Screening by Q Exactive liquid chromatography/tandem mass spectrometry identified Choline, 25-hydroxyvitamin D2, and SM(d18:0/16:1(9Z) (OH)) as biomarkers for high-grade serous ovarian cancer.

High-grade serous ovarian cancer (HGSOC) has a high death rate and poor prognosis. The main causes of poor prognosis are asymptomatic early disease, no effective screening method at present, and advanced disease. Changes in cellular metabolism are characteristic of cancer, and plasma metabolome analysis can be used to identify biomarkers. In this study, we used Q Exactive liquid chromatography tandem mass spectrometry (LC-MS/MS, QE) to compare the differentiation between plasma samples (22 HGSOC samples and 22 normal samples). In total, we detected 124 metabolites, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish HGSOC patients from healthy controls. Choline, 25-hydroxyvitamin D2, and sphingomyelin (d18:0/16:1(9Z) (OH))/SM(d18:0/16:1(9Z) (OH)) showed significantly differential plasma levels in HGSOC patients under the conditions of variable importance in projection (VIP) > 1, p < 0.05 using Student's t-test, and fold change (FC)  ≥ 1.5 or ≤ 0.667. Metabolic pathway analysis can provide valuable information to enhance the understanding of the underlying pathophysiology of HGSOC. In conclusion, the Q Exactive LC/MS/MS method validation-based plasma metabolomics approach may have potential as a convenient screening method for HGSOC and may be a method to monitor tumor recurrence in patients with HGSOC after surgery SIGNIFICANCE: High-grade serous ovarian cancer (HGSOC) has a high death rate and poor prognosis. The main causes of poor prognosis are asymptomatic early disease, no effective screening method at present, and advanced disease. Changes in cellular metabolism are characteristic of cancer, and plasma metabolome analysis can be used to identify biomarkers. In this study, we used Q Exactive liquid chromatography tandem mass spectrometry (LC-MS/MS, QE) to compare the differentiation between plasma samples (20 HGSOC samples and 20 normal samples). In total, we detected 124 metabolites, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish HGSOC patients from healthy controls. Choline, 25-hydroxyvitamin D2, and sphingomyelin (d18:0/16:1(9Z) (OH))/SM(d18:0/16:1(9Z) (OH)) showed significantly differential plasma levels in HGSOC patients under the conditions of variable importance in projection (VIP) > 1, p < 0.05 using Student's t-test, and fold change (FC) ≥ 1.5 or ≤ 0.667. Metabolic pathway analysis can provide valuable information to enhance the understanding of the underlying pathophysiology of HGSOC. In conclusion, the Q Exactive LC/MS/MS method validation-based plasma metabolomics approach may have potential as a convenient screening method for HGSOC and may be a method to monitor tumor recurrence in patients with HGSOC after surgery.

Analysis of vitamin D3-sulfate and 25-hydroxyvitamin D3-sulfate in breastmilk by LC-MS/MS.

Sulfated metabolites of vitamin D have been suggested to be in breastmilk, although current methods to measure sulfated vitamin D compounds in breastmilk by liquid chromatography-tandem mass spectrometry (LC-MS/MS) have not adequately accounted for increased aqueous solubility of these sulfated metabolites. The purpose of this study was to generate a method of LC-MS/MS for measuring vitamin D3-3-sulfate (VitD3-S) and 25-hydroxyvitamin D3-3-sulfate (25OHD3-S) specifically in human breastmilk. The resulting method uses methanol to precipitate protein and solid phase extraction to prepare the samples for LC-MS/MS. The limits of quantification for analytes in solvent were 0.23 ng/mL VitD3-S and 0.2 ng/mL 25OHD3-S. Various experiments observed concentrations ranging 0.53 to 1.7 ng/mL VitD3-S and ≤ 0.29 ng/mL 25OHD3-S. Both analytes were present in aqueous skim milk, demonstrating the enhanced aqueous solubility of these vitamin D sulfates. In conclusion, we describe an effective method for measuring VitD3-S and 25OHD3-S in breastmilk by LC-MS/MS.

Vitamina D y embarazo: una experiencia piloto / Vitamin D and pregnancy: a pilot experience

La insuficiencia de vitamina D (VD) en el embarazo se relaciona con una mayor incidencia de cesáreas, preeclampsia y partos prematuros. Objetivo: evaluar si el grado de insuficiencia de VD se asocia a mayor número de cesáreas y evaluar la correlación entre la 25 hidroxivitamina D (25OHD) materna y en sangre del cordón del recién nacido. Las mujeres (n=127) se dividieron según sus niveles de 25OHD (ng/mL):G1:<20 (deficiencia), G2:20-30 (insuficiencia), G3:>30 (suficiencia). Se registraron edad; edad gestacional (EG); índice de masa corporal (IMC); tensión arterial sistólica y diastólica; tipo de parto y la estación del año en que se tomó la muestra. Se determinaron calcemia (ng/mL); 25OHD; parathormona intacta (pg/mL); fosfatasa alcalina ósea (UI/L) y crosslaps (pg/mL). La edad media fue de 26±6 años y la EG de 35,8±2,7 semanas, sin diferencias entre grupos. El porcentaje de cesáreas fue mayor en G1 que en G2 y G3 (31,3%, 21,4% y 25%, respectivamente; p<0,05). El mayor porcentaje de muestras se tomó en primavera (p<0,05). No se observaron diferencias en las demás variables maternas estudiadas. La 25OHD materna correlacionó positivamente con los valores de la sangre de cordón de sus respectivos recién nacidos (r= 0,67; p<0,0001). Independientemente de la época del año y del IMC, se observó que un porcentaje significativo de las mujeres embarazadas estudiadas tenía niveles de 25OHD inferiores a 30 ng/mL. Conclusión: evidenciamos que la deficiencia de VD materna se asoció al número de cesáreas. Asimismo, los niveles séricos de 25OHD en sangre de cordón umbilical correlacionaron significativamente con los maternos. (AU)

