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Jędrzej Sniadecki (1768-1838) on the Cure of Rickets

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Abstract

IT is a view generally accepted that the English physician, Dr. T. A. Palm, first directed the attention of the scientific world to the curative effect of sunlight on rickets. L. J. Harris1, when dealing with the frequency of the occurrence of rickets in relation to the climate, writes: ``The explanation was given by an English medical man, Dr. T. A. Palm, in 1890. He it was who first pointed out that rickets is prevalent wherever there is little sunlight and unknown or comparatively rare wherever sunshine is abundant''.

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... 1,25-dihydroxycholecalciferol (1,25-dihydroxyvitamin D 3 , calcitriol, 1,25D3) and 1,25-dihydroxyergocalciferol (1,25-dihydroxyvitamin D 2 , 1,25D2) ( Figure 1) are no longer considered just as "vital amines" [1,2] that maintain the calcium and phosphate homeostasis [3], they are also pleiotropic hormones [4] that regulate key physiological processes [5,6]. Several active vitamin D metabolites, their precursors, and synthetic analogs are used as drug substances in the treatment of bone diseases (type I rickets, osteomalacia, hypoparathyroidism, pseudohypoparathyroidism, renal osteodystrophy, and osteoporosis), and hyperproliferative skin diseases such as psoriasis [7,8]. ...
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Article
The microsomal cytochrome P450 3A4 (CYP3A4) and mitochondrial cytochrome P450 24A1 (CYP24A1) hydroxylating enzymes both metabolize vitamin D and its analogs. The three-dimensional (3D) structure of the full-length native human CYP3A4 has been solved, but the respective structure of the main vitamin D hydroxylating CYP24A1 enzyme is unknown. The structures of recombinant CYP24A1 enzymes have been solved; however, from studies of the vitamin D receptor, the use of a truncated protein for docking studies of ligands led to incorrect results. As the structure of the native CYP3A4 protein is known, we performed rigid docking supported by molecular dynamic simulation using CYP3A4 to predict the metabolic conversion of analogs of 1,25-dihydroxyvitamin D2 (1,25D2). This is highly important to the design of novel vitamin D-based drug candidates of reasonable metabolic stability as CYP3A4 metabolizes ca. 50% of the drug substances. The use of the 3D structure data of human CYP3A4 has allowed us to explain the substantial differences in the metabolic conversion of the side-chain geometric analogs of 1,25D2. The calculated free enthalpy of the binding of an analog of 1,25D2 to CYP3A4 agreed with the experimentally observed conversion of the analog by CYP24A1. The metabolic conversion of an analog of 1,25D2 to the main vitamin D hydroxylating enzyme CYP24A1, of unknown 3D structure, can be explained by the binding strength of the analog to the known 3D structure of the CYP3A4 enzyme.
... Introduction P roximal muscle weakness and hypotonia are well-described symptoms accompanying rickets/osteomalacia. (1) Since 1922, when a healing effect of sun exposure on rickets was first described, vitamin D and muscle health has been associated. (2)(3)(4) Since the 1980s, when assays of 25-hydroxyvitamin D (25(OH)D) was developed as a marker of vitamin D status, multiple observational studies have supported the hypothesis of an inverse association between vitamin D status and muscle health. ...
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Article
The objective of this study was to investigate the effects of vitamin D supplementation versus placebo on muscle health. For this systematic review and trial‐level meta‐analysis of placebo‐controlled trials, a systematic search of randomized controlled trials published until October 2020 was performed in Medline, Embase, and Google Scholar. We included studies in humans (except athletes) on supplementation with vitamin D2 or D3 versus placebo, regardless of administration form (daily, bolus, and duration) with or without calcium co‐supplementation. The predefined endpoints were physical performance reported as timed up and go test (TUG; seconds), chair rising test (seconds), 6‐minute walking distance (m), and Short Physical Performance Battery (SPPB; points). Furthermore, endpoints were maximum muscle strength (Newton) measured at handgrip, elbow flexion, elbow extension, knee flexion, and knee extension, as well as muscle (lean tissue) mass (kg). Falls were not included in the analysis. Cochrane Review Manager (version 5.4.1.) calculating mean difference (MD) using a random effect model was used. In total, 54 randomized controlled trials involving 8747 individuals were included. Vitamin D versus placebo was associated with a significantly longer time spent performing the TUG (MD 0.15 [95% confidence interval (CI) 0.03 to 0.26] seconds, N = 19 studies, I2 = 0%, n = 5223 participants) and a significant lower maximum knee flexion strength (MD –3.3 [−6.63 to −0.03] Newton, N = 12 studies, I2 = 0%, n = 765 participants). Total score in the SPPB showed a tendency toward worsening in response to vitamin D compared with placebo (MD −0.18 [−0.37 to 0.01] points, N = 8 studies, I2 = 0%, n = 856 participants). Other measures of muscle health did not show between‐group differences. In subgroup analyses, including studies with low vitamin D levels, effects of vitamin D supplementation did not differ from placebo. Available evidence does not support a beneficial effect of vitamin D supplementation on muscle health. Vitamin D may have adverse effects on muscle health, which needs to be considered when recommending vitamin D supplementation. © 2021 American Society for Bone and Mineral Research (ASBMR).
... During the industrialization period, when people started to live in the overcrowded cities, decreased access to the sun resulted in a massive outbreak of rickets, due to vitamin D deficiency. It has been proposed by Jedrzej Śniadecki in 1822 that the exposure of children to the sun has an antirachitic effect [3]. Nowadays, rickets is rare, but since most of the people live in the areas where the access to sun is limited for approximately half a year, and in sunny days the use of sunscreens is advised, most people are not vitamin D sufficient. ...
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Article
Vitamin D is synthesized in the skin from 7-dehydrocholesterol subsequently to exposure to UVB radiation or is absorbed from the diet. Vitamin D undergoes enzymatic conversion to its active form, 1,25-dihydroxyvitamin D (1,25D), a ligand to the nuclear vitamin D receptor (VDR), which activates target gene expression. The best-known role of 1,25D is to maintain healthy bones by increasing the intestinal absorption and renal reuptake of calcium. Besides bone maintenance, 1,25D has many other functions, such as the inhibition of cell proliferation, induction of cell differentiation, augmentation of innate immune functions, and reduction of inflammation. Significant amounts of data regarding the role of vitamin D, its metabolism and VDR have been provided by research performed using mice. Despite the fact that humans and mice share many similarities in their genomes, anatomy and physiology, there are also differences between these species. In particular, there are differences in composition and regulation of the VDR gene and its expression, which is discussed in this article.
... vitamin D 2 • ergocalciferol • edible mushrooms WSTĘP Z badań oceniających stan wysycenia organizmu witaminą D, przeprowadzonych zarówno w Polsce, jak i na świecie, wynika, że niedobór tej witaminy dotyczy znacznej części populacji [7,8,11,18,22,31]. Pierwszą przesłanką, pozwalającą na wskazanie najważniejszej przyczyny niedoboru witaminy D, było odkrycie zależności między zbyt krótkim czasem przebywania na słońcu a występowaniem krzywicy u dzieci, dokonane przez Jędrzeja Śniadeckiego w 1822 r. [39]. Wyniki wielu późniejszych doświadczeń potwierdziły, że główną przyczyną obserwowanego powszechnie niedoboru tej witaminy jest niewystarczająca synteza skórna cholekalcyferolu, spowodowana m.in. ...
