ABSTRACT
Micronutrients are substances required in small amounts, typically 5-10 micrograms daily, for proper functioning of the human body. Vitamins are one class of micronutrients, which cannot be synthesized in sufcient quantities within the body and therefore must be obtained exogenously. Of these, vitamin D, a fat-soluble vitamin can be synthesized in the human skin but is virtually absent from most natural foods (Wang 2009) with the exception of amounts found in sh liver oils, fatty sh species, whole egg, and beef liver (Ovesen et al. 2003). Vitamin D is a lipidsoluble prohormone obtained via de novo skin synthesis as a result of UV-light-induced photolytic conversion of 7-dehydrocholesterol to previtamin D3 followed by thermal isomerization to vitamin D3 or ingested through the diet. It is subsequently activated in a sequential two-step process (Holick and Adams 1998; Dusso and Brown 1998; Holick 2007) (Figure 11.1). The rst step is the 25-hydroxylation in the liver to produce 25(OH) vitamin D (25D). The second and more regulated step is the 1-hydroxylation, which is classically thought to occur primarily in the kidney via the 25-hydroxyvitamin D-1-alpha hydroxylase enzyme to produce the active product 1,25(OH)2 vitamin D3 (1,25D) or calcitriol (Holick and Adams 1998; Dusso and Brown 1998; Holick 2007). 1,25D binds to the vitamin D receptor (VDR), a nuclear receptor and a member of the steroid/ thyroid hormone superfamily receptors, which acts as a ligand-activated transcription factor. VDR functions as a heterodimer with the retinoid X receptor. Upon ligand binding the VDR undergoes a conformational change that promotes retinoid X receptor-VDR heterodimerization. The bound
Nutrition and Vitamin D................................................................................................................. 215 Clinical Epidemiology ................................................................................................................... 216 Mechanisms of Vitamin D Action .................................................................................................. 218 Classical and Nonclassical Functions of Vitamin D ...................................................................... 219 Genomic Effects of Vitamin D on Cardiovascular Disease ...........................................................220
