Vitamin D and respiratory health

Abstract

Vitamin D is now known to be of physiological importance outside of bone health and calcium homeostasis, and there is mounting evidence that it plays a beneficial role in the prevention and/or treatment of a wide range of diseases. In this brief review the known effects of vitamin D on immune function are described in relation to respiratory health. Vitamin D appears capable of inhibiting pulmonary inflammatory responses while enhancing innate defence mechanisms against respiratory pathogens. Population-based studies showing an association between circulating vitamin D levels and lung function provide strong justification for randomized controlled clinical trials of vitamin D supplementation in patients with respiratory diseases to assess both efficacy and optimal dosage.

Fig. 1

Simplified version of vitamin D metabolism. Vitamin D, produced mainly from ultraviolet B (UVB) action on the skin, but also available from the diet, binds vitamin D binding protein (DBP) and is transported to the liver where different mitochondrial cytochrome P450 enzymes (CYP) hydroxylate it to form 25(OH)D. This is transported by DBP predominantly to the kidneys, where CYP enzymes hydroxylate it to the active form, 1,25(OH)₂D₃. However, immune cells also have the CYP enzymes required to activate 1,25(OH)₂D₃. Being lipophilic, 1,25(OH)₂D₃ is able to traverse the cell membrane and act within the cell by binding to vitamin D receptors (VDR) in the nucleus. VDR are ligand-activated transcription factors that interact with vitamin D response elements (VDRE) on vitamin D-regulated genes either as homodimers or heterodimers with the retinoid X receptors (RXR). Vitamin D is also regulated by CYP enzymes which inactivate calcitriol into water-soluble derivatives. Vitamin D binding to the VDR enhances CYP24A1 and down-regulates CYP27B1, which is an important negative feedback mechanism regulating vitamin D levels. For more detail refer to [7].