Vitamin D (VD) insufficiency in pregnancy is associated with a higher incidence of cesarean section, preeclampsia, and preterm delivery. Objective: to evaluate if the degree of VD insufficiency is associated with the incidence of cesarean section and to determine the correlation between maternal and newborn cord blood 25-hydroxy VS (25OHD). Women (n=127) were divided according to their 25OHD levels (ng/mL): G1:<20 (deficiency), G2:20-30 (insufficiency), G3:>30 (sufficiency). Age; gestational age (GA); body mass index (BMI); systolic and diastolic blood pressure (mmHg); type of delivery and the season of the year in which the sample was taken were recorded. Calcemia (ng/mL); 25OHD; intact parathormone (pg/mL); bone alkaline phosphatase (IU/L) and Crosslaps (pg/mL) levels were determined. Mean age was 26±6 years and GA was 35.8±2.7 weeks with no differences among groups. The % of cesarean sections was higher in G1 than in G2 and G3 (31.3%, 21.4% and 25%; p<0.05). The highest % of samples were taken in spring (p<0.05). No differences were observed in the other maternal variables studied. Maternal serum 25OHD levels correlated positively with those of cord blood from their respective newborns (r=0.67; p<0.0001). Regardless the season of the year and BMI, a high % of the studied pregnant women presented 25OHD levels lower than 30 ng/ml. Conclusion: we found that maternal VD deficiency is associated with the number of cesarean sections. In addition, 25OHD levels in the newborn significantly correlate with maternal serum levels. (AU)

The importance of optimal 25-hydroxyvitamin D levels in the glycemic control of older adults with type 2 Diabetes Mellitus: Data from the study on aging and longevity EELO

INTRODUCTION: Optimal serum levels of vitamin D are of great importance, especially in populations with comorbidities such as Diabetes Mellitus (DM). OBJECTIVE: The study evaluated the relationship between hypovitaminosis D and glycemic control in older adults with type 2 DM. METHODS: Cross-sectional and prospective study, part of the EELO project (Study on Aging and Longevity), conducted in Southern Brazil. Glycated hemoglobin (diabetes ≥6.5%) and serum levels of vitamin D (25(OH)D) were evaluated. Hypovitaminosis D was determined using cutoff points <20 and <30 ng/mL). Multivariate logistic regression was used to assess the risk of having uncontrolled DM. RESULTS: Of the 120 older adults included in the study, aged between 60 and 87 years, 74.2% were women, 66.7% used hypoglycemic medications and 75.8% exhibited uncontrolled diabetes. An inverse correlation was observed between the levels of 25(OH) D and glycated hemoglobin (rS=-0.19, p=0.037), suggesting that low levels of vitamin D are associated with poor glycemic control in diabetic individuals. The prevalence of hypovitaminosis D when using the cutoff points of <20 and <30 ng/mL were 34.2% and 75.0%, respectively. The odds ratio (OR) analysis showed that individuals with 25(OH)D<20ng/mL have almost 4 times more risk of having uncontrolled DM (OR:3.94; CI95%:1.25-12.46, p=0.02) when compared to the older adults with sufficient levels of vitamin D. CONCLUSION: The results indicate that the optimal serum levels currently recommended for 25(OH)D should preferably be 30 ng/mL or higher to contribute to better glycemic control in older adults with type 2 DM.

INTRODUÇÃO: Os níveis séricos ideais de vitamina D são de grande importância, especialmente na população com comorbidades como o Diabetes Mellitus (DM). OBJETIVO: O estudo avaliou a relação entre hipovitaminose D e controle glicêmico em idosos com DM tipo 2. MÉTODOS: Estudo transversal e prospectivo, parte do projeto EELO (Estudo sobre Envelhecimento e Longevidade), no Sul do Brasil. A hemoglobina glicada (diabetes ≥6,5%) e os níveis séricos de vitamina D (25(OH)D) foram avaliados. Hipovitaminose D foi determinada usando ponto de corte <20 e <30 ng/mL. Regressão logística multivariada foi utilizada para avaliar o risco de ter DM descompensado. RESULTADOS: Dos 120 idosos incluídos no estudo, idade entre 60 a 87 anos, 74,2% eram mulheres, 66,7% faziam uso de medicamentos hipoglicemiantes e 75,8% apresentavam diabetes descompensada. Uma correlação inversa foi observada entre os níveis de 25(OH)D e hemoglobina glicada (rS=-0,19; p=0.037), sugerindo que baixos níveis de vitamina D está associado a um pior controle glicêmico em diabéticos. A prevalência de hipovitaminose D quando se utiliza ponto de corte <20 e <30 ng/mL foi de 34,2% e 75,0%, respectivamente. A análise Odds ratio (OR) mostrou que indivíduos com 25(OH)D<20 ng/mL tem quase 4 vezes mais risco de ter DM descompensado (OR:3,94; IC95%:1,25­12,46; p=0,02) quando comparado aos idosos com níveis suficientes de vitamina D. CONCLUSÃO: Os resultados indicam que os níveis sérios ideais atualmente recomendados para 25(OH)D maior ou igual a 30 ng/ml contribuem para o melhor controle glicêmico na população idosa com DM tipo 2.

