Vitamin D is a group of fat-soluble prohormones which were identified after the discovery of the anti-rachitic effect of cod liver oil in the early part of the 20th
century. The vitamin found in cod liver oil was designated "D" following Vitamin A, B and C, which had been discovered earlier [1
]. The two major biologically inert precursors of vitamin D are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol) [2
]. Vitamin D3 is formed when 7-dehydrocholesterol in the skin is exposed to solar ultraviolet B (UVB, 290-320 nm), and then converted to previtamin D3. In a heat-dependent process, previtamin D3 is immediately converted to vitamin D. Excess UVB rays transform previtamin D3 into biologically inactive metabolites, tachysterol and lumisterol. Vitamin D2 is plant derived, produced exogenously by irradiation of ergosterol, and enters the circulation through diet [1
Both vitamin D precursors resulting from exposure to the sunshine and the diet are converted to 25-hydroxyvitamin D [25(OH)D] (calcidiol) when they enter the liver [4
]. 25(OH)D is the major circulating form of vitamin D and is used to determine vitamin D status. In order to be biologically active, additional hydroxylation in the kidneys is needed to form active 1,25-dihydroxyvitamin D [1,25(OH)2D] (calcitriol) [5
]. The process of vitamin D formation is summarized in Figure . Humans obtain vitamin D through dietary intake and exposure to sunlight. Very few foods naturally contain vitamin D. Oily fish such as salmon, mackerel, and sardines are rich in vitamin D3. Egg yolks are reported to contain vitamin D though the amounts are highly variable. Moreover, the cholesterol content of egg yolks makes it a poor source of vitamin D. Also, a small number of foods are fortified with vitamin D such as milk, orange juice and some bread and cereals [6
]. A list of vitamin D content in different food sources is shown in Table .
Sources, sites, and processing of vitamin D metabolites.
Vitamin D3 and D2 sources and content*
Vitamin D plays an important role in maintaining an adequate level of serum calcium and phosphorus. Without vitamin D, only 10 to 15% of dietary calcium and about 60% of phosphorus is absorbed [8
]. Therefore vitamin D has a great effect in forming and maintaining strong bones. It has also recently been found that vitamin D receptors exist in a variety of cells thus it has a biological effect on more than mineral metabolism. The aim of this report is to review key aspects relating to vitamin D deficiency, its causes, and studies on prevention of and treatment of major conditions/diseases. Thus, following a general literature review on deficiency and its causes, an overview of major meta-analyses of Vitamin D supplementation is given. This systematic approach covers meta-analyses listed in Pubmed during the past 2 decades.