Vitamin D - General Research
Vitamin D, first identified as a vitamin early in the 20th century, is now recognized as a prohormone. A unique aspect of vitamin D as a nutrient is that it can be synthesized by the human body through the action of sunlight. These dual sources of vitamin D make it challenging to develop dietary reference intake values.
Vitamin D, also known as calciferol, comprises a group of fat-soluble seco-sterols. The two major forms are vitamin D2 and vitamin D3. Vitamin D2 (ergocalciferol) is largely human-made and added to foods, whereas vitamin D3 (cholecalciferol) is synthesized in the skin of humans from 7-dehydrocholesterol and is also consumed in the diet via the intake of animal-based foods. Both vitamin D3 and vitamin D2 are synthesized commercially and found in dietary supplements or fortified foods. The D2 and D3 forms differ only in their side chain structure. The differences do not affect metabolism (i.e., activation), and both forms function as prohormones. When activated, the D2 and D3 forms have been reported to exhibit identical responses in the body, and the potency related to the ability to cure vitamin D–deficiency rickets is the same (Fieser and Fieser, 1959; Jones et al., 1998; Jurutka et al., 2001). Experimental animal studies have indicated that vitamin D2is less toxic than vitamin D3, but this has not been demonstrated in humans.
The activation steps involved in converting vitamin D from the diet and cutaneous synthesis are illustrated in . Vitamin D, in either the D2 or D3 form, is considered biologically inactive until it undergoes two enzymatic hydroxylation reactions. The first takes place in the liver, mediated by the 25-hydroxylase (most likely cytochrome P450 2R1 [CYP2R1]) which forms 25-hydroxyvitamin D (hereafter referred to as 25OHD). The second reaction takes place in the kidney, mediated by 1α-hydroxylase (CYP27B1), which converts 25OHD to the biologically active hormone, calcitriol (1,25-dihydroxyvitamin D). The 1α-hydroxylase gene is also expressed in several extra-renal tissues, but its contribution to calcitriol formation in these tissues is unknown. 25OHD, the precursor of calcitriol, is the major circulating form of vitamin D; it circulates bound to a specific plasma carrier protein, vitamin D binding protein (DBP). DBP also transports vitamin D and calcitriol.