Academic literature on the topic 'Vitamin D'

Interest in vitamin D and the VDR gene is increasing as putative roles in human health and evolutionary processes are explored. This review looks beyond the classic biochemistry that links vitamin D to calcium homeostasis; it explores how vitamin D interacts with light in a broader perspective than simple skin photosynthesis. It examines how the vitamin influences circadian rhythm, and how it may have helped drive the evolution of skin pigmentation. To this end, the nutrient–nutrient relationship with folate is also explored. The VDR gene is additionally examined as a factor in the evolutionary selection of skin depigmentation at higher latitudes to allow vitamin D synthesis. Evidence is given to show that VDR polymorphisms exhibit a latitudinal gradient in allele prevalence consistent with such a paradigm. Overall, the review examines new evo-devo ideas that link light-sensitive vitamins to human health/phenotype, both within and across the lifecycle.

It has been estimated that deficiency and insufficiency of Vitamin D affect one bilion people worldwide. Vitamin D deficiency can befound not only in countries with four (4) seasons, but also in countries with sunlight exposure all year long The objective of this studywas to know whether vitamin D deficiency can occur in Indonesia as well and to explore the role of vitamin D in people‘s health, althoughIndonesia is a country in the equator region. To avoid long term negative health consequences 25 hydroxyvitamin D/25 (OH) D serumlevel should be between 30 and 100 ng/mL. The main source of vitamin D is by synthesis at the skin which is exposed to ultraviolet Bradiation. The other source of vitamin D is from food. There are a lot of causes of vitamin D deficiency, for example: decreased vitaminD synthesis, nutritional intake of vitamin D, maternal vitamin D stores and exclusive breastfeeding, mal absorption and decreasedsynthesis or increased degradation of 25 (OH) D. From the above factors, decreased vitamin D synthesis is the main cause of vitamin Ddeficiency. The vitamin D deficiency is estimated and plays an important role in multiple disorders, such as: osteoporosis, fracture, cancer,cardiovascular disease, diabetes mellitus, autoimmune disease and infectious disease. A good strategy in managing vitamin D deficiencyis needed in order to solve the related problems.

Povezanost vitamina D i kože započinje sintezom vitamina D u koži, a neprestano se istražuju i uočavaju novi mehanizmi kojima najistraživaniji vitamin utječe na najveći organ ljudskoga tijela. Cilj je ovoga rada dati pregled dosadašnjih spoznaja o interakciji vitamina D i kože te utjecaju razina vitamina D na kožne bolesti. Po nekim istraživanjima suboptimalne razine vitamina D nalaze se u čak 30 – 90 % stanovništva, a procjenjuje se da postoji manjak vitamina D u oko jedne milijarde ljudi na cijelome svijetu. U 25,6 – 68 % pacijenata sa psorijazom postoji nedostatak vitamina D, a manjak vitamina D nazočan je u čak 97 % pacijenata. Nadalje, niz opservacijskih studija i metaanaliza dokazalo je da su serumske razine kalcidiola niže u djece i odraslih s atopijskim dermatitisom, a pojedina istraživanja dokazala su da u čak 70,5 % pacijenata s vitiligom postoji nedostatak vitamina D. Niske razine vitamina D povezuju se i s progresijom malignog melanoma, no nepoznato je u kojem trenutku izloženosti UV zračenju vitamin D prestaje djelovati protektivno i započinje biti rizični čimbenik za razvoj tumora kože. Unatoč brojnim provedenim istraživanjima, još uvijek nije poznata priroda odnosa vitamina D i pojedinih kožnih bolesti, odnosno je li on uzročnoposljedičan ili slučajan, dok se u drugih dermatoza, poput psorijaze, dokazi o povezanosti s razinom vitamina D primjenjuju u svakodnevnom radu s pacijentima – u dijagnostici i liječenju.

Bu çalışmada, enjektabl preparatlarda vitamin D 3'ün stabilitesi için uygun saklama koşullarının belirlenmesi amaçlanmıştır. Enjekte edilebilir D vitamini preparatlarında vitamin D 3'ün farklı saklama koşulları altında zamana göre değişimleri belirlendi. Mühürsüz (analizin 0. gününde müstahzar mührü açılmış, diğer günlerde analizler için aynı müstahzar kullanılmıştır) ve mühürlü müstahzarlarda (her analiz gününde yeni müstahzar mührü açılarak analiz yapılmıştır) vitamin D analizleri yapılmıştır. 0, 7, 14, 28 ve 56. günlerde güncel ABD Farmakopesinin değiştirilmiş ve doğrulanmış bir yöntemiyle gerçekleştirilmiştir. D3 vitamini değişikliklerinin 4 °C'de saklama koşulları altında 25 °C'ye göre daha yüksek olduğu bulundu. D vitamini oranı 3Mühürsüz müstahzarlardaki değişiklikler, farklı saklama koşulları altındaki mühürlü müstahzarlara kıyasla önemli ölçüde arttı. Sonuç olarak, enjekte edilebilir vitamin preparatları açıldıktan sonra, oda sıcaklığında ve ışıksız çevre koşullarında uygun şekilde saklanabilmektedir.

