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In this study, the conversion of vitamin D 3 (VD 3 ) to its two active forms 25(OH)VD 3 and 1α, 25(OH) 2 VD 3 was carried out by engineering the hydroxylase CYP105A1 and its redox partners Fdx and Fdr. CYP105A1 and Fdx-Fdr were respectively expressed in E. coli BL21(DE3) and purified. The electron transport chain Fdx-Fdr had higher selectivity for the coenzyme NADH than NADPH. HPLC analysis showed that CYP105A1 could hydroxylate the C25 and C1α sites of VD 3 and convert VD 3 to its active forms. Finally, a one-bacterium-multi-enzyme system was constructed and used in whole-cell catalytic experiments. The results indicated that 2.491 mg/L of 25(OH)VD 3 and 0.698 mg/L of 1α, 25(OH) 2 VD 3 were successfully produced under the condition of 1.0% co-solvent DMSO, 1 mM coenzyme NADH and 35 g/L biocatalyst loading. This study contributes to a basis for the industrial production of active VD 3 in future., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

1α,25-Dihydroxyvitamin D 3 (abbreviated here as 1,25D 3 ) is a hormonally active form of vitamin D 3 (D 3 ), and is produced from D 3 by CYP27 A1-mediated hydroxylation at C25, followed by CYP27B1-mediated hydroxylation at C1. Further hydroxylation of 25D 3 and 1,25D 3 occurs at C23, C24 and C26 to generate corresponding metabolites, except for 1,25R,26D 3 . Since the capability of CYP27B1 to hydroxylate C1 of side-chain-hydroxylated metabolites other than 23S,25D 3 and 24R,25D 3 has not been examined, we have here explored the role of CYP27B1 in the C1 hydroxylation of a series of side-chain-hydroxylated D 3 derivatives. We found that CYP27B1 hydroxylates the R diastereomers of 24,25D 3 and 25,26D 3 more effectively than the S diastereomers, but shows almost no activity towards either diastereomer of 23,25D 3 . This is the first report to show that CYP27B1 metabolizes 25,26D 3 to the corresponding 1α-hydroxylated derivative, 1,25,26D 3 . It will be interesting to examine the physiological relevance of this finding., (© 2021 Wiley-VCH GmbH.)

While we generally understand the optimal ultraviolet B (UVB) environment for the growth and reproduction of female Panther Chameleons Furcifer pardalis, we do not know the relative importance of UVB irradiance and dose for optimal husbandry outcomes. Accordingly, we experimented with Panther Chameleon females to test the hypothesis that UVB dose (irradiance × exposure duration) determines the outcome, regardless of the combination of UVB irradiance and exposure duration generating the dose. We varied UVB irradiance and exposure duration across treatment groups while keeping dose similar and within a range previously documented to result in reproductive success. The growth rate, age of maturity, and measurable vitamin D status were not significantly different among the treatment groups. Individuals in all groups produced viable eggs that successfully hatched. Thus, we found some support for the hypothesis that the UVB dose determines the outcome regardless of UVB irradiance. However, mean egg vitamin D 3 concentration and percent hatching were higher in the highest UVB irradiance group, despite similar doses among the three groups. Preliminary field data reveal that this species occupies UV irradiance Zone 4 in Madagascar, the highest zone for reptiles recorded. Only the irradiance of the high UVB irradiance group in our experiment approached this zone and resulted in the best reproductive success. Biosynthesis of vitamin D 3 and provisioning to eggs is more efficient when exposure to UVB irradiance is similar to that in their natural environment. Establishing an optimal UVB environment, based on knowledge of the natural UVB environment, is important for the propagation of Panther Chameleons in captivity., (© 2021 Wiley Periodicals LLC.)

Vitamin D is an important regulator of calcium and phosphorus homeostasis in animals. It can be acquired from the diet or synthesised de novo when skin is exposed to UVb. Vitamin D deficiency can lead to a complex of diseases collectively called metabolic bone disease (MBD). Diurnal lizards without access to UVb are prone to develop vitamin D deficiency, even when dietary vitamin D 3 is provided. A trial was conducted to determine whether juvenile nocturnal lizards require access to UVb to prevent vitamin D deficiency. All leopard geckos (Eublepharis macularius) were supplemented with dietary vitamin D 3 . One group was exposed to low level UVb radiation (33-51 μW/cm 2 ) from hatching until 6 months of age and a second group remained unexposed. Animals were fed ad libitum and their growth and weight gain compared with non-exposed controls. At the end of the trial, blood samples were analysed for vitamin D 3 metabolites. The concentration of the vitamin D 3 metabolite, 25(OH)D 3 , was higher in UVb exposed animals (61 ± 20 vs. 38 ± 8 nmol/L), confirming cutaneous synthesis with UVb exposure. Growth and weight gain were similar in both groups, and this, together with the absence of clinical symptoms, suggests that dietary vitamin D 3 alone can meet the vitamin D requirements for growth of this nocturnal gecko, during the first six months of life. It remains to be investigated whether the higher vitamin D metabolite levels holds other health benefits for this species, such as improved bone density or immune response., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Homo sapiens evolved in East Africa and had dark skin, hair, and eyes, in order to protect against deleterious consequences of intensive UV radiation at equatorial latitudes. Intensive skin pigmentation was thought to bear the risk of inefficient vitamin D 3 synthesis in the skin. This initiated the hypothesis that within the past 75 000 years, in which humans migrated to higher latitudes in Asia and Europe, the need for vitamin D 3 synthesis served as an evolutionary driver for skin lightening. In this review, we summarize the recent archeogenomic reconstruction of population admixture in Europe and demonstrate that skin lightening happened as late as 5000 years ago through immigration of lighter pigmented populations from western Anatolia and the Russian steppe but not primarily via evolutionary pressure for vitamin D 3 synthesis. We show that variations in genes encoding for proteins being responsible for the transport, metabolism and signalling of vitamin D provide alternative mechanisms of adaptation to a life in northern latitudes without suffering from consequences of vitamin D deficiency. This includes hypotheses explaining differences in the vitamin D status and response index of European populations., (© 2020 The Authors. Experimental Dermatology published by John Wiley & Sons Ltd.)

