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The prevailing medical opinion up to the 1960s held that vitamin D was a risk factor for cardiovascular disease, arising from research showing that megadoses of vitamin D caused arteriosclerosis in animals. However, the development of competitive protein-binding assays for 25-hydroxyvitamin D [25(OH)D] in the 1970s showed that only a small proportion of body vitamin D comes from diet, with more than 80% synthesized from sun exposure. A 1981 review of the epidemiology, which found that cardiovascular disease rates increased in winter with increasing latitude and were reduced at high altitudes, led to the hypothesis that ultraviolet radiation, by increasing vitamin D levels, protects against cardiovascular disease. Since then, observational epidemiological studies have reported inverse associations between serum 25-hydroxyvitamin D levels and risk of cardiovascular disease. However, randomized clinical trials are required to confirm that vitamin D protects against cardiovascular disease. Several mechanisms have been proposed for the putative protective effect of vitamin D against cardiovascular disease. These include beneficial changes in cardiac function, blood pressure (including endothelial function), insulin resistance, and inflammatory processes. [ABSTRACT FROM AUTHOR]

This chapter will examine the role of vitamin D in the innate immune system as a mediator of human host defense mechanisms against microbial disease, focusing on tuberculosis. The first section will examine tuberculosis and the innate immune response to the intracellular pathogen, Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis. This is followed by a discussion of the known associations, genetic and mechanistic, between the vitamin D pathway and tuberculosis susceptibility. Finally, the chapter will conclude with a discussion on the potential for adjuvant treatment of tuberculosis with vitamin D. [ABSTRACT FROM AUTHOR]

Although the kidney was initially thought to be the sole organ responsible for the production of 1,25-dihydroxyvitamin D3 [1,25(OH)2D] via its enzyme CYP27B1, it is now appreciated that the expression of CYP27B1 in tissues other than the kidney is widespread. However, the kidney is the major source for circulating 1,25(OH)2D. Therefore the existence of the capacity for extrarenal 1,25(OH)2D production begs the question why, and in particular whether the extrarenal production of 1,25(OH)2D has physiologic importance. In this chapter this question will be discussed. First a compilation of the extrarenal sites for CYP27B1 expression is provided. This is followed by a discussion of the regulation of CYP27B1 expression and activity in extrarenal tissues, pointing out that such regulation is tissue specific and different from that of CYP27B1 in the kidney. Finally the physiologic significance of extrarenal 1,25(OH)2D production is examined, with special focus on the role of CYP27B1 in regulation of cellular proliferation and differentiation, hormone secretion, and immune function. At this point the data do not clearly demonstrate an essential role for CYP27B1 expression in any tissue outside the kidney, but several examples pointing in this direction are provided. With the availability of the mouse enabling tissue-specific deletion of CYP27B1, the role of extrarenal CYP27B1 expression can now be addressed definitively. [ABSTRACT FROM AUTHOR]