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Edible mushrooms exposed to sunlight or UV irradiation convert ergosterol to ergocalciferol (vitamin D2), which is well absorbed and has a similar bioavailability to vitamin D3. Consumption of vitamin D2-enhanced mushrooms significantly increases circulating levels of 25-hydroxyvitamin D2 that is further metabolized to the biologically active form – 1,25(OH)2D2. Dietary supplementation with UV-irradiated mushrooms has been shown to lower parathyroid hormone (PTH) concentrations in the blood and to increase bone mineral density, to suppress an immune response, to decrease circulating plasminogen activator inhibitor 1 (PAI-1) levels, as well as to improve cognitive performance in dementia syndromes. Current evidence indicates that more than half of the world’s population is vitamin D deficient, mushrooms enriched with ergocalciferol may therefore prove useful as a natural dietary source of this vitamin – incorporating them into the diet can help meet the body’s daily requirement and restore vitamin D status.
... Bereits im Jahr 1822 vermutete der Warschauer Arzt Sniadecki eine mangelnde Sonnenlichtexposition als Ursache der Wachstumsstörungen, nachdem er beobachtet hatte, dass Kinder der städtischen Bevölkerung häufiger von Rachitis betroffen waren als ihre Altersgenossen in ländlichen Regionen (Mozołowski, 1939). In Bezug auf andere Krankheiten war die Heilkraft der Sonne zu dieser Zeit bereits anerkannt (Finsen, 1899). ...
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Thesis
Hintergrund und Ziele Sonnenschutz im Kindesalter stellt einen entscheidenden Beitrag zur Primärpräven-tion von Hautkrebs dar. Gleichzeitig ist Sonnenstrahlung auch für die körpereigene Bildung von Vitamin D notwendig. Für eine optimale Entwicklung sind Kinder auf eine ausreichende Versorgung mit diesem Vitamin angewiesen. Die verstärkte Aufmerksamkeit für die positiven Gesundheitswirkungen des Vitamin D sowie Ver-öffentlichungen über die schlechte Versorgungslage bei Kindern könnten das Son-nenschutzverhalten negativ beeinflussen. Das Ziel dieser Arbeit war es daher, den Stellenwert der Vitamin D-Versorgung für den kindlichen Sonnenschutz bei Eltern und Erziehern zu ermitteln, die Bedeutung verschiedener Einflussgrößen für die Einstellung zum Vitamin D zu erheben und Zusammenhänge zwischen der Vitamin D-Einstellung und dem Sonnenschutzverhalten gegenüber den Kindern zu analysie-ren. Methoden Im Sommer 2016 wurde in 208 Nürnberger Kindergärten eine Befragung der Kin-dergartenleitungen und der Eltern von drei- bis sechsjährigen Kindergartenkindern durchgeführt. Die Erhebung der Daten erfolgte bei den Leitern der jeweiligen Ein-richtung im Rahmen eines standardisierten Interviews; die Befragung der Eltern wurde mittels eines anonymen, selbst auszufüllenden Fragebogens durchgeführt. An der Studie beteiligten sich insgesamt 190 Kindergartenleitungen (Responserate Erzieherbefragung 64,2%) und 3.220 Eltern (Responserate Elternbefragung 37,7%). Für die Analysen der vorliegenden Arbeit wurden sowohl die Angaben der Eltern als auch der Kindergartenleitungen berücksichtigt. Ergebnisse und Beobachtungen Die Vitamin D-Versorgung der Kinder war nur für einen geringen Anteil der Teil-nehmer bei Entscheidungen zum Sonnenschutz relevant. Dabei wurde die Vitamin D-Versorgung im Kollektiv der Eltern häufiger beachtet als im Erzieherkollektiv (30,0% vs. 11,0%). Weitere 27,0% der teilnehmenden Eltern und 11,6% der Erzie-her fühlten sich zum Thema Vitamin D nicht ausreichend informiert. Die Beachtung der kindlichen Vitamin D-Versorgung unterlag verschiedenen Ein-flussfaktoren. In der Befragung der Erzieher war sie assoziiert mit einem höheren Alter der Teilnehmer. In der Elternbefragung zeigte sich eine positive Assoziation zwischen der Berücksichtigung der Vitamin D-Versorgung und einem Migrations-hintergrund. Teilnehmer mit einem akademischen Bildungsabschluss beachteten die Vitamin D-Versorgung der Kinder dagegen seltener. Aufmerksamkeit gegenüber Vitamin D war darüber hinaus assoziiert mit einer Bräunungsintention der Eltern, geringeren Erfahrungen mit Hautkrebs und besseren Kenntnissen zum UV-Index. Die Beachtung der Vitamin D-Versorgung hatte keine negativen Auswirkungen auf das Sonnenschutzverhalten. Unter Berücksichtigung des Einflusses der soziodemo-graphischen Faktoren zeigte sich sogar ein positiver Effekt der Aufmerksamkeit gegenüber Vitamin D auf die Summe der bei den Kindern praktizierten Sonnen-schutzmaßnahmen. Es ergab sich außerdem eine kürzere Aufenthaltsdauer im Freien sowie ein selteneres Auftreten von Hautrötungen bei Kindern Vitamin D-sensitiver Eltern. Schlussfolgerungen Die Studie zeigt, dass der Stellenwert der kindlichen Vitamin D-Versorgung bei Sonnenschutzentscheidungen für die Betreuungspersonen eher gering ist und ein nicht unerhebliches Informationsdefizit besteht. Es bedarf daher bei Erziehern und Eltern intensiver Aufklärungsarbeit zum Thema Vitamin D. Diese sollte in Form von Fortbildungen und Elterninformationsabenden im Kindergarten erfolgen und mit Aufklärung zum Thema Sonnenschutz kombiniert werden, um die Vereinbarkeit der beiden Themen deutlich zu machen. Weitere Untersuchungen sollten unter anderem die Beweggründe für die unter-schiedlichen Einstellungen zum Vitamin D erheben und konkrete Wissenslücken zur Thematik ermitteln, um Hindernisse in der praktischen Umsetzung erkennen und zukünftige Informationskampagnen zielgerichtet gestalten zu können. Die Ergeb-nisse der vorliegenden Arbeit geben dabei keinen Anlass zu der Sorge, dass eine vermehrte Thematisierung der Vitamin D-Versorgung zu einer Vernachlässigung der UV-Protektion und damit zu einer möglichen Hautschädigung führt.
... The importance of sunlight for human health came into light with the industrial revolution in Northern Europe [7]. Sniadecki first published an article in 1822 about high prevalence of rickets in children who lived in the inner city in comparison to those who lived in the rural areas [8]. Many observations regarding the sun exposure and rickets have been published in the course of time. ...
