Introdução: A Deficiência de vitamina A (DVA) é uma das carências nutricionais mais prevalentes no mundo. É um problema de saúde pública com elevada morbidade e mortalidade em vários países em desenvolvimento. Acomete principalmente crianças pré-escolares, gestantes e nutrizes. Poucos trabalhos estudam a prevalência de DVA entre adolescentes. Objetivos: verificar a prevalência de DVA em adolescentes atendidos em um ambulatório de pediatria geral no município de Ribeirão Preto (SP); estudar a influência de indicadores socioeconômicos e bioquímicos no \"status\" de vitamina A desta população. Materiais e métodos: Desenho: estudo descritivo transversal de prevalência; Amostragem: 80 adolescentes do sexo masculino entre 10 e 19 anos. Métodos: teste +S30DR (o adolescente recebeu uma dose oral de 200.000UI de vitamina A imediatamente antes da primeira coleta de sangue. Uma segunda amostra foi obtida 30 a 45 dias após para determinação do +S30DR); dosagem da Proteína C Reativa; entrevista e avaliação antropométrica. Resultados: 43,8% (35/80) adolescentes apresentaram testes +S30DR positivos. As médias dos níveis de retinol sérico pré e pós-suplementação foram de 1,30 \'micro\'mol/l (DP:0,41) e 1,54\'micro\'mol/l (DP:0,41), respectivamente (p= 0,01; teste \"t\" de Student). Idade, renda familiar, número de pessoas no domicilio e escolaridade dos pais não se mostraram como fatores de risco para a DVA. Os níveis séricos de PCR e os episódios febris e diarréicos não alteraram os valores finais de +S30DR. Conclusões: A elevada prevalência de DVA nesta população sugere a realização de novos estudos que possam comprovar ser pertinente a inclusão desta faixa etária em programas de prevenção e erradicação desta carência nutricional / The adolescent received an oral dose of 200,000 IU vitamin A immediately after the first blood collection. A second blood sample was obtained 3045 days after supplementation in order to determine the +S30DR) 1.30 mol/l (DP:0.41) and 1.54mol/l (DP:0.41), respectively (p= 0.01; test t of Student). Ag Background: Vitamin A Deficiency (VAD) is one of the most prevalent nutritional deficiencies in the world. It constitutes a public health problem with high morbidity and mortality rates for many developing countries. It mainly affects preschool children, pregnant and lactating women and few studies have been done to evaluate its prevalence among adolescents. Objectives: To determine the prevalence of VAD among adolescents treated at a day-care pediatric clinic in Ribeirao Preto (Sao Paulo); to study the influence of socioeconomic and biochemical indicators on the status of vitamin A in this population. Materials and Method: Design: A descriptive cross- sectional study of prevalence; sampling: 80 male 10 to 19-year-old adolescents. Methods: +S30DR test ( ; dosage of C-reactive protein; interview and anthropometric measurements. Results: a total of 43.8% (35/80) adolescents presented positive +S30DR tests. The mean serum retinol pre and pos- supplementation levels were e, income, number of people in the home or parents\' education did not present as risk factors for VAD. Serum levels of CRP and fever and diarrhea episodes did not alter the final values of + S30DR. Conclusions: The high prevalence of VAD in this population would suggest the need for further studies which could prove that it would be relevant to include this age group in programs for the prevention and eradication of this nutritional deficiency. Descriptors: adolescent; vitamin A deficiency; retinol; public health.

