Vitamin D metabolism in critically ill patients with acute kidney injury: a prospective observational study.

BACKGROUND: Vitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH). METHODS: In this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed. RESULTS: Serial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients' serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels. CONCLUSIONS: Critically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI. Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.

Fatores associados à deficiência de vitamina D em mulheres gestantes e lactantes / Factores asociados a la deficiencia de vitamina D en mujeres embarazadas y lactantes / Factors associated with vitamin d deficiency in pregnant and lactatingwomen

Introdução: A deficiência de vitamina D durante a gestação e a lactação pode repercutir negativamente no desenvolvimento fetal e infantil, devido seu papel fundamental nos sistemas imunológico, cardíaco, ósseo, muscular e neural. Objetivo: Realizar uma revisão de literatura para integrar estudos que evidenciam a deficiência de vitamina D em gestantes e lactantes, e os fatores de risco associados a essa carência. Metodologia: Foi realizado um levantamento bibliográfico entre agosto e outubro de 2021, com atualização entre outubro e novembro de 2022 através de pesquisas às bases Pubmed e Scielo, bem como às listas de referências dos artigos selecionados. Foram empregados os descritores consumo alimentar, vitamina D, deficiência de vitamina D, gestantes e lactantes, usando-se o operador booleano AND para a associação entre eles. Como critérios de inclusão foram adotados o tipo de estudo (epidemiológicos, ensaios clínicos e revisões integrativa e sistemática), o idioma (espanhol, inglês e português) e o período de publicação (2010 a 2022). Resultados: Evidenciou-se que existem vários fatores de riscos para a inadequação do status de vitamina D em gestantes e lactantes como a baixa exposição da pele à luz solar e fatores relacionados (uso excessivo de protetor solar, menor tempo de atividades ao ar livre, clima, religião e hábitos culturais, maior escolaridade);a pigmentação mais escura da pele; o baixo consumo alimentar de vitamina D e variáveis associadas; a menor idade materna; o primeiro trimestre gestacional; a primiparidade e o excesso de tecido adiposo. Conclusões: Em gestantes e lactantes, a carência de vitamina D associa-se a distintos fatores, com destaque principalmente para a baixa exposição à luz solar, a pigmentação mais escura da pele e o excesso de tecido adiposo, sendo de extrema importância que sejam abordados com cautela, visando ações voltadas a variáveis modificáveis, de modo a auxiliar na redução da hipovitaminose D nestes grupos (AU).

Introduction: Vitamin D deficiency during pregnancy and breastfeeding can have a negative impact on fetal and infant development due to its fundamental role in the immune, cardiac, bone, muscular and neural systems. Objective: To conduct a literature review to integrate studies which show the Vitamin D deficiency in pregnant andlactating women, and the risk factors associated with this deficiency. Methodology: A bibliographic survey was carried out between August and October 2021, with an update between October and November 2022 through searches in the Pubmed and Scielo databases, as well as the reference lists of the selected articles. The descriptors food consumption, vitamin D, vitamin D deficiency, pregnant and lactating women were used, using the Boolean operator AND for the association between them. The type of study (epidemiological, clinical trials and integrative and systematic reviews), language (Spanish, English and Portuguese) and publication period (2010 to 2022) was adopted as inclusion criteria.Results:It was shown that there are several risk factors for inadequate vitamin D status in pregnant and lactating women, such as low skin exposure to sunlight and related factors (excessive use of sunscreen, less time spent outdoors, climate, religion and cultural habits, higher education); darker skin pigmentation; low dietary intake of vitamin D and associated variables; the lowest maternal age; the first gestational trimester; primiparity and excess adipose tissue.Conclusions: Vitamin D deficiency in pregnant and lactating women is associated with different factors, witha main emphasis on low exposure to sunlight, darker skin pigmentation and excess adipose tissue. Furthermore, it is extremely important that these factors are approached with caution, implementing actions aimed at modifiable variables in order to help reduce hypovitaminosis D in these groups (AU).

Introducción: La deficiencia de vitamina D durante el embarazo y la lactancia puede tener un impacto negativo en el desarrollo fetal e infantil, por su papel fundamental en los sistemas inmunológico, cardíaco, óseo, muscular y neural. Objetivo: Realizar una revisión bibliográfica para integrar estudios que evidencien la deficiencia de vitamina D en mujeres embarazadas y lactantes, y los factores de riesgo asociados. Metodología:Se realizó un levantamiento bibliográfico entre agosto y octubre de 2021, con actualizaciones entre octubre y noviembre de 2022 mediante búsquedas en las bases de datos Pubmed y Scielo, así como en las listas de referencias de los artículos seleccionados. Se utilizaron los descriptores consumo de alimentos, vitamina D, deficiencia de vitamina D, gestantes y lactantes, utilizándose el operador booleano AND para la asociación entre ellos. Se adoptaron como criterios de inclusión el tipo de estudio (epidemiológicos, clínicos, revisiones integradoras y sistemáticas), idioma (español, inglés y portugués) y período de publicación (2010 a 2022).Resultados: Existen varios factores de riesgo para un estado inadecuado de vitamina D en mujeres embarazadas y lactantes, como la baja exposición de la piel a la luz solar y factores relacionados (uso excesivo de protector solar, menor tiempo al aire libre, clima, religión y hábitos culturales, educación más alta); pigmentación de la piel más oscura; baja ingesta dietética de vitamina D y variables asociadas; la edad materna más baja; el primer trimestre gestacional; Primiparidad y exceso de tejido adiposo. Conclusiones:En mujeres embarazadas y lactantes, el déficit de vitamina D se asocia a diferentes factores, especialmente la baja exposición solar, la pigmentación de la piel más oscura y el exceso de tejido adiposo, y es de suma importancia abordarlos con precaución, apuntando a acciones dirigidas a variables modificables, con el fin de ayudar a reducir la hipovitaminosis D en estos grupos (AU).

