Vitamin D and skin

BACKGROUND: The vitamin D receptor (VDR) mediates the major cellular activities of vitamin D and regulates various signaling pathways implicated in cancer development and progression. VDR variants have been found associated with the risk of developing melanoma; however, previous epidemiological studies are inconsistent. We have systematically reviewed the published epidemiological literature and conducted a meta-analysis to assess associations between common VDR variants and melanoma risk...

Interest in vitamin D and the VDR gene is increasing as putative roles in human health and evolutionary processes are explored. This review looks beyond the classic biochemistry that links vitamin D to calcium homeostasis; it explores how vitamin D interacts with light in a broader perspective than simple skin photosynthesis. It examines how the vitamin influences circadian rhythm, and how it may have helped drive the evolution of skin pigmentation. To this end, the nutrient-nutrient relationship with folate is also explored...

Laboratory studies suggest that vitamin D (VD) supplementation inhibits skin carcinogenesis. However, epidemiologic studies report mixed findings in the association between circulating VD levels and skin cancer risk. We conducted a clinical study to determine whether oral cholecalciferol supplementation would exert direct bioactivity in human skin through modulation of the VD receptor (VDR). We enrolled 25 individuals with serum 25-hydroxyvitamin-D levels <30 ng/mL and with skin photodamage to take 50,000 IU of cholecalciferol biweekly for 8 to 9 weeks...

Deregulated melanogenesis is involved in melanomagenesis and melanoma progression and resistance to therapy. Vitamin D analogs have anti-melanoma activity. While the hypercalcaemic effect of the active form of Vitamin D (1,25(OH)2D3) limits its therapeutic use, novel Vitamin D analogs with a modified side chain demonstrate low calcaemic activity. We therefore examined the effect of secosteroidal analogs, both classic (1,25(OH)2D3 and 25(OH)D3), and novel relatively non-calcemic ones (20(OH)D3, calcipotriol, 21(OH)pD, pD and 20(OH)pL), on proliferation, colony formation in monolayer and soft-agar, and mRNA and protein expression by melanoma cells...

An adequate vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D) concentration, is important in humans for maintenance of healthy bones and muscle function. Serum 25(OH)D concentration was assessed in participants from Melbourne, Australia (37.81S, 144.96E), who were provided with the current Australian guidelines on sun exposure for 25(OH)D adequacy (25(OH)D ≥50 nmol/L). Participants were interviewed in February (summer, n=104) and August (winter, n=99) of 2013. Serum 25(OH)D concentration was examined as a function of measures of sun exposure and sun protection habits with control of key characteristics such as dietary intake of vitamin D, body mass index (BMI) and skin colour, that may modify this relationship...

Query of sun-related habits or ancestry could help screen for risk of vitamin D insufficiency (serum 25-hydroxyvitamin D<75nmol/L). We evaluated the association between Sun Exposure Score (calculated from recall of Time Exposed to Sun and Skin Exposed to Sun in the previous week), demographics and anthropometrics (including self-reported ancestry and skin melanin reflectometry), and serum 25(OH)D levels in healthy young Canadian adults in the Greater Toronto Area (GTA; 43°N) during fall. 310 adults (67% female) of European, East Asian, and South Asian ancestries were evaluated...

BACKGROUND: The hormonally active vitamin D metabolite calcitriol and its analogues exert potent effects on cellular differentiation and regulation of immune responses. Although topical vitamin D analogues are widely used for treatment of psoriasis and vitamin D has been increasingly implicated in prevention and protection from several autoimmune diseases, experimental and clinical data in autoimmune bullous diseases are generally lacking. OBJECTIVE: Here, we investigated the effects of calcitriol on keratinocytes treated by bullous pemphigoid (BP) autoantibodies...

Vitamin D can be synthesized following exposure to ultraviolet radiation (UVR), ingested in the diet or provided through oral supplementation. The medical literature frequently states that humans obtain most of their vitamin D from sunshine and that UVR exposure is essential to maintain vitamin D levels. A systematic review was conducted to determine the requirement for UVR in maintaining adequate (> 50 nmol L(-1) ) serum 25-hydroxyvitamin D [25(OH)D] levels. Studies reporting serum 25(OH)D during situations of negligible UVR exposure were sought...

CYP11A1 hydroxylates the side chain of vitamin D3 (D3) in a sequential fashion [D3→20S(OH)D3→20,23(OH)2D3→17,20,23(OH)3D3], in an alternative to the classical pathway of activation [D3→25(OH)D3→1,25(OH)2D3]. The products/intermediates of the pathway can be further modified by the action of CYP27B1. The CYP11A1-derived products are biologically active with functions determined by the lineage of the target cells. This pathway can operate in epidermal keratinocytes. To further define the role of these novel secosteroids we tested them for protective effects against UVB-induced damage in human epidermal keratinocytes, melanocytes and HaCaT keratinocytes, cultured in vitro...

BACKGROUND: Narrowband ultraviolet B phototherapy (nbUVB) is an established treatment modality for patients with severe atopic dermatitis (AD) and is known to increase serum vitamin D levels (SVD). The relationship between SVD and AD remains unclear. OBJECTIVES: To assess SVD and disease severity in patients with AD before and after nbUVB and establish whether a change in SVD correlates to response to nbUVB. Methods: A single-centre, open observational study recruited 21 male and 17 female patients with AD between November and April...