Introdução: A deficiência de vitamina A (DVA) constitui grave problema de saúde pública em muitas regiões do mundo, atingindo principalmente o grupo matemo-infantil e aumentando a morbimortalidade na infância. A suplementação materna pode ser uma estratégia eficaz no combate ao problema. Objetivos: Verificar o impacto da suplementação materna com vitamina A sobre a concentração de retinol do leite matemo e do soro no binômio mãe-filho, além de estimar a prevalência da DVA neste grupo, verificar a associação entre mãe e filho e a influência de alguns fatores envolvidos na gênese da DVA. Casuística e métodos: 33 puérperas receberam cápsulas com 200.000 UI de vitamina A entre o 20º e o 30º dias pós-parto (grupo suplementado) e 33 receberam cápsulas idênticas com óleo de soja (grupo placebo). Amostras de sangue e leite matemos foram colhidas antes (T0) e após (T1) a intervenção (três meses pós-parto). Sangue dos lactentes foi colhido aos três meses. O retinol foi analisado pelo método de HPLC. Concentrações inferiores a 0,70 \'mü\'mol/l no soro e 1,05 \'mü\'mol/l no leite foram indicativas de DVA. Peso e altura foram aferidos e dados sociodemográficos e clínicos foram obtidos através de entrevista. Resultados: Concluíram a pesquisa 61 pares mãe-filho. Nas mães suplementadas, a concentração sérica de retinol aumentou de 1,05 \'+ OU -\' 0,31 \'mü\'mol/l no T0 para 1,17\'+ OU -\' 0,34 \'mü\'mol/l no T1 (p=0,026), mostrando diferença estatisticamente significante em relação ao grupo placebo, cuja média foi 1,02 \'+ OU -\' 0,28 \'mü\'mol/l (p=0,032). No leite materno, houve redução significativa da concentração de retinol somente no grupo que não recebeu a vitamina (1,98 \'+ OU -\' 0,78 \'mü\'mol/l no T0 e 1,34 \'+ OU -\' 0,89 \'mü\'mol/l no T1, p=0,003). Nos lactentes, não houve diferença estatística nas médias de retinol entre os grupos (0,64\'+ OU -\' 0,30 \'mü\'mol/l e 0,69 \'+ OU -\' 0,26 \'mü\'mol/l). Quanto à DVA materna sérica, encontrou-se 6,7% (TO) e 16,7% (T1) no grupo placebo e 6,5% (TO) e 3,2% (T1) no suplementado. DVA no leite materno foi observada em 7,4% (T0) e 55,6% (T1) das amostras do grupo placebo e 22,6% (T0) e 16,1% (T1) do suplementado. A DVA esteve presente em 66% dos lactentes (69% no grupo placebo e 63,3% no suplementado). Apenas uma puérpera apresentou subnutrição e um lactente apresentou risco nutricional. DVA materna associou-se à DVA no leite (p=0,015) e houve correlação positiva significante entre retinol sérico materno e do leite (r = 0,28; p=0,032). Não houve influência das variáveis paridade, escolaridade, renda, uso de polivitamínico, febre e diarréia no retinol de puérperas e lactentes. O retinol sérico materno não se alterou com o IMC, mas a idade das puérperas se correlacionou positivamente com o retinol (r = 0,29; p=0,024). Conclusões: A suplementação materna com 200.000 UI de vitamina A mostrou impacto positivo na concentração de retinol da mãe e do leite materno, porém não atingindo o lactente. Apesar de a população estudada ter sido considerada eutrófica em praticamente sua totalidade, elevada prevalência de DVA foi encontrada, principalmente nos lactentes de três meses de idade, questionando-se o ponto de corte empregado para esta faixa etária / Background: Vitamin A deficiency (VAD) is a severe public health problem in many regions of the world, affecting mainly the mother-infant group and increasing the morbimortality in childhood. The maternal supplementation can be an effective strategy to combat this problem. Objectives: To evaluate the impact of maternal vitamin A supplementation on serum and breast milk retinol concentrations; to estimate the VAD prevalence; to assess the association between mother and infant and the influence of some factors involved in the genesis of VAD. Subjects and Methods: 33 lactating women received capsules with 200.000 lU of vitamin A between the 20th day and the 30th day after delivery (supplemented group) and 33 lactating women received identical capsules with soybean oil (placebo group). Maternal blood and milk samples were collected before (T0) and after (T1) the intervention (three months after delivery). Infants\' blood was collected at three months old. Retinol was determined by HPLC method. Levels lower than 0.70 \'mü\'mol/l in serum and 1.05 \'mü\'mol/l in milk indicated V AD. Weight and height measurements were collected and socio-demographic and clinical data were obtained through interview. Results: 61 mother-infant pairs concluded the study. In supplemented mothers, the serum retinol concentration increased from 1.05 \'+ OU -\' 0.31 \'mü\'mol/l at T0 to 1.17 \'+ OU -\' 0.34 \'mü\'mol/1 at T1 (p=0.026), showing statistically significant difference in relation to placebo group, whose mean was 1.02 \'+ OU -\' 0.28 \'\"mü\'mol/l (p=0.032). In breast milk, there was significant reduction of retinol concentration only in the group that did not received the vitamin (1.98 \'+ OU -\' 0.78 \'mü\'mol/l at T0 and 1.34 \'+ OU -\' 0.89 \'mü\'mol/l at