O que as revisões sistemáticas Cochrane mostram sobre a vitamina D? / What do Cochrane systematic reviews show about vitamin D?

Contextualização: A vitamina D tem sido utilizada na prática clínica e amplamente divulgada na mídia como opção preventiva ou terapêutica em muitas doenças esqueléticas e não esqueléticas, mas sua efetividade, em muitos casos, é ainda incerta. Objetivos: Sumarizar as evidências de revisões sistemáticas da Cochrane, referentes à efetividade da vitamina D para tratamento e prevenção de doenças. Métodos: Trata-se de overview de revisões sistemáticas Cochrane. Procedeu-se à busca na Cochrane Library (2023), sendo utilizado o descritor MeSH "VITAMIN D". Todas as revisões sistemáticas de ensaios clínicos foram incluídas. O desfecho primário de análise foi a melhora clínica, a redução dos sintomas ou a prevenção da doença. Resultados: 22 estudos foram incluídos, totalizando 284.404 participantes. Há evidência de baixa qualidade relativa a benefícios da suplementação da vitamina D na gestação para mãe e recém-nascido, não sendo encontrados, até o momento, benefícios para outras condições avaliadas. Discussão: Nenhuma intervenção mostrou efetividade com evidência de boa qualidade. Embora haja descrição de benefícios na redução do risco de pré-eclâmpsia, diabetes gestacional, baixo peso do bebê ao nascimento, redução no risco de hemorragia grave pós-parto e redução de fraturas em idosos (quando associada à suplementação de cálcio), esses achados têm evidência limitada e carecem de melhor análise no futuro próximo, a partir de novos ensaios clínicos. Conclusão: Atualmente, não há suporte com bom nível de evidência para a maioria das intervenções com suplementação de vitamina D, sendo recomendada a realização de novos ensaios clínicos para melhor robustez dos achados desses estudos.

The Effect of Vitamin D Supplementation on Incidence of Type 2 Diabetes: A Systematic Review.

With the clinical increase in Type 2 Diabetes worldwide, several interventions to decrease its incidence have been investigated. One such intervention is Vitamin D supplementation, as it affects Insulin secretion from the pancreas and Insulin receptors in the cells of the body. This systematic review addresses whether or not Vitamin D supplementation has a role in reducing the risk of developing Type 2 Diabetes. Systematic searches were conducted on PubMed, and Cochrane Library mainly but also checked Google Scholar. Randomized controlled trials, systematic trials and cohort studies were retrieved that included keywords pertaining to Vitamin D supplementation and the incidence of Type 2 Diabetes. Exclusion criteria included studies that looked at different forms of Diabetes, studies including patients aged less than 18 or more than 85 years of age and studies that were not English language. For all the trials identified, the incidence of Type 2 Diabetes among the cohort receiving vitamin D supplementation was compared to the cohort receiving placebo medication. Additionally, the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was analyzed to observe if there was a difference between Insulin resistance among these two cohorts between the start of the trials and the end. Thirteen randomized controlled trials were identified. Seven of these identified incidences of Type 2 Diabetes as a research outcome, out of which six showed no statistically significant impact of vitamin D on the incidence of Type 2 Diabetes. Out of the 13 trials, 10 analyzed the impact of vitamin D supplementation on patients' HOMA-IR. In six of these trials, patients receiving vitamin D supplementation had a decrease in their HOMA-IR, while it increased in 4 trials. In seven of the ten trials that analyzed for HOMA-IR, the HOMA-IR was less in the vitamin D cohort than the placebo cohort. There is insufficient evidence to suggest that vitamin D supplementation significantly reduces the incidence of Type 2 Diabetes despite its effects on insulin resistance. Further research in this area would be helpful in order to influence clinical guidelines on vitamin D supplementation among patients at risk of Type 2 Diabetes.

Deficiency and Insufficiency of Vitamin D in Women of Childbearing Age: A Systematic Review and Meta-analysis / Deficiência e insuficiência de vitamina D em mulheres na idade reprodutiva: Uma revisão sistemática e meta-análise

Abstract Objective To estimate the prevalence of inadequate vitamin D level and its associated factors for women of childbearing age in Brazil. Methods A systematic reviewwas conducted (last updatedMay 2020).Meta-analyses were performed using the inverse-variance for fixed models with summary proportion calculation by Freeman-Tukey double arcsine. Reporting and methodological quality were assessed using the Joanna Briggs Institute tool for prevalence studies. Results Our review identified 31 studies, comprising 4,006 participants. All the studies had at least one weakness, mainly due to the use of convenience sampling and small sample size. The overall prevalence of vitamin D deficiency, insufficiency, and both deficiency and insufficiency were 35% (confidence interval, 95%CI: 34-37%), 42% (95%CI: 41-44%), and 72% (95%CI: 71-74%), respectively. Conclusion Although the magnitude of the prevalence of inadequate levels of vitamin D is uncertain, the evidence suggests that presence of vitamin D deficiency or insufficiency in women of reproductive age can cause moderate to severe problems.

