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.

Suplementación efectiva de vitamina D en pacientes con fractura tibial / Effective vitamin D supplementation in patients with tibial fracture

OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.

OBJETIVOS Determinar la prevalencia de déficit de vitamina D, así como evaluar la seguridad y efectividad de un nuevo método de carga con colecalciferol en pacientes adultos con fractura de tibia. MATERIALES Y MÉTODOS Se reclutaron a 56 pacientes consecutivos con edades entre 18 y 65 años con fractura de tibia ingresados en nuestro hospital durante 1 año. Se determinó el nivel de 25-hidroxivitamina D ([25(OH)-D]) al ingreso y tras suplementación con 100.000 UI semanales de colecalciferol, durante 3 o 5 semanas, en casos de insuficiencia ([25(OH)-D] entre 20 ng/mL y 29,9 ng/mL) o deficiencia ([25(OH)-D] < 20 ng/mL), respectivamente. Se determinó la prevalencia de hipovitaminosis D, el porcentaje de normalización de [25(OH)-D], y los efectos adversos. RESULTADOS Se evaluaron 56 pacientes; 98,2% presentó hipovitaminosis D, y 28 (73,7%) y 10 (26,3%) presentaron déficit e insuficiencia, respectivamente. Tras la suplementación, 92,1% alcanzaron niveles [25(OH)-D] normales. Ningún paciente presentó efectos adversos. DISCUSIÓN La prevalencia de deficiencia de vitamina D en nuestra población fue mayor a la reportada en la literatura. Comprobamos que un esquema de suplementación en altas dosis de vitamina D es seguro, y más efectivo que los previamente recomendados. Este esquema de suplementación puede ser implementado en futuros estudios randomizados. CONCLUSIÓN La prevalencia de hipovitaminosis D en pacientes adultos chilenos con fractura de tibia fue alta (98,2%). El esquema de suplementación con vitamina D propuesto fue efectivo y seguro.

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.

Vitamin D3 mediates spatial memory improvement through nitric oxide mechanism in demyelinated hippocampus of rat

Abstract Studies have revealed beneficial role of vitamin D3 in neuro-cognitive function. There is also supporting evidence on the involvement of nitric oxide (NO) in the neuro-protective action. However, its over production could contribute to brain disorders. In this study, demyelination was induced by ethidium bromide (EB) injection into the right side of the hippocampus area of male rats. Vitamin D3 was administered to rats for 7 and 28 days prior to behavioral experiments using Morris water maze (MWM). Travelled distance, time spent to reach the platform, and time spent in target zone, were considered for learning and spatial memory evaluation. Nitrite oxide (NO2-) concentration was measured as an indicator for nitric oxide production. The time spent to reach the platform and the travelled distance were decreased significantly by 28 days of vitamin D3 administration (compared to 7 days experiment). Time spent in target quadrant was significantly lowered by administered vitamin on day 28. Therefore, considering a number of studies that have shown the effect of vitamin D3 on cognition, these findings could support their potential effect. Besides, nitric oxide concentration significantly differed in 28 days of vitamin D3 treated group compared with the groups treated with EB or 7 days of vitamin D3.

Adipose tissue-derived stromal/stem cells + cholecalciferol: a pilot study in recent-onset type 1 diabetes patients

