[Biosynthesis of fat-soluble vitamins].

Vitamins are the essential organic substances to ensure the normal life activities of the human body. At present, vitamins are widely used in the pharmaceutical, food, animal farming, beauty and other industries, appearing in increasing application scenarios. Accordingly, the global demand for vitamins has also increased greatly. The current methods of vitamin production mainly include chemical synthesis and biosynthesis, with the latter being greener, more environmentally friendly, safer, and lower in energy consumption. Establishing the method for the biosynthesis of vitamins is of great scientific significance for achieving the goals of low carbon, energy saving, and emission reduction, as well as carbon emission peak and carbon neutrality in China. This paper reviews the research progress in the biosynthesis of vitamins, especially fat-soluble vitamins (vitamins A, D, E, and K), in recent years.

Recent advances in microalgae-based vitamin D metabolome: Biosynthesis, and production.

Vitamin D (VD) production-based microalgae biosynthesis presents various benefits including sustainability, fast expansion, and the capacity to generate substantial quantities. However, this approach suffers from serious challenges that require effective cultivation methods and extraction processes. Indeed, further researches are of significant interest to understand the biosynthesis pathways, enhance the processes, and ensure its viability. In this context, the present review focuses on an in-depth understanding of the chemistry of VD and its analogues and provides a comprehensive explanation of the biosynthesis pathways, precursors, and production methods. In addition, this work discusses the state of the art reflecting the recent advances researches and the global market of microalgae as a potential source of VD. In sum, this paper demonstrates that microalgae can efficiently biosynthesize various forms of VD, presenting a sustainable alternative for VD production.

Exposure to UV Radiation in Lifeguards on Barcelona's Beaches: An Underestimated Occupational Risk. / [Artículo traducido] Exposición a radiación ultravioleta en socorristas de las playas de Barcelona: un riesgo laboral infravalorado.

BACKGROUND: The development of skin cancer is closely related to high exposure to UV radiation. Lifeguards are at an increased risk of excessive sun exposure. OBJECTIVES: The main objective of this study was to measure the exposure of Barcelona's beach lifeguards to UV radiation. METHODS: Measurements in the work chair were taken every 30min on a typical working day from 10:45 am to 19:15 pm. These measurements were carried out on four different days. These data were used to calculate the erythematous doses received during working hours, as well as those potentially received throughout the summer season. Vitamin D production was also estimated for the four days that the radiation received was measured, and the amount generated was calculated for the entire summer season. RESULTS: Exposure to UV radiation among Barcelona lifeguards far exceeds safety limits. In some locations, the exposure to UVB radiation is more than 16 times the minimum erythematous dose for phototype II skin. LIMITATIONS: This study assessed the radiation received during only four days. However, is a much higher number than most of the published papers. CONCLUSION: Although the health risks of excessive exposure to UV radiation are known, Barcelona's beach lifeguards are insufficiently protected.

Air pollutants are negatively associated with vitamin D-synthesizing UVB radiation intensity on the ground.

Atmospheric levels of pollutants may reduce the UVB intensity at the earth's surface, with a subsequent reduction in cutaneous vitamin D synthesis. We investigated the association of various pollutants with UVB intensity on the ground. Four-year data obtained from four weather stations from across Kuwait were analyzed by median regression. Pollutants that were negatively associated with UVB were [ß (95% CI)]: benzene [- 2.61 (- 4.13, - 1.09)], ethyl-benzene [- 2.20 (- 3.15, - 1.25)], ozone [- 0.23 (- 0.28, - 0.17)], nitric oxide [- 0.11 (- 0.15, - 0.06)], sulfur dioxide [- 0.10 (- 0.17, - 0.04)] and particulate matter PM10 [- 0.002 (- 0.003, - 0.002)]. Pollutants that were negatively associated with the UVB/UVA ratio were [ß (95% CI)]: benzene [- 15.57 (- 24.94, - 6.20)], nitric oxide [- 0.53 (- 0.81, - 0.25)], ozone [- 0.38 (- 0.70, - 0.06)], and total hydrocarbon [- 0.02 (- 0.04, - 0.01)]. Furthermore, benzene and nitric oxide levels were higher in the morning and evening hours, which are the times of most solar exposure in this region due to high temperature during midday. In addition to other known factors, attenuation of UVB by these pollutants may contribute to lower vitamin D levels in populations. In addition to direct public health hazard, these pollutants may contribute to the very high prevalence of VDD in this region.