25-hydroxyvitamin D levels in the early healing of osteoporotic hip fracture and their relationship with clinical outcome / Niveles de 25-hidroxivitamina D en la fase precoz de la fractura osteoporótica de cadera y su relación con los resultados clínicos

INTRODUCTION: vitamin D is involved in recovery after an osteoporotic hip fracture (OHF). Previous studies have reported decreased serum vitamin D levels during fracture healing. OBJECTIVES: our aim was to evaluate: a) serum 25-hydroxyvitamin D3 (25OHD3) levels in patients with OHF at hospital admission and 8 days post-admission, and b) the relationship between 25OHD levels and clinical outcomes. METHODS: a prospective study including 66 patients aged over 65 years hospitalized for OHF. We gathered data on baseline demographic characteristics, medical history, Mini Mental State (MMS) assessment, Activities of Daily Living (ADL) results, nutritional assessment, and type of fracture and surgery. Laboratory results were collected on bone biomarkers, albumin, 25OHD3, and IL6. Clinical outcomes included length of stay, complications, and mortality. In the statistical analysis, a t-test was used for continuous variables and a chi-square test for qualitative variables. Linear regression models were used for the multivariate analysis, adjusted for covariates. RESULTS: our study population had low serum vitamin D levels at admission, with a mean [(standard error of the mean (SEM)] of 12.04 (1.03) ng/mL. Both 25OHD3 and interleukin 6 (IL-6) levels significantly declined (p < 0.001) during the early post-fracture phase. A greater decline in 25OHD3 levels was significantly associated with longer hospital stay (p = 0.042, multivariate analysis). Serum 25OHD3 levels were also associated with cognitive status as assessed using the MMS exam. CONCLUSIONS: 25OHD3 levels were reduced in OHF patients at admission, and significantly decreased during the first 8 days post-admission. 25OHD3 levels were associated with MMS-assessed cognitive status. A greater decline in serum 25OHD3 was associated with a longer hospital stay

INTRODUCCIÓN: la vitamina D se ha relacionado con la recuperación tras la fractura osteoporótica de cadera (FOC). Estudios previos muestran un descenso de los niveles de vitamina D en la fase precoz tras la fractura. OBJETIVOS: evaluar: a) los niveles séricos de 25-hidroxivitamina D3 (25OHD3) al ingreso y a los 8 días del ingreso en hospitalizados por FOC; b) la relación de los niveles de 25OHD3 con los resultados clínicos, así como con el nivel cognitivo y funcional. MÉTODOS: estudio prospectivo de 66 pacientes (> 65 años) ingresados por FOC. Se estudiaron las características demográficas, los antecedentes personales, la valoración nutricional, el test Mini Mental State (MMS), el cuestionario Activities of Daily Living (ADL), el tipo de fractura y de cirugía, y parámetros bioquímicos del metabolismo óseo, la 25OHD3, la albúmina y la interleuquina 6. Como resultados clínicos se analizaron: estancia hospitalaria, complicaciones y mortalidad durante el ingreso. El análisis estadístico consistió en: a) prueba de la t para las variables continuas y χ2 para las cualitativas; b) análisis multivariable utilizando modelos de regresión lineal ajustados según el análisis de la covarianza. RESULTADOS: la población estudiada muestra niveles bajos de 25OHD3 al ingreso: media [± error estándar de la media (EEM)] = 12,04 (1,03) ng/mL. Durante el ingreso, 25OHD3 e interleuquina 6 decrecen significativamente (p < 0,001). El descenso de 25OHD3 se asocia con la estancia hospitalaria (p = 0,042 en análisis multivariable). Los valores disminuidos de 25OHD3 se asocian a un bajo nivel cognitivo (p = 0,042). CONCLUSIONES: los pacientes ingresados por fractura osteoporótica de cadera tienen niveles bajos de 25OHD3 que decrecen significativamente tras 8 días de ingreso. El descenso de 25OHD3 se asocia significativamente a la estancia hospitalaria. Los niveles disminuidos de 25OHD3 se asocian a un peor estado cognitivo evaluado mediante el MMS

Association of serum vitamin D levels with chronic disease and mortality / Asociación de los niveles séricos de vitamina D con la enfermedad crónica y la mortalidad

INTRODUCTION: whether hypovitaminosis D is an overarching cause of increased mortality or a prognostic marker of poor health has not been well elucidated. OBJECTIVES: we sought to determine the association of serum 25-hydroxyvitamin D [25-(OH)-D3] levels with the clinical biochemical parameters and mortality risk in chronic diseases. METHODS: we reviewed the clinical charts and collected the clinical biochemical parameters of patients diagnosed with chronic conditions who had at least one 25-(OH)-D3 determination, with or without calcium and vitamin D supplementation, and who were selected using a cluster random sampling design (n = 1,705). The analysis was focused on metabolic disorders (type-2 diabetes mellitus [T2DM] and obesity), autoimmune disorders, and mortality. Multivariate logistic regression analyses were performed. RESULTS: low 25-(OH)-D3 levels were reported in 1,433 (84.0 %) patients, of which 774 (45.4 %) had insufficiency (20-29 ng/mL) and 659 (38.6 %) patients had deficiency (< 20 ng/mL). Lower 25-(OH)-D3 levels in T2DM patients were associated with higher glycosylated hemoglobin levels (p < 0.001). Patients with 25-(OH)-D3 levels < 12.5 ng/mL had a higher mortality risk than those with levels ≥ 12.5 ng/mL (HR: 3.339; 95 % CI: 1.342-8.308). We observed lower 25-(OH)-D3 levels in patients with grade-III obesity (p = 0.01). We found a higher risk of 25-(OH)-D3 deficiency in rheumatoid arthritis, type-1 diabetes, and systemic lupus erythematosus (p = 0.032, p = 0.002, p = 0.049, respectively). CONCLUSIONS: we found a significant relationship between 25-(OH)-D3 levels and glycemic control, body mass index, autoimmune disease, and mortality risk. Nevertheless, whether hypovitaminosis D plays a causal role or is a consequence of chronic disease remains controversial