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Chapter
The pleiotropic effects of vitamin D on the various metabolic, anticancer, and immunomodulatory functions of the body based on the presence of vitamin D receptors (VDR) on various cell types has been recognized worldwide now. Of few understood mechanisms of immunomodulatory actions of vitamin D are the suppressive action on the maturation of antigen-presenting cells and decrease in the levels of pro-inflammatory cytokines. Vitamin D deficiency has been implicated in the immune diseases like rheumatic diseases, asthma, psoriasis, and multiple sclerosis. Vitamin D deficiency has been associated with increased frequency and severity of disease flares in rheumatic diseases like lupus and rheumatoid arthritis. Other studies have shown higher prevalence of persistence and evolution in to more definite rheumatic disorder in undifferentiated arthritis and undifferentiated connective tissue disorder patients with vitamin D deficiency. Multiple factors like avoidance of sunlight, the use of corticosteroids and hydroxychloroquine, skin pigmentation, etc. should be considered when evaluating vitamin D levels in these patients, needless to say the consideration of higher-dose supplement for these patients. It is thus prudent that all patients with established or undifferentiated rheumatic diseases are evaluated for vitamin D status and an adequate supplemen-tation is recommended to prevent the associated consequences.
... The importance of sunlight for human health came into light with the industrial revolution in Northern Europe [7]. Sniadecki first published an article in 1822 about high prevalence of rickets in children who lived in the inner city in comparison to those who lived in the rural areas [8]. Many observations regarding the sun exposure and rickets have been published in the course of time. ...
... The word "rickets" was first used in 1634. 1 From reports of the Royal Infirmary in Manchester, cod liver oil was found to heal rickets. 1 In 1822, Sniadecki pointed out the relationship between sunlight and rickets. 2 At the end of World War I, when rickets was an untreatable major problem in Vienna, Harriet Chick led a group from the British Medical Research Council to study it. 3 They concluded both cod liver oil and sun exposure could heal rickets. ...
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Article
Severe vitamin D deficiency may cause rickets in infants or children and osteomalacia in adults, though it is now uncommon in developed countries. However, subclinical vitamin D deficiency is more prevalent, and it is associated with osteoporosis and higher incidence of falls or fractures. It was reported that 96% children with rickets were breastfed, since breast milk contains inadequate vitamin D. The American Academy of Pediatrics 2008 recommended infants who were exclusively or partially breastfed required 400 international units vitamin D daily from the first few days of life. Furthermore, since vitamin D receptors are present all over the body, insufficient vitamin D status may correlate with several extra-skeletal effects, such as pregnancy-related complications and immune dysfunction. This paper discusses the researches regarding system-based vitamin D effects, the possible risk factors leading to vitamin D deficiency, and the recommendations of vitamin D requirements. It is well-known that vitamin D can be obtained by sun exposure or limited natural dietary sources. The American Academy of Dermatology declared ultraviolet radiation to be a known skin carcinogen, so it may not be safe or efficient to obtain vitamin D via sun exposure or other artificial sources. Therefore, many pediatricians and physicians recommend appropriate vitamin D supplementation to achieve optimal plasma concentration. Trials assessing the effects of vitamin D repletion and establishing its optimum serum level are ongoing. Medical advice for vitamin D supplementation should be individualized accordingly.
... The last decade brought a tremendous number of studies on vitamin D function in human body. In fact, those studies have begun in 1822 when the Polish physician Dr. Jedrzej Sniadecki discovered that the lack of sunlight exposure directly contributes to the onset of rickets (Mozolowski 1939). Later, in 1918 Sir Edward Mellanby showed that nutritional intervention with cod liver oil may replace sunlight in the cure and prevention of rickets (Mellanby 1918). ...
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Article
Purpose This review provides a current perspective on the mechanism of vitamin D on skeletal muscle function with the emphasis on oxidative stress, muscle anabolic state and muscle energy metabolism. It focuses on several aspects related to cellular and molecular physiology such as VDR as the trigger point of vitamin D action, oxidative stress as a consequence of vitamin D deficiency. Method The interaction between vitamin D deficiency and mitochondrial function as well as skeletal muscle atrophy signalling pathways have been studied and clarified in the last years. To the best of our knowledge, we summarize key knowledge and knowledge gaps regarding the mechanism(s) of action of vitamin D in skeletal muscle. Result Vitamin D deficiency is associated with oxidative stress in skeletal muscle that influences the mitochondrial function and affects the development of skeletal muscle atrophy. Namely, vitamin D deficiency decreases oxygen consumption rate and induces disruption of mitochondrial function. These deleterious consequences on muscle may be associated through the vitamin D receptor (VDR) action. Moreover, vitamin D deficiency may contribute to the development of muscle atrophy. The possible signalling pathway triggering the expression of Atrogin-1 involves Src-ERK1/2-Akt- FOXO causing protein degradation. Conclusion Based on the current knowledge we propose that vitamin D deficiency results from the loss of VDR function and it could be partly responsible for the development of neurodegenerative diseases in human beings.
... 30 This vitamin D deficiency may have important consequences in ELGANs. Vitamin D is necessary for bone health, 31,32 and it also is important for the saccular and alveolar stages of lung development, 1,2 the dysregulation of which contributes to BPD in ELGANs. Pups of vitamin D (9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) .39 ...
... Humans obtain vitamin D from either exposure to sunlight or from dietary intake, both whole food and supplementation. It was first identified in 1822 by the Polish physician Dr. Jedrzej Sniadecki that the lack of sunlight exposure directly contributed to the onset of rickets [17], leading to the expansion upon these observations by the English physician Dr. Theobald A. Palm in 1890 [18]. In 1918, the nutritional benefits of cod liver oil in the cure and prevention of rickets were first demonstrated by Sir Edward Mellanby [19] followed by Dr. Elmer McCollum et al. (1922) who official termed this nutritional factor vitamin D [20]. ...
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Article
Vitamin D plays an essential role in the regulation of skeletal metabolism as well as calcium and phosphate homeostasis, while vitamin D receptor (VDR) regulates de novo lipid synthesis, thereby contributing to the development of obesity. Furthermore, obese individuals are at a greater risk for vitamin D deficiency which may increase the potential risk for chronic inflammation, insulin resistance, and metabolic syndrome. While acute exercise enhances the activation of inflammatory signaling pathways, chronic exercise training may attenuate elevated pro-inflammatory cytokine production, resulting in the improvement of cardiovascular and metabolic health in obese individuals. Supplementation with vitamin D coupled with exercise or mild caloric restriction has been shown to improve markers of fitness and inflammation as well as cholesterol. Therefore, this review primarily addresses the impact of vitamin D deficiency in obesity-related inflammatory imbalances and how exercise and weight-loss interventions may enhance the beneficial effects on vitamin D-mediated inflammation in obesity.
... However, in the nineteenth century his studies were considered as incomprehensible and remained largely unnoticed . Of note, it was great Polish biochemist, Professor Włodzimierz Mozołowski, who brought backŚniadeckìs observations to the scientific community (Mozolowski, 1939). Another scientist, who predicted the relationship between exposure to the sunlight and occurrence of rickets , was a British epidemiologist, Theobald Palm. ...