Aim: A commercially available light emitting diode (LED) that transmitted narrow band ultraviolet B (UVB) radiation was evaluated for its efficacy and efficiency to produce vitamin D 3 in human skin., Materials and Methods: Human skin samples were obtained from surgical procedures. The LED had peak emission wavelength of 295 nm. Skin samples were exposed to the UVB-LED for varying times and then were analyzed by high-pressure liquid chromatography (HPLC) to determine the vitamin D 3 content., Results: There was a statistically significant time- and dose-dependent increase in the percent of 7-dehydrocholesterol that was converted to vitamin D 3 in the skin type II samples; 1.3%±0.5, 2.3%±0.6 and 4.5%±1.67 after exposure to 0.75 (11.7 mJ/cm 2 ), 1.5 (23.4 mJ/cm 2 ) and 3 (46.8 mJ/cm 2 ) minimal erythemal doses (MEDs), respectively., Conclusion: The UVB-LED was effective and efficient in generating vitamin D 3 in human skin, in vitro. The amount of vitamin D 3 production increased in a dose-dependent fashion with increased UVB energy. UVB-LEDs can be developed for devices that can efficiently produce vitamin D 3 in human skin., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To assess the effectiveness of three UV emitting lamps on the cutaneous production of vitamin D 3 , a marker of DNA damage and nitric oxide production in human skin., Materials and Methods: Human skin samples (skin types II, III and IV) obtained from surgery were exposed to three different UV emitting lamps for varying times and then extracted and chromatographed to determine the vitamin D 3 content. The skin samples exposed to the 3 UV emitting lamps were also evaluated for 8-hydroxy-2'-deoxyguanosine (a marker of DNA damage) and nitric oxide production., Results: It was observed that the spectral output of the 3 lamps had different effects on the cutaneous production of vitamin D 3 , 8-hydroxy-2'-deoxyguanosine and nitric oxide production. One lamp demonstrated optimal production of vitamin D 3 with the least amount of DNA damage and intermediate production of nitric oxide suggesting that it could be developed into a device for treating vitamin D deficiency., Conclusion: The spectral output of the experimental UVB emitting lamps significantly influenced the cutaneous production of vitamin D 3 8-hydroxy-2'-deoxyguanosine and nitric oxide., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Understanding of vitamin D physiology is important because about half of the population is being diagnosed with deficiency and treated with supplements. Clinical guidelines were developed based on observational studies showing an association between low serum levels and increased cardiovascular risk. However, new randomized controlled trials have failed to confirm any cardiovascular benefit from supplementation in the general population. A major concern is that excess vitamin D is known to cause calcific vasculopathy and valvulopathy in animal models. For decades, administration of vitamin D has been used in rodents as a reliable experimental model of vascular calcification. Technically, vitamin D is a misnomer. It is not a true vitamin because it can be synthesized endogenously through ultraviolet exposure of the skin. It is a steroid hormone that comes in 3 forms that are sequential metabolites produced by hydroxylases. As a fat-soluble hormone, the vitamin D-hormone metabolites must have special mechanisms for delivery in the aqueous bloodstream. Importantly, endogenously synthesized forms are carried by a binding protein, whereas dietary forms are carried within lipoprotein particles. This may result in distinct biodistributions for sunlight-derived versus supplement-derived vitamin D hormones. Because the cardiovascular effects of vitamin D hormones are not straightforward, both toxic and beneficial effects may result from current recommendations., (© 2018 American Heart Association, Inc.)

Health-optimum-exposure index (HOEI) is proposed to assess if the prescribed amount of vitamin D 3 (target value) could be synthesized in the human skin without erythema appearance. It is defined as the ratio between the vitamin D 3 quantity received during the maximum allowed outdoor exposure without erythema risk and the target value. Sunbathing is safe for HOEI>1 and 1/HOEI represents a part of minimal erythema dose (MED) necessary to obtain the target value. We examine the following targets: a vitamin D 3 quantity equivalent to 1000 IU vitamin D 3 taken orally, and an optimal vitamin D 3 quantity defined by Krzyścin et al. (2016). The biologically weighted (previtamin D 3 and erythemal) doses from the Northern Hemisphere midlatitudinal stations are analyzed to find HOEI dependence on personal and meteorological factors. HOEI depends mostly on the exposed skin area, person's age, and sun elevation at noon but not on the Fitzpatrick skin phototype. We found that only young adults (<21 yr) could safely obtain vitamin D 3 quantity, which is equivalent to 1000 IU taken orally, almost throughout the whole year. Duration of such exposures appears <1 h only in the warm subperiods of the year (April-September) for a person with minimal erythema dose of 330 J m -2 . Exposing larger part of the body (~30%) enables the oldest persons (>59 yr) to reach 1000 IU target during warm days in spring and summer. The optimal daily vitamin D 3 quantity could only be synthesized only by young adults for about 40-60% of days in the May-August period if they expose at least 1/3 part of their body surface area. Vitamin D 3 supplementation seems to be necessary over the whole year for the oldest persons with daily dosage of ~2000 IU but reduced to ~1000 IU in summer for sunseekers exposing significant part of the body., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Vitamin D, the sunshine vitamin is important for health. Those with fat malabsorption disorders malabsorb vitamin D and thus must rely on cutaneous production of vitamin D 3 . Vitamin D 3 is generated secondary to exposure to ultraviolet B (UVB) radiation (whether from the sun or from an artificial source). Light emitting diodes (LEDs) have been developed to emit ultraviolet radiation. Little is known about the efficiency of UVB emitting LEDs tuned to different wavelengths for producing vitamin D 3 in human skin. Ampoules containing 7-dehydrocholesterol were exposed to a LED that emitted a peak wavelength at 293, 295, 298 or 305 nm to determine their efficiency to produce previtamin D 3 . The 293 nm LED was best suited for evaluating its effectiveness for producing vitamin D in human skin due to the shorter exposure time. This LED was found to be 2.4 times more efficient in producing vitamin D 3 in human skin than the sun in less than 1/60 th the time. This has significant health implications for medical device development in the future that can be used for providing vitamin D supplementation to patients with fat malabsorption syndromes as well as patients with other metabolic abnormalities including patients with chronic kidney disease.