Resumo Objetivo Estimar a prevalência de níveis inadequados de vitamina D e seus fatores associados para mulheres em idade fértil no Brasil. Métodos Uma revisão sistemática foi realizada (última atualização em maio de 2020). As meta-análises foram realizadas usando o inverso da variância para o modelo fixo com cálculo de proporção sumarizada por transformação arco-seno duplo de Freeman-Tukey. A qualidade metodológica e de reporte foi avaliada usando a ferramenta do Joanna Briggs Institute para estudos de prevalência. Resultados Nossa revisão identificou 31 estudos, compreendendo 4.006 participantes. Todos os estudos apresentaram pelo menos uma limitação, principalmente devido ao uso de amostra de conveniência e tamanho amostral pequeno. As prevalências gerais de deficiência, insuficiência e deficiência de vitamina D foram 35% (intervalo de confiança, IC 95%: 34-37%), 42% (IC 95%: 41-44%) e 72% (IC 95%: 71-74%), respectivamente. Conclusão Embora a magnitude da prevalência de níveis inadequados de vitamina D seja incerta, a evidência sugere que presença de deficiência ou insuficiência de vitamina D em mulheres em idade reprodutiva pode causar problemas moderados a graves.

Population pharmacokinetics and dose optimisation of colecalciferol in paediatric patients with chronic kidney disease.

AIMS: The prevalence of vitamin D deficiency is high in children with chronic kidney disease (CKD). However, current dosing recommendations are based on limited pharmacokinetic (PK) data. This study aimed to develop a population PK model of colecalciferol that can be used to optimise colecalciferol dosing in this population. METHODS: Data from 83 children with CKD were used to develop a population PK model using a nonlinear mixed effects modelling approach. Serum creatinine and type of kidney disease (glomerular vs. nonglomerular disease) were investigated as covariates, and optimal dosing was determined based on achieving and maintaining 25-hydroxyvitamin D (25(OH)D) concentration of 30-48 ng/mL. RESULTS: The time course of 25(OH)D concentrations was best described by a 1-compartment model with the addition of a basal concentration parameter to reflect endogenous 25(OH)D production from diet and sun exposure. Colecalciferol showed wide between-subject variability in its PK, with total body weight scaled allometrically the only covariate included in the model. Model-based simulations showed that current dosing recommendations for colecalciferol can be optimised using a weight-based dosing strategy. CONCLUSION: This is the first study to describe the population PK of colecalciferol in children with CKD. PK model informed dosing is expected to improve the attainment of target 25(OH)D concentrations, while minimising the risk of overdosing.

Vitamin D concentrations and their relationship with iron parameters in patients with chronic kidney disease / Concentrações de vitamina D e sua relação com parâmetros de ferro em pacientes com doença renal crônica

ABSTRACT Objective To investigate the relationship between calcidiol (25(OH)D3) concentrations and iron parameters in patients with chronic kidney disease. Methods This is a cross-sectional, descriptive, and quantitative study. The sample consisted of 86 adult patients of both sexes undergoing dialysis. 25(OH)D3 concentrations were determined by chemiluminescence; food consumption was assessed using 24-hour recalls, and the serum levels of hemoglobin, iron, ferritin, and transferrin saturation were assessed. Data analysis was performed using the program Stata, with a significance level of p<0.05. Results The results pointed to 25(OH)D3 concentrations compatible with sufficiency, iron levels consistent with normality, and ferritin and transferrin saturation above the reference values. The consumption of carbohydrates and lipids was higher in females. There was no relationship between the adequacy of 25(OH)D3 and the presence of anemia and iron parameters. Conclusion Considering that the mean serum levels of iron and 25(OH)D3 were adequate, it is suggested that resistance to erythropoietin and the inflammatory process may have contributed to the percentage of anemic individuals found in the study.

RESUMO Objetivo Investigar a relação entre as concentrações de calcidiol (25(OH)D3) e os parâmetros de ferro em pacientes com doença renal crônica. Métodos É um estudo transversal, descritivo e quantitativo. A amostra foi composta por 86 pacientes, adultos, de ambos os sexos, em terapia dialítica. As concentrações de 25(OH)D3 foram determinadas pelo método de quimioluminescência; o consumo alimentar foi avaliado pela aplicação de Recordatórios de 24 horas e foram avaliados os níveis séricos de hemoglobina, ferro, ferritina e saturação de transferrina. A análise dos dados foi realizada no programa Stata, com nível de significância p<0.05. Resultados Os resultados apontaram para concentrações de 25(OH)D3 compatíveis com suficiência, níveis de ferro compatíveis com a normalidade e ferritina e saturação de transferrina superiores à referência. O consumo de carboidratos e lipídios foi superior no sexo feminino. Não foi verificada relação entre a adequação de 25(OH)D3 e a presença de anemia e parâmetros de ferro. Conclusão Tendo em vista que os níveis médios séricos de ferro e 25(OH)D3 estavam adequados, sugere-se que a resistência à eritropoietina e o processo inflamatório podem ter contribuído para o percentual de anêmicos constatado no estudo.

Vitamin D significance in pathogenesis of endometriosis.