INTRODUCCIÓN: si la hipovitaminosis D constituye una causa general de mayor mortalidad o un marcador de mal pronóstico para la salud no se ha dilucidado por completo. OBJETIVOS: determinar la asociación de los niveles séricos de 25-hidroxivitamina D [25-(OH)-D3] con los parámetros clínico-bioquímicos y el riesgo de mortalidad en la enfermedad crónica. MÉTODOS: se revisaron los expedientes clínicos y recopilamos los parámetros clínico-bioquímicos de pacientes diagnosticados de enfermedades crónicas que tenían al menos una determinación de 25-(OH)-D3, con o sin suplemento de calcio y vitamina D, y que se seleccionaron mediante muestreo aleatorio por grupos (n = 1705). El análisis se centró en los trastornos metabólicos (diabetes mellitus de tipo 2 [DM2] y obesidad), los trastornos autoinmunes y la mortalidad. Se realizaron análisis multivariados de regresión logística. RESULTADOS: se encontraron niveles bajos de 25-(OH)-D3 en 1433 (84,0 %) pacientes, de los cuales 774 (45,4 %) tenían insuficiencia (20-29 ng/mL) y 659 (38,6 %) tenían deficiencia (< 20 ng/mL) de esta vitamina. Los niveles más bajos de 25-(OH)-D3 en los pacientes con DM2 se asociaron a niveles más altos de hemoglobina glucosilada (p < 0,001). Los pacientes con niveles de 25-(OH)-D3 < 12,5 ng/mL tenían mayor riesgo de mortalidad que aquellos con niveles ≥ 12,5 ng/mL (HR: 3,339; IC del 95 %: 1,342-8,308). Apreciamos niveles más bajos de 25-(OH)-D3 en los pacientes con obesidad de grado III (p = 0,01). Se encontró un mayor riesgo de deficiencia de 25-(OH)-D3 en la artritis reumatoide, la diabetes de tipo 1 y el lupus eritematoso sistémico (p = 0,032, p = 0,002, p = 0,049, respectivamente). CONCLUSIONES: apreciamos una relación significativa entre los niveles de 25-(OH)-D3 y el control glucémico, el índice de masa corporal, la enfermedad autoinmune y el riesgo de mortalidad. Sin embargo, sigue siendo controvertido si la hipovitaminosis D desempeña un papel causal o constituye una consecuencia de las enfermedades crónicas

Serum 25-hydroxyvitamin D level is negatively associated with serum phosphorus level among stage 3a-5 chronic kidney disease patients / El nivel de 25-hidroxivitamina D sérica está asociado negativamente con el nivel de fósforo sérico en pacientes con enfermedad renal crónica en estadio 3a-5

BACKGROUND: Serum 25-hydroxyvitamin D (25(OH)D) negatively correlates with serum phosphorus level of stage 3a-5 chronic kidney disease (CKD) patients. So far, no explanation has been provided for this negative association. OBJECTIVE: To confirm this negative association and determine if this relationship is mediated through other known co-morbid factors. Cases and methods: One hundred (57 male and 43 female) pre-dialysis stage 3a-5 CKD patients were selected. Estimated glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), 25 (OH)D, parathyroid hormone (PTH), and intact fibroblast growth factor-23 (FGF23) were assessed. A correlation analysis between serum 25(OH)D and the different parameters studied was performed. Multivariate linear regression analysis was carried out to determine predictors of 25(OH)D. RESULTS: The negative association between serum 25 (OH)D and serum P was confirmed in univariate and multivariate correlation analysis. On the other hand, we failed to detect a significant association between 25 (OH)D and serum FGF23. Serum P is the most important independent predictor of 25 (OH)D in these patients (partial R2 = 0.15, p < 0.0001). CONCLUSION: Serum P is likely to have a direct negative impact on serum 25 (OH)D. Further studies are needed to determine the underlying mechanism

ANTECEDENTES: La 25-hidroxivitamina D (25(OH)D) sérica se correlaciona negativamente con el nivel de fósforo sérico en pacientes con enfermedad renal crónica (ERC) en estadio 3a-5. Hasta la fecha, no se dispone de ninguna explicación sobre esta asociación negativa. OBJETIVO: Confirmar la asociación negativa y averiguar si esta relación está mediada por otros factores de comorbilidad conocidos. Casos y métodos: Se seleccionaron 100 pacientes (57 varones y 43 mujeres) con ERC en estadio 3a-5 prediálisis. Se evaluaron la tasa de filtración glomerular estimada (TFRe), el calcio sérico (Ca), el fósforo (P), la 25(OH)D, la hormona paratiroidea (HPT) y el factor de crecimiento de fibroblastos 23 intacto (FGF23). Se realizó un análisis de correlación entre la 25(OH)D sérica y los distintos parámetros estudiados. Se llevó a cabo un análisis de regresión lineal multivariable para determinar los factores pronósticos de 25(OH)D. RESULTADOS: Se confirmó la asociación negativa entre la 25(OH)D sérica y el P sérico en análisis de correlación univariable y multivariable. Por otro lado, no detectamos ninguna asociación significativa entre la 25(OH)D y el FGF23 sérico. El P sérico es el factor predictivo independiente más importante de la 25(OH)D en estos pacientes (R2 parcial=0,15; p < 0,0001). CONCLUSIÓN: Es probable que el P sérico tenga un impacto negativo directo sobre la 25 (OH)D sérica. Es necesario realizar más estudios para averiguar el mecanismo subyacente

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.

