Vitamin D is also of great interest in dermatology. Indeed, there is a dual relationship between it and the skin. On the one hand, it is synthesised by keratinocytes in response to sun exposure and, on the other, it works actively on the skin itself. This two-way process has been named the photoendocrine system of vitamin D.
From a biochemical perspective, the skin synthesises the prohormone vitamin D3 (cholecalciferol) through the interaction between 7-dehydrocholesterol and ultraviolet light. This process can meet up to 80% of our daily needs.
Many factors influence the skin’s ability to synthesise vitamin D. Amongst the most important are latitude, seasonality, phototype and means of sun exposure. A minority percentage of the requirement, 20%, is taken up through the food supply in the form of vitamin D2 (ergocalciferol), found in fruit and vegetables, and vitamin D3, contained in high amounts especially in salmon and herring. The biologically-inactive vitamin D3 is converted in the liver into 25-hydroxy-vitamin D3 (calcifediol), the form most commonly found in the systemic circulation. Calcifediol is again hydrosilylated in the kidney into 1,25-dihydroxy-vitamine D3 (calcitriol) which, by interacting with specific nuclear receptors called Vitamin D Receptors (VDRs), is the main driver of the biological effects of this molecule.
Vitamin D plays a fundamental role for bone tissue, regulating phospho-calcium homeostasis whilst a deficiency causes osteomalacia, osteoporosis and increased susceptibility to bone fractures.
However, the effects of this vitamin are not limited to the skeleton. There is growing evidence of its ubiquitous antiproliferative and immunomodulatory properties. Vitamin D deficiency has been documented in various cardiovascular, oncological, neurological, autoimmune and infectious diseases.
Of particular interest are the multiple functions that vitamin D performs in the body. By acting on the keratinocytes through an autocrine and paracrine mechanism, it controls their differentiation and proliferation whilst stimulating their production of ceramides, which are essential lipids for maintaining skin hydration. Vitamin D also plays an important role in the defence against skin infections by inducing the production of antimicrobial peptides, such as cathelicidin LL-37 and beta-defensin. Vitamin D exerts a relevant immunomodulatory function by inhibiting antigen presentation by Langerhans cells and the proliferation of both B- and T-lymphocytes, inducing an overall shift from a Th1 response to a Th2. This inhibits the production of proinflammatory cytokines such as IL-1, -6, -8, -12, TNF-alpha and interferon-gamma, whilst inducing the production of anti-inflammatory cytokines, such as IL-10, and the differentiation of regulatory T-cells.
The main dermatological diseases associated with vitamin D deficiency include both skin neoplasms and some of the most frequent immune-mediated diseases, like atopic dermatitis, psoriasis and vitiligo.