Genital endometriosis (GE) is a widespread multifactorial disease thus making it necessary to carry on studying its pathogeny in order to work out target therapy techniques. Studying vitamin D role in GE pathogeny is a new promising research trend. PATIENTS AND TECHNIQUE: 25(ОН)D level was determined in peripheral blood (PB) of 440 patients with GE and in peritoneal fluid (PF) - in 49 GE patients; the same test in PB was performed in 30 patients of the control group with the ovulatory menstrual cycle and no gynecologic pathology. 129 patients with GE, as well as 82 women of the control, underwent examination of vitamin D receptor (VDR) polymorphism gene in BsmI, FokI, and TaqI polymorphic locus. We examined vitamin D receptor expression in the eutopic and ectopic endometrium in 32 women with GE and in the endometrium of 20 women from the control group. We also compared the efficacy of combined therapy involving colecalciferol to the standard hormone modulating therapy. RESULTS: It was established that the prevalent GE forms are characterized by lower 25(ОН)D levels both in PB and in PF. It was also found that G/G genotype of VDR BsmI gene polymorphic variant 1.9 times increases GE occurrence risk. VDR expression was authentically lower in the ectopic endometrium compared to the eutopic endometrium. Patients with GE show no VDR expression cyclic variations in the endometrium which is contrary to the control. Therapy in combination with colecalciferol promotes a more expressed decrease of endometriosis-associated pain syndrome and psycho-emotional stabilization of GE patients compared to the standard hormone modulating therapy. CONCLUSION: Vitamin D deficiency plays a significant role in the pathogenesis of GE and Vit D may be applied as its targeted therapy.

Efecto sinérgico de un bifosfonato con vitamina D / Synergic effect of a biphosphonate with vitamin D

Introducción: Los bifosfonatos son considerados como un grupo de fármacos de gran utilidad en el tratamiento de enfermedades del tejido óseo ya que promueven su resorción. Han sido la primera línea para el tratamiento de la osteoporosis, enfermedad de Paget, mieloma múltiple e hipercalcemia maligna. Por su parte, la vitamina D es un nutriente esencial cuya función principal es la homeostasis de calcio (Ca+2) y fosfato (P4 3-). Objetivo: Describir los aspectos moleculares y farmacológicos de la acción de un bifosfonato (alendronato sódico) y la vitamina D, por los cuales potencian mutuamente sus efectos en enfermedades óseas. Métodos: Fueron seleccionadas las referencias más actualizadas que abordaran aspectos relevantes acerca del alendronato y la vitamina D. Se consultaron las bases de datos de PubMed, Uniprot y Protein Databank. Conclusiones: El sinergismo entre alendronarto y vitamina D generan efectos benéficos en el tejido óseo. Sin embargo, existen efectos colaterales que pueden afectar a otros tejidos, por lo que su uso debe ser controlado(AU)

Introduction: Biphosphonates are considered to be a group of very useful drugs used to treat osseous tissue conditions, since they foster resorption. They are first line in the treatment of osteoporosis, Paget's disease, multiple myeloma and malignant hypercalcemia. Vitamin D, on the other hand, is an essential nutrient whose main function is calcium (Ca+2) and phosphate (P4 3-) homeostasis. Objective: Describe the molecular and pharmacological aspects of the action of a biphosphonate (alendronate sodium) and vitamin D on osseous diseases. Methods: A selection was made of the most updated references about relevant aspects of alendronate and vitamin D. The databases consulted were Pubmed, Uniprot and Protein Databank. Conclusions: The synergy between alendronate and vitamin D generates beneficial effects on osseous tissue. However, their use should be controlled, since side-effects may affect other tissues(AU)

Seasonal variation of vitamin D among healthy adult men in a subtropical region

SUMMARY OBJECTIVE: To evaluate seasonal variation of 25(OH)vitamin D [25(OH)D3] levels, and factors associated with it, in healthy adult men, who exercised outdoors for 50 min., at least twice a week, from 10AM to 4PM, in a Brazilian semitropical region. METHODS: Blood samples were collected at the end of each season for 25(OH)D3, measured by liquid chromatography with tandem mass spectrometry. Ultraviolet irradiation was estimated by radiometer, calculating the daily photobiological response to vitamin D synthesis in human skin (D-VitD). The prevalence of 25(OH)D3 <20ng/mL changed with the seasons (p=0.000): 8.7% (n=6/69), 1.5% (n=1/66), 0 (n=0/64), and 21.7% (n=13/60), respectively, at the end of winter, spring, summer, and autumn. The prevalence, adjusted for multiple comparisons, was higher in winter than summer (p=0.026), and in autumn than spring (p=0.001) and summer (p=0.000). There were no associations of 25(OH) D3 levels with BMI (p=0.207), body fat (p=0.064), and phototype (p=0.485), in univariate analysis. It was associated with D-VitD in the 30 days before blood sampling (p=0.000), after adjustment to body fat. The prevalence of 25(OH)D3 <30ng/mL varied seasonally (p=0.000): 69.6% (n=48/69), 68.2% (n=45/66), 43.8% (n=28/64), and 88.4% (n=53/60), respectively, in winter, spring, summer, and autumn. CONCLUSIONS: In a Brazilian subtropical region, a seasonal variation in 25(OH)D3 was observed in healthy adult males, although they spent at least 50 min outdoors twice a week, wearing shorts and T-shirts. 25(OH)D3 <20ng/mL was 21.7% in autumn; D-vitD 30 days prior to blood sampling was the only factor independently associated with 25(OH)D3 levels.