The lower risk of some internal cancers at lower latitudes has been linked to greater sun exposure and consequent higher levels of ultraviolet radiation (UVR)-produced vitamin D 3 (D 3 ). To separate the experimental effects of sunlight and of all forms of D 3 , a mouse in which UVR does not produce D 3 would be useful. To this end we have generated mice carrying a modified allele of sterol C5-desaturase (Sc5d), the gene encoding the enzyme that converts lathosterol to 7-dehydrocholesterol (7-DHC), such that Sc5d expression can be inactivated using the Cre/lox site-specific recombination system. By crossing to mice with tissue-specific expression of Cre or CreER 2 (Cre/estrogen receptor), we generated two lines of transgenic mice. One line has constitutive keratinocyte-specific inactivation of Sc5d (Sc5d k14KO ). The other line (Sc5d k14KOi ) has tamoxifen-inducible keratinocyte-specific inactivation of Sc5d. Mice deleted for keratinocyte Sc5d lose the ability to increase circulating D 3 following UVR exposure of the skin. Thus, unlike in control mice, acute UVR exposure did not affect circulating D 3 level in inducible Sc5d k14KOi mice. Keratinocyte-specific inactivation of Sc5d was proven by sterol measurement in hair - in control animals lathosterol and cholesta-7,24-dien-3β-ol, the target molecules of SC5D in the sterol biosynthetic pathways, together constituted a mean of 10% of total sterols; in the conditional knockout mice these sterols constituted a mean of 56% of total sterols. The constitutive knockout mice had an even greater increase, with lathosterol and cholesta-7,24-dien-3β-ol accounting for 80% of total sterols. In conclusion, the dominant presence of the 7-DHC precursors in hair of conditional animals and the lack of increased circulating D 3 following exposure to UVR reflect attenuated production of the D 3 photochemical precursor 7-DHC and, consequently, of D 3 itself. These animals provide a useful new tool for investigating the role of D 3 in UVR-induced physiological effects and, more broadly, for investigations of the cholesterol synthetic pathway in the skin and other targeted tissues., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In cattle, there are 2 significant forms of vitamin D: ergocalciferol (ERG) from fungi on roughage and cholecalciferol (CHO) from vitamin supplements or endogenous synthesis in the skin. The hypothesis of the present study is that vitamin D from the 3 sources is transported in different plasma fractions in the body. This is hypothesized to explain the lower efficiency of ERG compared to CHO in securing a sufficient plasma status of 25-hydroxyvitamin D and explain the inefficient excretion of dietary CHO into milk compared to endogenous CHO. Twenty vitamin D-depleted cows were assigned to 5 treatments: D2, housed indoor and fed 625-μg/d (25.000 IU) ERG; D3, housed indoor and fed 625-μg/d CHO; D2+D3, housed indoor and fed 625-μg/d ERG and 625-μg/d CHO; SUN, let out for daily pasture to facilitate CHO synthesis from sunlight; and D2+SUN, fed 625-μg/d ERG and let out for daily pasture. Blood samples were taken twice weekly and plasma fractionated by ultracentrifugation into 3 fractions: light lipoprotein (LLP), heavy lipoprotein (HLP), and protein and analyzed for content of ERG and CHO and their liver derived metabolites 25-hydroxyergocalciferol (25ERG) and 25-hydroxycholecalciferol (25CHO), respectively. Liver biopsies were taken on the last day of the study to asses gene expression related to vitamin D metabolism. During 4 wk of study, the vitamin D status in plasma increased to 19.3 to 22.8 ng/mL 25ERG in ERG-treated cows with the highest concentration in D2 (P ≤ 0.05) and to 25.0 to 33.4 ng/mL 25CHO in pasture or CHO-treated cows with the highest concentration in SUN (P ≤ 0.01). In plasma fractions, CHO was mainly found in the HLP fraction, whereas 25CHO was almost exclusively found in the protein fraction, probably due to its reported high binding affinity to vitamin D-binding protein. About 70% to 90% of 25ERG was found in the protein fraction and the remaining 25ERG was found in HLP, whereas ERG was found in both HLP and LLP fractions. In liver tissue, the expression of vitamin D-25-hydroxylase was lower in D2+D3 (P ≤ 0.05) and SUN (P ≤ 0.05) than that in the remaining groups, and the vitamin D receptor was expressed in the liver to a larger extent in D2+SUN than that in D2+D3 (P ≤ 0.05) and SUN (P ≤ 0.05). In conclusion, different plasma transport mechanisms may explain the lower physiological efficiency of ERG compared to CHO in securing the vitamin D status in plasma but do not explain the lower efficiency of synthetic CHO compared to endogenous CHO from sunlight or UV light in securing a high CHO content in milk., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The link between UV light (sunlight) and endogenous cholecalciferol (vitamin D 3 ) synthesis in the skin of humans has been known for more than a 100 years, since doctors for the first time successfully used UV light to cure rickets in children. Years later, it was shown that UV light also had a significant effect on the cholecalciferol status in the body of cattle. The cholecalciferol status in the body is measured as the plasma concentration of 25-hydroxycholecalciferol, which in cattle and humans is the major circulating metabolite of cholecalciferol. Very little is, however, known about the quantitative efficiency of UV light as a source of cholecalciferol in cattle nutrition and physiology. Hence, the aim of this study was to determine the efficiency of using UV light for increasing the plasma 25-hydroxycholecalciferol concentration in cholecalciferol-deprived cattle. Twelve cows deprived of cholecalciferol for 6 months were divided into three treatment groups and exposed to UV light for 30, 90 or 120 min/day during 28 days. UV-light wavelengths ranged from 280 to 415 nm and 30-min exposure to the UV light was equivalent to 60-min average summer-sunlight exposure at 56 °N. Blood samples were collected every 3-4 days and analysed for 25-hydroxycholecalciferol and cholecalciferol. Results showed that increasing the exposure time from 90-120 min/day did not change the slope of the daily increase in plasma 25-hydroxycholecalciferol. Hence, it appears that cholecalciferol-deprived dairy cattle are able to increase their plasma 25-hydroxycholecalciferol concentration by a maximum of 1 ng/ml/day from UV-light exposure., (Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.)

Vitamin D3 photosynthesis in the skin is formulated as a set of reaction equations, including side-reactions to lumisterol, tachysterol and toxisterols, and the accompanying reverse reactions, isomerisation of previtamin D3 to vitamin D3 and photodegradation of vitamin D3. The solution of this set is given for the stationary irradiance spectrum. The effective action spectrum for the instantaneous vitamin D3 production changes shape as a function of exposure, and therefore, no single action spectrum can be used. We assessed the action spectrum for unexposed skin and for skin that has been exposed to 7.5 Standard Erythemal Doses (SED). We constructed two new estimates: (1) the RIVM action spectrum, based on absorption spectra, quantum yields and skin transmission spectra, and (2) the modified QUT action spectrum, which is adjusted for self-absorption and skin transmission. For previously unexposed skin, the modified QUT action spectrum gives a qualitatively similar, but larger estimate than the RIVM action spectrum. We have not been able to solve the lack of quantitative agreement between the vitamin D production estimates from the three action spectrum estimates (RIVM, modified QUT and CIE). All new action spectra have stronger emphasis on the short wavelengths than the CIE action spectrum. We showed that, for wavelengths larger than 300 nm, the bandwidth that was used in the experiment that formed the basis of the CIE action spectrum, gives a red-shift of about 1 nm. Generally, with the formation of previtamin D3, the return reaction to provitamin D3 limits the production of vitamin D3. After some exposure, the new action spectrum has negative values for the longer wavelengths in the UVB. For the RIVM action spectrum, this happens after 7.5 SED, for the modified QUT action spectrum already after 1.25 SED, and after 7.5 SED the net production rate is largely cancelled. Thus prolonged exposure of previously unexposed skin saturates vitamin D3 formation. For maximum vitamin D production after 1.25 SED, sunscreens should block wavelengths larger than 310 nm. Sunscreens that block only UVB could result in reduction in vitamin D production after prolonged exposure, or even a destruction of vitamin D that has just been formed.

Unlabelled: Evaluation of ultraviolet B index (UVBI) and its impact on vitamin D synthesis is important. We observed the maximum UVBI between 11 am and 1 pm. There was no increase in serum 25(OH)D levels following sun exposure during winter as the UVBI was significantly low, emphasizing the need for vitamin D supplementation during these months., Introduction: The amount of vitamin D3 synthesizing UVB irradiation (290-320 nm) reaching the earth's surface at different altitudes and seasons in different parts of India and it's impact on vitamin D synthesis has not been well studied., Methods: The hourly UVB index (UVBI) from 10 am to 3 pm everyday for 12 months was measured by a solar meter in 4 different zones (North, Northeast, West and South) of the country. To study the impact of sun light exposure on vitamin D synthesis during winter, healthy school children aged 10-15 years were exposed to sunlight for a period of 30 min per day, between 11 am to 12 noon with 10 % body surface area, for 4 weeks. The main outcome measures were serum 25(OH)D, PTH, calcium, phosphate, and alkaline phosphatase levels before and after sun exposure., Results: The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. The highest UVBI was recorded from the North zone (4.5 ± 2.7 μW/Cm(2)), while the least was recorded in the Northeast zone (2.1 ± 1.2 μW/Cm(2)). UVBI readings in the Northeast zone were consistently low throughout the year, while all the other three zones showed significant seasonal fluctuations. Surprisingly, we observed a significant decrease in serum 25(OH)D levels from baseline (6.3 ± 4.6 to 5.1 ± 2.7 ng/mL; p < 0.001) despite sun exposure., Conclusion: The mean UVBI was highest between 11 am and 1 pm throughout the year in all locations. No increase in the serum 25(OH)D levels was observed following sun exposure in winter, emphasizing the need for vitamin D supplementation during these months.