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Article
There is no doubt that vitamin D plays a crucial role in the maintenance of musculoskeletal system. But the function of this ancient molecule presumably ranges far beyond hormone-like regulation, as it could be generated by simple unicellular organisms. First, we are going to discuss the role of vitamin D as a global regulator of homeostasis from a historical perspective, but later we will focus on current views and its relevance to human physiology and pathology. Three milestones are defining the impact of vitamin D on science and humanity. Firstly, discovery that vitamin D is the cure for rickets, brought us supplementation programs and rapid irradiation of this devastating disease. Secondly, detail description of photoproduction of vitamin D, its subsequent metabolism and interaction with vitamin D receptor VDR, provided mechanistic background for future discoveries. Finally, recent large epidemiological studies provided indirect, but strong evidence that optimal level of vitamin D in serum has beneficial effects on our health and protects us from multiple diseases, including cancer. Furthermore, existence of alternative pathways of vitamin D metabolism and multiple intracellular targets broadens our understanding of its physiological activities and offers new and very promising tools for prophylactics and treatment of many diseases of civilization. Although vitamin D (and its derivatives) should not be regarded as a cure-all for every human disease, its beneficial effects on the human health have to be taken under consideration.
... In 1724-1926 Schenk 25 and Schutte 26 wrote that cod liver oil by mouth for 5 weeks could cure rickets. In 1822, Sniadeki 27 from Poland wrote 'the sun, the direct action of which on our bodies must be regarded as one of which on our bodies, must be regarded as the most efficient methods for the prevention and cure of this disease'. Later Trousseau, 28 in 1868 described, very elegantly, how he came to treat rickets with cod liver oil. ...
Article
The story of rickets leading to the discovery of vitamin D is an extraordinary tale, spread over many centuries and involving some remarkable characters with much speculation and a few mysteries, before reaching an exciting climax. It would be wrong to credit a single person as discovering rickets or being the first to describe its features, for reasons that will be set out here. Yet the emergence of the term 'rickets' is as important as the discovery of vitamin D itself and the possible causes of its deficiency. It permitted identification of a hitherto ill-defined disease entity, typically occurring in infants and children. It also provided a way for deciding if features of diseases that had been described earlier in the history of medicine could be seen as the symptoms and signs of related conditions.
... Vitamin D was first identified as a key regulator of calcium homeostasis, since its deficiency was associated with rickets and osteomalacia 54 . Humans can introduce vitamin D with the diet, even if few foods, like oily fishes, cod liver oil and dairy products, naturally contain it 55 ; the major production of vitamin D occurs in the skin, where the photochemical action of UVB light is able to transform 7-dehydrocholesterol to previtamin D, which is converted in turn to vitamin D through a non-enzymatic thermal isomerization. ...
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Article
Hypovitaminosis D is a very common disorder, regarding both Western and developing countries. A growing amount of data over the last years have shown vitamin D deficiency to be high prevalent among HIV-positive subjects. In addition to "classic" risk factors, such as female sex, low dietary intake, dark skin pigmentation and low sun exposure, HIV-related factors, including immune activation and antiretroviral adverse effects, may affect vitamin D status. Even if both protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been associated with low vitamin D levels, available evidences have failed to univocally associate hypovitaminosis D with specific antiretroviral class effects. Low vitamin D is known to have a negative impact not only on bone health, but also on neurocognitive, metabolic, cardiovascular and immune functions. Similarly to the general population, several studies conducted on HIV-infected subjects have associated hypovitaminosis D with a greater risk of developing osteopenia/osteoporosis and fragility fractures. Analogously, vitamin D deficiency has been described as an independent risk factor for cardiovascular disease and metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. Last EACS guidelines suggest to screen for hypovitaminosis D every HIV-positive subject having a history of bone disease, chronic kidney disease or other known risk factors for vitamin D deficiency. Vitamin D repletion is recommended when 25-hydroxyvitamin D levels are below 10 ng/ml. Furthermore, it may be indicated in presence of 25OHD values between 10 and 30 ng/ml, if associated with osteoporosis, osteomalacia or increased parathyroid hormone levels. The optimal repletion and maintenance dosing regimens remain to be established, as well as the impact of vitamin D supplementation in preventing comorbidities.
... Rickets was fi rst described in England by Whistler ( 1645 ) and Glisson ( 1650 ). In the next century, Sniadecki established a connection between skeleton malformation and lack of sunlight among children in Warsaw (Mozolowski 1939 ). The disease became known as the English disease in many countries. ...
Chapter
Vitamin D was discovered as a result of its ability to cure rickets, but recently many other important functions for it in the human body have been discoverred, and it counteracts several other diseases, such as diabetes and some forms of cancer. The nuclear vitamin D receptor has been found throughout the vertebrate phylum down to jawless fishes, but not in invertebrates. Its role in those organisms that are repsonsible for the main input to the aquatic food web and to human nutrition, i.e., phytoplankton and zooplankton, is not understood.This chapter summarizes the discovery of vitamin D and the chemistry and photochemistry of its precursors, transformations, and metabolites. The physiological roles of 1,25-dihydroxyvitamin D are briefly described, as well as evolutionary aspects of the signaling in animals based on this compound. The chapter is concluded with an overview of what is known about the occurrence and role of vitamin D in the plant kingdom, biogeographical aspects of vitamin D, and the relatively recent discovery of nonphotochemical production of vitamin D.
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We present a hypothesis for low vitamin D as a sign of untimely relocation of the human being during its history. This improper displacement prone our species to infectious and non-infectious diseases during our life journey, low vitamin D is a sign that needs to be addressed as a marker of the unsafe journey in our lifetime not the cause for diseases that are associated with it and replacement of vitamin D is the least that we have done.
Article
Introduction: Rickets is typically characterized by bone deformities due to defective bone mineralization and chondrocyte maturation in growing bones. However, infantile rickets often goes unrecognized, because the skeletal abnormalities are more subtle and often can only be detected radiologically. Nutritional rickets is a major public health concern in several regions worldwide. It is most commonly caused by vitamin D and/or calcium deficiency. Area covered: We provide an overview of historical perspective, epidemiology, and pathophysiology of nutritional rickets. Additionally, we outline diagnostic approaches and highlight challenges in radiographic diagnosis of rickets. Finally, we present strategies for prevention and treatment of rickets. Expert opinion: Despite the evidence from clinical databases that rickets is a rare disease, it is likely that rickets is clinically underdiagnosed as studies designed to screen healthy children for radiographic evidence of rickets reported surprisingly much higher prevalence. It has been reported that some of the radiologic features of rickets can be misinterpreted as fractures. To prevent nutritional rickets, most if not all infants and young children, should receive vitamin D from formulas and foods that are fortified with vitamin D or supplementation to achieve a serum 25-hydroxyvitamin D of at least 20 ng/mL as recommended by the Institute of Medicine. It has been recommended by the Endocrine Society that to achieve maximum bone health for children and adults, a serum concentration of 25-hydroxyvitamin D should be at least 30 ng/mL and preferably 40-60 ng/mL. Pregnant women who are unable to obtain an adequate amount of vitamin D from sunlight exposure and natural and fortified diets should take a vitamin D supplement of 1500-2000 IUs daily as recommended by the Endocrine Society since it has been demonstrated that 600 IUs daily will not maintain a circulating 25-hydroxyvitamin D of at least 20 ng/mL and most pregnant women. If lactating women take approximately 6400 IUs of vitamin D daily, they provide enough vitamin D in their milk to satisfy their infant's requirement thereby preventing rickets.
