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

Abstract

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.

Nutrition, Epigenetics, and Major Depressive Disorder: Understanding the Connection

“…For its part, vitamin D deficiency is one of the most repeated manifestations in MDD ( 145 ), and the reasons are not only subjacent an insufficient dietary intake but also an insufficient outdoor exposure to sunshine ( 80 ). The clinical relevance of these observations is known, thanks to preclinical models that have identified their immunomodulator and neuromodulator roles, with protective effects for oxidative stress as well ( 146 ). It is known that vitamin D is key for the proper development of dopaminergic neurons and the expression of GDNF ( 147 ), and now many vitamin D receptors (VDRs) are found in the substantia nigra, where the enzyme 1α-hydroxylase (CYP27B1) converts it to its active form ( 148 , 149 ).…”

Vitamin D Deficiency, Osteoporosis and Effect on Autoimmune Diseases and Hematopoiesis: A Review

“…In fact, the VD system is controlled by epigenetic mechanisms, but, on the other hand, it is implicated in controlling epigenetic events [226]. Similarly, other studies will be needed to better define the effects of VD in maintaining mitochondrial respiratory functions [234,235] and in the control of normal homeostasis that guarantees well-being.…”

Epigenetic Aspects and Prospects in Autoimmune Hepatitis

“…Interventions that affect target recognition by pivotal miRNAs have involved engineered molecules that mask the chosen gene product or substitute a decoy (251)(252)(253)(254)(255)(256). Interventions that stabilize the epigenome have included riskreduction, lifestyle modifications (19,34,257) and dietary supplementation with S-adenosylmethionine (258,259), methyl group donors (260,261), vitamin C (122), or vitamin D (262)(263)(264)(265)(266)(267). The major concerns have been the lack of target selectivity and the uncertain risk of deleterious off-target consequences (19,43).…”

“…Dietary supplements have also been described in experimental animals that enhance the supply of methyl groups (S-adenosylmethionine, diverse methyl donors) ( 258 – 261 ), activate the TET enzymes that de-methylate DNA (vitamin C) ( 122 ), and alter the transcription of mRNAs that promote hepatic fibrosis (vitamin D) ( 262 – 267 ) ( Table 5 ). S-adenosylmethionine has inhibited demethylase activity and preserved DNA methylation in cell lines ( 258 , 259 ).…”

“…1, 25-dihydroxyvitamin D has repressed the transcription of mRNAs for TGF-β and tissue inhibitors of metalloproteinases (TIMP). It has also up-regulated the transcription of metalloproteinases and prevented progressive hepatic fibrosis ( 262 – 267 ). These promising pre-clinical experiences await validation in randomized clinical trials that define their utility in specific diseases ( 259 ).…”