Background/aim: The angular distribution of solar radiance and its spectral characteristics is required for the determination of vitamin D3 production in humans., Materials and Methods: The vitamin D3 weighted exposure can be calculated by integrating the incident solar spectral radiance over all relevant parts of the human body. A novel instrument allowing simultaneous measurements of spectral radiance from more than 100 directions has been developed. A large solar simulator for controlled experiments is described., Results: In summer it is relatively easy to obtain sufficient vitamin D because sun exposure times are short. In winter solstice vitamin D3 cannot be obtained with realistic clothing even if the exposure were extended to all daylight hours., Conclusion: Improved and controlled experiments to determine vitamin D3 production are required to assess the positive effects of solar UV radiation and to assess its natural variability., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Cholecalciferol (vitamin D3), produced in the skin by UVB irradiation (290-315nm) of 7-dehydrocholesterol, is metabolized in the liver into 25-hydroxyvitamin D [25(OH)D] which is a major circulating metabolite., Aim: To examine changes in serum concentrations of cholecalciferol and its metabolites after UVB exposure of different skin areas., Methods: 21 healthy Caucasians (skin type II and III, aged 23-47years) were exposed to broadband UVB (290-320nm) and randomized to either exposure to one minimal erythema dose given as a single dose, or a suberythemic dose given for 3 subsequent days. The following areas were exposed: face and back of hands, upper half of the body and the whole body, respectively. Serum cholecalciferol and 25(OH)D were measured immediately before start and 24h after the 1st and last exposure, respectively., Results: Subjects with whole body exposure had an average S-cholecalciferol increase per dose unit of 0.18ngml(-1)mJ(-1)cm(2), 0.95 CI: (0.16, 0.20), upper body treatment 0.13ngml(-1)mJ(-1)cm(2), 0.95 CI: (0.10, 0.15) and face and hands exposure 0.013ngml(-1)mJ(-1)cm(2), 0.95 CI: (-0.012, 0.037). The increase in cholecalciferol correlated positively to the UVB dose and skin erythema and negatively to body mass index (BMI) when controlling for other factors. Exposure of face and hands induces smaller cholecalciferol production in comparison with exposure of larger skin areas., Conclusion: Size of the exposed skin area, UVB dose, skin erythema and BMI were the major determinants for serum levels of skin synthesized cholecalciferol. Exposure of hands and face induces smaller cholecalciferol production in comparison with exposure of larger skin areas., (Copyright © 2015 Elsevier B.V. All rights reserved.)

UV-activated 7-dehydrocholesterol (7-DHC) has been successfully used as a biocompatible coating for titanium (Ti) implants producing active vitamin D with positive effect on osteoblast differentiation. Since an osseointegrating implant must promote bone formation while delay resorption, here we determine the effect of this coating on the pre-osteoclast cell line RAW 264.7. Moreover, D3 synthesis was optimized by (1) the supplementation with VitE of the 7-DHC coating to reduce 7-DHC oxidation and (2) the addition of an incubation step (48 h at 23°C) after UV-irradiation to favor isomerization. In vitro results with RAW264.7 cells showed no cytotoxic effect of the coatings and a significant decrease of osteoclastogenesis. Indeed, TRAP immunostaining suggested an inhibition of Trap-positive multinucleated cells and the mRNA levels of different phenotypic, fusion, and activity markers were reduced, particularly with 7-DHC:VitE. In conclusion, we demonstrate an improvement of the D3 synthesis from UV-activated 7-DHC when combined with VitE and show that these implants inhibit osteoclastogenesis in vitro., (© 2014 Wiley Periodicals, Inc.)

Many amphibian species are dependent on ex situ conservation interventions for their long-term persistence. However, projects have been jeopardised by husbandry issues involving poor calcium metabolism and nutritional metabolic bone disease (NMBD). Healthy calcium metabolism requires appropriate dietary calcium content and access to vitamin D3 . In many animals, vitamin D3 can be photobiosynthesised in skin exposed to UVB radiation, as well as extracted from the diet, but the extent of vitamin D3 photobiosynthesis in amphibians is poorly known. Additionally, prey insects for captive amphibians are deficient in calcium and calcium content must be artificially increased, but the effects of different levels of augmentation and their interaction with UVB exposure are also little understood. We fed captive fire-bellied toads (Bombina orientalis) with crickets augmented to contain 5% and 10% calcium and housed them with and without UVB exposure. Despite additional dietary vitamin D3 supplementation, we found that toads exposed to UVB radiation exhibited significantly higher serum vitamin D3 levels, indicating that this species may partly rely on photobiosynthesis sources of vitamin D3 . These data are the first to show a direct link between UVB exposure and serum vitamin D3 in an amphibian. We found significant positive effects of UVB exposure and 10% dietary calcium content on skeletal structure, as well as complex interactions between treatments. We also found UVB radiation exposure resulted in more rapid natural coloration acquisition. Together, this indicates that standard calcium plus vitamin D3 supplementation methods may not fully substitute for UVB exposure and for increased feeder insect calcium content. This may have implications for the success of ex situ amphibian conservation, as well as for the welfare of captive amphibians in general. Our data lend support for the provision of UVB radiation for captive, basking amphibians., (Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.)

Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the presence of the BCR‑ABL1 fusion gene, a constitutively active, oncogenic tyrosine kinase that is responsible for the clinical features of CML. Tyrosine kinase inhibitors, such as imatinib, have markedly altered the treatment of CML. However, tyrosine kinase inhibitors are associated with side effects on bone metabolism, in adult and pediatric patients. Vitamin D3 is involved in the complex cycle of bone remodeling, therefore the present study aimed to investigate the influence of imatinib on vitamin D3 metabolism in the HaCaT human keratinocyte cell line, using commercially available enzyme assays. Imatinib was shown to significantly reduce the production of calcidiol and calcitriol. Based on interaction studies of imatinib with the cytochrome P450 (CYP450) inhibitors VID400 and ketoconazole, it is proposed that imatinib may interfere with the vitamin D3 cascade due to its metabolism by CYP27B1, which is involved in vitamin D3 metabolism.