D vitamini çatışmazlığı 21-ci əsrin pandemiyasıdır. Vitamin D həm qadınlarda, həm də kişilərdə reproduktiv proseslərin tənzimlənməsində mühüm rol oynayır. Vitamin D reseptorları yumurtalıq, endometrium və fallopiya toxumalarında mövcuddur.borularda, həmçinin desidua və plasentada. Vitamin D steroidogenezdə iştirak edir. Məqalədə D vitamini çatışmazlığının bir çox ginekoloji problemlərin, o cümlədən polikistik yumurtalıq sindromu, endometrioz, uşaqlıq leyomyoması, dismenoreya kimi xəstəliklərin inkişafındakı rolundan bəhs edilir.

This group of vitamins consists of vitamin D2 and vitamin D3, which are synthesized in the body of some invertebrates and plants, but also in the human body. Ultraviolet rays cause vitamin D to integrate under the skin. The vitamin is transported via specific proteins to all parts of the body, where it performs numerous roles. The low level of vitamin D in blood is a current public health problem. Vitamin D deficiency is especially pronounced among the elderly and obese. Currently, vitamin D deficiency is associated with an increase in bone and cardiovascular diseases, diabetes, malignant, autoimmune and allergies diseases. That is why it is extremely essential to establish and correct the deficiency of this vitamin in a timely manner. Compensation can be done partly through food, but also through oral supplements, and in more severe cases, by intramuscular administration of vitamins.

Background Vitamin supplements are commonly used in women of reproductive age. There is a range of vitamin supplements such as iron, folate, vitamin B and vitamin D that are used. Deficiencies in vitamin D can result in adverse health outcomes, such as exacerbation of asthma and fractures. Some studies suggest that vitamin D deficiency may be associated with increases in depressive symptoms and severity. These associations need further exploration to ascertain confirmation, with more vigorous research. Furthermore, there has been limited research on the reasons behind vitamin supplement use in women of reproductive age who originate from culturally and linguistically diverse (CALD) populations. These need further exploration to examine the beliefs, attitudes and practices of women regarding vitamin supplement use. Aims and Objectives Aims: To explore vitamin supplements use in women of reproductive age in terms of their beliefs, attitudes and practices particularly in CALD communities, with a focus on vitamin D and its potential role in depression in women of reproductive age. Objectives: 1) To investigate any association of vitamin D deficiency with depression in women of reproductive age. 2) To examine whether vitamin D supplementation results in a decrease depressive symptoms and severity. 3) To explore the beliefs, attitudes and practices of women of reproductive age, including those from CALD backgrounds, in relation to vitamin supplement use. 4) To explore the beliefs, attitudes and practices of CALD women regarding the Hijab and vitamin D. Content of this thesis This thesis is made up of four chapters. Chapter 1 contains the background. The challenges identified in Chapter 1 led to the exploration of the effect of vitamin D on depression in women of reproductive age via a systematic review in Chapter 2. The qualitative study in Chapter 3 describes the factors behind the beliefs, attitudes and practices of women of reproductive age in terms of vitamin supplement use. Lastly Chapter 4 presents general discussion and conclusions from the work described in this thesis. Methods A systematic review was conducted to investigate the effect of vitamin D on depression in women of reproductive age based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement checklist (Chapter 2). A systematic search strategy was deployed in ten databases including Medline, EMBASE, PsycINFO, CINAHL, AMED, International pharmaceutical abstracts, Maternal and infant care, EBM ALL, Global health, and PubMed to identify primary studies that met eligibility criteria. A qualitative study using semi-structured interviews was undertaken to explore the use of vitamin supplements in women of reproductive age. A semi-structured interview guide was developed and applied to facilitate the interview. Participants were recruited through advertisements in pharmacies, medical centres and community centres as well as via the distribution of flyers across a large university campus in Sydney, through social media, word of mouth and snowball sampling. Interviews were audio-recorded and transcribed. Interviews were conducted until thematic saturation was achieved and data was analysed. NVivo12 Plus Qualitative Data Analysis software (QSR International Pty Ltd. Version 12, 2019) was used to analyse the emerging themes. Initial codes were highlighted and organised into general themes and sub-themes, which were reviewed and refined. Results Chapter 2 Systematic review identified a total of 2377 studies through comprehensive search and search of cited references. After removing duplicates and based on title and abstract screening, 128 studies remained. Full text review yielded 21 observational studies (11 cohort studies and 10 cross-sectional studies) that assessed the association between vitamin D deficiency and depression and two intervention studies (two RCTs) that investigated women of reproductive age of 15-49 years in US, Australia, New Zealand, Asia, Europe, Middle East and South America. Two cohort studies that showed no difference in depression scores in relation to vitamin D, while 9 other cohort studies reported that after measuring participants’ depression scores and vitamin D level over time, lower vitamin D levels were associated with higher depression scores. Similarly, there were two cross sectional studies that did not find an association between vitamin D level and depression scores. However, eight other cross-sectional studies showed that low vitamin D levels were linked with higher depression scores. One RCT did not find any improvement in depression symptoms and severity based on the supplementation of vitamin D used. Another RCT showed a reduction in depression scores compared to controls. Chapter 3 Semi-structured interviews were conducted with 25 women aged 19-49 years old, all from CALD backgrounds. The beliefs, attitudes and practices regarding the use of vitamin supplements of women from CALD backgrounds were explored. Thematic analysis generated four main themes: 1) health literary 2) cultural factors that influence vitamin supplement use 3) life circumstances and 4) women’s perception of health outcomes. Health literacy and information sources were key factors that affected women’s decision-making about taking vitamin supplements; and sources such as Google were heavily relied upon. Moreover, cultural factors greatly influenced women’s initiation of vitamin supplement therapy. There were discrepancies regarding the impact of wearing the Hijab on vitamin D status and more research in this area is needed. Conclusion Prior to this research, there has been limited data