Spectral Homeostasis - The Fundamental Requirement for an Ideal Sunscreen.

Sunscreen application to UV-exposed skin is promoted to prevent skin cancer and sun damage, within a comprehensive photoprotection strategy that also includes sun avoidance and wearing UV protective clothing. The benefits of sunscreen are verified in preventing sunburn but appear to be largely presumptive in skin cancer prevention. Contemporary science establishes UVA as a primary driver of melanoma and photoaging. Consequentially, the traditional UVB-skewed protection of sunscreens provides an intellectual and logical explanation for rising skin cancer rates and, in particular, their failure to protect against melanoma. Better protection could be achieved with more balanced UVB/UVA sunscreens, toward spectral homeostasis protection. Greater balanced protection has another advantage of attenuating fewer UVB rays, which aid synthesis of vitamin D and nitric oxide. Percutaneous absorption of Soluble Organic UV Filters leads to systemic exposure, which becomes the relevant safety consideration. It is minimized by selecting Insoluble UV Filters with low absorption potential from a molecular weight above 500 Da. The filters must also be very hydrophilic, very lipophilic, or consist of particles. The risk-benefit ratio is a medical imperative, more so for cosmetics or sunscreens, since in principle there should be no risk from their use. The production of ideal sunscreens that mimic the effective, balanced UVB/UVA attenuation of textiles and shade is now possible, while maintaining an acceptable therapeutic margin of safety in humans and a favorable ecologic profile. Sunscreens with a favorable risk-benefit ratio and good esthetic properties or other consumer-friendly attributes will improve compliance and may achieve substantial clinical benefits.

Sun Exposure and Vitamin D.

Vitamin D is generally accepted in its importance on the regulation of calcium homeostasis and bone metabolism. Moreover, further health effects due to vitamin D are under discussion. In its effect, vitamin D is more like a hormone. In the classic view, a vitamin is an essential nutrient, which cannot be synthesized independently in the body. Besides nutrition, vitamin D will be produced in the body itself. The skin contains the provitamin D3 7-dehydrocholesterol, a precursor of vitamin D. Provitamin D3 will be photoconverted to previtamin D3 by UVB radiation that penetrates the skin superficially. In this way, the vitamin D metabolism will be started independent of the nutrition. In everyday life, this photosynthesis will be carried out due to the solar UVB radiation penetrating the uncovered skin. In the same spectral waveband range of UVB radiation, which causes the beneficial health effect of starting the vitamin D metabolism, the UVB radiation causes simultaneously acute and chronic harmful health effects as UV erythema (sunburn), skin aging and skin cancer. There is no vitamin D production in the skin without simultaneous DNA damage in the skin. Against this background, risks and benefits have to be balanced carefully.

The Formula for Best Sunscreen Performance: Beer-Lambert's Law Under the Microscope.

Sunscreens used for the protection of human skin work by attenuating the potentially harmful solar UV radiation. In recent years, the quantitative understanding of this attenuating effect has grown tremendously, enabling model calculations of sunscreen performance. Such calculations are based on the simulation of the UV transmission of the sunscreen film applied on human skin. However, there are 2 prerequisites assumed to hold. The first prerequisite is the applicability of the Beer-Lambert law for sunscreen films, and the second is that the thickness variation of the sunscreen film can be described with a gamma distribution of film heights. There is strong evidence from recent experimental work that both assumptions are correct. For several applications, calculations of sunscreen performance have been shown to be useful, for instance, in the design of new sunscreen formulations aiming for a certain sun protection factor or other characteristics, prediction of pre-vitamin D production in the skin in the presence of sunscreen, in vitro measurement of water resistance, and assessment of the ecotoxicological profile of a sunscreen formulation or the influence of oil polarity on UV-filter absorbance and the consequence for sunscreen performance.

