Without vitamin D, only 10–15% of dietary calcium and about 60% of phosphorus are absorbed. 1,25(OH)2D stimulates intestinal calcium absorption. However, 25(OH)D requires a further hydroxylation in the kidneys by the 25(OH)D-1-OHase (CYP27B1) to form the biologically active form of vitamin D 1,25(OH)2D. Vitamin D that comes from the skin or diet is biologically inert and requires its first hydroxylation in the liver by the vitamin D-25-hydroxylase (25-OHase) to 25(OH)D. Vitamin D (D represents D 2, or D 3, or both) that is ingested is incorporated into chylomicrons, which are absorbed into the lymphatic system and enter the venous blood. Human beings do not make vitamin D 2, and most oil-rich fish such as salmon, mackerel, and herring contain vitamin D 3. UVB light from the sun strikes the skin, and humans synthesize vitamin D 3, so it is the most “natural” form. Vitamin D 2 is obtained from the UV irradiation of the yeast sterol ergosterol and is found naturally in sun-exposed mushrooms. Vitamin D is unique because it can be made in the skin from exposure to sunlight. In this review, we will focus on the biology of vitamin D and summarize the mechanisms that are presumed to underlie the relationship between vitamin D and its clinical implications. A meta-analysis published in 2007 showed that vitamin D supplementation was associated with significantly reduced mortality. Many health care providers have increased their recommendations for vitamin D supplementation to at least 1000 IU. Emerging research supports the possible role of vitamin D against cancer, heart disease, fractures and falls, autoimmune diseases, influenza, type-2 diabetes, and depression. The high prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population. Black people absorb more UVB in the melanin of their skin than do white people and, therefore, require more sun exposure to produce the same amount of vitamin D. This pandemic of hypovitaminosis D can mainly be attributed to lifestyle and environmental factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin. An estimated 1 billion people worldwide, across all ethnicities and age groups, have a vitamin D deficiency (VDD). Vitamin D insufficiency affects almost 50% of the population worldwide. In this review, we will summarize the mechanisms that are presumed to underlie the relationship between vitamin D and understand its biology and clinical implications. Treatment with either vitamin D2 or vitamin D3 is recommended for deficient patients. It is also suggested to measure the serum 25-hydroxyvitamin D level as the initial diagnostic test in patients at risk for deficiency. As few foods contain vitamin D, guidelines recommended supplementation at suggested daily intake and tolerable upper limit levels. As the number of people with VDD continues to increase, the importance of this hormone in overall health and the prevention of chronic diseases are at the forefront of research. Current studies suggest that we may need more vitamin D than presently recommended to prevent chronic disease. High prevalence of vitamin D insufficiency is a particularly important public health issue because hypovitaminosis D is an independent risk factor for total mortality in the general population. This pandemic of hypovitaminosis D can mainly be attributed to lifestyle (for example, reduced outdoor activities) and environmental (for example, air pollution) factors that reduce exposure to sunlight, which is required for ultraviolet-B (UVB)-induced vitamin D production in the skin.
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