ABSTRACT Objective: Adipose tissue-derived stromal/stem cells (ASCs) and vitamin D have immunomodulatory actions that could be useful for type 1 diabetes (T1D). We aimed in this study to investigate the safety and efficacy of ASCs + daily cholecalciferol (VIT D) for 6 months in patients with recent-onset T1D. Materials and methods: In this prospective, dual-center, open trial, patients with recent onset T1D received one dose of allogenic ASC (1 x 106 cells/kg) and cholecalciferol 2,000 UI/day for 6 months (group 1). They were compared to patients who received chol-ecalciferol (group 2) and standard treatment (group 3). Adverse events were recorded; C-peptide (CP), insulin dose and HbA1c were measured at baseline (T0), after 3 (T3) and 6 months (T6). Results: In group 1 (n = 7), adverse events included transient headache (all), mild local reactions (all), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), scotomas (n = 2), and central retinal vein occlusion at T3 (n = 1, resolution at T6). Group 1 had an increase in basal CP (p = 0.018; mean: 40.41+/-40.79 %), without changes in stimulated CP after mixed meal (p = 0.62), from T0 to T6. Basal CP remained stable in groups 2 and 3 (p = 0.58 and p = 0.116, respectively). Group 1 had small insulin requirements (0.31+/- 0.26 UI/kg) without changes at T6 (p = 0.44) and HbA1c decline (p = 0.01). At T6, all patients (100%; n = 7) in group 1 were in honeymoon vs 75% (n = 3/4) and 50% (n = 3/6) in groups 2 and 3, p = 0.01. Conclusions: Allogenic ASC + VIT D without immunosuppression was safe and might have a role in the preservation of β-cells in patients with recent-onset T1D. ClinicalTrials.gov: NCT03920397.

Resultados perinatales tras la suplementación de una cohorte de gestantes con vitamina D / Perinatal results after vitamin D supplementation in a pregnant women cohort

INTRODUCCIÓN Y OBJETIVOS: La deficiencia de vitamina D es muy prevalente durante la gestación, siendo cada vez más numerosos los estudios que relacionan esta condición con peores resultados perinatales. El objetivo del presente trabajo es describir los resultados perinatales y el curso del embarazo de una cohorte de gestantes deficitarias en vitamina D durante el primer trimestre del embarazo, suplementándolas con colecalciferol, así como establecer una comparación entre los resultados perinatales de aquellas pacientes con déficit o insuficiencia que lograron niveles normales de vitamina D en el tercer trimestre frente a aquellas que no lo lograron. Como objetivo secundario se describe el curso del embarazo de una cohorte de pacientes que durante el mismo periodo de tiempo del estudio presentaban normovitaminosis al inicio de la gestación. MÉTODOS: La cohorte de 190 pacientes analizada procede de casos consecutivos en la primera consulta de embarazo. Se determinaron los niveles de 25-hidroxivitamina D (25-OH-D) en la analítica del primer trimestre de 190 gestantes diferenciando entre valores normales (>30ng/mL), insuficiencia (30-15 ng/mL) y deficiencia (<15 ng/mL). Las pacientes con insuficiencia se suplementaron con 1000 UI/día de colecalciferol y las pacientes con deficiencia con 2000 UI/día. En el tercer trimestre se determinaron de nuevo los niveles de 25-OH-D en las pacientes suplementadas, suspendiendo la prescripción en caso de haberse normalizado los valores. Se comparan estadísticamente los resultados perinatales entre aquellas pacientes que mejoraron con la suplementación frente a aquellas que no lo hicieron. RESULTADOS: De las 190 pacientes analizadas, un 45% presentaban insuficiencia; un 27,5% deficiencia; y un 27,5% valores normales. De forma global, un 61% de las pacientes suplementadas habían normalizado sus niveles de vitamina D en la analítica del tercer trimestre, suspendiéndose la prescripción. De ese 61% normalizado, un 63% pertenecían al grupo de insuficiencia y un 37% al de deficiencia. Dentro del grupo suplementado con colecalciferol, un 1,4% de las pacientes desarrollaron hipertensión arterial, mientras que un 33% desarrollaron diabetes en el embarazo, de las cuales un 87% la controlaron exclusivamente con dieta y un 13% precisaron insulina. Un 3,6% de las gestaciones cursaron con retraso del crecimiento y la tasa de prematuridad fue igualmente del 3,6%. La tasa de cesáreas fue del 23%, de las cuales un 77% fueron indicadas intraparto y un 23% cesáreas programadas. El peso medio al nacimiento fue 3205g. Dentro del grupo con valores normales de 25-OH-D en el primer trimestre de la gestación, ninguna paciente desarrolló hipertensión arterial, mientras que un 15% presentaron diabetes gestacional controlada con dieta. Un 3,8% de dichas gestaciones cursaron con retrasos del crecimiento y la tasa de prematuridad fue del 1,9%. La tasa de cesáreas fue del 23%, de las cuales un 50% fueron indicadas intraparto y el 50% restante programadas. El peso medio al nacimiento fue de 3280g. En el análisis comparativo de los resultados perinatales entre el grupo de pacientes suplementadas que normalizaron sus cifras de vitamina D y aquellas que no lo hicieron, no se hallan diferencias estadísticamente significativas para ninguno de los parámetros analizados. CONCLUSIONES: La elevada tasa de hipovitaminosis D en la muestra analizada apoya la extensión del cribado y suplementación a todas las embarazadas y no solamente a aquellas con factores de riesgo. Dado que no se observaron diferencias estadísticamente significativas entre los niveles de vitamina D en el tercer trimestre y las variables perinatales estudiadas, podemos concluir que en nuestro estudio la suplementación con vitamina D no se ha comportado como factor protector de eventos obstétricos adversos.