on CALD women of reproductive age and their beliefs, attitudes and practices in terms of vitamin supplement usage. This body of research was the first to explore the use of vitamin supplements in women of reproductive age particularly from CALD backgrounds. Furthermore, it was also one of the few studies around the world that examined the effect of vitamin D on depression in women of reproductive age. Findings from this body of work demonstrated the reoccurring themes that shaped women’s beliefs, attitudes and practices towards vitamin supplement use specifically include health literacy, cultural factors, life circumstances and women’s perception of health outcomes. This study also ascertained that CALD women of reproductive age had differing levels of health literacy and use of a range of information sources. This study also highlighted differing views regarding the practice of Hijab and rate of vitamin D supplementation. In addition, this study provides a basis for further studies to explore whether the practice of Hijab affects vitamin D levels, which has consequences for recommendations around vitamin D supplementation in countries where the Hijab is commonly worn. There was an indication of an association between vitamin D deficiency and depression symptoms and severity from this research. However, the exact clinical association in terms of vitamin D being a causal factor in developing depression remains unclear. Supplementation with vitamin D that results in changing status from vitamin D deficient to vitamin D sufficient warrants further investigation, specifically to ascertain whether an optimal level is needed to achieve a reduction in depressive symptoms and severity. Thesis overview This thesis presents an analysis of previous research on the role of vitamin D deficiency in depression in women of reproductive age. It explores the role of supplementation with vitamin D on depression symptoms and severity. It also investigates the beliefs, attitudes and practices of women of reproductive age regarding their vitamin supplements usage. It examines the motivations behind usage in women particularly those from CALD backgrounds. Rationale for this study Vitamin D deficiency is common throughout the world, including Australia which has ample sunlight all year round. Low vitamin D status has been associated with multiple adverse health outcomes, one of which is depression (1). Consensus around the optimal level of vitamin D for women of reproductive age remains to be reached. It is critical to establish if a relationship between vitamin D levels and depression exists and what that relationship is in women of reproductive age. In order to evaluate this association, a systematic review of past studies was undertaken to examine the effect of vitamin D on depression in women of reproductive age. This is further discussed in Chapter 2 of this thesis. Similarly, vitamin supplementation use has grown in the last decade worldwide and in Australia (2). This may be due to increased advertising and availability, cultural influences, affordability and increase in the use of social media platforms. It is important to understand the beliefs, attitudes and cultural practices especially in women of reproductive age, around their use of vitamin supplements. In order to explore this research question, a qualitative study was undertaken to explore the use of vitamin supplements in women of reproductive age from CALD backgrounds. This is further discussed in Chapter 3 of this thesis. Research aim, objectives and research questions The overall aim of this project was to explore the use of vitamin supplements in women of reproductive age, with a focus on CALD communities as well as investigating vitamin D and its possible association with depression in women of reproductive age. The specific objectives of this research were to: • Evaluate the effect of vitamin D status on depression and depressive symptoms. • Explore the use of vitamin supplements in women of reproductive age, particularly in women of CALD backgrounds, with a particular focus on vitamin D • Describe the beliefs, attitudes, and practices of women of reproductive age, particularly women from CALD backgrounds, regarding vitamin supplement use. The research questions were: • Does vitamin D deficiency affect depression and depressive symptoms? • What level of vitamin D is needed to decrease depression severity and symptoms? • What level of vitamin D supplementation is required to increase level of vitamin D in order to decrease depression severity and symptoms? • What factors are involved when women of reproductive age initiate vitamin supplement use? • What are the beliefs, attitudes and practices of women of reproductive age around vitamin supplement use? • What are the beliefs and attitudes and practices of women from CALD backgrounds regarding vitamin supplement use? • What are the beliefs and practices of women from CALD backgrounds regarding the Hijab and its possible connection with vitamin D deficiency? Significance This research will contribute to the expanding body of knowledge related to vitamin D deficiency and depression as well as exploring vitamin supplement use in women of reproductive age particularly those from CALD backgrounds. It is the first study to systematically evaluate the effect of vitamin D on depression in women of reproductive age and explore the use of vitamin supplements in CALD women of reproductive age in Australia. This study complements current understanding of the links between vitamin D and depression as well as the differences in the beliefs, attitudes and practices of women from CALD backgrounds regarding vitamin supplement use. Considering existing evidence, public health interventions to decrease the prevalence of vitamin D deficiency in women of reproductive age in Australia are required, in addition to increasing awareness regarding the optimal vitamin D status in order to decrease the risk of depression and depressive symptoms. The identification of several motivating factors associated with vitamin supplement use in women of reproductive age and in particular those from CALD backgrounds is an important first step in future programs of public health research aimed at identifying and targeting culturally appropriate health related information that aides decision making when it comes to vitamin supplement use. This thesis investigates women’s use of vitamin supplements, vitamin D and its possible association with depression in women of reproductive age. The first chapter provides background information on vitamin supplements, vitamin D, depression and population characteristics. The second chapter examines the effect of vitamin D on depression in women of reproductive age in the form of a systematic review. The third chapter explores the use of vitamin supplements in women of reproductive age and in particular, women from CALD backgrounds through a qualitative study. The fourth chapter discusses the significance of all the findings, future research directions and conclusions.

