"Vitamin D" is the term commonly used to denote the lipid-soluble hormone critical for calcium homeostasis and skeletal maintenance. A precursor to the active compound is found in many plants and animal tissues and can be absorbed from the gut; it can also be derived from cell membranes in the epidermis during ultraviolet B irradiation. This compound is then hydroxylated sequentially in the liver and kidney to produce the active hormone 1,25(OH)(2)D that binds its nuclear receptor to modulate gene expression. Recently, vitamin D hydroxylases and the nuclear receptor have been identified in many tissues, suggesting previously unrecognized roles for vitamin D. Some epidemiologic studies have also correlated low levels of the inactive storage form 25(OH)D with an increased incidence or prevalence of a variety of diseases, suggesting that large oral supplements and/or increased ultraviolet (UV) exposure might therefore improve individual health. However, randomized, prospective controlled trials comparing vitamin D supplements with placebo have not supported this belief. Moreover, current evidence supports the conclusion that protection from UV radiation does not compromise vitamin D status or lead to iatrogenic disease. In contrast, high vitamin D levels appear to incur a risk of kidney stones and other adverse effects. In the case of true vitamin D deficiency, supplements are a more reliable and quantifiable source of the vitamin than UV exposure.
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