INTRODUCTION AND OBJECTIVES: Vitamin D deficiency is highly prevalent during pregnancy, with an increasing number of studies linking this condition with worse perinatal outcomes. The objective of this present work is to describe the perinatal results and the course of pregnancy in a cohort of pregnant women deficient in vitamin D during the first trimester of pregnancy, supplementing them with cholecalciferol, as well as to establish a comparison between perinatal results of those patients with deficiencnieve or insufficiency who achieved normal levels of vitamin D in the third trimester compared to those who did not. As a secondary objective, the course of pregnancy is described in a cohort of patients who presented normal levels at the beginning of gestation during the same period of time of the study. METHODS: The cohort of 190 patients analyzed comes from consecutive cases in the first pregnancy visit. The levels of 25-hydroxyvitamin D (25-OH-D) were determined in the analysis of the first trimester of 190 pregnant women, differentiating between normal values (> 30ng / mL), insufficiency (30-15 ng / mL) and deficiency (<15 ng / mL). Patients with insufficiency were supplemented with 1000 IU/day of cholecalciferol and patients with deficiency with 2000 IU/day. In the third trimester, the 25-OH-D levels were determined again in the supplemented patients, suspending the prescription if the values had normalized. Perinatal outcomes are statistically compared between those patients who improved with supplementation versus those who did not. RESULTS: Of the 190 patients analyzed, 45% had insufficiency; 27.5% deficiency; and 27.5% normal values. Overall, 61% of the supplemented patients had normalized their vitamin D levels in the third trimester analysis, suspending the prescription. Within that 61% normalized, 63% belonged to the insufficiency group and 37% to the deficiency group. In the group supplemented with cholecalciferol, 1.4% of the patients developed arterial hypertension, while 33% developed diabetes in pregnancy, of which 87% controlled it exclusively with diet and 13% required insulin. 3.6% of pregnancies had intrauterine growth restriction and the prematurity rate was also 3.6%. The caesarean section rate was 23%, of which 77% were indicated intrapartum and 23% scheduled caesarean sections. The mean weight at birth was 3205g. Within the group with normal 25-OH-D values in the first trimester of pregnancy, no patient developed hypertension, while 15% had diet-controlled gestational diabetes. 3.8% of these pregnancies had intrauterine growth restriction and the prematurity rate was 1.9%. The cesarean section rate was 23%, of which 50% were indicated intrapartum and the remaining 50% scheduled. The mean weight at birth was 3280g. In the comparative analysis of the perinatal results between the group of supplemented patients who normalized their vitamin D levels and those who did not, no statistically significant differences were found for any of the parameters analyzed. CONCLUSIONS: The high rate of hypovitaminosis D in the analyzed sample supports the extension of screening and supplementation to all pregnant women and not only to those with risk factors. Since no statistically significant differences were observed between vitamin D levels in the third trimester and the perinatal outcomes studied, we can conclude that in our study vitamin D supplementation has not behaved as a protective factor against adverse obstetric events.