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Vitamin D is necessary for musculoskeletal health, however, the supplementation of vitamin D above the sufficiency level does not bring additional bone mass density (BMD), unlike physical exercise which enhances the bone formatting process. Regular physical activity has been shown to upregulate VDR expression in muscles and to increase circulating vitamin D. Here we investigate whether a single bout of exercise might change 25(OH)D3 blood concentration and how it affects metabolic response to exercise. Twenty-six boys, 13.8 years old (SD ± 0.7) soccer players, participated in the study. The participants performed one of two types of exercise: the first group performed the VO2max test until exhaustion, and the second performed three times the repeated 30 s Wingate Anaerobic Test (WAnT). Blood was collected before, 15 min and one hour after the exercise. The concentration of 25(OH)D3, parathyroid hormone (PTH), interleukin-6 (IL-6), lactate, non-esterified fatty acids (NEFA) and glycerol were determined. 25(OH)D3 concentration significantly increased after the exercise in all boys. The most prominent changes in 25(OH)D3, observed after WAnT, were associated with the rise of PTH. The dimensions of response to the exercises observed through the changes in the concentration of 25(OH)D3, PTH, NEFA and glycerol were associated with the significant increases of IL-6 level. A single bout of exercise may increase the serum’s 25(OH)D3 concentration in young trained boys. The intensive interval exercise brings a more potent stimulus to vitamin D fluctuations in young organisms. Our results support the hypothesis that muscles may both store and release 25(OH)D3.
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Vitamin D is identified as an essential vitamin serving as a primer steroid in the metabolic and biological processes in the organism. Since Vitamin D is considered as having a structure of direct-indirect effect for many processes in the organism and its capability to serve as a steroid, it can be also denominated as hormone D. We did an editorial study which is based on the micro-analyse method, which contains the required definitions under the relevant subject scope, created by syncretizing the information, results and comments obtained from passed and actual studies. It is found that Vitamin D has effects on the muscular functions that the direct effect in respect of increase of the athletic performance (on athletes) has not become definitive, however, that's its deficiency can have negative effects on the performance. It is seen that Vitamin D deficiency has destructive effects on the muscle tissue (muscular atrophy, impairment of the cross-bridge formation, muscle weaknesses). It also causing bone mineralization disorders in adults that causes unfavourable conditions like pain and weakness in the muscles, bone pains, difficulties in walking. And it was determined, that the fibre type, which is mostly affected by such kind of negations occurred particularly in case of its deficiency, is the Type II (particularly muscular atrophy). It has also been defined, that qualified increase in the VDR (Vitamin D receptor) levels can be obtained by means of supplements provided to individuals with Vitamin D deficiency.
Article
Rickets was first described in great detail in the mid 17th century and was affecting a great number of children in major European cities. The disease, however, existed already in the Roman times. The etiology of this disease remained enigmatic until the 1920s when two different mechanisms, lack of exposure to sunlight and lack of a dietary factor were finally solved by the discovery of vitamin D and its dual origin. Soon thereafter, the implementation of vitamin D supplementation for all infants and small children largely eliminated nutritional rickets in Europe and North America. It took nearly a century to elucidate the complex chemistry, metabolism, mode and spectrum of activity of the vitamin D endocrine system. Nutritional rickets, whether due to simple vitamin D or calcium deficiency or both, remains widely ravaging many infants and children around the world. Asian countries and the Middle East are mainly confronted with vitamin D deficiency whereas many African and some Asian countries face calcium deficiency rickets. Immigrants and refugees or in general people with a darker skin living in moderate climate zone are also confronted with this disease. There is great consensus how this disease could be prevented or cured. In collaboration with most international professional societies, we prepare a memorandum, in line with the successful battle against iodine deficiency disorders, to convince the World Health Organization and its member states to start an implementation program to eradicate nutritional rickets by 2030.
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This chapter describes fundamental properties of molecular photochemistry including photochemical and photophysical processes, general information about light sources, and the overview of light technology in biomedical research. The topics in photochemistry include the basics of energy diagram, electronic structures, light absorption and fluorescence, electron and energy transfer, and photo-sensitizing properties. This chapter also describes utilization of light sources in photochemistry such as mercury arc lamps, a xenon lamp, light-emitting diodes as incoherent light sources, and lasers as coherent light sources. We review light technology for biomedical applications: photodynamic therapy and Photopharmacology for medicinal applications, laser scalpel and laser skin resurfacing for surgical applications, and optoporation for drug and gene delivery applications. We also briefly introduce a fascinating research topic of light therapy for treatment of psychotic depression and sleep disorder.
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Vitamin D is the sunshine vitamin. During exposure to sunlight 7-dehydrocholesterol in the skin absorbs ultraviolet B radiation converting it to previtamin D3. Previtamin D3 being thermodynamically unstable isomerizes within a few hours to form vitamin D3. A multitude of factors affect its synthesis including skin pigmentation, time of day, season, latitude, altitude, and sunscreen use. The body has a large capacity to produce vitamin D3, and sensible sun exposure can be effective in helping to maintain blood levels of 25-hydroxyvitamin D. Exposure to sunlight also provides other healthful benefits including the production of beta endorphin, which provides the feeling of being well, and nitric oxide, which helps to reduce blood pressure. The goal of this chapter is to provide a broad overview on the role of sunlight in providing vitamin D and other health benefits.
Article
The earliest record between sun exposure and skin disease goes back five millennia to the ancient Egyptians. The modern scientific era of medical light therapy and skin diseases started in 1877 when Downs and Blunt reported that exposure to light inhibited fungal growth in test tubes. Continuing research generated a growing medical interest in the potential the effects of light to treat and cure skin diseases considered as parasitic. This culminated in the awarding of the 1903 Nobel Prize in Medicine to Niels Finsen for his pioneering work showing that light could successfully treat cutaneous mycobacterium tuberculosis (lupus vulgaris), a disfiguring disorder common at the time. Cod liver oil was used as a folk remedy to treat rickets prior to 1789 in Manchester, UK and sunlight was published as the cure for this disease in 1921. The work by Hess and Weinstock in 1925 showed that food irradiated with ultraviolet (UV) light prevented rickets in rats, which paved the way for the discovery of vitamin D. The range of skin diseases treated by light therapy increased in the following years, to the point where a 1932 review by the American Medical Association on the use of UV therapy in dermatology listed 34 skin conditions for which UV radiation may be useful. This period coincided with the development of sanatoria in Europe and North America which used heliotherapy for the treatment of tuberculosis. UV therapy and vitamin D continued to be used successfully for the treatment of tuberculosis up to the 1950s when it was superseded by more effective antibiotics. Modern phototherapy developed in the 1980s with the discovery of the action spectrum for psoriasis leading to the development of narrow band UVB. Subsequently a biological mechanism by which UV light and vitamin D treated tuberculosis was identified in 2006. This involves activation of human macrophages via toll-like receptors to upregulate the vitamin D receptor gene resulting in induction of the antimicrobial peptide cathelicidin. The role of UV light and vitamin D in the treatment of skin diseases is currently an active area of research.