La vitamine D (D3 ou cholécalciférol du règne animal et D2 ou ergostérol du règne végétal) est une hormone pléiotrope qui possède de nombreux effets biologiques incluant la régulation du métabolisme du calcium et du phosphate. Chez l’Homme, ce composé est synthétisé au niveau cutané sous forme inactive. On décrit ainsi le métabolisme de la vitamine D qui conduit à la production de métabolites actifs (par les vitamine D 25- et 1α-hydroxylases codées par les gènes CYP2R1 et CYP27B1) et à leur dégradation par la vitamine D 24-hydroxylase (gène CYP24A1). L’expression des vitamine 1α- et 24-hydroxylases est finement et inversement régulée afin de maintenir l’homéostasie phosphocalcique, grâce à plusieurs boucles de rétrocontrôle impliquant entre autres la forme 1,25-dihydroxylée de la vitamine D et son récepteur VDR, la calcémie et la parathormone, la phosphatémie et le FGF23. La carence en vitamine D et les défauts de son activation sont associés à un phénotype de rachitisme, tandis que les excès en vitamine D sont associés à un phénotype d’hypercalcémie-hypercalciurie par intoxication (surdosage) ou hypersensibilité à la vitamine D (excès d’activation ou défaut de dégradation).L’objectif de ce travail de thèse est d’identifier des causes génétiques de dérégulation du métabolisme de la vitamine D et de préciser leurs mécanismes physiopathologiques par une description précise du phénotype associé. Pour ce faire, nous avons utilisé de façon conjointe les outils de la génétique (séquençage nouvelle génération et Sanger) et de la biochimie (dosage des métabolites) dans une cohorte de patients recrutés grâce au centre de référence maladies rares du métabolisme du calcium et du phosphate.Ce travail a permis de préciser le rôle de deux gènes dans les maladies liées à la dérégulation métabolisme de la vitamine D, CYP2R1 et CYP24A1, par la mise en évidence de mutations perte de fonction chez des patients avec un phénotype de rachitisme à 25-hydroxyvitamine D basse et d’hypersensibilité à la vitamine D respectivement. Notre étude a permis aussi de préciser le phénotype de ces affections. Dans la cohorte des patients étudiés, l’identification de mutations de gènes impactant le métabolisme du phosphate (SLC34A1 et SLC34A3), souligne l’intérêt de l’étude des facteurs régulateurs des activités vitamine D 1α- et 24-hydroxylases.Aucune variation significative dans les régions promotrices proximales de CYP27B1 et CYP24A1 n’a été identifiée. Le peu de connaissances sur l’ensemble des éléments régulateurs chez l’Homme n’a pas permis d’approfondir notre étude. L’identification et l’étude de ces éléments régulateurs distaux permettra de déterminer leur implication dans les maladies rares du métabolisme de la vitamine D
The vitamin D (D3 or cholecalciferol from animal kingdom and D2 or ergosterol from plan kingdom) is a pleiotropic hormone who has numerous biological effects including the regulation of calcium and phosphate metabolism. In humans, this compound is synthetized in skin in an inactive form. Thus, we call vitamin D metabolism the biological process which leads to the production of active metabolites (by enzymes 25- and 1α-hydroxylases encoded by CYP2R1 and CYP27B1 genes) and its degradation by vitamin D 24-hydroxylase (gene CYP24A1). The expression of 1α- and 24-hydroxylases is tightly and inversely regulated to maintain calcium and phosphate homeostasis, thanks to several feedback loops including 1,25-dihydroxyvitamin D and its receptor VDR, serum calcium and parathormone, serum phosphate and FGF23. Vitamin D deficiency and vitamin D activation deficiency are associated with rickets, while vitamin D excess are associated with hypercalcemia-hypercalciuria due to vitamin D intoxication (overdose) or hypersensitivity to vitamin D (activation excess or degradation deficiency).Our aim is to identify genetic causes of vitamin D metabolism deregulation and to specify pathophysiologic mechanisms describing phenotype. Thus, we jointly used the tools of genetics (next-generation and Sanger sequencing) and biochemistry (vitamin D metabolites assay) in a cohort of human patients ascertained thanks to the national center for rare diseases of calcium and phosphate metabolism.This work allowed us to specify the role of two genes in diseases of vitamin D metabolism, CYP2R1 and CYP24A1, showing loss of function mutations in patients with rickets and low 25-hydroxyvitamin D and hypersensitivity to vitamin D, respectively. Our study brought new phenotypic elements in these affections. In our cohort of patients, the identification of mutations leading to phosphate deregulation (in SLC34A1 and SLC34A3) highlights the putative role of regulators of vitamin D 1α- and 24-hydroxylases activities in pathophysiology.No significant variation have been identified in the proximal promoting regions of CYP27B1 and CYP24A1. We could not go further considering the lack of knowledge in regulating regions and factors in humans. Identifying distal regulators will allow to study their implication in rare diseases of vitamin D metabolism

