Summary of Study:
Background/Purpose: Ultraviolet (UV) B irradiation may provide a safe and effective method to treat vitamin D deficiency.The objective of this study was to assess the effectiveness of a novel Sperti D/UV-Fluorescent lamp in converting 7-dehydrocholesterol (7-DHC) to pre vitamin D3 in vitro and in raising serum 25-hydroxyvitamin D3 [25(OH)D3] in healthy adults.
Methods: The lamp was assessed in vitro using a 7-DHC solution and a human skin sample. In a prospective cohort study, five healthy adults with skin types II and III were exposed to a 0.75 minimal erythemal dose of UV radiation over ~9% of body surface area three times a week for 4 weeks. The main outcomes were percentage of conversion from 7-DHC to previtamin D3 in vitro and changes in serum 25(OH)D3 after irradiation in vivo.
Results: A dose response between UV irradiation time and conversion of 7-DHC to previta min D3wasseen in the 7-DHCsolution and surgically obtained human skin. The subjects had a significant increase in mean 25(OH)D3 from 18.4 8.2 to 27.3 7.6 ng/ml (P < 0.001) after 4 weeks of irradiation. No adverse events occurred. Conclusion: The Sperti D/UV-Fluorescent lamp is effective in converting 7-DHC to previta min D3 in vitro and in raising serum 25(OH)D3 in healthy adults
The synthesis of vitamin D begins in the skin with the photoconversion of 7-dehydrocholesterol (7-DHC) to pre vitamin D3 as a result of ultraviolet B (UVB) irradiation (1). Previtamin D3 subsequently undergoes a temperature-dependent process in the skin to form vitamin D3 that enters the circulation (2). In the liver, vitamin D3 undergoes hydroxylation by vitamin D-25 hydroxylases (CYP27A1 and CYP2R1) to form 25-hydroxyvitamin D3 [25(OH)D3], the major circulating metabolite, which is then converted into its active meta bolite 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] b y 25 hydroxyvitamin D-1a hydroxylase (CYP27B1) in the kidney (3). Prevalence of vitamin D deficiency among individuals with malabsorption syndromes, such as Crohn’s disease, ulcerative colitis, cystic fibrosis, short bowel syndrome, or those who have undergone gastric bypass is high due to the reduced ability to absorb vitamin D from diet (4–6). Oral vitamin D supplementation has limited role in many of these patients. It has been reported that irradiation with UVB can be used safely and effectively to treat vitamin D deficiency among these patients (7–10).
Studies have shown that 1,25(OH)2D induces activation of the innate immune system of the skin, including expression of the antimicrobial peptide cathelicidin (11, 12). Interestingly, 25(OH)D also induces this process due to the fact that keratino cytes express CYP27B1, allowing local activation of 25(OH)D and autocrine and paracrine effects of 1,25(OH)2D (11). It is possible that UVB exposure and locally synthesized vitamin D3 may modulate cutaneous immune function that could have sig nificant implications for both normal individuals and patients, particularly those who are not regularly exposed to sunlight. In the past, mercury arc sunlamps were approved for use in the United States for the production of vitamin D to prevent rickets in children (13).The Sperti D/UV-Fluorescent lamp (KBD, Inc, Crescent Springs, KY, USA), unlike previous mercury lamps, was designed to use UVB emitting fluorescent bulbs that have lower heat emission than mercury arc lamps and also allows a larger area of skin exposure. In addition, the unnecessary UVC has been removed from the output spectrum, and the lamp has been equipped with a timer for improved safety (14). However, the efficacy of this device has not been examined. The purpose of this study was to assess the efficacy of this lamp in converting 7-DHC to previtamin D3 in vitro and to assess the clinical efficacy of the lamp in raising serum 25(OH)D3 levels in healthy adults with Fitzpatrick skin types II and III
Methods In vitro studies