Critical analysis on the use of cholecalciferol as a COVID-19 intervention: a narrative review

ABSTRACT BACKGROUND: The World Health Organization has declared that a pandemic situation exists in relation to the disease caused by the new coronavirus, COVID-19. So far, the absence of a vaccine against the new coronavirus has led people worldwide to seek various therapeutic alternatives, including use of cholecalciferol. DESIGN AND SETTING: Narrative review developed by a research group at a public university in Recife (PE), Brazil. METHODS: We searched the literature on the use of cholecalciferol for prevention or treatment of COVID-19, using the MEDLINE and LILACS databases, with the keywords "vitamin D", "cholecalciferol", "SARS-CoV-2", "COVID-19" and "coronavirus", from January 1, 2020, to June 10, 2020. Narrative reviews, cohort studies and ecological studies were selected. RESULTS: We retrieved 32 references, of which 8 were considered eligible for intensive review and critical analysis. These comprised five narrative reviews, two observational studies and one protocol proposal. Most of the studies selected reported positive effects from use of vitamin D for prevention or treatment of COVID-19. However, there was little quantitative data to assess the real impact of using this vitamin as an intervention against this disease. CONCLUSIONS: Current studies on vitamin D used for purposes other than bone health promotion cannot be taken as support to justify its use in a disease as recent as COVID-19. Studies of greater robustness, with higher levels of clinical evidence, need to be conducted. Rational use of this vitamin needs to be ensured, thereby minimizing the impacts on the patient and the public healthcare system.

In vitro anti-inflammatory effects of vitamin D supplementation may be blurred in hemodialysis patients

OBJECTIVES: This study aimed to evaluate the potential anti-inflammatory effects of vitamin D supplementation under uremic conditions, both in vivo and in vitro, and its effects on the parameters of mineral metabolism. METHODS: Thirty-two hemodialysis patients were randomly assigned to receive placebo (N=14) or cholecalciferol (N=18) for six months. Serum levels of calcium, phosphate, total alkaline phosphatase, intact parathyroid hormone (iPTH), and vitamin D were measured at baseline and after three and six months. The levels of fibroblast growth factor-23 (FGF-23), interleukin-1β (IL-1β), and high-sensitivity C-reactive protein (hs-CRP) were also measured at baseline and at six months. Human monocytes were used for in vitro experiments and treated with cholecalciferol (150 nM) and uremic serum. Cell viability, reactive oxygen species (ROS) production, and cathelicidin (CAMP) expression were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, dichloro-dihydro-fluorescein diacetate assay, and real time-quantitative polymerase chain reaction, respectively. RESULTS: Both patient groups were clinically and biochemically similar at baseline. After six months, the levels of vitamin D and iPTH were higher and lower, respectively, in the cholecalciferol group than in the placebo group (p<0.05). There was no significant difference between the parameters of mineral metabolism, such as IL-1β and hs-CRP levels, in both groups. Treatment with uremic serum lowered the monocyte viability (p<0.0001) and increased ROS production (p<0.01) and CAMP expression (p<0.05); these effects were counterbalanced by cholecalciferol treatment (p<0.05). CONCLUSIONS: Thus, cholecalciferol supplementation is an efficient strategy to ameliorate hypovitaminosis D in hemodialysis patients, but its beneficial effects on the control of secondary hyperparathyroidism are relatively unclear. Even though cholecalciferol exhibited anti-inflammatory effects in vitro, its short-term supplementation was not effective in improving the inflammatory profile of patients on hemodialysis, as indicated by the IL-1β and hs-CRP levels.

Effect of Vitamin D3 to Platelet Activation Mediated by Tumor Cell Culture Medium / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of vitamin D3 to platelet activation by tumor cell culture medium.@*METHODS@#The peripheral blood platelets of BALB/c mice were isolated. The platelets were activated in 4T1 culture fluid for 24 h. The platelets were divided into 7 groups: control group, activation group, 1 nmol/L vitamin D3 group, 10 nmol/L vitamin D3 group, 50 nmol/L vitamin D3 group, 100 nmol/L vitamin D3 group, and positive drug (0.1 μmol/L eptifibatide) group. CCK-8 assay was used to detect the platelet proliferation at 24, 48 and 72 h. Flow cytometry was used to detect the expression of CD61 and CD62p and receptor for advanced glycation end products (RAGE) at 24, 48 and 72 h. ELISA was used to detect the level of platelet-endothelial cell adhesion molecule-1 (PECAM-1) at 24, 48 and 72 h.@*RESULTS@#The CD41@*CONCLUSION@#Vitamin D3 shows antiplatelet effect and can inhibit platelet proliferation and activation.