RESUMO OBJETIVOS: Avaliar a sazonalidade da 25(OH)vitamina D3 [25(OH)D3] e fatores associados em homens adultos saudáveis, que se exercitavam ao ar livre pelo menos 50 min duas vezes por semana, das 10 às 16h, em uma região subtropical. MÉTODOS: Sangue foi colhido no fim das estações para medir 25(OH)D3, por cromatografia líquida em tandem com espectroscopia de massas. A radiação ultravioleta foi estimada por radiômetro, calculando diariamente a resposta fotobiológica para sintetizar vitamina D na pele humana (D-VitD). RESULTADOS: A prevalência de 25(OH)D3 <20ng/mL foi sazonal (p=0.000): 8.7% (n=6/69), 1.5% (n=1/66), 0% (n= 0/64), e 21.7% (n=13/60), respectivamente, no final do inverno, primavera, verão e outono. A prevalência, ajustada para comparações múltiplas, foi maior no inverno do que no verão (p=0.026) e no outono do que na primavera (p=0.001) e verão (p=0.000). A 25(OH)D3 não se associou com o índice de massa corporal (p=0.207), gordura corporal (p=0.064) ou fototipo (p=0.485), na análise univariada. Associou-se à D-VitD nos 30 dias antes da coleta de sangue (p=0.000), ajustada para gordura corporal. Houve sazonalidade na prevalência de 25(OH)D3 <30ng/mL (p=0.000): 69.6% (n=48/69), 68.2% (n=45/66), 43.8% (n=28/64), e 88.4% (n=53/60), respectivamente, no inverno, primavera, verão e outono. CONCLUSÕES: Em uma região subtropical, houve sazonalidade na 25(OH)D3 em homens adultos, saudáveis, embora se exercitassem ao ar livre pelo menos 50 minutos duas vezes por semana, usando shorts e camiseta. 25(OH)D3 <20ng/mL foi 21.7% no outono e a D-vitD 30 dias antes da coleta do sangue foi o único fator associado de modo independente à 25(OH)D3.

Suplementação com Vitamina D atenua a resposta inflamatória aguda / Vitamin D supplementation attenuates acute inflammatory response

Este estudo avaliou os efeitos da suplementação diária de vitamina D na resposta inflamatória aguda em modelo experimental por diferentes agentes flogísticos: carragenina, prostaglandina e dextrana. Os animais (ratos) receberam por via oral (gavagem), dose única de vitamina D ou suplementação diária durante 7, 15 ou 30 dias antes da indução do edema de pata. A suplementação com vitamina D por 15 e 30 dias reduziu significativamente o processo inflamatório induzido por carragenina, o que poderia ser explicado, pelo menos parcialmente, pela redução dos níveis de fator de necrose tumoral α (TNFα). Os resultados indicam que a suplementação de vitamina D pode ser um útil adjuvante terapêutico para o controle do processo inflamatório agudo.

This study evaluated the effects of daily vitamin D supplementation on the acute inflammatory response in experimental model by different phlogistic agents: carrageenan, prostaglandin and dextran. Animals (rats) orally received (gavage) a single dose of vitamin D or daily supplementation for 7, 15 or 30 days prior to paw edema induced. Vitamin D supplementation for 15 and 30 days significantly reduced the carrageenan-induced inflammatory process, which could be at least partially explained by the reduction of tumor necrosis factor α levels (TNFα). Results indicate that vitamin D supplementation may be a useful therapeutic adjuvant for controlling the acute inflammatory process.

Hypovitaminosis D and Calcium Intake in Adult Population / Hipovitaminosis D y la ingesta de calcio en población adulta / Hipovitaminose de ingestão de cálcio em população adulta

Abstract: Background: Daily dietary calcium intake below the requirements has been related to low levels of vitamin D (Vit-D) and osteoarticular diseases. Objective: To determine the prevalence of Vit-D deficiency in the general population living in Bogotá, its relationship to dietary calcium intake, and the influence of socio-demographic factors and sunlight exposure. Materials and methods: In a pro-spective cohort of the general population (randomly selected), excluding individuals with conditions affecting calcium absorption or adequate Vit-D action, the prevalence of hypovitaminosis D (95 % ci) and regular consumption of calcium (RCI, mg/day) is measured according to socio-demographic, anthropometric, biochemical, and sunlight exposure variables. A multiple regression model is implemented (no intercept) to predict Vit-D concentration based on the factors described. Results: Ninety-seven patients are included, 61 % of which are women, with a median age of 23 years, a weight of 65 kg (IQR: 55.2-70.5), a height of 165 cm ± 8.9, and BMI of 22.8 kg/m2 (IQR: 21.2-25.2). The RCI was 393.7 mg/day, less than the benchmark for Colombian adults (p < 0.001); serum calcium concentration was 9.7 mg/dL. The mean Vit-D concentration (95 % ci) was 23.7 ng/mL (22.6-24.7); hypovitaminosis D was identified in 87 % of the sample (80.6-94.7 %), 24.7 % were classified as poor (15.6-33.8 %) and 62.9% as insufficient (52.8-73%). Vit-D concentration was predicted in a quadratic function by the interaction between sex, sunlight exposure, and RCI (R2 > 90 %). Conclusion: The suspected high prevalence of Vit-D deficiency is confirmed in the general Colombian adult population as a result of low dietary calcium intake, demographic factors, and sunlight exposure.

