistic and clinical evidence enlightening vitamin D's immunomodulatory role in RA pathogenesis and management. Methods: A comprehensive literature search was carried out on PubMed and MEDLINE databases using Medical Subject Headings (MeSH) terms: "Vitamin D", "Cholecalciferol", "Arthritis, Rheumatoid", "Seasons", "Epigenomics", "DNA Methylation", and "Therapy". The narrative review highlights evidence published mainly in the last 5 years on the link between vitamin D and RA, focusing on epigenetic interactions, circannual rhythms, and therapeutic implications. Results: Emerging data suggest that vitamin D-related epigenetic mechanisms (e.g., DNA methylation, histone acetylation, and microRNA regulation) and genetic polymorphisms have been associated with disease susceptibility and treatment outcomes. Latitude and seasonal fluctuations in serum 25-hydroxyvitamin D levels correlate with variations in RA disease activity, although results remain heterogeneous across studies.…
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