Risks and Benefits of UV Radiation.

While UV radiation is a skin carcinogen, this should not obscure the growing evidence that sunlight has significant health benefits, including impacts on cardiovascular and metabolic health. Epidemiological and mechanistic evidences for the importance of different wavelengths of sunlight, including blue light and UV radiation, are presented.

Erythemal and vitamin D weighted solar UV dose-rates and doses estimated from measurements in mainland France and on Réunion Island.

Solar UV radiation causes beneficial and detrimental changes in human health. International and national Health agencies recommend avoiding sun exposure when the solar rays are strongest (typically 2 h before and after solar noon). In this study we detail and refine such recommendations. We estimated biologically-effective radiation (inductive of erythema and pre-vitamin D) using spectral solar UV radiation measurements on a horizontal plane at three French sites equipped with spectroradiometers: Villeneuve d'Ascq (VDA) (North of France); Observatoire de Haute-Provence (OHP) (French Southern Alps); and Saint-Denis de La Réunion (SDR) on Réunion Island, in the Indian Ocean. These sites are very different: VDA is a semi-urban site in a flat region, OHP a rural mountainous site and SDR a coastal urban site on a small mountainous island. Biologically active radiation was analyzed by studying erythema induction and measuring pre-vitamin D synthesis. Dose-rates, doses and times for sunburn induction and vitamin D production were derived. Regarding the level of vitamin D dose considered here (1000 IU), we found that at mainland sites time required for vitamin D synthesis was relatively long, even around solar noon, in winter months this could be 2-3 h for phototype II individuals exposing their face and hands. In the tropics vitamin D could always be synthesized in a reasonable time (e.g. 20 min in winter). By contrast, in summer, the required duration times (exposing face, hands, arms and legs) are very short, approximately 2-4 min on the mainland and 1 min in the tropics for phototype II individuals. In all skin phototypes the duration of sun exposure required to induce erythema was generally longer than that to produce vitamin D. These quantitative results, obtained using an instrument measuring on a horizontal plane and with an unobstructed view, do not represent realistic values for human exposure. To account for realistic human body exposure, received doses and times of exposure were adjusted. Our study shows that, mostly in summer, the time periods where limited solar exposure is recommended should be extended, especially at low latitude locations.

A revised action spectrum for vitamin D synthesis by suberythemal UV radiation exposure in humans in vivo.

Action spectra are important biological weighting functions for risk/benefit analyses of ultraviolet (UV) radiation (UVR) exposure. One important human benefit of exposure to terrestrial solar UVB radiation (∼295 to 315 nm) is the cutaneous synthesis of vitamin D3 that is initiated by the photoconversion of 7-dehydrocholesterol to previtamin D3 An action spectrum for this process that is followed by other nonphotochemical steps to achieve biologically active vitamin D3 has been established from ex vivo data and is widely used, although its validity has been questioned. We tested this action spectrum in vivo by full- or partial-body suberythemal irradiation of 75 healthy young volunteers with five different polychromatic UVR spectra on five serial occasions. Serum 25-hydroxyvitamin D3 [25(OH)D3] levels, as the most accurate measure of vitamin D3 status, were assessed before, during, and after the exposures. These were then used to generate linear dose-response curves that were different for each UVR spectrum. It was established that the previtamin D3 action spectrum was not valid when related to the serum 25(OH)D3 levels, as weighting the UVR doses with this action spectrum did not result in a common regression line unless it was adjusted by a blue shift, with 5 nm giving the best fit. Such a blue shift is in accord with the published in vitro action spectra for vitamin D3 synthesis. Thus, calculations regarding the risk (typically erythema) versus the benefit of exposure to solar UVR based on the ex vivo previtamin D3 action spectrum require revision.