Resumen: El consumo diario de calcio en la dieta por debajo de los requerimientos se ha relacionado con bajos niveles de Vitamina D (Vit-D) y con enfermedades osteoarticulares. Objetivo: Determinar la prevalencia de la deficiencia de Vit-D en la población general que vive en Bogotá, su relación con la ingesta de calcio en la dieta y la influencia de factores sociodemográficos y de la exposición a la luz solar. Materiales y métodos: En una cohorte prospectiva seleccionada aleatoriamente de la población general, excluyendo individuos con condiciones que afectaran la absorción de calcio o la acción de la Vit-D, se midió la prevalencia de hipovitaminosis D (IC 95 %) y el consumo habitual de calcio (CHC, mg/día), según variables sociodemográficas, antropométricas, bioquímicas y de exposición solar; se implementó un modelo de regresión múltiple (sin el intercepto) para predecir la concentración de Vit-D en función de los factores descritos. Resultados: Se incluyeron 97 pacientes, edad mediana 23 años, 61 % mujeres; con peso mediano 65 kg (RIC; 55,2-70,5), estatura 165 cm ± 8,9 e IMC 22,8 kg/m2 (RIC; 21,2-25,2). El CHC fue 393,7 mg/día, menor que el recomendado para adultos colombianos (p < 0,001); la concentración de calcio sérico fue 9,7 mg/dL. La concentración media (IC 95 %) de Vit-D fue 23,7 ng/mL (22,6-24,7), se identificó hipovitaminosis D en 87% (80,6-94,7%); 24,7% se clasificaron como deficientes (15,6-33,8 %) y 62,9 % como insuficientes (52,8-73 %). La concentración de Vit-D se logró predecir, en función cuadrática, por la interacción entre el sexo, la exposición solar y el CHC (R2 > 90 %). Conclusiones: Teniendo en cuenta los resultados obtenidos, se confirma la sospecha de alta prevalencia de hipovitaminosis D en población general colombiana adulta, relacionada con un bajo consumo de calcio en la dieta habitual, factores demográficos y de exposición solar.

Resumo: Introdução: O consumo diário de cálcio na dieta abaixo dos requerimentos necessários tem sido relacionado com baixos níveis de vitamina D (Vit-D) e com doenças osteoarticulares. Objetivo: Determinar a prevalência da deficiência de Vit-D na população geral que vive em Bogotá, Colômbia, sua relação com a ingestão de cálcio na dieta, a influência de fatores sociodemográficos e a exposição à luz solar. Materiais e métodos: em uma coorte prospectiva selecionada aleatoriamente da população geral, excluindo indivíduos com condições que afetassem a absorção de cálcio ou a ação de Vit-D, foi medida a prevalência de hipovitaminose D (IC 95 %) e o consumo habitual de cálcio (CHC, mg/dia), segundo variáveis sociodemográficas, antropométricas, bioquímicas e exposição solar; foi implementado um modelo de regressão múltipla (sem o intercepto) para predizer a concentração de Vit-D em função dos fatores descritos. Resultados: Foram incluídos 97 pacientes, com idade média 23 anos, 61 % mulheres; com peso médio de 65 kg (RIC; 55,2-70,5), estatura 165 cm ± 8,9 e IMC 22,8 kg/ m2 (RIC; 21,2-25,2). O CHC foi 393,7 mg/dia, menor do que o recomendado para adultos colombianos (p < 0,001); a concentração sérica de cálcio foi 9,7 mg/dL. A concentração média (IC 95 %) de Vit-D foi 23,7 ng/mL (22,6-24,7), foi identificada hipovitaminose D em 87 % (80,6-94,7 %), foram classificados deficientes 24,7% (15,6-33,8%) e insuficientes 62,9% (52,8-73%). A concentração de Vit-D foi possível predizer, em função quadrática, pela interação entre sexo, exposição solar e CHC (R2 > 90%). Conclusões: A partir dos resultados obtidos, é confirmada a suspeita de alta prevalência de hipovita-minose D em população geral colombiana adulta, relacionada com um baixo consumo de cálcio na dieta habitual, fatores demográficos e exposição solar.

The molecular mechanisms by which vitamin D improve glucose homeostasis: A mechanistic review.

Diabetes mellitus (DM) is a complex metabolic disorder involving multiple deleterious molecular pathways and cellular defects leading to disturbance in the biologic milieu. It is currently a global health concern with growing incidence, especially among younger adults. There is an unmet need to find new therapeutic targets for the management of diabetes. Vitamin D is a promising target in the pathophysiology of DM, especially since vitamin D deficiency is common in patients with diabetes compared to people without diabetes. Evidence suggests that it can play significant roles in improving peripheral insulin sensitivity and glucose metabolism, however, the exact pathophysiological mechanism is not clarified yet. In this current study, we have reviewed the evidence on the effect of vitamin D in improving insulin resistance via distinct molecular pathways.

Colecalciferol Initiation Post Minimal Trauma Fracture.

