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      Sustained Increase of 25-Hydroxyvitamin D Levels in Healthy Young Women during Wintertime after Three Suberythemal UV Irradiations—The MUVY Pilot Study

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          Abstract

          Objectives

          Vitamin D (VitD) deficiency is a health problem prevalent not only in the elderly but also in young adults. The primary objective of our observational pilot study “MUVY” ( Mood, UVR, Vitamin D in Young women) was to test both the short-term and long-term effects of a series of three suberythemal UV radiation (UVR) exposures on the VitD status and well-being of young healthy women during winter in a repeat measure design.

          Methods

          20 healthy young women (Fitzpatrick skin types I–III, aged 21–25 years) received three full body broad band UVR exposures with an escalating erythemally weighted dose schedule during one week in winter, and completed self-report questionnaires monitoring symptoms of depression (Beck Depression Inventory, BDI) and affective state/well-being (Profile of Mood States, POMS) at baseline and three days after the last UVR exposure. 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH) 2D) were measured in serum at baseline, and at study days 8, 36 and 50.

          Results

          Mean baseline 25(OH)D level was 54.3 nmol/L (standard deviation (s.d.) = 24.1), with seven women having VitD deficient status. Relevant symptoms of depression, as indicated by low BDI total scores (0–8), were absent. After the three UVR exposures the increment of 25(OH)D was an average of 13.9 nmol/L (95% confidence interval (CI) = 9.4–18.4) and 26.2 pmol/L (95%CI = 7.2–45.1) for 1,25(OH) 2D. Δ25(OH)D, and corresponding baseline levels were significantly and inversely associated (rho = -0.493, p = 0.027). Only 25(OH)D remained significantly increased above baseline for at least six weeks after the last UVR exposure. A strong inverse correlation of the POMS subscale “Vigor/Activity” and the increment in 1,25(OH) 2D was found (rho = -0.739, p<0.001) at day 8.

          Conclusions

          Three suberythemal whole body UVR exposures during one week are a simple and suitable method for improving 25(OH)D levels during winter, for at least six weeks, and especially in young women with VitD deficient status.

          Trial Registration

          German Clinical Trials Register (Deutsches Register Kinischer Studien) DRKS00009274

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          Most cited references 48

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          Design and analysis of pilot studies: recommendations for good practice.

          Pilot studies play an important role in health research, but they can be misused, mistreated and misrepresented. In this paper we focus on pilot studies that are used specifically to plan a randomized controlled trial (RCT). Citing examples from the literature, we provide a methodological framework in which to work, and discuss reasons why a pilot study might be undertaken. A well-conducted pilot study, giving a clear list of aims and objectives within a formal framework will encourage methodological rigour, ensure that the work is scientifically valid and publishable, and will lead to higher quality RCTs. It will also safeguard against pilot studies being conducted simply because of small numbers of available patients.
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            In vivo evidence for a novel pathway of vitamin D₃ metabolism initiated by P450scc and modified by CYP27B1.

            We define previously unrecognized in vivo pathways of vitamin D(3) (D3) metabolism generating novel D3-hydroxyderivatives different from 25-hydroxyvitamin D(3) [25(OH)D3] and 1,25(OH)(2)D3. Their novel products include 20-hydroxyvitamin D(3) [20(OH)D3], 22(OH)D3, 20,23(OH)(2)D3, 20,22(OH)(2)D3, 1,20(OH)(2)D3, 1,20,23(OH)(3)D3, and 17,20,23(OH)(3)D3 and were produced by placenta, adrenal glands, and epidermal keratinocytes. We detected the predominant metabolite [20(OH)D3] in human serum with a relative concentration ∼20 times lower than 25(OH)D3. Use of inhibitors and studies performed with isolated mitochondria and purified enzymes demonstrated involvement of the steroidogenic enzyme cytochrome P450scc (CYP11A1) as well as CYP27B1 (1α-hydroxylase). In placenta and adrenal glands with high CYP11A1 expression, the predominant pathway was D3 → 20(OH)D3 → 20,23(OH)(2)D3 → 17,20,23(OH)(3)D3 with further 1α-hydroxylation, and minor pathways were D3 → 25(OH)D3 → 1,25(OH)(2)D3 and D3 → 22(OH)D3 → 20,22(OH)(2)D3. In epidermal keratinocytes, we observed higher proportions of 22(OH)D3 and 20,22(OH)(2)D3. We also detected endogenous production of 20(OH)D3, 22(OH) D3, 20,23(OH)(2)D3, 20,22(OH)(2)D3, and 17,20,23(OH)(3)D3 by immortalized human keratinocytes. Thus, we provide in vivo evidence for novel pathways of D3 metabolism initiated by CYP11A1, with the product profile showing organ/cell type specificity and being modified by CYP27B1 activity. These findings define the pathway intermediates as natural products/endogenous bioregulators and break the current dogma that vitamin D is solely activated through the sequence D3 → 25(OH)D3 → 1,25(OH)(2)D3.
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              Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland

              To investigate whether novel pathways of vitamin D3 (D3) and 7-dehydrocholesterol (7DHC) metabolism initiated by CYP11A1 and previously characterized in vitro, occur in vivo, we analyzed samples of human serum and epidermis, and pig adrenals for the presence of intermediates and products of these pathways. We extracted human epidermis from 13 individuals and sera from 13 individuals and analyzed them by LC/qTOF-MS alongside the corresponding standards. Pig adrenal glands were also analyzed for these steroids and secosteroids. Epidermal, serum and adrenal samples showed the presence of D3 hydroxy-derivatives corresponding to 20(OH)D3, 22(OH)D3, 25(OH)D3, 1,25(OH)2D3, 20,22(OH)2D3, 20,23(OH)2D3, 20,24(OH)2D3, 20,25(OH)2D3, 20,26(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3, plus 1,20(OH)2D3 which was detectable only in the epidermis. Serum concentrations of 20(OH)D3 and 22(OH)D3 were only 30- and 15-fold lower than 25(OH)D3, respectively, and at levels above those required for biological activity as measured in vitro. We also detected 1,20,24(OH)3D3, 1,20,25(OH)3D3 and 1,20,26(OH)3D3 in the adrenals. Products of CYP11A1 action on 7DHC, namely 22(OH)7DHC, 20,22(OH)27DHC and 7-dehydropregnenolone were also detected in serum, epidermis and the adrenal. Thus, we have detected novel CYP11A1-derived secosteroids in the skin, serum and adrenal gland and based on their concentrations and biological activity suggest that they act as hormones in vivo.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                19 July 2016
                2016
                : 11
                : 7
                Affiliations
                [1 ]Department of Rheumatology and Clinical Immunology, Charité–Universitätsmedizin Berlin, Germany
                [2 ]Department of Psychiatry and Psychotherapy, Charité–Universitätsmedizin Berlin, Germany
                [3 ]Medical Photobiology Group, Department of Internal Medicine, Charité–Universitätsmedizin Berlin, Germany
                Geisel School of Medicine at Dartmouth, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: MGB MH RU VHZ TB JD HP. Performed the experiments: MGB MH VHZ TB JD. Analyzed the data: MGB MH LF PK JD. Contributed reagents/materials/analysis tools: RU VHZ TB FB GRB JD HP. Wrote the paper: MGB LF PK VHZ TB FB GRB JD HP.

                Article
                PONE-D-15-42154
                10.1371/journal.pone.0159040
                4951026
                27434043
                © 2016 Biersack et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 3, Tables: 3, Pages: 19
                Product
                Funding
                The authors have no support or funding to report.
                Categories
                Research Article
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Mood Disorders
                Depression
                Research and Analysis Methods
                Research Design
                Pilot Studies
                Physical sciences
                Physics
                Electromagnetic radiation
                Light
                Ultraviolet radiation
                Ultraviolet B
                Medicine and Health Sciences
                Dermatology
                Erythema
                Medicine and Health Sciences
                Diagnostic Medicine
                Signs and Symptoms
                Erythema
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
                Signs and Symptoms
                Erythema
                Medicine and Health Sciences
                Dermatology
                Photodermatology and Skin Aging
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Contraceptive Therapy
                Oral Contraceptive Therapy
                Physical sciences
                Chemistry
                Chemical compounds
                Organic compounds
                Vitamins
                Vitamin D
                Physical sciences
                Chemistry
                Organic chemistry
                Organic compounds
                Vitamins
                Vitamin D
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized

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