Effect of a single high-dose vitamin d3 on the length of hospital stay of severely 25-hydroxyvitamin d-deficient patients with COVID-19

OBJECTIVES: In this ancillary analysis of a multicenter, double-blinded, randomized, placebo-controlled trial, we investigated the effect of a single high dose of vitamin D3 on the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19. METHODS: The primary outcome was length of hospital stay, defined as the total number of days that patients remained hospitalized from the date of randomization until the date of hospital discharge. Secondary outcomes included serum levels of 25-hydroxyvitamin D, mortality during hospitalization, number of patients admitted to the intensive care unit, and number of patients who required mechanical ventilation. ClinicalTrials.gov: NCT04449718. RESULTS: Thirty-two patients were included in the study. The mean (SD) age was 58.5 (15.6) years, body mass index was 30.8 (8.6) kg/m2, and 25-hydroxyvitamin D level was 7.8 (1.6) ng/mL. No significant difference was observed in the median interquartile range of length of hospital stay between the vitamin D3 group (6.0 [4.0-18.0] days) versus placebo (9.5 [6.3-15.5] days) (log-rank p=0.74; hazard ratio, 1.13 [95% confidence interval (CI), 0.53-2.40]; p=0.76). Vitamin D3 significantly increased serum 25-hydroxyvitamin D levels in the vitamin D3 group compared with that in the placebo group (between-group difference, 23.9 ng/mL [95% CI, 17.7-30.1]; p<0.001). CONCLUSIONS: A dose of 200.000 IU of vitamin D3 did not significantly reduce the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19.

Effects of aspirin, vitamin D3, and progesterone on pregnancy outcomes in an autoimmune recurrent spontaneous abortion model

High proportions of placental lymphocytes expressing DX5+/CD25+/FOXP3+/CD45+/CD4+ are beneficial to maintain immune tolerance and improve pregnancy outcomes. This study aimed to compare and evaluate the therapeutic effects of aspirin, vitamin D3 (VitD3), and progesterone on the autoimmune recurrent spontaneous abortion (RSA) model. The autoimmune RSA mouse model was constructed, and the embryo loss rate was calculated for each group. Then, primary mouse placental lymphocytes were isolated, and the expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ was detected through flow cytometry. The serum levels of anti-cardiolipin antibody (ACA), β2-GP1, CXCL6, IFN-γ, and IL-6 were measured by ELISA to evaluate the proportion of Th1 and Th2 cells. Autoimmune RSA significantly increased the embryo loss rate, which was improved by aspirin, VitD3, and progesterone treatment, and progesterone treatment had the best effect among the three treatments. The positive expression of DX5+/CD25+/FOXP3+/CD45+/CD4+ in the VitD3 and progesterone groups was significantly higher than that in the autoimmune RSA group, and the expression was highest in the progesterone treatment group. In the plasma of autoimmune RSA mice, the ACA, β2-GP1, CXCL6, and IFN-γ levels were significantly higher and the IL-6 level was lower than the levels in control mice. All these changes could be reversed by aspirin and progesterone treatment. In conclusion, aspirin, VitD3 and progesterone treatment improved pregnancy outcomes in autoimmune RSA mice by regulating the Th1/Th2 balance and cytokines, and progesterone had the best effect of the three treatments.

Vitamin D deficiency in pediatric patients using antiepileptic drugs: systematic review with meta-analysis / Deficiência de vitamina D em pacientes pediátricos que fazem uso de fármacos antiepilépticos - revisão sistemática com metanálise

