Oral administration of 1,25-dihydroxyvitamin D3 completely protects NOD mice from insulin-dependent diabetes mellitus

Lower prediagnostic serum 25-hydroxyvitamin D concentration is associated with higher risk of insulin-requiring diabetes: a nested case–control study

“…Higher serum 25(OH)D concentration provides the substrate for biosynthesis of 1,25(OH) 2 D, which inhibits occurrence of insulin-requiring diabetes in animal models [16]. Vitamin D deficiency is associated with major effects on the innate immune system [17].…”

Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

“…Similarly, the doses in studies on NOD mice, in which a protective association was reported, were pharmacological; in addition vitamin D was administered in the form of the bioactive hormone, i.e. 1,25-dihydroxyvitamin D3 or its analogues [4][5][6][7].…”

“…In studies with NOD mice, lack of vitamin D at an early age has been found to increase the later risk of autoimmune diabetes [3,4]. In several NOD mice studies, pharmacological doses of bioactive vitamin D in the form of 1,25-dihydroxyvitamin D 3 or its analogues were seen to protect from autoimmune diabetes [4][5][6][7] and other autoimmune diseases [8]. Vitamin D has several effects on the immune system that could be of relevance in the pathogenesis of type 1 diabetes [8,9].…”

The paradoxical effects of vitamin D on type 1 mediated immunity

“…Measurements of 1,25(OH) 2 D 3 are meaningless in the face of these measurement problems. Furthermore, excess 1,25(OH) 2 D 3 has been given to animals with Th1 mediated diseases and the symptoms of the disease as well as the Th1 response were significantly reduced in many experiments by many investigators (Lemire et al 1991;Cantorna et al 2000;Zella et al 2003;Mathieu et al 2004). More work is needed to determine whether immune mediated production of 1,25(OH) 2 D 3 is biologically significant, pathogenic, or protective.…”

“…In particular, poor vitamin D status has been linked to the development of a number of different type-one (Th1) mediated autoimmune diseases including type-1 diabetes, multiple sclerosis (MS), and inflammatory bowel diseases (IBD) (Cantorna et al 2004). In addition the active form of vitamin D (1,25 (OH) 2 D 3 ) has been shown to completely block the development of experimental models of these autoimmune diseases (Cantorna et al 1996;Cantorna et al 2000;Zella et al 2003). Th1 mediated immunity is critical for the ability of the host to mount a protective immune response to many different infections.…”