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25-Hydroxyvitamin D constitutes the major circulating form of vitamin D, and the sum of 25-hydroxyvitamin D 2 and 25-hydroxyvitamin D 3 concentrations in serum is used as an indicator of vitamin D nutritional status (3). Exposure to sunlight or dietary intake of vitamin D increases serum concentrations of 25-hydroxyvitamin D. In hepatocytes (liver cells), vitamin D is hydroxylated to form 25-hydroxyvitamin D (calcidiol calcifediol).
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Indeed, following dietary intake or synthesis in the epidermis of skin after UVB exposure, both forms of vitamin D enter the circulation and are transported to the liver by the vitamin D-binding protein (and to a lesser extent by albumin).
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Function Vitamin D metabolismĬholecalciferol and ergocalciferol are biologically inactive precursors of vitamin D and must be converted to biologically active forms in the liver and kidneys ( Figure 1). When vitamin D 3 in skin is inadequate due to insufficient exposure to UVB radiation, oral intake of vitamin D is necessary to meet vitamin D requirements. Vitamin D 2 (ergocalciferol) is a vitamin D analog photosynthesized in plants, mushrooms, and yeasts vitamin D 2 is also sometimes used in vitamin D food fortification (2). While it can also be obtained from dietary sources or supplements, vitamin D 3 (cholecalciferol) is synthesized in the human skin from 7-dehydrocholesterol upon exposure to ultraviolet-B (UVB) radiation from sunlight (see the separate article on Vitamin D and Skin Health). Vitamin D is a fat-soluble vitamin that regulates calcium homeostasis and is vital for bone health (1). Preliminary studies have shown that vitamin D supplementation may offer promising improvements in the management of atopic dermatitis (eczema) and Crohn’s disease. Observational studies have documented an association between vitamin D deficiency and increased incidence and severity of the coronavirus disease, COVID-19. Safety and benefits of vitamin D supplementation during pregnancy both need to be evaluated in clinical trials. Vitamin D insufficiency in pregnant women may be associated with several adverse effects for the mother and newborn. Randomized clinical trials are currently investigating whether vitamin D supplementation can limit cognitive deterioration and disease progression in subjects with neurodegenerative disease. It is not yet known whether correcting vitamin D deficiency in individuals with glucose intolerance can decrease the risk of progression to type 2 diabetes mellitus. (More information)Ĭurrent evidence from observational studies suggests an inverse relationship between circulating vitamin D concentrations and risk of type 2 diabetes mellitus. Various observational studies have reported inverse associations between vitamin D status and the susceptibility or severity of autoimmune diseases, including type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus. Randomized controlled trials are needed to evaluate whether cancer prevention may benefit from vitamin D supplementation. Observational studies have reported associations between low sun exposure, poor vitamin D status, and increased risk of developing colorectal and breast cancer. Vitamin D can regulate cell differentiation and growth by binding to the vitamin D receptor found in most body cells.
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Randomized clinical trials indicate that supplementation with at least 800 IU/day of vitamin D may reduce the risk of falls and fractures in older individuals. Secondary hyperparathyroidism due to vitamin D insufficiency can increase bone breakdown and precipitate osteoporosis. Severe vitamin D deficiency causes rickets in children and osteomalacia in adults. Vitamin D is important for normal bone development and maintenance. Vitamin D also exhibits many non-skeletal effects, particularly on the immune, endocrine, and cardiovascular systems. Vitamin D is essential for maintenance of bone mineralization through the regulation of calcium and phosphorus homeostasis. Through binding to the vitamin D receptor (VDR), 1α,25-dihydroxyvitamin D can regulate the expression of hundreds of genes involved in skeletal and other biological functions. Vitamin D can be synthesized in the skin upon exposure to sunlight and is then metabolized in the liver and kidney to the metabolically active form called 1α,25-dihydroxyvitamin D.
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