Abstract Objectives: To measure the prevalence of vitamin D deficiency (through the 25-hydroxyvitamin D metabolite) in pediatric patients using antiepileptic drugs. Source of data: Meta-analysis of studies identified through search in the PubMed, Embase, LILACS, and Cochrane Library databases, on February 19, 2019. Summary of data: A total of 748 articles were identified, 29 of which were relevant to the objectives of this study. The prevalence of vitamin D deficiency found was 0.32 (95% CI = 0.25-0.41; I 2 = 92%, p < 0.01). In the subgroup analyses, the most significant results were observed in the group of patients using cytochrome P450-inducing antiepileptic drugs, with a prevalence of 0.33 (95% CI = 0.21-0.47; I 2 = 86%, p < 0.01) and, considering the study design, in the subgroup of cohort studies, with a prevalence of 0.52 (95% CI = 0.40-0.64; I 2 = 76%, p < 0.01). Conclusions: Taking into account the deleterious effects of vitamin D deficiency on the bone health of individuals using antiepileptic drugs, it is suggested to include in their care 25-hydroxyvitamin D monitoring, cholecalciferol supplementation, and treatment of the deficiency, when present.

Resumo Objetivos: Mensurar a prevalência de deficiência de vitamina D (através do metabólito 25-hidroxivitamina D) em pacientes pediátricos em uso de fármacos antiepilépticos. Fonte dos dados: Metanálise de estudos identificados por meio de pesquisa nas bases de dados Pubmed, Embase, LILACS e Cochrane em 19 de fevereiro de 2019. Síntese dos dados: Foram identificados 748 artigos, dos quais 29 mostraram-se relevantes aos objetivos deste estudo. A prevalência de deficiência de vitamina D encontrada foi de 0,32 (IC 95% = 0,25-0,41) (I2 = 92%, p < 0,01). Nas análises por subgrupos, os resultados mais expressivos foram observados no grupo de pacientes em uso de fármacos antiepilépticos indutores do citocromo P450, que apresentou prevalência de 0,33 (IC 95% = 0,21-0,47) (I2 = 86%, p < 0,01). Considerou-se o delineamento dos estudos, no subgrupo de estudos de coorte, com prevalência de 0,52 (IC 95% = 0,40-0,64) (I2 = 76%, p < 0,01). Conclusões: Levando-se em consideração os efeitos deletérios da deficiência de vitamina D na saúde óssea dos sujeitos em uso de fármacos antiepilépticos, sugere-se incluir em seu atendimento, o monitoramento de 25-hidroxivitamina D, suplementação com colecalciferol e tratamento de deficiência quando existente.

El efecto de la vitamina D3 y su relación. con el nivel de glóbulos blancos en las mujeres con aborto espontáneo, inyección intracitoplasmática de espermatozoides (ICSI) técnicao / The effect of vitamin D3 and its relationship with the level of white blood cells in women spontaneous miscarriage undergoing intracytoplasmic sperm injection (ICSI) technique

Women were studied undergoing ICSI for 84 who suffer non-pregnancy at the Fertility Center, Al-Sadr Medical Hospital in Najaf Governorate, Period between January 2019 and March 2020. WBC, Vitamin D3 and ß-hCG were measured, The pregnant women was divided into (Pregnancy Group, and spontaneous miscarriage) and then demonstrate the immunological effect on pregnancy of women after ICSI technique. Current resultsstudy showed a significant increase (p<0.05) in hormone level ß-hCG is evidence of the presence of high success rates for pregnancy in women who performed operations IVF, where the success rate at the beginning of the matter reached 61.9%, after which it decreased to 33.3% after the first three months due to the occurrence of spontaneous miscarriage of pregnant women due to various immunological and physiological reasons, a positive correlation between the level of ß-hCG and other parameters in the study (Vitamin D3 -WBC).Also The current resultsshowed a significant decrease in a groups (pregnancy failure) and the group (spontaneous miscarriage) compared with the control group (continued pregnancy) in relation to the level of vitamin D3 Also, The current results showed a significant increasein (pregnancy failure) and (spontaneous miscarriage) compared with control groups (continuation of pregnancy) in relation WBC numbers, and the present study founds a negative relationship between the level of vitamin D3 and WBC.

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.