T1, p=0.003). In infants, there was not statistically difference in retinol means between groups (0.64 \'+ OU -\' 0.30 \'mü\'mol/l and 0.69 \'+ OU -\' 0.26 \'mü\'mol/l). Regarding serum maternal VAD, it was found 6.7% (T0) and 16.7% (T1) in placebo group and 6.5% (T0) and 3.2% (T1) in supplemented group. Breast milk VAD was found in 7.4% (T0) and 55.6% (T1) of the placebo and 22.6% (T0) and 16.1% (T1) of the supplemented group samples. The VAD was present in 66% of infants (69% in the placebo and 63.3% in the supplemented group). Only one lactating mother had malnutrition and one infant presented nutritional risk. Maternal VAD was associated to breast milk VAD (p=0.015) and maternal serum retinol was positively correlated to breast milk retinol (r = 0.28; P = 0.032). There was no influence of variables parity, education, income, use of multivitamin, fever and diarrhea on both infants and mothers retinol. The maternal serum retinol did not change with BMI, but the age of the lactating women was positively correlated to retinol (r = 0.29; P = 0.024). Conclusions: The maternal supplementation with 200.000 lU of vitamin A showed positive impact on maternal serum and milk retinol concentration, but it did not reach the infant. Although the study population was considered healthy in almost its entirety, high prevalence of VAD was found, mainly in infants from three months old, leading us to question the cut-off point used for this age group

Introdução: A Deficiência de vitamina A (DVA) é uma das carências nutricionais mais prevalentes no mundo. É um problema de saúde pública com elevada morbidade e mortalidade em vários países em desenvolvimento. Acomete principalmente crianças pré-escolares, gestantes e nutrizes. Poucos trabalhos estudam a prevalência de DVA entre adolescentes. Objetivos: verificar a prevalência de DVA em adolescentes atendidos em um ambulatório de pediatria geral no município de Ribeirão Preto (SP); estudar a influência de indicadores socioeconômicos e bioquímicos no \"status\" de vitamina A desta população. Materiais e métodos: Desenho: estudo descritivo transversal de prevalência; Amostragem: 80 adolescentes do sexo masculino entre 10 e 19 anos. Métodos: teste +S30DR (o adolescente recebeu uma dose oral de 200.000UI de vitamina A imediatamente antes da primeira coleta de sangue. Uma segunda amostra foi obtida 30 a 45 dias após para determinação do +S30DR); dosagem da Proteína C Reativa; entrevista e avaliação antropométrica. Resultados: 43,8% (35/80) adolescentes apresentaram testes +S30DR positivos. As médias dos níveis de retinol sérico pré e pós-suplementação foram de 1,30 \'micro\'mol/l (DP:0,41) e 1,54\'micro\'mol/l (DP:0,41), respectivamente (p= 0,01; teste \"t\" de Student). Idade, renda familiar, número de pessoas no domicilio e escolaridade dos pais não se mostraram como fatores de risco para a DVA. Os níveis séricos de PCR e os episódios febris e diarréicos não alteraram os valores finais de +S30DR. Conclusões: A elevada prevalência de DVA nesta população sugere a realização de novos estudos que possam comprovar ser pertinente a inclusão desta faixa etária em programas de prevenção e erradicação desta carência nutricional / The adolescent received an oral dose of 200,000 IU vitamin A immediately after the first blood collection. A second blood sample was obtained 3045 days after supplementation in order to determine the +S30DR) 1.30 mol/l (DP:0.41) and 1.54mol/l (DP:0.41), respectively (p= 0.01; test t of Student). Ag Background: Vitamin A Deficiency (VAD) is one of the most prevalent nutritional deficiencies in the world. It constitutes a public health problem with high morbidity and mortality rates for many developing countries. It mainly affects preschool children, pregnant and lactating women and few studies have been done to evaluate its prevalence among adolescents. Objectives: To determine the prevalence of VAD among adolescents treated at a day-care pediatric clinic in Ribeirao Preto (Sao Paulo); to study the influence of socioeconomic and biochemical indicators on the status of vitamin A in this population. Materials and Method: Design: A descriptive cross- sectional study of prevalence; sampling: 80 male 10 to 19-year-old adolescents. Methods: +S30DR test ( ; dosage of C-reactive protein; interview and anthropometric measurements. Results: a total of 43.8% (35/80) adolescents presented positive +S30DR tests. The mean serum retinol pre and pos- supplementation levels were e, income, number of people in the home or parents\' education did not present as risk factors for VAD. Serum levels of CRP and fever and diarrhea episodes did not alter the final values of + S30DR. Conclusions: The high prevalence of VAD in this population would suggest the need for further studies which could prove that it would be relevant to include this age group in programs for the prevention and eradication of this nutritional deficiency. Descriptors: adolescent; vitamin A deficiency; retinol; public health.

