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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 &lt;30 ng/mL and with skin photodamage to take 50,000 IU of cholecalciferol biweekly for 8 to 9 weeks. Then, we obtained baseline and end-of-study skin biopsies from photodamaged (PD) and photoprotected (PP) skin, and from benign nevi (BN) and tested for mRNA expression of VDR and cytochrome P450-24 (CYP24), and markers of keratinocytic differentiation. High-dose cholecalciferol supplementation significantly elevated circulating levels of 25-hydroxyvitamin-D (P &lt; 0.0001) and 1,25-dihydroxyvitamin-D (P &lt; 0.0001). VDR expression in PD- and PP-skin showed minimum changes after supplementation. CYP24 expression in PD- and PP-skin was increased after supplementation by 186%, P = 0.08, and 134%, P = 0.07, respectively. In BNs from 11 participants, a trend for higher VDR and CYP24 expression was observed (average of 20%, P = 0.08, and 544%, P = 0.09, respectively). Caspase-14 expression at the basal layer in PD skin samples was the only epidermal differentiation marker that was significantly increased (49%, P &lt; 0.0001). High-dose cholecalciferol supplementation raised serum VD metabolite levels concurrently with CYP24 mRNA and caspase-14 levels in the skin. Our findings of significant variability in the range of VDR and CYP24 expression across study samples represent an important consideration in studies evaluating the role of VD as a skin cancer chemopreventive agent.

Pilot Study on the Bioactivity of Vitamin D in the Skin after Oral Supplementation