Vitamina D / Vitamin D

O termo vitamina D engloba um grupo de moléculas secosteroides derivadas do 7- deidrocolesterol (7-DHC ou provitamina D) interligadas através de uma cascata de reações fotolíticas e enzimáticas que acontecem em células de diferentes tecidos. (CASTRO, 2011). Nos seres humanos, apenas 10% a 20% da vitamina D necessária à adequada função do organismo provém da dieta. (CASTRO, 2011). O restante, cerca de 80%, da vitamina D é produzida na pele após a exposição à radiação ultravioleta B ­ UVB (HOLICK, 2008)

The term vitamin D encompasses a group of secosteroid molecules derived from 7- dehydrocholesterol (7-DHC or provitamin D) interconnected through a cascade of photolytic and enzymatic reactions that occur in cells of different tissues. (CASTRO, 2011). In humans, only 10% to 20% of the vitamin D needed for proper body function comes from the diet. (CASTRO, 2011). The remainder, about 80%, of vitamin D is produced in the skin after exposure to ultraviolet radiation B ­ UVB (HOLICK, 2008)

Ultraviolet radiation, vitamin D, and COVID-19.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has become pandemic on March 11th, 2020. COVID-19 has a range of symptoms that includes fever, fatigue, dry cough, aches, and labored breathing to acute respiratory distress and possibly death. Health systems and hospitals have been completely rearranged since March 2020 in order to limit the high rate of virus spreading. Hence, a great debate on deferrable visits and treatments including phototherapy for skin diseases is developing. In particular, as regards phototherapy very few data are currently available regarding the chance to continue it, even if it may be a useful resource for treating numerous dermatological patients. However, phototherapy has an immunosuppressive action possibly facilitating virus infection. In the context of COVID-19 infection risk it is important to pointed out whether sunlight, phototherapy and in particular ultraviolet radiation (UV-R) constitute or not a risk for patients. In this review we aimed to focus on the relationship between UV-R, sunlight, phototherapy, and viral infections particularly focusing on COVID-19.

Dysregulation of vitamin D synthesis pathway genes in colorectal cancer: A case-control study.

BACKGROUND: The cytochromes P450 are a superfamily of enzymes that control the synthesis of the biologically active form of vitamin D, 1,25-dihydroxyvitamin D3. These enzymes contribute to the formation of 1,25-dihydroxyvitamin D3, which starts with a 25-hydroxylation by CYP2R1 and CYP27A1 and a subsequent 1α-hydroxylation via CYP27B1. METHODS: By using quantitative real-time polymerase chain reaction (qRT-PCR), we analyzed the expression ratio of CYP2R1, CYP27A1 and CYP27B1 genes within the vitamin D metabolic pathway in a total of 75 colorectal cancer (CRC) tissues compared to the adjacent tissues. Furthermore, we evaluated the association of CYP27B1 rs4646536 and CYP2R1 rs12794714 and rs10766196 polymorphisms with CRC risk in a total of 490 subjects, including 245 CRC patients and 245 non-cancer controls. The genotyping was performed using tetra-primer amplification refractory mutation system polymerase chain reaction (TP-ARMS-PCR) method. RESULTS: The results indicated 2.3 and 2.7 upregulation of CYP2R1 and CYP27B1 genes in colorectal cancer tissues compared to the adjacent tissues, respectively. Rs12794714 AG genotype increased the risk of CRC (P = .03). Furthermore, a significant association was observed under the dominant inheritance model (P = .039). CONCLUSION: CYP2R1 and CYP27B1 genes were over-expressed in CRC samples compared to the adjacent control tissues. Furthermore, CYP2R1 rs12794714 variant was associated with the risk of CRC in the studied samples. CYP2R1 rs10766196 and CYP27B1 rs4646536 are not responsible for CYP2R1 and CYP27B1 genes expression alteration, respectively, but CYP2R1 rs12794714 polymorphism may be the reason of CYP2R1 upregulation and increased the risk of CRC.