Introdução: Uma elevada prevalência de deficiência de vitamina D (DVD) em crianças tem sido observada em todo o mundo, mas poucos são os estudos com relação ao estado nutricional da vitamina D (VD) em lactentes saudáveis. A principal causa da deficiência em crianças saudáveis é o aleitamento materno sem suplementação e a falta ou insuficiência de exposição solar. Objetivos: Determinar as concentrações séricas de VD e verificar sua associação com concentrações de paratormônio (PTH), fosfatase alcalina (FA), cálcio (Ca), fósforo (P) e albumina e uso da suplementação de VD em lactentes saudáveis com idades entre >= 6 e <= 24 meses atendidos em duas Unidades Básicas de Saúde do município de Ribeirão Preto, SP, Brasil. Métodos: Estudo transversal, observacional e analítico em que foram determinadas as concentrações séricas de 25 (OH)D, PTH, FA, Ca, P e albumina de 155 lactentes saudáveis. Informações sobre exposição solar, aspectos sociodemográficos das mães e características clínico-nutricionais dos lactentes foram obtidas por entrevistas com os responsáveis dos lactentes. Concentrações séricas de 25(OH)D maiores que 20ng/ml foram consideradas adequadas, entre 12 a 20ng/ml insuficientes e < 12ng/ml deficientes. Resultados: Dez lactentes (6,5%, Intervalo de Confiança 95% 3,5-11,4) apresentaram insuficiência de VD e nenhum apresentou DVD. Nenhuma alteração nas concentrações séricas de P, Ca e albumina foram detectadas. Apenas um lactente apresentou aumento nas concentrações séricas de PTH e 35,5% dos lactentes apresentaram FA elevada, porém nenhum apresentou DVD ou insuficiência de VD. Não foram encontradas associações entre as concentrações séricas de 25(OH)D e as de FA, Ca e albumina. Houve associação entre concentrações séricas de 25(OH)D e PTH mesmo após ajuste para sexo, idade e Índice de Massa Corporal; também foi observada associação entre concentrações séricas de 25(OH)D e P apenas após o ajuste pelas covariáveis. Não foram verificadas associações entre insuficiência de VD, exposição solar e suplementação de VD. Conclusões: Uma baixa prevalência de concentrações insuficientes de 25(OH)D foi observada. Não foram encontradas associações entre as concentrações séricas de 25(OH)D e PTH, FA, Ca, P e albumina. Da mesma forma, não foram encontradas associações entre de concentrações séricas de 25(OH)D, exposição solar e suplementação de VD. / Introduction: A high prevalence of vitamin D deficiency (VDD) in children has been observed worldwide, but there are few studies on the nutritional status of vitamin D (VD) in healthy infants. The main cause of deficiency in healthy children is breastfeeding without supplementation and lack or insufficiency of sun exposure. Objective: To determine serum concentrations of VD and verify its association with parathyroid hormone (PTH) levels and use of VD supplementation in healthy infants aged >= 6 to <= 24 months attended at two Basic Health Units in Ribeirão Preto city, São Paulo, Brazil. Methods: A cross-sectional, observational and analytical study was performed in which were determined serum concentrations of 25 (OH) D, PTH, alkaline phosphatase (AP), calcium (Ca), phosphorus (P) and albumin of 155 healthy infants. Information of sun exposure, sociodemographic aspects of mothers and clinical and nutritional characteristics of infants were obtained through interviews with responsible for infants. Serum concentrations of 25(OH)D greater than 20ng / ml were considered adequate, between 12 to 20ng / ml insufficient and <12ng/ml, deficient. Results: Ten infants (6.5%, 95% Confidence Interval 3.5-11.4) presented VD insufficiency and none presented DVD. Only one infant had an increase in PTH serum concentrations and 35.5% of infants had high AP but none presented DVD or VD insufficiency. No changes in serum P, Ca and albumin concentrations were detected. No associations were found between serum concentrations of 25 (OH) D and AP, Ca and albumin. There was an association between serum concentrations of 25(OH)D and PTH even after adjusting for sex, age and body mass index; an association between serum concentrations of 25(OH)D and P was observed only after adjustment for covariates. There were no associations between VD insufficiency, sun exposure and VD supplementation. Conclusions: A low prevalence of insufficient concentrations of 25 (OH)D was observed. No associations were found between serum concentrations of 25 (OH)D and PTH, FA, Ca, P and albumin. Likewise, no associations were found between serum concentrations of 25 (OH)D, sun exposure and VD supplementation.