Vitamin D and calcium are well-established regulators of keratinocyte proliferation and differentiation. Therefore, it was not a great surprise that deletion of the vitamin D receptor (VDR) should predispose the skin to tumor formation, and that the combination of deleting both the VDR and calcium sensing receptor (CaSR) should be especially pro-oncogenic. In this review I have examined 4 mechanisms that appear to underlie the means by which VDR acts as a tumor suppressor in skin. First, DNA damage repair is curtailed in the absence of the VDR, allowing mutations in DNA to accumulate...

7-Dehydrocholesterol (7DHC) serves as the sterol substrate for both cholesterol and vitamin D3 (cholecalciferol) synthesis. The pivotal enzyme in these two pathways is 7-dehydrocholesterol reductase (DHCR7), which converts 7DHC to cholesterol. Treatment of adult human epidermal keratinocytes (HEKa) with 10μM cholecalciferol resulted in a rapid decrease in DHCR7 activity (19% of control activity at 2h). This loss of activity was observed only in HEKa cells, a primary cell line cultured from normal human skin, and not in an immortalized skin cell line (HaCaT cells) nor in two hepatoma cell lines...

Non-secosteroidal vitamin D receptor (VDR) ligands are promising candidates for many clinical applications. We recently developed novel non-secosteroidal VDR agonists based on p-carborane (an icosahedral carbon-containing boron cluster) as a hydrophobic core structure. Here, we report the design, synthesis and biological evaluation of carborane-based vitamin D analogs bearing various substituents at the diol moiety. Among the synthesized compounds, methylene derivative 31 exhibited the most potent vitamin D activity, which was comparable to that of the natural hormone, 1α,25(OH)2D3...

BACKGROUND: Cell junctions are crucial for the formation and maintenance of the paracellular barrier and for cell polarity in simple epithelia and endothelia. Altered localization and formation of tissue junction proteins in the epidermis have been described in plaque-type psoriasis. Vitamin D receptor (VDR) is a nuclear hormone involved in anti-proliferative and pro-differentiation pathways in keratinocytes. However, still to date, vitamin D/VDR signalling involved in tissue barrier related to psoriasis remains largely unknown...

Positive as well as negative health effects of exposure of human skin to UV radiation depend on spectra and fluence rates, both of which being dependent on latitude, time of the day and several other factors. The major positive effects are related to vitamin D photosynthesis and the major negative effect is skin cancer development. The action spectra for these effects are different. This lead us to conclude that for optimal vitamin D synthesis at minimal risk of cutaneous malignant melanoma (CMM), the best time for sun exposure is between 10 a...

Vitamin D is primarily produced by a photochemical reaction in skin, using the energy of ultraviolet B radiation. Ultraviolet radiation in sunlight is also responsible for several types of DNA damage, immunosuppression and photoaging. A number of adaptive responses are known to occur in skin to increasing UV exposure, including increased pigmentation, increased thickness of the cornified layer of skin and upregulation of DNA repair pathways. In addition to these known responses, there is now sufficient evidence to suggest that the local vitamin D system in skin, which includes local production of the active hormone, 1,25 dihydroxyvitamin D, together with metabolites of over-irradiation products, and vitamin D receptor(s), also provide an adaptive response to UV...

Vitamin D is the sunshine vitamin for good reason. During exposure to sunlight, the UV B photons enter the skin and photolyze 7-dehydrocholesterol to previtamin D3 which in turn is isomerized by the body's temperature to vitamin D3. Most humans have depended on sun for their vitamin D requirement. Skin pigment, sunscreen use, aging, time of day, season and latitude dramatically affect previtamin 13 synthesis. Vitamin D deficiency was thought to have been conquered, but it is now recognized that more than 50% of the world's population is at risk for vitamin D deficiency...

Alopecia (hair loss) in vitamin D receptor (VDR)-null mice is due to absence of ligand-independent actions of the VDR that are required for initiation of postmorphogenic hair cycles. Investigations were undertaken to determine whether the VDR is required for the induction of signaling pathways that play an important role in this process. The induction of cWnt and hedgehog target genes that characterizes early anagen was found to be dramatically attenuated in VDR(-/-) mice, relative to wild-type (WT) mice. To determine whether this reflects impaired responsiveness to cWnt ligands, in vitro studies were performed in primary keratinocytes...

BACKGROUND: Although vitamin D analogs have been used in the topical treatment of psoriasis, their mechanisms of action are not well understand. Calcitriol, the hormonally active vitamin D3 metabolite, has been demonstrated to exert immunomodulatory effects in the skin by down-regulating the expression of Toll-like receptors (TLRs) and proinflammatory cytokines. OBJECTIVE: We investigated the effects of calcitriol on the expression of TLR2, TLR4, antimicrobial peptide LL-37, and proinflammatory cytokines in cultured human keratinocytes...

Calcitriol, the hormonally active form of vitamin D, is well known for its diverse pharmacological activities, including modulation of cell growth, neuromuscular and immune function and reduction of inflammation. Calcitriol and its analogs exert potent effects on cellular differentiation and proliferation, regulate apoptosis and produce immunomodulatory effects. The purpose of this review is to provide information on various physiological and pharmacological activities of calcitriol and its newly discovered analogs...