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In the last few decades, we have witnessed the resurgence of rickets (clinical vitamin D deficiency disorder) in vulnerable populations of infants. Recent National Health and Nutrition Examination surveys also show high rates of biochemical vitamin D insufficiency and deficiency in representative samples of healthy adolescents and adults in the USA. Scientific advances in the vitamin D field have emphasized the relevance of optimal vitamin D status for skeletal and nonskeletal health outcomes. In this context of refocused attention on vitamin D, we have reviewed the history of vitamin D and rickets, and the historical perspectives on vitamin D metabolism.
Article
The beneficial uses of light have been noted and observed since ancient times; it is only since the last century that these beneficial effects have also been studied and explored from a scientific point of view leading to more specific applications as well as a better understanding of the mechanisms of action, both chemical and biological, responsible for the observed effects. Among the fields of medicine that have taken it upon themselves to deal with the therapeutic effects of light, dermatology is considered to be a major representative. As examples for the medical uses of light we concentrate on the following: phototherapy (use of UV-A and UV-B radiation without added photosensitizer), photochemotherapy, extracorporeal photochemotherapy (both of which combine photosensitizers and ultraviolet radiation), and photodynamic therapy (using photosensitizers activated by light in the red or blue range). Some other very widespread medicinal uses of light are briefly covered.
Article
Harmful effects of ultraviolet radiation (UVR) including sunburns, DNA damage, photocancerogenesis and photoaging are well proven. Simultaneously, UVB is strictly responsible for vitamin D synthesis, which occurred to play multiple important roles in human organism. Knowledge of harmful effects of UVR resulted in recommendation of the use of sunscreens. Theoretical ability of sunscreens to completely/totally inhibit vitamin synthesis in epidermis raised a wide discussion in literature whether sunscreen use can impose/cause harmful effects on human health. In the article, literature review and various controversies as well as distinct opinions on the subject are presented.
Article
Vitamin D is a group of liposoluble components that organisms can obtain either via endogenous production from sun exposure or directly taken from foods and dietary supplements. In addition to its involvement in calcium metabolism, its presence plays other important functions in human health (e.g. reduction of inflammation and effects on cell proliferation and differentiation). The discovery that most tissues and cells in the body have a vitamin D receptor and that several possess the enzymatic machinery to convert the primary circulating form of vitamin D (25-hydroxycholecalciferol, hydroxylated vitamin D3) to the active form (1,25-dihydroxycholecalciferol, calcitriol) has provided new insights into the function of this vitamin. Of great interest is the role it can play in decreasing the risk of many chronic illnesses, including common autoimmune diseases, cardiovascular disease, and cancers among others. This chapter reviews the nature of vitamin D deficiency, its causes and effects on the human organism, and suggest strategies for its prevention and treatment by both natural sources and/or vitamin D supplements.
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Studies on bone mineral health from different parts of India indicate wide prevalence of vitamin D deficiency (VDD) in all age groups including neonates, infants, school children, pregnant/lactating women, and adult males and females residing in rural and urban India. These have resulted due to poor sun exposure, dark skin complexion, vegetarian food habits, sedentary lifestyle, and lack of vitamin D food fortification programme. Supranormal serum parathyroid hormone values and low peak bone mass in apparently healthy children and adults reported in various studies could be linked to hypovitaminosis D in Indians. In such a scenario active intervention may be required in the form of a national policy for vitamin D fortification programme in our country.
Article
Vitamin D was discovered as a result of its ability to cure rickets, but recently a wide range of other functions for it in the human body has been suggested. Vitamin D is not a vitamin in the strict sense as it can be synthesised in the human body following exposure of the skin to ultraviolet radiation. Provitamin D (7-dehydrocholesterol) is converted to previtamin D which is further modified by a series of reactions to the active form, 1,25-dihydroxyvitamin D. This Chapter summarises the discovery of vitamin D and reviews the chemistry and photochemistry of its precursors, transformations and metabolites. The production of vitamin D in various human populations is described, and how to assess vitamin D status. The skeletal and non-skeletal effects of vitamin D are discussed, particularly its role in immunomodulation with consequences for protection against a variety of human diseases. The Chapter concludes with evolutionary aspects, the occurrence and role of vitamin D in the plant kingdom, biogeographical considerations, and the nonphotochemical production of vitamin D in certain plants.
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The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3 or calcitriol), is known to inhibit the proliferation and invasiveness of many types of cancer cells, including breast, colon, pancreatic, prostate, and liver cancer cells. These findings support the use of 1α,25(OH)2D3 for the treatment of these types of cancer. However, 1α,25(OH)2D3 can cause hypercalcemia, so analogs of 1α,25(OH)2D3 that are less calcemic but exhibit more potent anti-tumor activity would be good candidates as therapeutic agents. Therefore, a series of 19-norvitamin D analogs, in which the methylidene group on C19 is replaced with 2 hydrogen atoms, have been synthesized by several laboratories. In our laboratory, we have designed and synthesized a series of 2α-functional group substituted 19-norvitamin D3 analogs and examined their anti-proliferative activity. Among them, 2α- and 2β-(3-hydroxypropyl)-1α,25-dihydroxy-19-norvitamin D3 (MART-10 and MART-11) were found to be the most promising. Here, we review the rationale and approaches for the synthesis of different 19-norvitamin D analogs, and the pre-clinical studies using these analogs in breast cancer cells, in particular, we chose MART-10 for its potential application to the prevention and treatment of breast cancer.
Article
We studied prevalence of hypovitaminosis D, its determinants, and whether achievement of recommended dietary vitamin D intake (10 μg/d) is associated with absence of hypovitaminosis D in adults. The study is part of the Cardiovascular Risk in Young Finns Study. We collected serum samples of 25-hydroxyvitamin D as part of the 27-year follow-up (994 men and 1,210 women aged 30-45 years). Hypovitaminosis was defined as vitamin D concentration ≤ 50 nmol/L. Hypovitaminosis D was found in 38% of men and 34% of women. Dietary vitamin D intake (OR 0.90, 95% CI 0.86-0.93), use of vitamin-mineral supplements (0.66, 0.51-0.85), sunny holiday (0.55, 0.41-0.75), and oral contraceptive use in women (0.45, 0.27-0.75) were independently associated with reduced odds of hypovitaminosis. Increase in body mass index (1.06, 1.03-1.09), being a smoker (1.36, 0.97-1.92), investigation month (December versus other) (1.35, 1.12-1.61), and risk alleles in genotypes rs12785878 (1.31, 1.00-1.70) and rs2282679 (2.08, 1.66-2.60) increased odds of hypovitaminosis. Hypovitaminosis D was common also when recommended dietary intake was obtained (men 29%, women 24%). Several factors were associated with hypovitaminosis D. The condition was common even when recommended vitamin D intake was reported. The results support the importance of vitamin D fortification and nutrient supplement use.