Vitamin D deficiency in patients with chronic kidney disease, measured by reduced serum concentrations of 25 hydroxy vitamin D, is highly prevalent and associated with both endothelial dysfunction and an increased risk of cardiovascular disease. Observational studies in chronic kidney disease have demonstrated that vitamin D therapy reduces the risk of cardiovascular disease. In patients with chronic kidney disease and concomitant vitamin D deficiency, the effect of vitamin D therapy on endothelial function, which is associated with cardiovascular disease, is poorly understood. The mechanism by which vitamin D affects endothelial function is unclear. Methods Presented in this thesis, two studies have addressed these issues: 1. A double blind, randomized controlled trial evaluating the effect of ergocalciferol compared to placebo on microcirculatory endothelial function in patients with non-dialysis chronic kidney disease and concomitant vitamin D deficiency 2. In vitro and in vivo experiments to determine the mechanistic effect of ergocalciferol on endothelial function in an experimental model of uraemia. Results In the clinical study, ergocalciferol increased vitamin D serum concentrations and improved microcirculatory endothelial function measured by laser Doppler flowmetry after iontophoresis of acetylcholine. Oxidative stress measured by skin autofluorescence for advanced glycation end products did not change in the ergocalciferol group but increased significantly in the placebo group. Ergocalciferol increased endothelial nitric oxide synthase expression and activity in cultured human endothelial cells and improved endothelial function in an in vivo model of mild uraemia. The findings from the in vivo and clinical studies occurred independently of changes in blood pressure, conduit artery function, serum calcium, phosphate and parathyroid hormone supporting in vitro findings that ergocalciferol acts directly on the endothelium. Conclusion Ergocalciferol improved endothelial function in both rodent and human subjects with chronic kidney disease. Experimental evidence suggests this effect occurs through an endothelium dependent mechanism involving changes in the upregulation and function of endothelial nitric oxide synthase.

BACKGROUND: The prevalence of Vitamin D deficiency is roughly 40% in the world and is increasing every year. Populations 65 years and older show a higher prevalence of vitamin D deficiency, because the aging process decreases the capacity of the skin to produce vitamin D. Some studies have reported that the prevalence of vitamin D deficiency is higher in the winter, however the effect of seasonal change on serum vitamin D level remains controversial in some specific populations. Moreover, this association remains uncertain in the elderly population because there is no study that specifically targets individuals over the age of 65. This study investigated the effect of seasonal changes and serum 25-hydroxyvitamin D among individuals 65 years and older residing in the Boston, Massachusetts and Stockholm, Sweden. METHODS: Cross-sectional and longitudinal cohort designs were both adapted to examine an existing data from VIVE2 parent study; the data was collected from 2012 to 2014. Data from the subjects who had finished this 6-month trial were analyzed for this study. Serum 25(OH)D levels, BMI, sex, study sites and age were collected and analyzed by univariate regression analysis and t-test. Serum 25(OH)D and confounders were included in multivariate analysis. Study sites were analyzed by effect modification model. RESULTS: In total, the prevalence of vitamin D deficiency (serum 25(OH)D levels less than 20 ng/ml) was 70%, while the mean serum 25(OH)D level was 20 ng/ml in summer and 16.4 ng/ml in winter. The average of seasonal serum 25(OH)D level changes were 6 ng/ml and 3 ng/ml in Stockholm, Sweden and Boston, MA, respectively. In addition, the prevalence of vitamin D deficiency increased 80% during winter (95CI: 1.1 – 2.9). There was no significant different in serum 25(OH)D levels among elderly populations between low latitude study site Boston, MA and high latitude site Stockholm, Sweden. There was no significant relation found in BMI, age and sex with serum 25(OH)D levels in the study. The seasonal serum 25(OH)D level changes was significantly different in the cross-sectional study design but not in the longitudinal study. CONCLUSION: Serum 25(OH)D levels were higher in the summer than in the winter among the elderly population resided in Boston, MA and Stockholm, Sweden.

Vitamin D is a fat-soluble hormone primarily responsible in maintaining plasma calcium and phosphorus homeostasis in humans. Vitamin D insufficiency and deficiency is a global health issue. Very few foods naturally contain vitamin D; a major source is oily fish such as salmon. Several studies have analyzed vitamin D content in various fish, however studies concerning canned fish are lacking. In particular, this study was interested in evaluating the vitamin D content in canned sardines in not only the whole fish but also in the olive oil or water it was canned in. It was hypothesized that the vitamin D content in sardines canned in water would be greater than sardines canned in olive oil due to the fat-soluble nature of vitamin D to be more easily extracted into olive oil than water. Sardines (~100g) canned in olive oil had a slightly greater vitamin D content than the sardines in water (2,555.6±234.2 and 1,993.7±2,411.3 IUs (p<0.05) respectively). An evaluation of the vitamin D3 content in the olive oil and water used to can the sardines revealed 701.4±471.1 and 149.1±42.2 IUs in the total olive oil and water respectively recovered from the cans. It was determined that of the total vitamin D content in the can (sardines in olive oil or water) 20.9%±12.8% of vitamin D3 is found in the olive oil compared to only 14.2%±10.4% (p<0.05) vitamin D3 found in water. These results support the concept that sardines packed in olive oil may have less vitamin D3 than similar sardines packed in water. The analysis of the sardines revealed that they had more than 13 times the amount of vitamin D3 than that is reported in the USDA table of nutritional facts for canned sardines. This could be because the sardines were caught in the summer months when they are more likely to be consuming food containing vitamin D3 as a result of reduced synthesis of vitamin D3 in zooplankton and other lower life forms that the sardines consume. An alternative explanation for this increase in vitamin D3 content is the process of canning the sardines. Vital Choice, the supplier of the sardines, immediately ices the fish upon retrieval from the ocean (to ensure freshness) and then are canned in less than 5 hours after being caught. This process of freshness preservation could explain why the vitamin D content was so high; possibly an accurate representation of the original vitamin D content in the sardines.