Introdução - A concentração sérica de vitamina D pode variar em indivíduos de diferentes grupos etários e de diversas regiões geográficas e pode ser influenciada pela exposição solar, estação do ano, bem como pelos valores de IMC e paratormônio (PTH). A classificação utilizada para definir concentração sérica adequada de vitamina D refere valores de 25(OH)D acima de 30 ng/mL. Porém, essa classificação pode estar inapropriada para a população brasileira, devido às particularidades climáticas e alimentares. Objetivo - Verificar as concentrações séricas médias de 25(OH)D e PTH e sua relação com IMC, exposição solar e estação do ano e identificar os valores de corte da 25(OH)D associados à elevação do paratormônio (PTH) em adultos e idosos de amostra representativa da população do município de São Paulo. Métodos - Para esta dissertação foi desenvolvido um artigo original. O artigo original descreve o estudo transversal realizado com indivíduos do estudo ISA-Capital, estudo multicêntrico e de base populacional, onde foram investigados 589 indivíduos, de ambos os sexos, dos grupos etários: 20 a 59 (adultos) e 60 e mais (idosos). Foram coletadas amostras de sangue, para dosagens de 25(OH)D e PTH. Os indivíduos que aceitaram participar da coleta de sangue, também responderam um questionário sobre exposição solar. A análise estatística incluiu a curva ROC, testes t de Student, correlação e ANOVA. Os cálculos foram realizados pelo software SPSS versão 17.0. e p 0,05 foi considerado significante. Resultados - No artigo original observou-se idade média de 54,83 (19,21) anos, sendo 61,3 por cento do sexo feminino e 38,7 por cento do sexo masculino. A concentração sérica média de 25(OH)D foi 50,02 (22,69) ng/mL, já entre os grupos foi de 47,48 (23,03) (adultos) e 52,68 (22,06) ng/mL (idosos) havendo diferença significativa entre eles (p=0,005). Observou-se variação sazonal da concentração sérica de 25(OH)D e correlação positiva entre 25(OH)D e IMC (r = 0,114, p = 0,006). O novo valor de corte 55.8 ng/mL, determinado pela análise da curva ROC, encontrou 67,6 por cento dos indivíduos insuficientes de 25(OH)D e entre os grupos 72,1 por cento (adultos) e 62,8 por cento (idosos). Conclusão - Os resultados demonstram a presença de variação sazonal nas concentrações séricas de 25(OH)D no municipio de São Paulo. O ponto de corte proposto para nossa população indicou elevada prevalência de insuficiência de vitamina D. Portanto, se faz necessário políticas públicas de prevenção de insuficiência de vitamina D visando os efeitos benéficos na saúde e qualidade de vida desta população.
Introduction - The serum concentration of vitamin D may vary in individuals of different age groups and geographic regions and may be influenced by sun exposure, season and by BMI and parathyroid hormone (PTH). The classification widely used as a cut-off for appropriate vitamin D status refers serum 25 (OH) D above 30 ng/mL. However, this classification may be inappropriate for the Brazilian population, due to the particular food and the climate of our population. Objective - To determine the mean serum concentrations of 25(OH)D and PTH and correlate them with BMI, sunlight exposure and season and to identify the cutoff values of 25 (OH) D associated with elevation in PTH. Methods For this dissertation, one original article were developed. Original article describe cross-sectional study performed with subjects from the ISA Capital, multicenter population-based. We investigated 589 individuals were of both sexes, age groups: 20-59 (adults) and 60 (elderly). Blood samples for laboratory measurements of 25(OH)D and PTH were collected. Individuals, who agreed to participate in blood collection, also answered a questionnaire on sunlight exposure. Statistical analysis included ROC curve, Student t test, correlation tests, ANOVA. The calculations were performed by the software SPSS version 17.0. and p 0.05 was considered significant. Results - In the original article, the mean age of participants was 54.83 (19.21) years, 61.3 per cent female and 38.7 per cent were male. The mean serum 25 (OH) D was 50.02 (22.69) ng/mL, between the groups was 47.48 (23.03) (adults) and 52.68 (22.06) ng/ mL (elderly) and significant difference between them (p = 0.005). A seasonal variation in serum 25 (OH) D was observed and positive correlation between 25(OH)D and BMI (r = 0.114, p = 0.006). The new cutoff value 55.8 ng / mL, determined by ROC curve analysis found 67.6 per cent of subjects insufficient 25 (OH) D and between groups 72.1 per cent (adults) and 62.8 per cent (elderly). Conclusion - The results demonstrate the presence of seasonal variation in serum 25 (OH) D in the municipality of Sao Paulo. The cutoff point proposed for our population showed a high prevalence of insufficient vitamin D. Therefore, public policy is needed to prevent vitamin D insufficiency in order to beneficial effects on health and quality of life in this population.