Purpose: The purpose of this study was to determine the proportion of patients admitted to a major tertiary teaching hospital in Australia aged 50 years and older with a confirmed neck of femur or vertebral minimal trauma fracture, who are commenced on colecalciferol supplementation by discharge, and to describe the doses prescribed. Methods: A subanalysis of a retrospective audit of electronic medical files for patients admitted with a minimal trauma fracture of the hip or vertebra between January 1, 2016, and June 30, 2016, was conducted. Results: A total of 406 patients were screened and 64 patients were included in the audit. In this subanalysis of these 64 patients eligible for inclusion, 38 were not on any vitamin or mineral supplementation at admission. Of these, 26 patients (68.4%) had their serum colecalciferol levels measured, and 21 patients (55.2%) overall were initiated on colecalciferol. Conclusion: Over half of patients with a minimal trauma fracture were commenced on colecalciferol therapy, but a noteworthy proportion of patients remain untreated. Patients with colecalciferol levels are more likely to be initiated on therapy compared with those of whom levels were not taken during admission. This is a missed opportunity for intervention that may place patients at a higher risk of subsequent fracture; therefore, effective strategies should be implemented to address this treatment gap in the future.

Native vitamin D in pre-dialysis chronic kidney disease.

Chronic kidney disease patients have a high prevalence of vitamin D insufficiency/deficiency. Vitamin D deficiency has been associated with a variety of bone, metabolic and cardiovascular disorders. However, the role of native vitamin D supplementation (ergocalciferol, cholecalciferol or calcifediol) remains unclear in chronic kidney disease (CKD), particularly in the pre-dialytic phase. Several international guidelines have been developed on CKD-Mineral and Bone Disorder, but the optimal strategy for native vitamin D supplementation and its clinical benefit remains a subject of debate in the scientific community. This paper aims to review the available literature, including randomized clinical trials that evaluated the effects of native vitamin D supplementation on pre-dialysis CKD on biochemical and clinically relevant outcomes.

Vitamin D: too much testing and treating?

There is clinical uncertainty as to the testing of serum 25--Hydroxy vitamin D (25[OH]D) concentrations and when to use high-dose supplementation. Data show that there has been a rapid increase in the number of tests performed within the Northumbria Healthcare NHS Foundation Trust over the past 8 years and an increase in high-dose supplementation over the past 5 years. We performed a retrospective analysis of the 25(OH)D test requests over the period from January to -October 2017. A total of 17,405 tests were performed in this time period. The overall average concentration was 57.5 nmol/L and this figure was similar across age groups, although a larger proportion of patients aged over 75 had a concentration <25 nmol/L. Test requests were classified into 'appropriate', 'inappropriate' and 'uncertain' categories based on current expert opinion. We found that between 70.4% and 77.5% of tests could be inappropriate, depending on whether the 'uncertain' categories of falls and osteoporosis are considered to be justified. Tiredness, fatigue or exhaustion was the reason for testing in 22.4% of requests. We suggest that a more rational approach to testing, and subsequent treating, could lead to reductions in costs to the healthcare system and patients.

Vitamina D y riesgo de preeclampsia: revisión sistemática y metaanálisis / Vitamin D and risk of preeclampsia: A systematic review and meta-analysis

Resumen Introducción. Cada vez son más los hallazgos sobre la relación entre las concentraciones de vitamina D en el ser humano y diversas condiciones clínicas. Hay una gran cantidad de estudios que informan sobre dicha asociación, especialmente con complicaciones obstétricas, incluidas la preeclampsia y la diabetes mellitus de la gestación, entre otras, pero sus resultados todavía no son definitivos, por lo que se requieren estudios de intervención de calidad que confirmen la relación de la vitamina D con dichos resultados. Objetivo. Revisar la información plasmada en estudios en torno al papel de la vitamina D materna y el desarrollo de la preeclampsia. Materiales y métodos. La metodología usada siguió las recomendaciones de la guía Cochrane para la elaboración de revisiones sistemáticas y de la guía del grupo Meta-analysis of Observational Studies in Epidemiology (MOOSE) para los metaanálisis. La búsqueda incluyó estudios observacionales y ensayos clínicos controlados. Resultados. Los niveles bajos de vitamina D, medida con el examen de 25-hidroxivitamina D, son comunes en el embarazo. Los resultados de esta revisión sistemática y del metaanálisis sugieren una asociación inversa entre los niveles de vitamina D y el desarrollo de preeclampsia. Hubo heterogeneidad en los estudios en cuanto a su diseño, población y ubicación geográfica, así como a las definiciones de exposición y resultado. Los ensayos clínicos controlados aleatorizados se excluyeron del metaanálisis. Conclusión. Se encontró una asociación inversa que sugiere que, a mayores concentraciones de vitamina D, menor es la probabilidad de desarrollar preclampsia, a pesar de la heterogeneidad de la medida global en este tipo de análisis.

Abstract Introduction: Human vitamin D levels have been increasingly related to a wide range of clinical outcomes. There is a large amount of reports on its associations, especially with obstetric complications, including preeclampsia and gestational diabetes. These results are scarcely consistent and there is still a lack of quality intervention studies to confirm the role of vitamin D in those outcomes. Objective: To review the available scientific evidence on the role of maternal vitamin D in the development of preeclampsia. Materials and methods: The methodology used followed the recommendations of the Cochrane guide for the preparation of systematic reviews, and for metaanalysis, the Guide of the Metaanalysis of Observational Studies in Epidemiology group (MOOSE). The search included both observational studies and controlled clinical trials. Results: Low vitamin D levels, measured by the 25-hydroxyvitamin D test, are common in pregnancy. The results of this systematic review and metaanalysis suggest an inverse ratio between vitamin D levels and the development of preeclampsia. There was heterogeneity among the studies with regard to the design, population, geographic location, definitions of exposure, and the outcome. We excluded randomized controlled trials from this meta-analysis. Conclusion: The inverse association we found suggests that the higher the levels of vitamin D the lesser the probability of developing preeclampsia, in spite of the heterogeneity of the global measurement in this type of analysis.