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.

Introdução: A deficiência de vitamina A (DVA) constitui grave problema de saúde pública em muitas regiões do mundo, atingindo principalmente o grupo matemo-infantil e aumentando a morbimortalidade na infância. A suplementação materna pode ser uma estratégia eficaz no combate ao problema. Objetivos: Verificar o impacto da suplementação materna com vitamina A sobre a concentração de retinol do leite matemo e do soro no binômio mãe-filho, além de estimar a prevalência da DVA neste grupo, verificar a associação entre mãe e filho e a influência de alguns fatores envolvidos na gênese da DVA. Casuística e métodos: 33 puérperas receberam cápsulas com 200.000 UI de vitamina A entre o 20º e o 30º dias pós-parto (grupo suplementado) e 33 receberam cápsulas idênticas com óleo de soja (grupo placebo). Amostras de sangue e leite matemos foram colhidas antes (T0) e após (T1) a intervenção (três meses pós-parto). Sangue dos lactentes foi colhido aos três meses. O retinol foi analisado pelo método de HPLC. Concentrações inferiores a 0,70 \'mü\'mol/l no soro e 1,05 \'mü\'mol/l no leite foram indicativas de DVA. Peso e altura foram aferidos e dados sociodemográficos e clínicos foram obtidos através de entrevista. Resultados: Concluíram a pesquisa 61 pares mãe-filho. Nas mães suplementadas, a concentração sérica de retinol aumentou de 1,05 \'+ OU -\' 0,31 \'mü\'mol/l no T0 para 1,17\'+ OU -\' 0,34 \'mü\'mol/l no T1 (p=0,026), mostrando diferença estatisticamente significante em relação ao grupo placebo, cuja média foi 1,02 \'+ OU -\' 0,28 \'mü\'mol/l (p=0,032). No leite materno, houve redução significativa da concentração de retinol somente no grupo que não recebeu a vitamina (1,98 \'+ OU -\' 0,78 \'mü\'mol/l no T0 e 1,34 \'+ OU -\' 0,89 \'mü\'mol/l no T1, p=0,003). Nos lactentes, não houve diferença estatística nas médias de retinol entre os grupos (0,64\'+ OU -\' 0,30 \'mü\'mol/l e 0,69 \'+ OU -\' 0,26 \'mü\'mol/l). Quanto à DVA materna sérica, encontrou-se 6,7% (TO) e 16,7% (T1) no grupo placebo e 6,5% (TO) e 3,2% (T1) no suplementado. DVA no leite materno foi observada em 7,4% (T0) e 55,6% (T1) das amostras do grupo placebo e 22,6% (T0) e 16,1% (T1) do suplementado. A DVA esteve presente em 66% dos lactentes (69% no grupo placebo e 63,3% no suplementado). Apenas uma puérpera apresentou subnutrição e um lactente apresentou risco nutricional. DVA materna associou-se à DVA no leite (p=0,015) e houve correlação positiva significante entre retinol sérico materno e do leite (r = 0,28; p=0,032). Não houve influência das variáveis paridade, escolaridade, renda, uso de polivitamínico, febre e diarréia no retinol de puérperas e lactentes. O retinol sérico materno não se alterou com o IMC, mas a idade das puérperas se correlacionou positivamente com o retinol (r = 0,29; p=0,024). Conclusões: A suplementação materna com 200.000 UI de vitamina A mostrou impacto positivo na concentração de retinol da mãe e do leite materno, porém não atingindo o lactente. Apesar de a população estudada ter sido considerada eutrófica em praticamente sua totalidade, elevada prevalência de DVA foi encontrada, principalmente nos lactentes de três meses de idade, questionando-se o ponto de corte empregado para esta faixa etária / Background: Vitamin A deficiency (VAD) is a severe public health problem in many regions of the world, affecting mainly the mother-infant group and increasing the morbimortality in childhood. The maternal supplementation can be an effective strategy to combat this problem. Objectives: To evaluate the impact of maternal vitamin A supplementation on serum and breast milk retinol concentrations; to estimate the VAD prevalence; to assess the association between mother and infant and the influence of some factors involved in the genesis of VAD. Subjects and Methods: 33 lactating women received capsules with 200.000 lU of vitamin A between the 20th day and the 30th day after delivery (supplemented group) and 33 lactating women received identical capsules with soybean oil (placebo group). Maternal blood and milk samples were collected before (T0) and after (T1) the intervention (three months after delivery). Infants\' blood was collected at three months old. Retinol was determined by HPLC method. Levels lower than 0.70 \'mü\'mol/l in serum and 1.05 \'mü\'mol/l in milk indicated V AD. Weight and height measurements were collected and socio-demographic and clinical data were obtained through interview. Results: 61 mother-infant pairs concluded the study. In supplemented mothers, the serum retinol concentration increased from 1.05 \'+ OU -\' 0.31 \'mü\'mol/l at T0 to 1.17 \'+ OU -\' 0.34 \'mü\'mol/1 at T1 (p=0.026), showing statistically significant difference in relation to placebo group, whose mean was 1.02 \'+ OU -\' 0.28 \'\"mü\'mol/l (p=0.032). In breast milk, there