Background: Cholecalciferol is an essential steroid produced in the skin by solar ultraviolet B radiation (UVB 290-315nm). Skin production of cholecalciferol depends on factors affecting UVB flux, age and exposed skin area., Purpose: Serum cholecalciferol and 25-hydroxyvitamin D3 [25(OH)D3] concentrations were measured after UVB irradiation of 3 different skin areas to compare the skin capacity to produce vitamin D in different anatomic sites in the same individuals., Method: Ten voluntary Caucasians (skin photo type II & III, aged 48±12years (±SD)) were exposed to broadband UVB (280-320nm) between February and April. Hands and face, upper body and whole body were exposed to a suberythemic dose of UVB (median 101mJ/cm(2) (min 66, max 143)) (for 3 subsequent days 24h apart with a wash out period of about 3weeks (median 18days (min 11, max 25)) between the exposures of respective area. Serum concentrations of cholecalciferol and 25(OH)D3, were measured immediately before the first and 24h after the last dose of radiation., Results: There was a significantly higher increase in serum cholecalciferol after UVB exposure of the two larger skin areas compared to face and hands, but no difference in increase was found between upper body and whole body exposures., Conclusion: Exposure of a larger skin area was superior to small areas and gave greater increase in both serum cholecalciferol and serum 25(OH)D3 concentrations. However, exposure of face and hands, i.e. only 5% of the body surface area, was capable of increasing serum concentrations of 25(OH)D3., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Vitamin D3 is a secosteroid mainly synthesized from the conversion of the skin precursor 7-dehydrocholesterol (7DHC) to vitamin D3 by ultraviolet (UV) B sunlight. Extrarenal synthesis of vitamin D3 has been reported in many tissues and cells, including barrier sites. This study characterizes the expression of components of vitamin D3 signaling in human ocular barrier cells., Methods: Primary human scleral fibroblasts (HSF), human corneal endothelial (HCEC-12), nonpigmented ciliary body epithelial (ODM-2), and adult retinal pigment epithelial (ARPE-19) cell lines were analyzed for the expression of vitamin D receptor (VDR), the vitamin D3 activating enzymes 1α-hydroxylase (CYP27B1), 25-hydroxylases (CYP27A1 and CYP2R1), the vitamin D3 inactivating enzyme 24-hydroxylase (CYP24A1), and the endocytic receptors cubilin and megalin using a combination of RT-PCR, immunocytochemistry, and enzyme immunoassay (EIA)., Results: The HSF, HCEC-12, ODM-2, and ARPE-19 express mRNA and protein for all vitamin D3 synthesizing and metabolizing components. The cell types tested, except HSF, are able to convert inactive 25-hydroxyvitamin D3 (25[OH]D3) into active 1,25-hydroxyvitamin D3 (1,25[OH]2D3)., Conclusions: This novel study demonstrated that ocular barrier epithelial cells express the machinery for vitamin D3 and can produce 1,25(OH)2D3. We suggest that vitamin D3 might have a role in immune regulation and barrier function in ocular barrier epithelial cells.

Polysulphone (PS) dosimetry is a well-known technique broadly used to assess the erythemally effective solar UV dose received by anatomical sites (personal exposure). We investigate the capability of PS dosimetry to convert doses absorbed by PS badges into biologically effective solar UV exposures taking as examples two relevant effects for human skin: erythema induction and pre-vitamin D3 production. PS calibration curves for erythemal and pre-vitamin D3 were distinctly determined by using an empirical relationship between the biologically effective UV exposures and the PS absorbance change. This relationship is parameterized by a coefficient, distinct for each of the two considered biological effects, multiplying the same cubic polynomial function. It is shown how the multiplying coefficient is related to the ratio between the biologically effective and the PS weighted irradiances which is the prevailing factor affecting the accuracy of the calibration and, consequently, the capability of PS films for measuring biologically effective solar UV exposures. The points addressed in this paper can be extended to other biological effects of interest whose action spectra have some similarity with the PS film response.

The demand for analysis of 25-hydroxyvitamin D has increased dramatically throughout the world over the past decade. As a consequence, a number of new automated assays have been introduced for 25-hydroxyvitamin D measurement. Automated assays have shown variable ability to meet the technical challenges associated with 25-hydroxyvitamin D measurement. Assays are able to meet performance goals for precision at high concentrations but fail to do so at low concentrations of 25-hydroxyvitamin D. The overall accuracy of automated methods has improved over recent years and generally shows good overall agreement with reference methods; however, discrepancies persist for individual samples. Liquid chromatography-tandem mass spectrometry is used by some routine laboratories for 25-hydroxyvitamin D analysis but its widespread use is hampered by limited sample throughput. 1,25-Dihydroxyvitamin D is an important analyte in specific clinical situations, which remains in the hands of specialised laboratories using manual analytical methods., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The magnitude of vitamin D inputs in individuals not taking supplements is unknown; however, there is a great deal of information on quantitative response to varying supplement doses. We reanalyzed individual 25-hydroxyvitamin D [25(OH)D] concentration data from 8 studies involving cholecalciferol supplementation (total sample size = 3000). We extrapolated individual study dose-response curves to zero concentration values for serum 25(OH)D by using both linear and curvilinear approaches and measured seasonal oscillation in the serum 25(OH)D concentration. The total basal input (food plus solar) was calculated to range from a low of 778 iu/d in patients with end-stage renal disease to a high of 2667 iu/d in healthy Caucasian adults. Consistent with expectations, obese individuals had lower baseline, unsupplemented 25(OH)D concentrations and a smaller response to supplements. Similarly, African Americans had both lower baseline concentrations and lower calculated basal, all-source inputs. Seasonal oscillation in 4 studies ranged from 5.20 to 11.4 nmol/L, reflecting a mean cutaneous synthesis of cholecalciferol ranging from 209 to 651 iu/d at the summer peak. We conclude that: 1) all-source, basal vitamin D inputs are approximately an order of magnitude higher than can be explained by traditional food sources; 2) cutaneous, solar input in these cohorts accounts for only 10-25% of unsupplemented input at the summer peak; and 3) the remainder must come from undocumented food sources, possibly in part as preformed 25(OH)D.

Background: Cholangiocarcinoma is a deadly biliary tumour with limited treatment strategies. Vitamin (1,25(OH)2D) has anti-proliferative effects on several cancers. Vitamin D3 is synthesized by the enzyme, CYP27B1, and signals via the nuclear vitamin D3 receptor. The enzyme, CYP24A1, degrades vitamin D3., Aims: (i) Measure the expression of CYP27B1, CYP24A1, and vitamin D3 receptor in human nonmalignant and cholangiocarcinoma lines and biopsy control or tumour samples; and (ii) evaluate the effects of vitamin D3 on vitamin D3 synthesis and cholangiocarcinoma growth., Methods: In vitro studies were performed in malignant and nonmalignant cholangiocytes. Vitamin D3 receptor, CYP24 and CYP27 expression was measured in cell lines and biopsy samples. Cell lines were stimulated with vehicle or vitamin D3 from 30min to 48h. Cell viability was assessed by MTS assays and BrdU incorporation. Vitamin D3 receptor, CYP24A1 and CYP27B1 expression was measured in cholangiocarcinoma cells stimulated with vehicle or vitamin D3., Results: In cholangiocarcinoma lines and biopsy samples, vitamin D3 receptor and CYP24A1 expression increased compared to controls, whereas CYP27B1 expression was decreased or unchanged. Vitamin D3 induced nuclear translocation of vitamin D3 receptor in cholangiocarcinoma and decreased cholangiocarcinoma growth., Conclusion: Treatment with vitamin D3 decreased CYP24A1, whereas CYP27B1 expression increased. Modulation of vitamin D3 synthesis may be important in the management of cholangiocarcinoma., (Published by Elsevier Ltd.)