25-Hydroxyvitamin D levels of children are inversely related to adiposity assessed by body mass index

Vitamin D deficiency is associated with wide range of pathologies. Some evidences have shown that low vitamin D circulating levels in children and adolescent are related to fat mass and obesity. The objectives of the present study were to characterize vitamin D status in children and adolescents and to determine if serum 25-hydroxyvitamin D (25(OH)D) concentration is related to adiposity assessed by body mass index (BMI). Serum 25(OH)D levels were measured by LIAISON method in 471 children and adolescents (2 to 18 years age) and analyzed according to gender, pubertal period, age, and BMI. An overall prevalence of 25(OH)D insufficiency and deficiency was present in the 67.1%. Lower 25(OH)D levels were found in females (25.56 ± 14.03 vs 29.71 ± 17.10 ng ml−1; P = 0.004) and pubertal children (25.52 ± 13.97 vs 29.21 ± 16.83 ng ml−1; P = 0.011). In addition, an inverse relation of BMI and age on 25(OH)D concentrations was observed in children. In conclusion, low vitamin D status was highly prevalent among children and adolescents. Of note, a non-lineal regression model showed that 39.6% of vitamin D levels variability was explained by BMI. These results indicate that adiposity assessed by BMI impacts vitamin D status

Are Serum Vitamin D Levels Associated With Dry Eye Disease? Results From the Study Group for Environmental Eye Disease / 예방의학회지

OBJECTIVES: Dry eye disease (DED) is an increasingly important public health problem in Korea. Previous studies conducted in Korea have reported inconsistent results regarding the protective effects of vitamin D on DED, and these discrepancies may be related to the relatively simple questionnaire that has been used. Thus, we evaluated the association of serum vitamin D levels with DED using the ocular surface disease index (OSDI). METHODS: The present study evaluated data from participants in the Study Group for Environmental Eye Disease (2014-2015). This group included data from 752 participants, and data from 740 participants (253 men and 487 women) were analyzed in the present study. DED severity was evaluated using the OSDI. RESULTS: Higher serum vitamin D levels were associated with a non-significantly reduced risk of DED in the crude analysis (odds ratio [OR], 0.991; 95% confidence interval [CI], 0.971 to 1.011) and in the adjusted analysis (OR, 0.988; 95% CI, 0.966 to 1.010). In the crude analysis of no/mild DED vs. moderate/severe DED, men exhibited a decreased risk with increasing serum vitamin D levels (OR, 0.999; 95% CI, 0.950 to 1.051), while women exhibited an increased risk (OR, 1.003; 95% CI, 0.979 to 1.027). In these analyses, we found no significant associations. CONCLUSIONS: The findings of the present study support previous reports that serum vitamin D levels are not associated with DED.

Niveles de 25-hidroxivitamina D en pacientes con melanoma y factores asociados con su insuficiencia / 25-hydroxyvitamin D in patients with melanoma and factors associated with inadequate levels

INTRODUCCIÓN Y OBJETIVOS: Los pacientes con melanoma parecen llevar al extremo las medidas de protección, lo que puede influir en los niveles de 25-hidroxivitamina D-25(OH)D-. El objetivo del estudio fue evaluar los niveles de 25(OH)D en pacientes con melanoma cutáneo e identificar factores relacionados con niveles inadecuados. MATERIAL Y MÉTODOS: Se midieron prospectivamente los niveles séricos de 25(OH)D en pacientes diagnosticados de melanoma cutáneo durante un periodo de seguimiento de un año. Se evaluaron qué factores ambientales, fenotípicos y genotípicos se relacionaban con niveles insuficientes y deficientes mediante regresión logística. RESULTADOS: De un total de 215 pacientes solo un 24,7% tenían valores normales de 25(OH)D y un 8,8% tenían valores deficientes (< 10 ng/ml). La obesidad (OR: 4,2; IC 95% OR: 1,3-13,3) y la extracción de sangre realizada en otoño/invierno (OR: 2,1; IC 95% OR: 1,1-4) se asociaron a niveles insuficientes (< 30 ng/ml). Los niveles deficitarios (< 10 ng/m) se asociaron a la obesidad (OR: 7,1; IC 95% OR: 1,1-46,9), la extracción de sangre realizada en otoño/invierno (OR: 9,0; IC 95% OR: 1,7-47,0), la ausencia de efélides (OR: 5,4; IC 95% OR: 1,2-23,4) y, marginalmente, a la presencia de tener < 2 polimorfismos no sinónimos en el receptor 1 de la melanocortina (MC1R) (OR: 5,0; IC 95% OR: 0,9-28,9). Limitaciones: No se han incluido en el análisis algunos factores, como la alimentación, relacionados con los niveles de 25(OH)D. CONCLUSIONES: Se deberían monitorizar los niveles de 25(OH)D en los pacientes con melanoma y valorar dar suplementos orales en los casos que lo precisen

INTRODUCTION AND OBJECTIVES: Patients with melanoma appear to take extreme sun-protection measures, which could influence 25-hydroxyvitamin D [25(OH)D] levels. The aim of this study was to measure 25(OH)D levels in patients with cutaneous melanoma and identify factors associated with inadequate levels. MATERIAL AND METHODS: Over a period of 1 year, we prospectively measured serum 25(OH)D in patients with cutaneous melanoma and used logistic regression analysis to identify environmental, phenotypic, and genotypic factors that were associated with insufficient and deficient levels. RESULTS: Of 215 patients analyzed, 8.8% had deficient 25(OH)D levels (< 10 ng/mL) and just 24.7% had normal levels. Insufficient levels (< 30 ng/mL) were associated with obesity (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.3-13.3) and blood sampling in autumn/winter (OR, 2.1; 95% CI, 1.1-4). Deficient levels (< 10 ng/mL) were associated with obesity (OR, 7.1; 95% CI, 1.1-46.9), blood sampling in autumn/winter (OR, 9.0; 95% CI, 1.7-47.0), absence of freckles (OR, 5.4; 95% CI, 1.2-23.4), and, with marginal significance, the presence of fewer than 2 nonsynonymous melanocortin-1 receptor (MC1R) polymorphisms (OR, 5.0; 95% CI, 0.9-28.9). Limitations: Some factors related to 25(OH)D levels, such as food, were not included in the analyses. CONCLUSIONS: 25(OH)D levels should be monitored in patients with melanoma and the need for oral supplements should be contemplated where appropriate

Hypovitaminosis D in Children with Hashimoto’s Thyroiditis / Hipovitaminosis D en niños con tiroiditis de Hashimoto