was significant reduction of retinol concentration only in the group that did not received the vitamin (1.98 \'+ OU -\' 0.78 \'mü\'mol/l at T0 and 1.34 \'+ OU -\' 0.89 \'mü\'mol/l at T1, p=0.003). In infants, there was not statistically difference in retinol means between groups (0.64 \'+ OU -\' 0.30 \'mü\'mol/l and 0.69 \'+ OU -\' 0.26 \'mü\'mol/l). Regarding serum maternal VAD, it was found 6.7% (T0) and 16.7% (T1) in placebo group and 6.5% (T0) and 3.2% (T1) in supplemented group. Breast milk VAD was found in 7.4% (T0) and 55.6% (T1) of the placebo and 22.6% (T0) and 16.1% (T1) of the supplemented group samples. The VAD was present in 66% of infants (69% in the placebo and 63.3% in the supplemented group). Only one lactating mother had malnutrition and one infant presented nutritional risk. Maternal VAD was associated to breast milk VAD (p=0.015) and maternal serum retinol was positively correlated to breast milk retinol (r = 0.28; P = 0.032). There was no influence of variables parity, education, income, use of multivitamin, fever and diarrhea on both infants and mothers retinol. The maternal serum retinol did not change with BMI, but the age of the lactating women was positively correlated to retinol (r = 0.29; P = 0.024). Conclusions: The maternal supplementation with 200.000 lU of vitamin A showed positive impact on maternal serum and milk retinol concentration, but it did not reach the infant. Although the study population was considered healthy in almost its entirety, high prevalence of VAD was found, mainly in infants from three months old, leading us to question the cut-off point used for this age group

Introduction Vitamin D status is an important public health issue due to the high prevalence of vitamin D insufficiency and deficiency, especially in high latitude areas. Furthermore, it has been reported to be associated with a number of diseases. In a previous umbrella review of meta-analyses of randomized clinical trials (RCTs) and of observational studies, it was found that plasma/ serum 25-hydroxyvitamin D (25(OH)D) or supplemental vitamin D has been linked to more than 130 unique health outcomes. However, the majority of the studies yielded conflicting results and no association was convincing. Aim and Objectives The aim of my PhD was to comprehensively explore the association between vitamin D and multiple outcomes. The specific objectives were to: 1) update the umbrella review of meta-analysis of observational studies or randomized controlled trials on associations between vitamin D and health outcomes published between 2014 and 2018; 2) conduct a systematic literature review of previous Mendelian Randomization studies on causal associations between vitamin D and all outcomes; 3) conduct a systematic literature review of published phenome wide association studies, summarizing the methods, results and predictors; 4) create a polygenic risk score of vitamin D related genetic variants, weighted by their effect estimates from the most recent genome wide association study; 5) encode phenotype groups based on electronic medical records of participants; 6) study the associations between vitamin D related SNPs and the whole spectrum of health outcomes, defined by electronic medical records utilising the UK Biobank study; 7) explore the causal effect of 25- hydroxyvitamin D level on health outcomes by applying novel instrumental variable methods. Methods First I updated the vitamin D umbrella review published in 2015, by summarizing the evidence from meta-analyses of observational studies and meta-analyses of RCTs published between 2014 and 2018. I also performed a systematic literature review of all previous Mendelian Randomizations studies on the effect of vitamin D on all health outcomes, as well as a systematic review of all published PheWAS studies and the methodology they applied. Then I conducted original data analysis in a large prospective population-based cohort, the UK Biobank, which includes more than 500,000 participants. A 25(OH)D genetic risk score (weighted sum score of 6 serum 25(OH)D-related SNPs: rs3755967, rs12785878, rs10741657, rs17216707, rs10745742 and rs8018720, as identified by the largest genome wide association study of 25(OH)D levels) was constructed to be used as the instrumental variable. I used a phenotyping algorithm to code the electronic medical records (EMR) of UK Biobank participants into 1853 distinct disease categories and I then ran the PheWAS analysis to test the associations between the 25(OH)D genetic risk score and 950 disease outcome groups (i.e. outcomes with more than 200 cases). For phenotypes found to show a statistically significant association with 25(OH)D levels in the PheWAS or phenotypes which were found to be convincing or highly suggestive in previous studies, I developed an extended case definition by incorporating