Although the importance of solar radiation for vitamin D3 synthesis in the human body is well known, the solar exposure time required to prevent vitamin D deficiency has not been determined in Japan. This study attempted to identify the time of solar exposure required for vitamin D3 synthesis in the body by season, time of day, and geographic location (Sapporo, Tsukuba, and Naha) using both numerical simulations and observations. According to the numerical simulation for Tsukuba at noon in July under a cloudless sky, 3.5 min of solar exposure are required to produce 5.5 μg vitamin D3 per 600 cm2 skin corresponding to the area of a face and the back of a pair of hands without ingestion from foods. In contrast, it took 76.4 min to produce the same quantity of vitamin D3 at Sapporo in December, at noon under a cloudless sky. The necessary exposure time varied considerably with the time of the day. For Tsukuba at noon in December, 22.4 min were required, but 106.0 min were required at 09:00 and 271.3 min were required at 15:00 for the same meteorological conditions. Naha receives high levels of ultraviolet radiation allowing vitamin D3 synthesis almost throughout the year.

Low levels of vitamin D have been implicated in a wide variety of health issues from calcemic diseases to cancer, diabetes and cardiovascular disease. For most humans, the majority of vitamin D(3) is derived from sunlight. How much vitamin D is produced under given exposure conditions is still widely discussed. We present a computational model for the production of (pre-)vitamin D within the skin. It accounts for spectral irradiance, optical properties of the skin and concentration profile of provitamin D. Results are computed for various sets of these parameters yielding the distribution of produced previtamin D in the skin.

Background: Sunlight contains ultraviolet B (UVB) radiation (290-315 nm) that affects human health in both detrimental (skin cancers) and beneficial (vitamin D3) ways. Serum 25-hydroxyvitamin D concentrations from young Americans (≤ 19 years) show that many have deficient (< 50 nmol/L, 20 ng/mL) or insufficient (< 75 nmol/L, 30 ng/mL) vitamin D levels, indicating that they are not getting enough sun exposure. Those findings are in conflict with some calculated, published values that suggest people make "ample" vitamin D3 (~ 1,000 IU/day) from their "casual," or everyday, outdoor exposures even if they diligently use sunscreens with sun protection factor (SPF) 15., Objective: We estimated how much vitamin D3 young Americans (n = ~ 2,000) produce from their everyday outdoor ultraviolet doses in the North (45°N) and South (35°N) each season of the year with and without vacationing., Methods: For these vitamin D3 calculations, we used geometric conversion factors that change planar to whole-body doses, which previous calculations did not incorporate., Results: Our estimates suggest that American children may not be getting adequate outdoor UVB exposures to satisfy their vitamin D3 needs all year, except some Caucasians during the summer if they do not diligently wear sunscreens except during beach vacations., Conclusion: These estimates suggest that most American children may not be going outside enough to meet their minimal (~ 600 IU/day) or optimal (≥ 1,200 IU/day) vitamin D requirements.

The purpose of this study was to quantify the ultraviolet B (UVB) output and in vitro previtamin D(3) synthesis over time from various artificial light sources. Three incandescent lamps, T-Rex Active UVHeat 160 watt spot, T-Rex Active UVHeat 160 watt flood, and ZooMed PowerSun 160 watt flood, and two 1.2 m fluorescent lamps, Sylvania Blacklight 350 BL and ZooMed Reptisun 5.0, were studied. Total UVB irradiance and concentration of previtamin D synthesized using an in vitro ampoule model were quantified initially and at monthly intervals for 1 year. Incandescent lamps were measured at distances of 0.9 and 1.5 m while fluorescent lamps were measured at distances of 30.5 and 45.7 cm at the lamp's center, using both the radiometer and ampoules. Fluorescent lamp irradiance was also measured at the lamp's ends. Data were analyzed as a repeated measures split-plot in time using SAS with all mean differences determined using Least Squares Means. Incandescent lamp irradiance differences were seen at various distances. The UVHeat lamps had consistently higher previtamin D(3) production and irradiance readings compared with the PowerSun lamp. Reptisun 5.0 was consistently higher in UVB irradiance over Sylvania BL 350 at both 30.5 and 45.7 cm. However, there were no differences when comparing conversion of 7-dehydrocholesterol to previtamin D(3). Irradiance differences were detected between the centers and ends of the fluorescent lamps. Until UVB requirements for vitamin D(3) synthesis in animals are determined, it is impossible to state that one light is superior to another., (© 2010 Wiley-Liss, Inc.)

Vitamin D has historically been considered to play a role solely in bone and calcium metabolism. Human disease associations and basic physiological studies suggest that vitamin D deficiency is plausibly implicated in adverse health outcomes including mortality, malignancy, cardiovascular disease, immune functioning and glucose metabolism. There is considerable evidence that low maternal levels of 25 hydroxyvitamin D are associated with adverse outcomes for both mother and fetus in pregnancy as well as the neonate and child. Vitamin D deficiency during pregnancy has been linked with a number of maternal problems including infertility, preeclampsia, gestational diabetes and an increased rate of caesarean section. Likewise, for the child, there is an association with small size, impaired growth and skeletal problems in infancy, neonatal hypocalcaemia and seizures, and an increased risk of HIV transmission. Other childhood disease associations include type 1 diabetes and effects on immune tolerance. The optimal concentration of 25 hydroxyvitamin D is unknown and compounded by difficulties in defining the normal range. Whilst there is suggestive physiological evidence to support a causal role for many of the associations, whether vitamin D deficiency is a marker of poor health or the underlying aetiological problem is unclear. Randomised controlled trials of vitamin D supplementation with an appropriate assessment of a variety of health outcomes are required., (2010. Published by Elsevier Ltd.)

The biologically active metabolite of vitamin D, 1,25(OH)(2)D(3), affects mineral homeostasis and has numerous other diverse physiologic functions including effects on growth of cancer cells and protection against certain immune disorders. This article reviews the role of vitamin D hydroxylases in providing a tightly regulated supply of 1,25(OH)(2)D(3). The role of extrarenal 1alpha(OH)ase in placenta and macrophages is also discussed, as well as regulation of vitamin D hydroxylases in aging and chronic kidney disease. Understanding specific factors involved in regulating the hydroxylases may lead to the design of drugs that can selectively modulate the hydroxylases. The ability to alter levels of these enzymes would have therapeutic potential for the treatment of various diseases, including bone loss disorders and certain immune diseases., (Copyright 2010 Elsevier Inc. All rights reserved.)