Background: Vitamin D deficiency or insufficiency may play a role in the pathogenesis of certain autoimmune diseases. Aim: To measure vitamin D levels in children with Hashimoto’s thyroiditis (HT) (either with subclinical or marked hypothyroidism) and in healthy controls. Material and Methods: We included 68 children with HT aged 12 ± 4 years (39 females) from a pediatric outpatient clinic and 68 healthy children aged 10 ± 4 years (37 females). Calcium metabolism parameters, thyroid function tests and anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) and 25 hydroxy vitamin D (25OHD) levels were measured. Results: Patients were older than controls but well matched by gender distribution. Mean 25OHD levels were significantly lower in HT patients than controls (16.8 ± 9.3 and 24.1 ± 9.4 ng/mL respectively, P < 0.01). Frequency of vitamin D deficiency was 76 and 35% in HT patients and controls, respectively (P < 0.001). Conclusions: Vitamin D deficiency is more common in children with HT than healthy controls.

Antecedentes: La deficiencia o insuficiencia de vitamina D puede tener un rol en la patogenia de enfermedades autoinmunes. Objetivo: Medir niveles de vitamina D en niños con tiroiditis de Hashimoto (TH) (con hipotiroidismo subclínico o marcado) y en controles sanos. Material y Métodos: Estudiamos 68 niños con TH, de 12 ± 4 años (39 mujeres) y 68 controles sanos de 10 ± 4 años (37 mujeres). Se les midió parámetros de metabolismo de calcio, pruebas de función tiroidea, anticuerpos anti peroxidasa y anti tiroglobulina y 25 hidroxi vitamina D (25 OH vit D). Resultados: Los pacientes eran mayores que los controles pero la distribución por género era homogénea en ambos grupos. Los niveles de 25 OH vit D en pacientes y controles fueron 16,8 ± 9,3 y 24,1 ± 9,4 ng/mL respectivamente, p < 0,01. La frecuencia de deficiencia de vitamina D fue de 76 y 35% en pacientes y controles, respectivamente. Conclusiones: La deficiencia de vitamina D es más común en niños con TH.

Concentración de 25-hidroxivitamina D. Un parámetro importante en los/las trabajadores/as con trabajos a turnos / 25-hydroxyvitamin D concentration. An important parameter in shift workers

No disponible

Vitamina D, determinante de la salud ósea y extra ósea; importancia de su suplementación en la leche y derivados / Vitamin D, determinant of bone and extrabone health. Importance of Vitamin D supplementation in milk and dairy products

La vitamina D se obtiene fundamentalmente a partir de la irradiación ultravioleta en la piel del 7-dehidrocolesterol para formar colecalciferol (vitamina D3) y mínimamente por la dieta, salvo que se tomen alimentos fortificados en vitamina D, fundamentalmente leche; en algunos países se emplea ergocalciferol (vitamina D2). En el hígado la vitamina D3 se hidroxila para formar 25-hidroxivitamina D3 (marcador del estatus nutricional corporal en vitamina D). La 25OHD3, se hidroxila para formar 1,25-dihidroxivitamina D3 (1,25OH)2D3 en el riñón, para controlar la homeostasis del calcio y la salud del hueso y en otras células o tejidos, mediante el estímulo del VDR, incluyendo piel, músculo, los sistemas cardiovascular e inmune, homeostasis de la glucosa, y proliferación celular en general; de tal manera, que alrededor del 3% del genoma humano está regulado por la hormona 1,25(OH)2 vitamina D3. Estudios de asociación describen acciones beneficiosas a nivel cardiovascular, hipertensión arterial, cáncer colorectal, de mama, esclerosis múltiple, función inmune e inflamación etc. Un objetivo mínimo irrenunciable, para la salud pública, debe ser conseguir niveles séricos de 25OHD superiores a 20 ng/ml, para asegurar un estatus óptimo para la salud ósea y preferiblemente mayor de 30 ng/ml, si nos proponemos alcanzar otros objetivos. 'Paradójicamente' en España se da una elevada prevalencia de insuficiencia o incluso franca deficiencia de vitamina D en niños y jóvenes, persiste en adultos, en mujeres postmenopáusicas (osteoporóticas o no), o ancianos que viven en sus casas, y que es mayor si viven en residencias, con una variación estacional que apenas llega a normalizar los niveles séricos de 25OHD después del verano-otoño. También se ha demostrado una elevada prevalencia de niveles inadecuados de vitamina D en mujeres posmenopáusicas en tratamiento por osteoporosis con niveles de 25-hidroxivitamina D menores de 30 ng/ml y 20 ng/ml en el 63 y 30% respectivamente, lo que constituye un importante factor contribuyente a falta respuesta ósea al tratamiento. Una adecuación de niveles séricos de vitamina D, permitiría que la dieta proporcionara el calcio necesario para conseguir una buena salud ósea. Dada la dificultad para conseguir niveles adecuados de vitamina D por irradiación UV y por dieta, la suplementación adecuada de leche y derivados con vitamina D supone una atractiva posibilidad y un reto, para la Salud Pública de España y la Unión Europea, que ha dado excelentes resultados en EEUU, Canadá, Países de Norte de Europa, etc (AU)