Article
Tuberculosis (TB) is a major global health problem and often coincides with vitamin D deficiency. High doses of vitamin D were widely used to treat TB during the pre-antibiotic era. Vitamin D exerts its action through vitamin D receptor (VDR), and VDR gene polymorphisms are associated with susceptibility or resistance to tuberculosis as well as sputum smear and culture conversion during anti-TB treatment. In-vitro studies have revealed that 1,25-dihydroxyvitamin D3 enhances innate immunity by increased expression of various antimicrobial peptides, including cathelicidin, and induction of autophagy of the infected cells thus restricts the intracellular growth of Mycobacterium tuberculosis in macrophages. On the other hand, vitamin D has been shown to suppress the pro-inflammatory cytokine response and enhance the anti-inflammatory response. Supplementation with vitamin D in concert with treatment for TB may be beneficial with respect to minimizing the excessive tissue damage that occurs during the active stage of tuberculosis disease. Several clinical trials have evaluated vitamin D supplementation as an adjunct therapy in the treatment for tuberculosis. However, results are conflicting, owing to variations in dose regimens and outcomes. Further investigations are needed to find the optimal concentration of vitamin D for supplementation with standard anti-TB drugs to optimize treatment, which could help to effectively manage both drug-sensitive and drug-resistant tuberculosis.
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While some representatives of the animal kingdom were improving their biological mechanisms and properties for adapting to ever-changing life conditions, the genus Homo was developing backward: human individuals were losing their adaptation to life areas conquered earlier. Losing step-by-step their useful traits including the body hair cover, the primitive genus Homo retained his viability only under very favorable conditions of the equatorial Africa. Protection from UV radiation danger was provided only by pigmentation of skin, hair, and eyes. However, "impoverished" individuals of this genus gained the ability to walk upright. Their hands became free from participation in movement and became fine tools for producing useful instruments, from the stone knife to the computer. The major consequence of upright movement and hand development became the powerful development of the brain. A modern human, Homo sapiens, appeared capable of conquering very diverse new habitats. The human's expansion on the Earth occurred somewhat limited by his dependence on vitamin D. His expansion into new areas with lower Sun activity was partially associated with the loss of skin pigmentation. But there is an open question, whether under these new conditions he is satisfactorily provided with vitamin D. This paper discusses the following problems: how can we ensure a sufficient intake of vitamin D, how much does an individual require for his existence and optimal life, what will be consequences of vitamin D deficiency, and what are the prospects for better provision with vitamin D?
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Vitamin D is the sunshine vitamin that has been produced on this earth for more than 500 million years. During exposure to sunlight 7-dehydrocholesterol in the skin absorbs UV B radiation and is converted to previtamin D3 which in turn isomerizes into vitamin D3. Previtamin D3 and vitamin D3 also absorb UV B radiation and are converted into a variety of photoproducts some of which have unique biologic properties. Sun induced vitamin D synthesis is greatly influenced by season, time of day, latitude, altitude, air pollution, skin pigmentation, sunscreen use, passing through glass and plastic, and aging. Vitamin D is metabolized sequentially in the liver and kidneys into 25-hydroxyvitamin D which is a major circulating form and 1,25-dihydroxyvitamin D which is the biologically active form respectively. 1,25-dihydroxyvitamin D plays an important role in regulating calcium and phosphate metabolism for maintenance of metabolic functions and for skeletal health. Most cells and organs in the body have a vitamin D receptor and many cells and organs are able to produce 1,25-dihydroxyvitamin D. As a result 1,25-dihydroxyvitamin D influences a large number of biologic pathways which may help explain association studies relating vitamin D deficiency and living at higher latitudes with increased risk for many chronic diseases including autoimmune diseases, some cancers, cardiovascular disease, infectious disease, schizophrenia and type 2 diabetes. A three-part strategy of increasing food fortification programs with vitamin D, sensible sun exposure recommendations and encouraging ingestion of a vitamin D supplement when needed should be implemented to prevent global vitamin D deficiency and its negative health consequences.
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The non-classical actions of vitamin D, namely anti-proliferation, pro-differentiation, immune function modulation, and anti-inflammation, have received great attention during the past decade, in particular, the potential of vitamin D analogs alone or in combination with other anticancer agents for the treatment of a variety of cancers. The association between vitamin D status and the higher incidence of many forms of cancer has suggested that vitamin D may play a role in the etiology of these types of cancer. Although it is still controversial whether this association exists for pancreatic cancer, biochemical evidence clearly indicates pancreatic cancer cells are responsive to the inhibitory effect of vitamin D and its analogs. In this review, we discuss briefly the origin and current therapy of pancreatic cancer, the history, source, metabolism and functions of vitamin D, the recent progress in the epidemiological studies of sunlight, and vitamin D status, and biochemical studies of vitamin D analogs in the prevention and treatment of pancreatic cancer.
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Summary Modern history about hormone D physiologic and biochemical mechanisms began with the works by Norwegian biochemist R. Nicolaysen, who, influenced by the work of diets in the several different animals, drew the conclusion that calcium uptake is guided by an unknown factor "warning" the bowl about calcium needs, and finished with the works of Sweden researcher Arvid Carlson, Novel Prize of medicine awarded by his studies about transduction signals at central nervous system; he carried out too several works related to Vitamin D and documented the same ideas proposed by Nicolaysen. Throughout these sixty years, hormone D history has been counted, Wasserman's studies described, and Hector De Luca remarkable works who discovered the 25 hydroxyvitamin D and Fraser and Kodiercek calcitriol. The knowledge of intestinal adaptation, vitamin D photobiology, the other vitamin D metabolites, hormone D analogues, CYP enzyme system, vitamin D receptor, transcaltachia and the new hormone D mechanisms are described. It remains to discover many effects of this hormone and that future may be even more promising.
Article
It has been known for a long time that vitamins are essential nutrients for humans and animals. These substances are important for regular cell function, growth and development. Relatively small amounts of vitamins are needed to perform vital functions. As a rule vitamins promote the actions of enzymes in order to improve its efficiency and in this role they are called coenzymes. There are 13 essential vitamins vitamin A, vitamin B1 (thiamine), vitamin B2 (riboflavin), vitamin B3 (niacin), pantothenic acid, biotin, vitamin B6 (pyridoxine), folate (folic acid, vitamin B9), vitamin B12, vitamin C, vitamin D, vitamin E, and vitamin K, which are needed for normal functioning of mammalians’ life. Normal neurosystem functioning depends on its structural and functional perfection. During life, the human body is exposed to many elements, which create free radicals. These free radicals are known to date as distractive agents for many biological systems include the neurosystem. Free radicals are atoms or groups of atoms with unpaired number of electrons and can be formed when oxygen interacts with certain molecules. Once these highly reactive radicals are formed, they can start a chain reaction – “domino effect”, which produces membranes damage. To prevent this damage, the body has an antioxidation defense system. Antioxidants are molecules, which can safely interact with free radicals and terminate the chain reaction before vital molecules are damaged. Antioxidative agents are intimately involved in the prevention of cellular damage – the common pathway for cancer, aging, and a variety of diseases. The antioxidant defense system is important in maintaining cellular homeostasis and preventing oxidative stress. According to the present invention, antioxidants like vitamins and other antioxidative agents may be considered as further active components because antioxidants inhibit free radical distractive activities. Antioxidants, especially lipid-soluble antioxidants, can be absorbed into the cell membrane to neutralize oxygen radicals and thereby protect the membrane. Although there are several enzyme systems within the body that scavenge free radicals, the principle vitamin antioxidants are vitamin E, beta-carotene, vitamin C and vitamins from the B group. Vitamins C, E and K are known to protect neurons from oxidative damage in stroke and in other neurodegenerative conditions. B vitamins are critically important in maintaining the normal functions of the brain. Deficiency in B vitamins results in a predictable sequence of different neurological and psychiatric disturbances. This chapter is focused on evidence from clinical and basic science studies supporting a role of several vitamins as potential neuroprotective compounds. Neuroprotective effects of them as add-on therapies merit further investigations in schizophrenia and mood disorders.