A 700bp portion of the promoter of CYP2D25, the porcine microsomal vitamin D 25-hydroxylase was isolated and sequenced. The computer analysis of the sequence revealed the existence of a putative VDRE at 220 bp upstream of the transcription start site. A CYP2D25 promoter-luciferase reporter plasmid was constructed in order to study the transcriptional regulation of the gene. Treatment with the vitamin D metabolites calcidiol and calcitriol suppressed the promoter, provided that the nuclear receptors VDR and RXR were overexpressed. Phenobarbital was also capable of suppressing the promoter if the nuclear receptors PXR or CAR were overexpressed. The 25-hydroxylases are not expressed solely in liver but in a wide array of other organs as well. It is therefore possible at least in theory to study the vitamin D 25-hydroxylation in human subjects using cells from extrahepatic organs, from which biopsy retrieval is easier than from the liver. Dermal fibroblasts are frequently used to study different pathological conditions in human subjects and they are easy to come by. Dermal fibroblasts were shown to express two vitamin D 25-hydroxylases: CYP27A1 and CYP2R1. The expression pattern of CYP2R1 displayed considerable interindividual variation. The fibroblasts were also capable of measurable vitamin D 25-hydroxylation, which makes dermal fibroblasts a possible tool in studying vitamin D 25-hydroxylation in human subjects. Little is known about the regulation of expression and activity of the human vitamin D 25-hydroxylases. Therefore dermal fibroblasts – expressing CYP2R1 and CYP27A1 – and human prostate cancer LNCaP cells, that express CYP2R1 and CYP2J2, were treated with calcitriol and phenobarbital and efavirenz, two drugs that give rise to vitamin D deficiency. Treatment decreased the mRNA levels of CYP2R1 and CYP2J2 provided that the treated cells also expressed the necessary nuclear receptors. CYP27A1 did not respond to any of the treatments. The treatments also managed to decrease the 25-hydroxylating activity of the cells. The results show that vitamin D 25-hydroxylases can be regulated by both endogenous and xenobiotic compounds.

The aim of this research was to apply analytical epidemiology to examine associations between hypertension and vitamin D status (serum 25-hydroxyvitamin D (25OHD)). The first objective was to appraise and synthesize the research evidence on the relationship between hypertension and 25OHD. The follow-up objective was to complete a sequence of studies exploring the association between hypertension and 25OHD in two populations with high hypertension and vitamin D deficiency rates, Finland and China. The results of the meta-analysis were that higher vitamin D levels were associated with lower hypertension rates. In a prospective study from Finland higher 25OHD levels at baseline were found to associate with less hypertension and a lower pulse rate. On follow-up only low pulse rate remained associated with higher 25OHD. A hypertension prevalence rate of 34% was reported from a cross-sectional survey in Macau 2012. Potentially modifiable predictors of hypertension were found to be smoking, obesity and lack of exercise, sunlight exposure and low intake of fish. Only 45% of this population on whom blood was collected were found to have sufficient vitamin D status (≥50 nmol/L). Young highly educated women were at greatest risk of not being sufficient. Higher sun exposure, fish intake and more physical activity and less sitting were associated with higher 25OHD levels. In the older population (≥55 years) higher 25OHD levels significantly predicted having either lower hypertension or lower pulse rates. The evidence from these series of studies indicates a small consistent association between vitamin D sufficiency and reduction in hypertension risk. These results are consistent with recent meta-analyses of observational studies. The unique finding from this study is that there is an age cohort differential with younger Chinese having lower vitamin D status and in a population with increasing hypertension this fact may have public health consequences in the future.