Aproximación diagnóstica de los errores innatos del metabolismo en la unidad de cuidado intensivo neonatal: acidosis metabólica, hiperamonemia e hipoglicemia / Diagnostic approach of inborn metabolism errors in the neonatal intensive care unit: metabolic acidosis, hyperammonemia and hypoglycemia

RESUMEN Los errores innatos del metabolismo del neonato son enfermedades que requieren una intervención temprana, dado que el manejo oportuno permite la prevención de secuelas severas o desenlaces fatales. Sin embargo, su diagnóstico se dificulta debido a las múltiples manifestaciones clínicas inespecíficas que lo acompañan y a las diversas alteraciones metabólicas que afectan la lectura de los estudios paraclínicos de rutina; sin embargo, una aproximación sistemática que tenga en cuenta las variaciones del metabolismo intermedio, interpretadas a través de pruebas básicas de laboratorio, permite alcanzar en la mayoría de los casos, un diagnóstico certero. La aproximación aquí propuesta se basa en la interpretación de tres estados metabólicos: acidosis metabólica, hiperamonemia e hipoglicemia, y su relación con los resultados de tests de laboratorio que están a la mano en la mayoría de unidades de neonatología. Se plantean diversas recomendaciones en relación a valores normales, flujogramas diagnósticos y recomendaciones sobre toma y conservación de muestras.

ABSTRACT Inborn metabolism errors of newborn babies are diseases that require early intervention since timely management allows the prevention of severe or fatal consequences. However, its diagnosis is difficult due to multiple non-specific clinical manifestations that accompany it and to various metabolic alterations that affect the reading of routine clinical laboratory studies. However, a systematic approach that takes into account the variations of the intermediate metabolism interpreted through basic laboratory tests allows reaching, in most cases, a correct diagnosis. The approach proposed here is based on the interpretation of three metabolic states: metabolic acidosis, hyperammonemia, and hypoglycemia and their relation to the results of laboratory tests that are available in most neonatal units. Various recommendations are presented regarding normal values, diagnostic flowcharts, and recommendations on taking and conservation of the samples.

Cuantificación de vitamina d: de la investigación a la práctica clínica / Quantification of vitamin d: from research to clinical practice

Las formas biológicamente activas de la vitamina D se han convertido en elementos de gran relevancia en la práctica clínica y la investigación, por lo tanto, su análisis se ha incrementado en años recientes. La vitamina D tiene un papel esencial en la regulación del metabolismo del calcio y fósforo; adicionalmente, esta vitamina es considerada un posible factor preventivo para diversas enfermedades crónicas como la diabetes mellitus tipo 2, algunos tipos de cáncer, cardiovasculares, autoinmunes, enfermedad pulmonar obstructiva crónica y la pre-eclampsia. Debido al posible papel en estas enfermedades y a los pocos estudios comparativos que se han realizado entre éstas y los niveles de vitamina D, los investigadores y clínicos están interesados en usar técnicas confiables y específicas que permitan determinar las concentraciones de vitamina D en el plasma. Sin embargo, no se ha establecido cuál es el mejor biomarcador que refleja la suficiencia de vitamina D y su función, ni tampoco cuál es la mejor técnica para su adecuada cuantificación. El objetivo de esta revisión es describir brevemente el metabolismo de la vitamina D y los retos que existen para su adecuada cuantificación con fines de investigación traslacional.

The analysis of the biologically active forms of vitamin D has increased in the last decades, becoming a relevant tool in the clinical practice and investigation. Vitamin D plays an essential role in regulating the metabolism of calcium and phosphorous. In addition, this vitamin is considered a potential preventive factor in a wide range of chronical diseases such as cardiovascular and autoimmune diseases, different kinds of cancer, type 2 diabetes, chronical obstructive pulmonary disease, and pre-eclampsia. Due to the possible role that vitamin D has in these diseases and the few existing comparative studies which have been conducted between these diseases and the vitamin D levels, clinicians and researchers are interested in using reliable and specific techniques to quantify the concentrations of vitamin D in plasma. Nevertheless, in the scientific literature reviewed have not been established which is the best biomarker that indicates the sufficiency and function of vitamin D nor which is the most appropriate technique for adequate quantification. The goal of this review is to briefly describe the metabolism of vitamin D and the current challenges for its proper quantification and use in translational research.

Recommended vitamin D levels in the general population. / Recomendaciones de vitamina D para la población general.

OBJECTIVE: To provide recommendations based on evidence on the management of vitaminD deficiency in the general population. PARTICIPANTS: Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. METHODS: Recommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the term VitaminD and the name of each issue. Papers in English and Spanish with publication date before 17 March 2016 were included. Recommendations were jointly discussed by the Working Group. CONCLUSIONS: This document summarizes the data about vitaminD deficiency in terms of prevalence, etiology, screening indications, adequate levels and effects of supplementation on bone and non-skeletal health outcomes.