Evidence of protective role of Ultraviolet-B (UVB) radiation in reducing COVID-19 deaths.

Prior studies indicate the protective role of Ultraviolet-B (UVB) radiation in human health, mediated by vitamin D synthesis. In this observational study, we empirically outline a negative association of UVB radiation as measured by ultraviolet index (UVI) with the number of COVID-19 deaths. We apply a fixed-effect log-linear regression model to a panel dataset of 152 countries over 108 days (n = 6524). We use the cumulative number of COVID-19 deaths and case-fatality rate (CFR) as the main dependent variables and isolate the UVI effect from potential confounding factors. After controlling for time-constant and time-varying factors, we find that a permanent unit increase in UVI is associated with a 1.2 percentage points decline in daily growth rates of cumulative COVID-19 deaths [p < 0.01] and a 1.0 percentage points decline in the CFR daily growth rate [p < 0.05]. These results represent a significant percentage reduction in terms of daily growth rates of cumulative COVID-19 deaths (- 12%) and CFR (- 38%). We find a significant negative association between UVI and COVID-19 deaths, indicating evidence of the protective role of UVB in mitigating COVID-19 deaths. If confirmed via clinical studies, then the possibility of mitigating COVID-19 deaths via sensible sunlight exposure or vitamin D intervention would be very attractive.

Sunlight, Vitamin D, and Xeroderma Pigmentosum.

Sunlight, in particular UV-B radiation, is an important factor for endogenous vitamin D production as 80-90% of the required vitamin D needs to be photosynthesized in the skin. The active form of vitamin D, vitamin D3 or calcitriol, binds to the ligand-activated transcription factor vitamin D receptor (VDR) for genomic and non-genomic effects. Recently, calcitriol and analogs have been shown to have antiproliferative effects in mouse and human BCC and SCC cell lines in vitro. As UV radiation plays a critical role in the photosynthesis of vitamin D, stringent sun protection, as recommended for xeroderma pigmentosum (XP) patients, may impact their vitamin D levels.XP is a rare autosomal recessive disorder with a worldwide prevalence of 1 in 1,000,000. XP can be divided into seven different complementation groups: XP-A to XP-G. The complementation groups correspond with the underlying gene defect. Defects in these genes lead to a defective nucleotide excision repair (NER), which is necessary to remove UV-induced DNA damage such as the UV photoproducts cyclobutane pyrimidine dimers (CPD) and 6-4 pyrimidine-pyrimidone (6-4 PP) dimer. Additionally, a variant form with a mutation in the translational polymerase η gene (PolH), also called XP variant (XPV), exists. Patients with XPV show a defect in translesion synthesis. Due to their inability to repair UV-induced lesions, XP patients exhibit an increased risk for UV-induced nonmelanoma skin cancer (NMSC) such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) as well as melanoma. Although no curative therapy for XP exists today, numerous options for the treatment and prophylaxis of skin cancer have become available.

Ultraviolet Exposure Scenarios: Balancing Risks of Erythema and Benefits of Cutaneous Vitamin D Synthesis.

Exposure to sunlight is a major source of vitamin D for most people. Yet public health advice has focused overwhelmingly on avoiding exposure of unprotected skin because of the risks of erythema and skin cancer. Given that there are also health risks associated with low vitamin D status, we explore the possibilities of achieving a range of targets associated with vitamin D and the accompanying erythema risk. We have calculated the exposure required to gain a number of proposed oral-equivalent doses of vitamin D, as functions of latitude, season, skin type and skin area exposed, together with the associated risk of erythema, expressed in minimum erythema doses. The model results show that a recommended daily intake of 400 IU is readily achievable through casual sun exposure in the midday lunch hour, with no risk of erythema, for all latitudes some of the year, and for all the year at some (low) latitudes. We also show that such daily, sub-erythemal doses at lunchtime during the summer months is sufficient to avoid winter-time vitamin D deficiency for the UK all-weather climate, provided that lower arms and legs are exposed in the warmer months. At the higher proposed vitamin D dose of 1000 IU, lunchtime sun exposure is still a viable route to the vitamin but requires the commitment to expose greater areas of skin and is effective for a shorter period of the year. The highest vitamin D requirement considered was 4000 IU per day. For much of the globe and much of the year, this is not achievable in a lunchtime hour and where it is possible large areas of skin must be exposed to prevent erythema. When the only variable considered was skin type, latitudinal and seasonal limits on adequate vitamin D production were more restrictive for skin type 5 than skin type 2.