Output spectrum of the Sperti D/UV-Fluorescent lamp (~280 to ~400 nm) overlaps with the wavelengths (260–315 nm) effective in producing vitamin D3 in the skin (1, 14, 15) (Fig. 1a). Borosilicate glass ampoules containing 7-DHC solution in ethanol (50 mg/ml) were exposed to UV radiation (UVR) from the lamp for 1, 2.5, 5, 7.5, 9, 10, and 15 min at a distance of 15 inches. We determined the percentage conversion of the irradiated 7-DHC solution to previtamin D3, tachysterol, and lumisterol using high-performance liquid chromatography (HPLC) as previously described (16, 17). To further evaluate the effectiveness of the lamp, a surgical sample of type II human skin was exposed to UVR from the lamp at 15 inches for 7.5 min. This skin sample was obtained at the time of an elective surgery from a 32-year-old male who was not part of the in vivo study. The epidermis was separated from the dermis, then the epidermis and the basal cells were analyzed by HPLC to determine the percentage conversion of 7-DHC to pre vitamin D3, tachysterol, and lumisterol as previously described (18). In vivo study The study was reviewed and approved by the Institutional Review Board of Boston University Medical Center, and written informed consent was obtained from each subject. Healthy subjects age 18 years and older, both males and females, with body mass index (BMI) between 18.5 and 30 kg/m2 and Fitzpatrick skin types II (beige skin, blue, or gray eyes; blonde or light brown hair and some freckles; with a strong tendency to sunburn outdoors, but sometimes tans) and III (light brown skin, brown eyes and hair; sometimes burns outdoors but always tans) were enrolled into the study. Women were on birth control and not pregnant based on a negative urine pregnancy test at the first study visit. Exclusion criteria included ongoing treatment with pharmacologic doses of vitamin D, treatment with vitamin D metabolites or analogues, history of photosensitivity, chronic hepatic or renal failure, history of skin cancer within 5 years, and use of medi cations known to cause photosensitivity reactions including hydrochlorothiazide and tetracycline. The study was performed at Boston University General Clinical Research Unit and consisted of 12 visits; three visits/week. At each visit, subjects were exposed to UVB from the lamp either on the back or abdomen of an area approximately 200 cm2 or ~9% of body surface area at a distance of 15 inches while wearing UV eye shield. Exposed areas were rotated at each visit. At each visit, subjects were questioned about their skin and systemic symptoms related to UV irradiation from the prior visit. In accordance with Food and Drug Administration guidelines, subjects received 75% of minimal erythemal dose (MED) of UVR. The exposure time that resulted in 0.75 MED for skin type II at the distance of 15 inches was determined using a radiometer (model 7.0, Solartech, Inc, Harrison Township, MI, USA) to be 4 min. The exposure time for subjects with skin type III was 20% longer than for subjects with skin type II. Blood draws for serum 25(OH)D3 were performed at baseline and subsequently every week. Serum 25(OH)D3 levels were determined by liquid chromatography tandem mass spectrometry (19). The intraassay coefficient of variation was 6.0%.The laboratory has been accredited by external quality control agency for serum 25(OH)D (20)
Statistical analysis
The analysis was performed using the data analysis tools package in Microsoft Excel, Office Suite 2007 (Microsoft Corp., Redmond, WA, USA) and Prism 5.0 (GraphPad Software, Inc, La Jolla, CA, USA). Repeated measures analysis of variance (ANOVA) was used to compare mean 25(OH)D3 levels between baseline and those at subsequent visits. Results In vitro studies The relationship between UV exposure time and conversion of 7-DHC to previtamin D3, lumisterol, and tachysterol in borosili cate glass ampoules containing 7-DHC in ethanol (50 mg/ml) is demonstrated in Figure 1b. A dose-response relationship between irradiation time and percentage conversion was observed. After the type II skin sample was exposed to UVR, 4% 7-DHC was converted to previtamin D3, compared with 8.4% of 7-DHC in a borosilicate ampoule (Fig. 1b). In vivo study Three adults with skin type II (one male and two females) and two adults with skin type III (both female) were enrolled into the study.
The baseline characteristics of these subjects are shown in Table 1.The mean 25(OH)D3 at baseline was 18.4 8.2 ng/ml (45.9 20.5 nmol/l) and the mean 25(OH)D3 at the end of the study was 27.1 7.8ng/ml (67.6 19.5nmol/l). Changes in serum 25(OH)D3 compared with baseline in each subject throughout the study is shown inTable 1. Repeated meas ures ANOVA demonstrated that changes in serum 25(OH)D3 levels from baseline to subsequent visits reached statistical significance (P < 0.01). All subjects tolerated the UV irradiation well, and none reported any skin burn, pain, or other symptoms subsequent to the UV exposures.
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