How hair-coated animals such as dairy cows synthesize endogenous vitamin D(3) during exposure to summer sunlight has been unclear since vitamin D(3) and its relation to sunlight was discovered. The fur of fur-bearing animals is thought to be comparable to clothing in humans, which prevents vitamin D(3) synthesis in the skin during exposure to sunlight. Different scenarios have been suggested but never tested in cows; for example, that vitamin D(3) is synthesized from sebum on the hair and ingested by cows during grooming or that body areas such as the udder and muzzle that have scant hair exclusively produce the vitamin. To test different scenarios, 16 Danish Holstein dairy cows were subjected to 4 degrees of coverage of their bodies with fabric that prevented vitamin D(3) synthesis in the covered skin areas. The treatments were horse blanket (cows fitted with horse blankets), udder cover (cows fitted with udder covers, horse blanket+udder cover (cows fitted with both horse blankets and udder covers), and natural (cows without any coverage fitted). The cows were let out to pasture daily between 1000 and 1500h for 4 wk in July and August 2009. Blood samples were collected 15 times during the study and analyzed for content of 25-hydroxyvitamin D(3) [25(OH)D(3)] indicative of the animals' vitamin D(3) status. Results showed that uncovered cows had a higher 25(OH)D(3) concentration in plasma after 28 d of access to sunlight compared with covered cows and that the plasma concentration of 25(OH)D(3) was strongly inversely correlated to the body surface area covered. These results are consistent with findings in humans, wherein the vitamin D(3) status of different individuals was inversely proportional to the amount of clothing worn during exposure to artificial sunlight. Hence, it appears that human clothing and cow hair are not comparable with respect to prevention of vitamin D(3) synthesis and that cows, like humans, synthesize vitamin D(3) evenly over their body surface. That vitamin D(3) should be synthesized from sebum on the hair and obtained by cows as a result of grooming is not supported by the findings in the present study either, because large differences were found between the treatment groups. If grooming were the source of vitamin D(3), then a relatively even 25(OH)D(3) concentration between treatments would be expected, because covered cows would obtain vitamin D(3) by grooming uncovered herdmates., (Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Abstract This paper reports on the variation of UV radiation in full sun and in shade and how this relates to the physiological production of vitamin D(3) for various latitudes. Calibrated spectral measurements were used to measure the UV radiation in the shade of numerous shade environments for varying solar zenith angles and seasons. This was for exposures to the horizontal, 45 degrees and vertical planes for the solar zenith angle (SZA) range of approximately 5 degrees to 80 degrees. For an SZA of approximately 5 degrees, average UV irradiances required for vitamin D(3) production (UV(D3)) were 0.67 W/m(2) and 0.20 W/m(2) for global and for shade with a sky view of greater than 40%, respectively. The best time to expose the human body to UV radiation while using shaded environments with a sky view of greater than 40% for vitamin D(3) synthesis is for SZAs less than approximately 45 degrees. Shade can be used throughout Australia during summer and winter. However, winter exposure times will vary depending on the latitude. Using shade for UV(D3) exposures can reduce total UV-radiation exposure by 37% to 58% compared to full sun UV(D3) exposures. This research indicates that an improved approach to optimize UV-radiation exposures for the production of vitamin D(3) is to use diffuse UV radiation under shade in and around the middle of the day.

Ultraviolet B radiation exposure is responsible for the majority of natural vitamin D stores in humans. The physiologic role of vitamin D in health and disease is continually expanding, and at the same time the population that is vitamin D deficient is increasing. The environmental characteristics and personal physical traits that contribute to vitamin D3 synthesis from sun exposure are discussed, and the effects of photoprotection on vitamin D status are examined. It is concluded that sunscreen, in the manner used by the general public, does not cause vitamin D insufficiency. Implementing guidelines suggesting sun exposure duration for sufficient vitamin D3 production is limited by the complex interaction of contributory factors, and no recommendation can be made that is both safe and accurate enough for general public usage.

The universally recognised action spectrum for the UV-induced conversion of 7-dehydrocholesterol to previtamin D(3) in human skin was published in 1982, and indicates a maximum at about 297 nm with essentially no production above 315 nm. This work represents a milestone in research on vitamin D, but limitations in the original data should be recognised. Various findings have arisen in recent years which cast doubts on the accuracy of the action spectrum and its application for spectral weighting in calculations of effective UV doses. In conclusion, the construction of an entirely new computational model to predict previtamin D levels is recommended.

Amphibians are currently suffering a period of mass extinction with approximately 20% of species under severe threat and more than 120 species already extinct. In light of this crisis there is an urgency to establish viable ex situ populations and also find the causes of in situ declines. The role of ultraviolet radiation and Vitamin D(3) in amphibian health directly influences both ex situ and in situ populations. Vitamin D(3) can be photosynthesised endogenously via UV-B radiation (UV-B), or acquired through the diet, and then metabolised to calcitriol the biologically active hormonal form. Although, there is a lack of literature concerning Vitamin D(3) requirements and calcitriol synthesis in amphibians, amphibians are likely to have similar Vitamin D(3) requirements and metabolic processes as other vertebrates due to the phylogenetically conservative nature of calcitriol biosynthesis. Deficiencies in calcitriol in amphibians result in nutritional metabolic bone disease (NMBD) and could compromise reproduction and immunity. However, excess biologically active UV radiation has also proven detrimental across all three amphibian life stages and therefore could impact both in situ and ex situ populations. Here we review the role and necessity of UV-B and calcitriol in amphibians and the potential for negative impacts due to excessive exposure to UV radiation. We also identify priorities for research that could provide critical information for maintaining healthy in ex situ and in situ populations of amphibians.

A comment on [W.J. Olds, A.R. McKinley, M.R. Moore, M.G. Kimlin, In vitro model of vitamin D(3) (cholecalciferol) synthesis by UV radiation: dose-response relationships, J. Photochem. Photobiol. B: Biol. 93 (2008) 88-93]. The article also discusses some related issues.

The short wavelength cut-off (lambdac), the wavelength of the maximum spectral UV (lambdaMax) of spectral pre-vitamin D3 effective solar UV irradiance (UVD3), and the spectral erythemal UV (UVEry) were compared at 5-min intervals over a 6-month period at solar zenith angles (SZA) ranging from 4.7 degrees to 80 degrees. Averaged over the entire period, lambdac for UVD3 is higher by 1.05 nm than that for UVEry. The lambdaMax is higher for UVD3 compared to UVEry for SZA55 degrees), the ratio of lambdaMax for UVD3 to that for UVEry is less than 1. As the erythemal action spectrum extends into the UVA, the ratio of UVD3 to UVEry irradiances decreases with increasing SZA, along with a decrease in the ratio of lambdaMax for UVD3 compared to UVEry. The changes in lambdac and lambdaMax influence both personal UVD3 and UVEry exposure and, to take this into account, a dual calibration technique for polysulphone dosimeters has been developed to simultaneously provide measurements of both types of exposure.

Vitamin D deficiency is a major health concern worldwide. Very little is understood regarding its production in the human body by exposure to UV radiation. In particular, we have no means of predicting how much vitamin D (cholecalciferol) will be produced in the skin after exposure to sunlight. Using a refined in vitro model, we found that there is a nonlinear relationship between UV dose and cholecalciferol synthesis. Two minimal erythemal doses (MED) of UV radiation produced 1.84 microg/mL of cholecalciferol whereas 4 MED produced 2.81 microg/mL. We also found that the production of cholecalciferol is restricted by the initial concentration of its precursor (7-dehydrocholesterol, 7-DHC). For example, using an initial concentration of 7-DHC of 102 microg/mL, the resultant cholecalciferol production was 1.05 microg/mL after receiving 4 MED exposure. Under the same exposure conditions, an initial concentration of 305 microg/mL yielded 2.81 g/mL of cholecalciferol. The data presented in this paper has important implications for humans, including: (1) increasing UV exposure does not result in a proportionate increase in the amount of cholecalciferol that is produced; and (2) the initial concentration of 7-DHC in the skin may impact the amount of cholecalciferol that can be synthesized. When translating these results to population groups, we will discuss how the sun exposure message needs to be carefully formulated to account for such considerations.