Effect of vitamin D3 supplementation on 25 OHD plasma levels in the presence of VDR gene polymorphisms / Efecto de la suplementación con vitamina D3 en los niveles plasmáticos de 25 OHD, en presencia de polimorfismos del gen VDR

The objective of this review was to investigate the effect of vitamin D3 supplementation on serum 25-hydroxyvitamin D concentration in individuals with single-nucleotide polymorphisms in the vitamin D receptor gene. The research was conducted on 241 articles found in the PubMed, Scopus, Science Direct, and Cochrane Library databases between November and December 2018. After article screening, three randomized double-blind placebo-controlled clinical trials were identified as eligible for this review. Participants were Australian, Brazilian, and Chinese individuals, who ingested doses of vitamin D3 ranging from 2000 IU to a megadose of 200,000 IU. The presence of the BB/Bb genotype of the BsmI polymorphism and the FokI G allele caused an increase in the serum concentrations of vitamin D after supplementation. Nonetheless, the few studies on this subject are not unanimous in their results. It is possible that differences among populations, sample sizes, doses, and time of supplementation have an impact on data and outcomes.

El objetivo de esta revisión fue investigar el efecto de la suplementación con vitamina D3 sobre la concentración sérica de 25-hidroxivitamina D en individuos con los polimorfismos de un solo nucleótido en el gen del receptor de la vitamina D. La investigación se realizó en 241 artículos encontrados en las bases de datos PubMed, Scopus, Science Direct y Cochrane Library entre noviembre y diciembre de 2018. Después de la selección del artículo, se identificaron tres ensayos clínicos aleatorios, controlados con placebo, doble ciego, como elegibles para esta revisión. Los participantes fueron australianos, brasileños y chinos, quienes ingirieron dosis de vitamina D3 que iban desde las 2000 UI hasta una megadosis de 200,000 UI. La presencia del genotipo BB / Bb del polimorfismo BsmI y el alelo FokI G causó un aumento en las concentraciones séricas de vitamina D después de la suplementación. No obstante, los pocos estudios sobre este tema no son unánimes en sus resultados. Es posible que las diferencias entre poblaciones, tamaños de muestra, dosis y tiempo de suplementación tengan un impacto en los datos y resultados de la investigación.

1,25-dihydroxy Vitamin D3 and Interleukin-6 Blockade Synergistically Regulate Rheumatoid Arthritis by Suppressing Interleukin-17 Production and Osteoclastogenesis

BACKGROUND: Immune cells express the vitamin (vit) D receptor, and vit D is a potent immune-modulator. A negative correlation between serum vit D levels and rheumatoid arthritis (RA) disease activity has been reported. Therefore, we aimed to investigate if the sufficient serum vit D level is helpful to control disease activity in RA patients treated with interleukin (IL)-6 receptor antibody tocilizumab.METHODS: RA patients taking tocilizumab were enrolled, and data were collected retrospectively. Disease activity scores (DAS) 28, serum vit D levels, modified Sharp scores of hand X-ray at the time of tocilizumab initiation, and follow-up data were analysed. Peripheral blood mononuclear cells were differentiated into T-helper (Th) 17 or osteoclasts in the presence of various concentrations of tocilizumab and/or 1,25(OH)₂D. Th17 proportions were analysed by fluorescence-activated cell sorting. Supernatant cytokine levels were determined by enzyme-linked immunosorbent assay.RESULTS: Among 98 RA patients taking tocilizumab, 34 (34.7%) had sufficient serum 25(OH)D levels (≥ 30 ng/mL) when tocilizumab was initiated. At 24 weeks, vit D sufficient patients had greater DAS28 reduction (64.6% ± 15.5% vs. 52.7% ± 20.7%, P = 0.004), and lower disease activity (91.2% vs. 70.3%, P = 0.018) or remission (82.4% vs. 57.8%, P = 0.014). These differences in DAS28 reduction and the proportion of patients with remission persisted at 48 weeks. However, there was no significant difference in hand and wrist erosion progression. In vitro, tocilizumab and 1,25(OH)₂D treatment synergistically suppressed IL-17 production and osteoclastogenesis.CONCLUSION: RA patients treated with IL-6 antibody show a better response when they have sufficient serum vit D. Tocilizumab and 1,25(OH)₂D synergistically suppress IL-17 production and osteoclast differentiation in RA patients.

An Empirical Study on the Effect of Short-Term Regular Vitamin D3 Supplement Therapy on Blood Pressure and Exercise Tolerance in Heart Failure Patients