Minireview: Vitamin D: is there a role in extraskeletal health?

Abstract

In recent years, vitamin D has received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries together with the identification of extraskeletal vitamin D receptor-mediated actions, suggesting unexpected benefits of vitamin D in health and diseases. Although there is increased awareness of the importance of vitamin D, the role of vitamin D in extraskeletal health has been a matter of debate. In this review, we will summarize what is known and indicate the questions that remain and need to be addressed.

Fig. 1.

1,25(OH)₂D₃ treatment reverses ongoing EAE. EAE was induced in C57BL/6 mice, and the mice were scored daily (1, limp tail; 2, hind limb weakness; 3, hind limb paralysis; and 4, hind limb and forelimb paralysis). At d 15 (peak of disease), mice were randomized, fed a diet containing no vitamin D, and treated with either vehicle (black circles) or 50 ng 1,25(OH)₂D₃ (open circles) (indicated by the line, d 15- 30). Treatment with 1,25(OH)₂D₃ reversed paralysis and protected against ongoing EAE. *, P < 0.05; **, P < 0.01. Studies using infiltrating mononuclear cells isolated from the spinal cord and brain after 3 d treatment with 1,25(OH)₂D₃ (arrowhead) showed that improvement in the clinical score after 1,25(OH)₂D₃ treatment is associated with inhibition of production of IL-17 (data not shown). From Joshi et al. (58).

Fig. 2.

1,25(OH)₂D₃ analog, RO26-2198 administered to NOD mice inhibits type 1 diabetes development. NOD mice were treated five times per week with vehicle (open circles) or with 0.03 μg/kg 1,25(OH)₂D₃ analog RO26-2198 from eight to 16 wk of age (black circles) or from eight to 12 wk of age (black squares). Note that the short course of treatment arrested the clinical onset of diabetes in the NOD mice. RO26-2198 did not induce hypercalcemia even after 40 administrations (data not shown). From Gregori et al. (68), with permission.