Vitamin D: a Review of its Effects on Epigenetics and Gene Regulation

Vitamin D is a secosteroid hormone with known beneficial effects on several body systems other than the musculoskeletal system. Both 25 dihydroxy vitamin D [25(OH)2D] and its active hormonal form, 1,25-dihydroxyvitamin D [1,25(OH)2D] are essential for hu-man physiological functions, including damping down inflammation and the excessive intracellular oxidative stresses. In the present study we set out to review all available literature on vitamin D and the role it plays in epigenetics and gene regulation. We searched the PubMed/Medline electronic database for studies published in the English language up to January 2020. The Medical Subject Headings (MeSH) database was searched with the keywords 'vitamin D', 'DNA methylation', 'nutritional supplements', 'epigenome' and 'pregnancy'. Observational studies, supplementation studies, and meta-analyses dealing with the effect of vitamin D on epigenetics and gene regula-tion were included in the review. The obtained information from the databases such as PubMed, Google Scholar, and ResearchGate was analysed and summarized. We found that hypovitaminosis D increases the incidence and severity of several age-related common diseases such as the oxidative stress-associated metabolic disorders. These include obesity, insulin resistance, type 2 diabetes, hypertension, pregnancy complications, memory disorders, osteoporosis, autoimmune diseases, certain cancers, and systemic inflammatory diseases. New understandings of vitamin D-related advances in metabolomics, transcriptomics, epigenetics, in relation to its ability to control oxidative stress in conjunc-tion with micronutrients, vitamins, and antioxidants, following normalization of serum 25(OH)D and tissue 1,25(OH)2D concentra-tions, are likely to promise better cost-effective clinical outcomes in humans. There is a strong reciprocity between the vitamin D system and epigenetic mechanisms. The vitamin D system is, on the one hand regu-lated by epigenetic mechanisms and, on the other hand, is involved in regulating epigenetic events.