Article
Considered in this paper is a broad range of evidence bearing on the calcium absorption hypothesis that has been advanced to explain high frequencies of the gene for persistence of lactase activity (PLA) among adults in northern Europe. According to that hypothesis, lactase‐sufficient individuals in early northern Europe enjoyed a selective advantage over lactase‐deficient ones that led to high incidences of PLA in adults of the region. Northern Europeans, the hypothesis goes, suffered from a dietary shortage of vitamin D and, in addition, were unable to synthesize adequate vitamin D from the sun's ultraviolet radiation because of northern Europe's cloudiness and its location in higher latitudes. This led to chronic vitamin D deficiency along with a reduced ability to absorb calcium from milk and lactose‐rich dairy products. As a result, the deficiency diseases rickets—which affects infants and children and can leave a child with bowlegs and other bone defects—and osteomalacia—which weakens and deforms the bones of adults—were common in early northern Europe, and represented powerful selective forces that contributed to development of the highly depigmented skin that is typical of the region's peoples. In addition, the hypothesis goes, calcium absorption was enhanced by a process independent of vitamin D. Such enhancement, found especially or solely among lactase‐sufficient individuals, was brought on by ingestion of lactose in milk and milk products. Thus, persons who enjoyed high lactase activity through life were favored in the struggle for survival, which ultimately led northern European peoples to have among the highest incidences of PLA in the world.In this article, evidence, much of it recent, is presented to show that lactase‐deficient humans are able to absorb calcium from milk as readily, or nearly as readily, as lactase‐sufficient humans. Evidence is also presented that rickets and osteomalacia occur in parts of the world that have an abundance of sunshine, whether originating from customs that limit exposure to sunshine or otherwise; that heavy cloud cover and high latitude need not result in vitamin D deficiency, rickets, and osteomalacia; that, indeed, osteological evidence from archeological sites in northern Europe indicates that rickets and osteomalacia were quite rare in antiquity; that those conditions appear to have become common in northern Europe only with the advent of the Industrial Revolution, too short a time to have been a significant factor in bringing on the high incidences of PLA that prevail today; and that, indeed, the calcium absorption hypothesis is not confirmed by historical, osteoarcheological, or bio‐medical evidence.
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Summary In this paper we review the historical aspects and the different authors who contributed to the knowl- edge of polymorphisms of the gene of vitamin D. Also a complete analysis is made of the epidemio- logic aspects of the rickets, the definition and the first descriptions of the same one, the concept of nutritional disease, the importance and historic of the use of cod-liver-oil, and the beginning of the knowledge about vitamin D related pathologies.
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Vitamin D, the sunshine vitamin, has received a lot of attention recently as a result of a meteoric rise in the number of publications showing that vitamin D plays a crucial role in a plethora of physiological functions and associating vitamin D deficiency with many acute and chronic illnesses including disorders of calcium metabolism, autoimmune diseases, some cancers, type 2 diabetes mellitus, cardiovascular disease and infectious diseases. Vitamin D deficiency is now recognized as a global pandemic. The major cause for vitamin D deficiency is the lack of appreciation that sun exposure has been and continues to be the major source of vitamin D for children and adults of all ages. Vitamin D plays a crucial role in the development and maintenance of a healthy skeleton throughout life. There remains some controversy regarding what blood level of 25-hydroxyvitamin D should be attained for both bone health and reducing risk for vitamin D deficiency associated acute and chronic diseases and how much vitamin D should be supplemented.
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Vitamin D, the sunshine vitamin, has been made on earth for at least 750 million years. Vitamin D evolved during this time into a hormone not only for regulating calcium and bone metabolism, but also for a variety of noncalcemic actions that have been related to decreasing risk of common cancers, autoimmune diseases, infectious diseases and heart disease. Vitamin D requires hydroxylations in the liver and kidneys to be activated to 1,25-dihydroxyvitamin D (1,25(OH)2D). 1,25(OH)2D interacts with its vitamin D receptor in target tissues to enhance intestinal calcium absorption, mobilize calcium from the skeleton and have a wide range of other genomic effects. 1,25(OH)2D3 is not only made in the kidneys, but made in many other tissues throughout the body for regulating cell proliferation, decreasing cellular malignancy and controlling the production of as many as 200 different gene products. Vitamin D status is determined by measuring serum 25-hydroxyvitamin D (25(OH)D). A blood level of 25(OH)D > 30 ng/ml is considered to be vitamin D sufficient, whereas < 20 ng/ml is deficient, and 21-29 is insufficient. Sun exposure is a major source of vitamin D for most humans. In the absence of sun exposure, at least 25 µg (1,000 IU) of vitamin D3 is required to satisfy the body's requirement.
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The major function of vitamin D (either vitamin D2 or D3) is to maintain healthy bone. Most humans obtain their vitamin D requirement through casual exposure of the skin to solar ultraviolet B and from dietary intake. The cutaneous synthesis of vitamin D is a function of 7-dehydrocholesterol concentration in epidermis, melanin pigmentation, and the solar zenith angle which depends on latitude, season, and time of day. Our recent study also indicates that altitude may influence the production of previtamin D3. One area which has shown more progress during the past decade is the use of simulated sunlamp to improve vitamin D production in patients with intestinal malabsorption and elderly who were infirmed or living in northern latitude. Vitamin D deficiency is common in infants, children, and adults worldwide. The major cause of vitamin D deficiency globally is an underappreciation of the crucial role of sunlight in providing humans with their vitamin D requirement. The association between vitamin D deficiency and the increased risk of cancers, autoimmune diseases, infectious diseases, and cardiovascular disease indicates the importance of sunlight, vitamin D, and overall health and well-being of the general population. Key WordsSunlight–vitamin D–previtamin D–latitude–season–sunscreen–melanin–black–tanning–ultraviolet B radiation
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The seminal discovery that sunlight was important in the prevention of nutritional rickets was made in 1890 by Theobald A. Palm, a medical missionary who contrasted the prevalence of rickets in northern European urban areas with similar areas in Japan and other tropical countries. He surmised that exposure to sunlight prevented rickets. Over the next 40 years his observation led to an understanding of ultraviolet irradiation and its role in vitamin D synthesis. This opened a new era of appreciation for the curative powers of the sun and "the sunshine vitamin". While Palm's observations were in some ways obscure, they had a potent effect on the development of photobiology.
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