self-reported data collected by UK Biobank baseline questionnaire and interview. The possible causal effect of vitamin D on those outcomes was then explored by the MR two-stage method, inverse variance weighted MR and Egger's regression, followed by sensitivity analyses. Results In the updated systematic literature review of meta-analyses of observational studies or RCTs, only studies on new outcomes which had not been covered by the previous umbrella review were included. A total of 95 meta-analyses met the inclusion criteria. Among the included studies there were 66 meta-analyses of observational studies, and 29 meta-analyses of RCTs. Eighty-five new outcomes were explored by meta-analyses of observational studies, and 59 new outcomes were covered by meta-analyses of RCTs. In the systematic review of published Mendelian Randomization studies on vitamin D, a total of 29 studies were included. A causal role of 25(OH)D level was supported by MR analysis for the following outcomes: type 2 diabetes, total adiponectin, diastolic blood pressure, risk of hypertension, multiple sclerosis, Alzheimer's disease, all-cause mortality, cancer mortality, mortality excluding cancer and cardiovascular events, ovarian cancer, HDL-cholesterol, triglycerides and cognitive functions. For the systematic literature review of published PheWAS studies and their methodology, a total of 45 studies were included. The processes for implementing a PheWAS study include the following steps: sample selection, predictor selection, phenotyping, statistical analysis and result interpretation. One of the main challenges is the definitions of the phenotypes (i.e., the method of binning participants into different phenotype groups). In the phenotyping step, an ICD curated phenotyping was widely used by previous PheWAS, which I also used in my own analysis. By applying the ICD curated phenotyping, 1853 phenotype groups were defined in the participants I used. In PheWAS, only phenotype groups with more than 200 cases were analysed (920 phenotypes). In the PheWAS, only associations between rs17216707 (CYP24A1) and "calculus of ureter" (beta = -0.219, se = 0.045, P = 1.14*10-6), "urinary calculus" (beta = -0.129, se = 0.027, P = 1.31*10-6), "alveolar and parietoalveolar pneumonopathy" (beta = 0.418, se = 0.101, P = 3.53*10-5) survived Bonferroni correction. Nine outcomes, including systolic blood pressure, diastolic blood pressure, body mass index, risk of hypertension, type 2 diabetes, ischemic heart disease, depression, non-vertebral fracture and all-cause mortality were explored in MR analyses. The MR analysis had more than 80% power for detecting a true odds ratio of 1.2 or larger for binary outcomes. None of explored outcomes were statistically significant. Results from multiple MR methods and sensitivity analyses were consistent. Discussion Vitamin D and its association with multiple outcomes has been widely studied. More than 230 outcomes have been linked with vitamin D by meta-analyses of observational studies and RCTs. On the contrary, evidence from Mendelian Randomization studies is lacking. In particular I identified only 20 existing MR studies and only 13 outcomes were suggested to be causally related to vitamin D. In the systematic literature review of previous PheWAS studies, I summarized the applied methods, predictors and results. Although phenotyping based on ICD codes provided good performance and was widely applied by previous PheWAS studies, phenotyping can be improved if lab data, imaging data and medical notes can be incorporated. Alternative algorithms, which takes advantage of deep learning and thus enable high precision phenotyping, needs to be developed. From the PheWAS analysis, the score of vitamin D related genetic variants was not statistically significantly associated with any of the 920 phenotypes tested. In the single variant analysis, only rs17216707 (CYP24A1) was shown to be associated with calculus outcomes statistically significantly. Previous studies reported associations between vitamin D and hypercalcemia, hypercalciuria, nephrolithiasis and nephrocalcinosis, may be due to the role of vitamin D in calcium homeostasis. In the MR analysis, I found no evidence of large to moderate (OR > 1.2) causal associations of vitamin D on a very wide range of health outcomes. These included SBP, DBP, hypertension, T2D, IHD, BMI, depression, non-vertebral fracture and allcause mortality which have previously been proposed to be influenced by low vitamin D levels. Further, even larger studies, probably involving the joint analysis of data from several large biobanks with future IVs that explain a higher proportion of the trait variance, will be required to exclude smaller causal effects which could have public health importance because of the high population prevalence of low vitamin D levels in some populations.