Vitamin D is obtained mainly from ultraviolet irradiation of 7-dehydrocholesterol in the skin to form cholecalciferol (vitamin D3), and minimally from diet, unless vitamin D fortified food is taken, mainly enriched milk. In some countries, vitamin D is added to diet as ergocalciferol (vitamin D2). In the liver, vitamin D3 is hydroxylated to form 25-hydroxyvitamin D3 (marker of body nutritional status of vitamin D). Subsequently, in the kidney, 25OHD3 is hydroxylated to form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). By VDR stimulation, (1,25)OH)2D3 controls calcium homeostasis and bone health and, what is more, many other cells and tissues including skin, muscle, cardiovascular and immune systems as well as glucose homeostasis. Thus, about 3% of the human genome is regulated by this hormone. Association and recent intervention studies describe beneficial effects on bone, cardiovascular disease, hypertension, diabetes mellitus type 2,colorectal cancer, breast cancer, multiple sclerosis, immune function inflammation etc. A minimum target for public health should be to achieve serum 25OHD levels above 20 ng/ml to ensure optimum status for bone health. However, levels above 30 ng/ml should be reached to achieve other health goals. Paradoxically, inadequacy (or even deficiency) in vitamin D levels is highly prevalent in children and youth in Spain. This deficit persists in adults, as well as in postmenopausal women (osteoporotic or not) and the elderly (especially amongst those institutionalized). Seasonal variation barely normalizes serum 25OHD levels after summer-autumn. Treated postmenopausal osteoporotic women also show high prevalence of inadequate levels of vitamin D, a major contributor to antiresortive treatments failure. A normalization of serum vitamin D enables diet to provide the calcium necessary to achieve a good bone health and an adequate response to antiresortive drugs. Given the difficulty to get adequate levels of vitamin D by UV irradiation and diet, a proper supplementation of milk with vitamin D is an attractive chance and a challenge for Public Health of Spain and the European Union. It has provided excellent results in the US, Canada, Northern Europe Countries, etc (AU)

Efficacy of the Measurement of 25-Hydroxyvitamin D2 and D3 Levels by Using PerkinElmer Liquid Chromatography-Tandem Mass Spectrometry Vitamin D Kit Compared With DiaSorin Radioimmunoassay Kit and Elecsys Vitamin D Total Assay

No abstract available.

Vitamin D Receptor Poly(A) Microsatellite Polymorphism and 25-Hydroxyvitamin D Serum Levels: Association with Susceptibility to Breast Cancer / 한국유방암학회지

PURPOSE: According to previous studies, vitamin D exhibits protective effects against breast cancer via the vitamin D receptor (VDR). There is growing evidence that breast cancer incidence is associated with various polymorphisms of the VDR gene. This study investigates the association of VDR poly(A) microsatellite variants with 25-hydroxyvitamin D (25(OH)D) serum levels and breast cancer risk. METHODS: Polymorphism analysis was performed on a total of 261 blood samples, which were collected from 134 women with breast cancer and 127 controls. Single strand conformation polymorphism was assessed by polymerase chain reaction in combination with sequencing to detect poly(A) lengths for each sample. The vitamin D levels of samples were determined by electrochemiluminescence. RESULTS: The poly(A) variant L allele frequency was significantly higher in cancer patients than in controls (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.16-2.57; p=0.006). Thus, carriers of the L allele (LS and LL genotypes) have a higher risk for breast cancer (OR, 1.86; 95% CI, 1.13-3.05; p=0.013). A larger increase in the risk for breast cancer was found in individuals with the L carrier genotype and lowered 25(OH)D levels. CONCLUSION: The results primarily suggest that VDR gene polymorphism in the poly(A) microsatellite is associated with 25(OH)D levels and that it can affect the breast cancer risk in the female population from northern Iran.

Interaction of Vitamin D and Smoking on Inflammatory Markers in the Urban Elderly / 예방의학회지

OBJECTIVES: Epidemiological studies have reported that vitamin D deficiency is associated with inflammatory disease. Smoking is a well-known risk factor for inflammation. However, few studies have investigated the interactive effect of vitamin D deficiency and smoking on inflammation. This study aims to investigate the interaction of vitamin D and smoking with inflammatory markers in the urban elderly. METHODS: We used data from the Korean Elderly Environmental Panel Study, which began in August 2008 and ended in August 2010, and included 560 Koreans > or =60 years old living in Seoul. Data was collected via questionnaires that included items about smoking status at the first visit. Vitamin D levels, high-sensitivity C-reactive protein (hs-CRP), and white blood cell (WBC) counts were repeatedly measured up to three times. RESULTS: The association of vitamin D and hs-CRP was significant after adjusting for known confounders (beta=-0.080, p=0.041). After separate analysis by smoking status, the association of vitamin D deficiency and hs-CRP in smokers was stronger than that in nonsmokers (smokers: beta=-0.375, p=0.013; non-smokers: beta=-0.060, p=0.150). Smoking status was an effect modifier that changed the association between vitamin D deficiency and hs-CRP (interaction estimate: beta=-0.254, p=0.032). Vitamin D was not significantly associated with WBC count (beta=0.003, p=0.805). CONCLUSIONS: Vitamin D deficiency was associated with hs-CRP in the urban elderly. Smoking status was an effect modifier of this association. Vitamin D deficiency was not significantly associated with WBC count.

Estudio de estabilidad de las concentraciones de cortisol, 25-hidroxivitamina D y corticotropina (ACTH) / Study of the stability of Cortisol, 25 OH vitamin D and adrenocorticotrophic hormone (ACTH) in plasma

Objetivo. Evaluar la estabilidad de las concentraciones de cortisol y 25-hidroxivitamina D (25OH-vit D) en suero y de corticotropina (ACTH) en plasma en función del tiempo de almacenamiento en las condiciones habituales de trabajo para estas muestras y comparar dos protocolos diferentes de centrifugación. Material y método. Se obtuvieron muestras de 25 voluntarios sanos (5 hombres y 20 mujeres) para el estudio de cortisol y 25OH-vit D. Para el estudio de ACTH se utilizaron muestras de 15 de estos voluntarios sanos. Las muestras se procesaron en el analizador Liaison® DiaSorin en tiempos comprendidos entre 90 minutos y 7 días desde la toma de la muestra hasta la obtención del resultado. Resultados. El cortisol y 25OH-vit D se mantuvieron estables a lo largo de todo el estudio en las condiciones especificadas. La ACTH se mantuvo estable hasta 8 horas a 4°C. En ninguna de las tres magnitudes se observaron diferencias significativas entre los resultados obtenidos en muestras centrifugadas tras su obtención o inmediatamente antes de su procesamiento hasta 6 horas después de la obtención de la muestra. Conclusiones. Las condiciones habituales de manejo de las muestras, 8 horas a temperatura ambiente con o sin centrifugación previa y posteriormente almacenadas a 4°C durante una semana, no comprometen la estabilidad en el caso de cortisol y 25OH-vit D. En el caso de ACTH es preciso congelar las muestras tras su obtención si no van a ser procesadas en un tiempo inferior a 8 horas (AU)