Les leishmaniosis són un grup de malalties causades per protozous del gènere Leishmania que es transmeten per vectors. La leishmaniosi visceral (LV) humana pot ser mortal si no es tracta, resultant en 26 000-65 000 morts a l’any. Els cànids són el principal reservori i hostes de Leishmania infantum, l’agent causant de la LV zoonòtica a la conca mediterrània. Es desconeixen els mecanismes que regulen el resultat final de la infecció, però és sabut que el sistema immunitari juga un paper clau en el control de la malaltia. Diversos estudis han demostrat que la vitamina D té un rol important en la resposta immune, activant el sistema immunitari innat i modulant la resposta adaptativa. A més, s’ha descrit la relació entre la deficiència de vitamina D i el risc de patir diverses malalties. L’objectiu de la tesis va ser estudiar si la vitamina D té una contribució rellevant en la leishmaniosi canina (LCan). Per això, es va mesurar la concentració de vitamina D en mostres de sèrum d’una població de gossos sans i malalts residents en zona altament endèmica i se’n va estudiar la relació amb paràmetres parasitològics i immunològics. Els gossos malalts presentaven nivells de vitamina D significativament més baixos que els no infectats i que els infectats asimptomàtics. A més, la deficiència de vitamina D es correlacionava amb paràmetres relacionats amb la progressió de la LCan. També vam investigar si variacions genètiques en el locus del gen del receptor de la vitamina D s’associa amb la progressió de la LCan, però les freqüències al·lèliques dels polimorfismes (SNPs) trobats no van resultar ser estadísticament diferents entre grups. Llavors, vam analitzar la concentració de vitamina D en mostres de sèrum preses en diferents períodes de l’any en una cohort de gossos sans. Els resultats van mostrar que no hi ha variació estacional dels nivells de vitamina D en gossos. També es va analitzar retrospectivament la concentració de vitamina D en gossos amb leishmaniosi clínica i gossos no-infectats a l’inici de l’estudi, quan tots els animals eren negatius a Leishmania, i un any després. Mentre que els gossos sans no van mostrar canvis en els nivells de vitamina D durant l’estudi, els que van desenvolupar leishmaniosi van mostrar una reducció significativa al final de l’estudi. Per tant, la concentració de vitamina D no és un factor de risc per desenvolupar LCan, sinó que disminueix amb el curs de la malaltia. Un model in vitro va demostrar que afegir vitamina D activa (1,25(OH)2D3) comporta una reducció significativa de la càrrega de L. infantum en macròfags canins. Analitzant l’expressió de gens relacionats amb la via de la vitamina D en monòcits canins primaris vam demostrar que l’expressió de la β-defensina CBD103 augmenta significativament amb l’addició de 1,25(OH)2D3. Els resultats van corroborar que la vitamina D juga un paper en el control del paràsit. Per últim, es va estudiar la viabilitat de la vitamina D com a adjuvant per potenciar l’efecte d’una vacuna enfront la leishmaniosi. Es va administrar vitamina D conjuntament amb una vacuna d’ADN encapsulada en liposomes a ratolins BALB/c. Dues setmanes després de la vacunació els animals van ser infectats amb L. infantum. Es va mesurar la càrrega parasitària en òrgans diana i es va avaluar la resposta immune abans de la infecció i sis setmanes després. La vacuna no va reduir significativament la càrrega parasitària, però amb la co-administració de vitamina D es va apreciar una tendència a disminuir-la. L’estudi de la resposta immunològica va suggerir que l’augment de limfòcits T CD4+ i CD8+ podrien haver contribuït en la protecció parcial aconseguida per la vacuna amb la vitamina D com a potenciador.
Las leishmaniosis son un grupo de enfermedades causadas por protozoos del género Leishmania que se transmiten por vectores. La leishmaniosi visceral (LV) humana puede ser mortal si no se trata, resultando en 26 000-65 000 muertes por año. Los cánidos son el principal reservorio y huéspedes de Leishmania infantum, el agente causante de la LV zoonótica en la cuenca mediterránea. Se desconoce el mecanismo que regula el resultado final de la infección, pero se sabe que el sistema inmunitario juega un papel clave en el control de la enfermedad. Varios estudios han demostrado que la vitamina D tiene un rol importante en la respuesta inmune, activando el sistema inmunitario innato y modulando la respuesta adaptativa. Además, se ha descrito la relación entre la deficiencia de vitamina D y el riesgo de sufrir algunas enfermedades. El objetivo de la tesis fue estudiar si la vitamina D tiene una contribución relevante en la leishmaniosis canina (LCan). Para ello se determinó la concentración de vitamina D en muestras de suero de una población de perros sanos y enfermos de leishmaniosis residentes en una zona altamente endémica y se estudió la relación de ésta con parámetros parasitológicos e inmunológicos. Los perros enfermos mostraron niveles de vitamina D significativamente más bajos que los no infectados y que los infectados asintomáticos. Además, la deficiencia de vitamina D se correlacionó con parámetros relacionados con la progresión de la enfermedad. También investigamos si las variaciones genéticas en el locus del gen del receptor de la vitamina D se asocia con la progresión de LCan, pero las frecuencias alélicas de los polimorfismos (SNPs) encontrados no resultaron ser estadísticamente diferentes entre grupos. Posteriormente se analizó la concentración de vitamina D en muestras de suero tomadas en diferentes periodos del año en una cohorte de perros sanos. Los resultados mostraron que no hay una variación estacional de los niveles de vitamina D en perros. También se analizó retrospectivamente la concentración de vitamina D en perros con leishmaniosis clínica y perros no infectados al inicio del estudio, cuando todos los animales eran negativos a Leishmania, y un año después. Mientras que los perros sanos no mostraron cambios en los niveles de vitamina D durante el estudio, los que desarrollaron leishmaniosis mostraron una reducción significativa al final del estudio. Por lo tanto, la concentración de vitamina D no es un factor de riesgo para desarrollar LCan, sino que disminuye con el curso de la enfermedad. Un modelo in vitro demostró que añadir vitamina D activa (1,25(OH)2D3) conlleva una reducción significativa de la carga de L. infantum en macrófagos caninos. Analizando la expresión de genes relacionados con la vía de la vitamina D en monocitos caninos primarios demostramos que la expresión de la β-defensina CBD103 aumenta significativamente con la adición de 1,25(OH)2D3. Los resultados corroboraron que la vitamina D juega un papel en el control del parásito. Por últimos, se estudió la viabilidad de la vitamina D como adyuvante para potenciar el efecto de una vacuna frente la leishmaniosis. Se administró vitamina D junto a una vacuna de ADN encapsulada en liposomas a ratones BALB/c. Dos semanas después de la vacunación los animales se infectaron con L. infantum. Se determinó la carga parasitaria en órganos diana y se evaluó la respuesta inmune antes de la infección y seis semanas después. La vacuna no redujo significativamente la carga parasitaria, pero con la coadministración de vitamina D se apreció una tendencia a reducirla. El estudio de la respuesta inmunológica sugirió que el aumento de linfocitos T CD4+ y CD8+ podrían haber contribuido a la protección parcial conseguida cuando se administró vitamina D como potenciador junto a la vacuna.