Importancia de la Vitamina D en la época del COVID-19 / Importance of Vitamin D in the time of COVID-19

"Los coronavirus pertenecen a una gran familia de virus (Coronaviridae) que infectan aves y varios mamíferos. El coronavirus actualmente denominado SARS-CoV-2, fue descubierto en diciembre de 2019 en Wuhan, provincia de Hubei, China, y es el agente causal de la epidemia de neumonía atípica actual" (COVID-19; Coronavirus Disease 2019). Los casos más graves presentan un síndrome de dificultad respiratoria aguda que puede conducir a la muerte. La vitamina D (VD), además del efecto bien conocido y positivo sobre la salud ósea y la homeostasis del calcio, tiene efecto pleiotrópico en varios órganos, con distribución casi universal del receptor de VD y de las enzimas de metabolización de 25 hidroxivitamina D (25OHD) en las células del organismo. Estas acciones extraesqueléticas dependen de la síntesis en dichas células del metabolito activo 1,25 dihidroxivitamina D por regulación paracrina y autocrina, dependiente de niveles circulantes óptimos de 25OHD. Por sus acciones inmunomoduladora, antiinflamatoria, antimicrobiana, reguladora del sistema renina-angiotensina-aldosterona, favorecedora de la indemnidad del epitelio respiratorio y la homeostasis redox celular, la VD podría tener efecto protector en la infección por COVID-19. Entre los grupos de riesgo para COVID-19 figuran los adultos mayores, obesos, diabéticos, hipertensos, con afecciones cardiovasculares, patologías con mayor incidencia en individuos con hipovitaminosis VD. La suplementación con VD, para alcanzar niveles óptimos de 25OHD de 40-60 ng/ml, podría reducir la incidencia, severidad y riesgo de muerte en la actual pandemia por COVID-19, como medida complementaria mientras se desarrollan la vacuna y otras medicaciones específicas. (AU)

Coronaviruses belong to a large family of viruses (Coronaviridae) that infect birds and various mammals. The novel coronavirus currently known as SARS-CoV-2 was discovered in December 2019 in Wuhan, Hubei province, China and is the causal agent of the current atypical pneumonia epidemic (COVID-19: Coronavirus Disease 2019); The most severe cases present with acute respiratory distress syndrome that can lead to death. Vitamin D (VD) has a pleiotropic effect on several organs, in addition to its wellknown and positive effect on bone health and calcium homeostasis, with an almost universal distribution of the VD receptor and the metabolites of 25hydroxyvitamin D (25OHD) in all cells of the body. These extra-skeletal actions depend on the synthesis of the active metabolite 1,25dihydroxyvitamin D in the cells depending on the optimal circulating levels of 25OHD and though paracrine and autocrine regulation. Due to its immunomodulatory, anti-inflammatory, antimicrobial, and regulatory actions on the renin angiotensin aldosterone system, which favors the compensation of the respiratory epithelium and cellular redox homeostasis, the VD could have a protective effect on COVID-19 infection. Among the risk groups for COVID-19 are obese, diabetic, and hypertensive patients, subjects with cardiovascular conditions, and elderly people. All these pathologies show a higher incidence in individuals with VD hypovitaminosis. VD supplementation, to achieve optimal 25OHD levels of 40-60 ng/ml, could reduce the incidence, severity, and risk of death in the current COVID-19 pandemic, as a complementary measure while the vaccine and other specific therapies are being developed. (AU)