Objective. To asses the stability of cortisol, and 25 (OH)-Vitamin D concentrations in serum, and adrenocorticotrophic hormone (ACTH) in plasma samples, according to the storage time under normal working conditions for these samples, and to compare two different centrifugation protocols. Material and method. The samples were obtained from 25 healthy volunteers (5 men and 20 women) for the study of cortisol and 25 OH-vit D. For the ACTH only 15 of the 25 samples were used. The samples were processed in the Liaison® DiaSorin analyser at times between 90minutes and 7 days from the time the sample was taken until the result was obtained. Results. Cortisol and 25 OH-Vit D remained stable during the time of the study under the specified conditions. ACTH remained stable only until the 8th hour at 4° C. There were no significant differences in relation to the time of centrifugation. Conclusions. The regular management conditions of the samples, 8hours at room temperature with or without previous centrifugation and later storage at 4° C for a week does not jeopardize the stability of cortisol and 25 OH-vit D. In the case of ACTH the samples have to be frozen after they are obtained if they are not going to be processed in less than 8 hours (AU)

Measurement of Serum Levels of 25-Hydroxyvitamin D3 and 25-Hydroxyvitamin D2 Using Diels-Alder Derivatization and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

BACKGROUND: Vitamin D has been recently shown to play important roles in the functioning of various systems. Most of the current analytical methods for measuring vitamin D levels are based on immunoassays. We simultaneously measured the levels of 25-hydroxyvitamin D3 [ 25(OH)D3 ] and 25-hydroxyvitamin D2 [ 25(OH)D2 ] in human serum by performing ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) after Diels-Alder derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) and evaluated the performance of our method. METHODS: After liquid-liquid extraction, samples were dried under N2 at 50degrees C for 1 hr followed by Diels-Alder derivatization with ethyl acetate containing 0.1 mg/mL PTAD. The samples were resuspended in 60 microL of methanol:10 mM ammonium formate solution (1:1, V/V). C18 UPLC column and positive ion multiple reaction monitoring transitions such as m/z 558.35-->298.1, 25(OH)D3; m/z 570.35-->298.1, 25(OH)D2; and m/z 564.35-->298.1, hexadeuterated-25(OH)D3 were used for UPLC-MS/MS. RESULTS: The within-run imprecision (CVs) for 25(OH)D3 and 25(OH)D2 were 3.5-4.0% and 3.8-4.2%, respectively, and the corresponding between-run CVs were 3.3-5.5% and 4.7-5.8%. The lower limit of quantification for 25(OH)D3 and 25(OH)D2 were 0.5 and 1.0 ng/mL, respectively. The curve for interassay calibration variability data obtained over concentrations of 0-120 ng/mL for 25(OH)D3 and 0-90 ng/mL for 25(OH)D2 was linear and reproducible [ 25(OH)D3, R2=0.993; 25(OH)D2, R2=0.998]. The total 25(OH)D levels in Koreans (average, 18.7 ng/mL) were lower than those in American Caucasians, and the percentage of people with total 25(OH)D levels under 10 ng/mL was 8.1%. CONCLUSIONS: Our method to measure 25(OH)D3 and 25(OH)D2 levels by performing UPLC-MS/MS after PTAD derivatization showed good performance as a sensitive and reproducible method for routine analysis of vitamin D status.

Performance Evaluation of Method for Detecting Serum 25-Hydroxyvitamin D2 and 25-Hydroxyvitamin D3 by Using PerkinElmer MSMS Vitamin D Kit / 임상검사와정도관리

BACKGROUND: Determining the concentration profiles of serum 25-hydroxyvitamin D (25OHD) may aid in the clinical diagnosis and treatment of vitamin D deficiency. To date, the standardized liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been used for accurate and precise determination of 25-hydroxyvitamin D levels. Here, we evaluated the performance of the recently developed and introduced PerkinElmer Vitamin D kit and compared the measurements obtained by RIA and LC-MS/MS methods. METHODS: We evaluated the accuracy, precision, linearity, lower limit of quantification (LLOQ), recovery, and carry-over of the MSMS Vitamin D kit. Clinical specimens from 80 patients were used for the comparison between the MSMS Vitamin D kit (PerkinElmer, USA) and the RIA kit (DiaSorin, USA). RESULTS: The MSMS Vitamin D kit was found to produce intra-assay and inter-assay coefficients of variation (CVs) of less than 6% for precision and showed a bias of less than 5%. The MSMS Vitamin D kit displayed linearity within the range for total vitamin D levels of 4.5-150 ng/mL, and the lower limit of quantification for 25OHD was 0.38 ng/mL. The RIA measurements of 25OHD showed a correlation of y=0.9931x+0.2216 (r2=0.74) with the LC-MS/MS values. CONCLUSIONS: The LC-MS/MS assay of 25OHD3 and 25OHD2 showed excellent performance when using the MSMS Vitamin D kit and in terms of 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) derivatization. Further, the results obtained were well correlated with those obtained using the RIA method. Thus, assays using the MSMS Vitamin D kit are considered as more standardized, and they enable quicker and more accurate analysis and help reduce inter-laboratory variation than that by other existing methods.