Vitamin D from the diet or dermal synthesis is biologically inactive and requires enzymatic conversion to active metabolites. Vitamin D is converted to 25-hydroxyvitamin D, the major circulating form of vitamin D, and then to 1,25-dihydroxyvitamin D, the active form of vitamin D, by enzymes in the liver and kidney. 1,25-dihydroxyvitamin D binds to the intracellular vitamin D receptor to activate vitamin D response elements within target genes. The half-life of 1,25-dihydroxyvitamin D is four to six hours, compared with two to three weeks for 25-hydroxyvitamin D and 24 hours for parent vitamin D.
The production and metabolism of vitamin D will be reviewed here. The causes and treatment of vitamin D deficiency are reviewed elsewhere. (See "Overview of vitamin D" and "Causes of vitamin D deficiency and resistance" and "Vitamin D insufficiency and deficiency in children and adolescents" and "Vitamin D deficiency in adults: Definition, clinical manifestations, and treatment" and "Etiology and treatment of calcipenic rickets in children".)
Very few foods contain vitamin D (fatty fish livers are the exception) and dermal synthesis is the major natural source of the vitamin. Previtamin D3 is synthesized nonenzymatically in skin from 7-dehydrocholesterol during exposure to the ultraviolet rays in sunlight. Previtamin D3 undergoes a temperature dependent rearrangement to form vitamin D3 (cholecalciferol). This system is exceedingly efficient, and it is estimated that brief casual exposure of the arms and face is equivalent to ingestion of 200 International Units per day . However, the length of daily exposure required to obtain the sunlight equivalent of oral vitamin D supplementation is difficult to predict on an individual basis and varies with the skin type, latitude, season, and time of day [2,3]. Prolonged exposure of the skin to sunlight does not produce toxic amounts of vitamin D3 because of photoconversion of previtamin D3 and vitamin D3 to inactive metabolites (lumisterol, tachysterol, 5,6-transvitamin D, and suprasterol 1 and 2) [4,5]. In addition, sunlight-induces production of melanin, which reduces production of vitamin D3 in the skin.
Infants, disabled persons and the elderly may have inadequate sun exposure, while the skin of those older than 70 years of age also does not convert vitamin D effectively. In addition, at northern latitudes, there is not enough radiation to convert vitamin D, particularly during the winter. For these reasons (in the United States), milk, infant formula, breakfast cereals, and some other foods have been fortified with synthetic vitamin D2 (ergocalciferol, which is derived from irradiation of ergosterol found in plants, the mold ergot, and plankton) or vitamin D3.
METABOLISM OF VITAMIN D
Hepatic — Dietary vitamin D is fat soluble and is absorbed in the small intestine incorporated into chylomicrons. Dietary vitamin D travels to the liver, bound to vitamin D–binding protein and in continued association with chylomicrons and lipoproteins, where it and endogenously synthesized vitamin D3 are metabolized [6,7]. The hepatic enzyme 25–hydroxylase places a hydroxyl group in the 25 position of the vitamin D molecule, resulting in the formation of 25-hydroxyvitamin D or calcidiol (figure 1). The association of oral vitamin D with chylomicra and lipoproteins permits more rapid hepatic delivery when compared with endogenously synthesized or parenterally administered hormone, which circulates exclusively on vitamin D-binding protein. This difference results in a rapid but less sustained increase in plasma 25-hydroxyvitamin D (25OHD) levels obtained with oral as opposed to parenteral administration or endogenous synthesis .