Leishmaniasis are a group of neglected vector-borne diseases caused by obligate intracellular protozoan parasites of the genus Leishmania. Human visceral leishmaniasis (VL) can be fatal if left untreated, resulting in 26 000-65 000 deaths per year. Canids are the main reservoir and hosts of L. infantum, the causative agent of zoonotic VL in the Mediterranean Basin. The mechanisms that regulate the outcome of the infection are undisclosed, although it is well known that immune system plays a key role in leishmaniasis disease control. Several studies have shown that vitamin D plays an important immunomodulatory role by activating innate immune system and modulating the adaptive immune response. Furthermore, the relationship between vitamin D deficiency and the risk of suffering from a plethora of health disorders has been described. The aim of the thesis was to study if vitamin D have a relevant contribution in canine leishmaniasis (CanL). Because of that, we measured vitamin D concentration in serum samples from a cohort of healthy and ill dogs from a highly endemic area and we have also studied the relationship of vitamin D concentration with parasitological and immunological parameters. The sick dogs presented significantly lower vitamin D levels than their non-infected and the asymptomatic counterparts. In addition, vitamin D deficiency correlated with several parameters linked to leishmaniasis progression. We also aimed to investigate whether genetic variation within the vitamin D receptor gene locus is associated with the progression of CanL, but the allelic frequencies of the four single nucleotide polymorphisms (SNPs) found were not statistically different between groups. Afterwards, we analysed retrospectively vitamin D concentration in serum samples from a cohort of healthy dogs collected in different periods of the year. The results showed that there is not a seasonal variation of vitamin D concentration in dogs. We also analysed retrospectively vitamin D concentration in serum samples from dogs with clinical leishmaniasis and non-infected healthy dogs, in which we measured vitamin D levels at the beginning of the study, when all dogs were negative for Leishmania, and 1 year later. Whereas non-infected dogs showed no changes in vitamin D levels along the study, those developing clinical leishmaniasis showed a significant vitamin D reduction at the end of the study. Therefore, vitamin D concentration is not a risk factor for developing canine leishmaniasis, but it diminishes with the onset of clinical disease. An in vitro model using a canine macrophage cell line proved that adding active vitamin D (1,25(OH)2D3) leads to a significant reduction in L. infantum load. Analyzing expression of genes related to vitamin D pathway on primary canine monocytes, we showed that defensin CBD103 expression was significantly enhanced after active vitamin D addition. The in vitro results corroborated that vitamin D plays a role in parasitic control. Finally, we studied the suitability of vitamin D as an adjuvant to enhance the effect of a DNA vaccine against VL. BALB/c mice were treated with vitamin D concomitantly with a DNA vaccine encapsulated in liposomes. Two weeks after vaccination, the animals were infected with L. infantum parasites. Parasite load was measured in target tissues and immune response was evaluated before challenge and six weeks post-infection. Our DNA vaccine did not significantly reduce parasite load in liver nor spleen, but vitamin D coadministration showed a tendency to diminish parasite load in target organs. The study of cell response in splenocytes suggested that higher levels of CD4+ and CD8+ T cells may be responsible for the partial protection mediated by the DNA vaccine with vitamin D as enhancer.
Universitat Autònoma de Barcelona. Programa de Doctorat en Farmacologia

Vitamin D is one of the necessary substances that must be available in food, and it can be made through the exposure of the skin to ultraviolet rays found in sunlight. Vitamin D has a significant role in metabolic processes and physiological functions, and has an effect to avoid damage to muscles and recovery processes. It also has a role in regulating calcium, as there is a strong relationship between vitamin D and bone health, as well as a role in muscle function and immune responses in athletes and normal people. This article focuses on the role of vitamin D for athletes and non athletes naturally and when it is taken as a dietary supplement by increasing their overall effectiveness and athletic performance. It was concluded that taking vitamin D as a nutritional supplement for athletes depending on the type of sports activity they perform and their continuity of sports training