The high prevalence of vitamin D deficiency and insufficiency in the human population results from its inadequate cutaneous production and low dietary intake. Vitamin D status in the organism is determined by circulating levels of 25-hydroxycholecalciferol [25(OH)D3]. 25(OH)D3 is metabolized by a renal 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1) into the vitamin D hormone 1,25 dihydroxycholecalciferol (calcitriol), which generates a wide range of biological responses via both the regulation of gene transcription and nongenomic pathways. Most of the circulating metabolite originates from cholecalciferol, which is synthesized in the skin upon exposure to the UVB spectrum of sunlight. The dietary source of vitamin D is extraordinarily low (10%) compared with endogenous production (90%). Recent epidemiological data demonstrated a strong association between poor vitamin D status (i.e. serum 25(OH)D3 levels below 50 nmol/l) and increased risk for chronic illnesses of various etiology. It is now recognized that maintaining a serum 25(OH)D3 level of 80 nmol/l (32 ng/ml) or greater is beneficial in the prevention of osteoporosis, cardiovascular diseases, certain autoimmune diseases, and some forms of cancer. It seems that sensible sun exposure and the use of supplements are the most effective ways of preventing vitamin D deficiency. The aim of the present article is to review new developments related to vitamin D deficiency and insufficiency and their consequences.

The reported low mortality rate from coronary heart disease in Portugal, Spain, Italy, Greece, and France, to a lesser extent, has been attributed in numerous nutritional studies to the consumption of a Mediterranean-type diet. There are still many unresolved issues about the direct causal effect of the Mediterranean dietary regime on low incidence of coronary heart disease. An analysis of coronary heart disease mortality rates in Europe from a latitudinal gradient perspective has shown to have a close correlation to incident solar radiation. It is surmised that the resulting increased in situ biosynthesis of Vitamin D(3) could be the critical missing confounder in the analysis of the beneficial health outcome of the Mediterranean diet.

Throughout evolution, exposure to sunlight and the photosynthesis of vitamin D(3) in the skin has been critically important for the evolution of land vertebrates. During exposure to sunlight, the solar UVB photons with energies 290-315 nm are absorbed by 7-dehydrocholesterol in the skin and converted to previtamin D(3). Previtamin D(3) undergoes a rapid transformation within the plasma membrane to vitamin D(3). Excessive exposure to sunlight will not result in vitamin D intoxication because both previtamin D(3) and vitamin D(3) are photolyzed to several noncalcemic photoproducts. During the winter at latitudes above approximately 35 degrees , there is minimal, if any, previtamin D(3) production in the skin. Altitude also has a significant effect on vitamin D(3) production. At 27 degrees N in November, very little ( approximately 0.5%) previtamin D(3) synthesis was detected in Agra (169 m) and Katmandu (1400 m). There was an approximately 2- and 4-fold increase in previtamin D(3) production at approximately 3400 m and at Everest base camp (5300 m), respectively. Increased skin pigmentation, application of a sunscreen, aging, and clothing have a dramatic effect on previtamin D(3) production in the skin. It is estimated that exposure in a bathing suit to 1 minimal erythemal dose (MED) is equivalent to ingesting between 10,000 and 25,000 IU of vitamin D(2). The importance of sunlight for providing most humans with their vitamin D requirement is well documented by the seasonal variation in circulating levels of 25-hydroxyvitamin D [25(OH)D]. Vitamin D deficiency [i.e., 25(OH)D < 20 ng/ml] is common in both children and adults worldwide. Exposure to lamps that produce UVB radiation is an excellent source for producing vitamin D(3) in the skin and is especially efficacious in patients with fat malabsorption syndromes. The major cause of vitamin D deficiency globally is an underappreciation of sunlight's role in providing humans with their vitamin D(3) requirement. Very few foods naturally contain vitamin D, and those that do have a very variable vitamin D content. Recently it was observed that wild caught salmon had between 75% and 90% more vitamin D(3) compared with farmed salmon. The associations regarding increased risk of common deadly cancers, autoimmune diseases, infectious diseases, and cardiovascular disease with living at higher latitudes and being prone to vitamin D deficiency should alert all health care professionals about the importance of vitamin D for overall health and well being.

Both calcitriol and UVB radiation exert potent antipsoriatic effects. We hypothesize that the therapeutical effect of UVB radiation may be attributed at least in part to UVB-triggered cutaneous synthesis of calcitriol. The optimum wavelength for initiation of the vitamin D(3) pathway was found to be in the range of 300+/-5 nm in vitro and in vivo. The narrowband Philips TL-01 lamp which is commonly used as UVB source for phototherapy of psoriasis has maximum spectral irradiance at around 311 nm which is presumed to be, however, of lesser importance in photochemical activation of the vitamin D(3) pathway. The aim of this study was to compare the vitamin D(3) and calcitriol-inducing potential of UVB from the TL-01 lamp with that of monochromatic UVB at 300+/-2.5 nm and 310+/-2.5 nm in organotypic cultures of keratinocytes supplemented with 25 microM 7-DHC. We found that maximum calcitriol-generating capacity of the TL-01 lamp at 500 mJ/cm(2) and 16 h after irradiation still amounts up to 44% of that found after monochromatic irradiation at 300+/-2.5 nm and 30 mJ/cm(2). Thus, the antipsoriatic effect of UVB emitted from the TL-01 lamp may, at least in part, based on the antiproliferative and prodifferentiative action of newly synthesized calcitriol on epidermal keratinocytes.

We are assured by responsible scientific and governmental organizations that sunscreens should be routinely worn to reduce skin cancer risk. We are also advised that wearing sunscreens will not hinder our ability to produce sufficient previtamin D3 (preD3) from casual sunlight exposure. We report the examination of a series of 166 solar spectra, obtained on different days throughout a year, evaluated for erythemic and preD3 effectiveness and the relative effects of recommended Sun protection factor (SPF) 15 sunscreen. The results show that the sunscreen is much more effective in blocking the formation of preD3, than its labeled SPF for preventing sunburn. In fact with sunscreen applied only miniscule amounts of preD3 are predicted to be made outdoors even with extensive exposure. This raises important questions regarding the safest way to use sunlight exposure to promote healthy vitamin D3 levels and suggests the need to modify the public safety "Safe Sun" messages.

It has been suggested that the major source of vitamin D should come from dietary sources and not sun exposure. However, the major fortified dietary source of vitamin D is milk which often does not contain at least 80% of what is stated on the label. Fish has been touted as an excellent source of vitamin D especially oily fish including salmon and mackerel. Little is known about the effect of various cooking conditions on the vitamin D content in fish. We initiated a study and evaluated the vitamin D content in several species of fish and also evaluated the effect of baking and frying on the vitamin D content. Surprisingly, farmed salmon had approximately 25% of the vitamin D content as wild salmon had. The vitamin D content in fish varied widely even within species. These data suggest that the tables that list the vitamin D content are out-of-date and need to be re-evaluated.