Genetic, sociodemographic and lifestyle factors associated with serum 25-hydroxyvitamin D concentrations in Brazilian adults: the Pró-Saúde Study / Fatores genéticos, sociodemográficos e de estilo de vida nas concentrações séricas de 25-hidroxivitamina D em adultos brasileiros: o Estudo Pró-Saúde / Factores genéticos, sociodemográficos y estilo de vida asociados con la concentración sérica 25-hidroxivitamina D en adultos brasileños: Estudio Pro-Salud

This study aims to investigate factors associated with serum 25-hydroxyvitamin D [25(OH)D] concentration in Brazilian adults considering sociodemographic and lifestyle factors, as well as vitamin D-related single nucleotide polymorphisms (SNPs). This is a cross-sectional study (n = 491; 34-79y; 251 women), nested within a prospective cohort (Pró-Saúde Study). Associations between serum 25(OH)D and sociodemographic characteristics, diet, use of supplement, physical activity, season of blood collection, body fat, skin type, sun exposure index, and SNPs CYP2R1-rs10741657 and GC-rs2282679 were explored by multiple linear regression. The prevalence of serum 25(OH)D < 50nmol/L was 55%. Serum 25(OH)D was lower among women (β = -4.38; 95%CI: -8.02; -0.74), those with higher visceral fat (β = -4.02; 95%CI: -5.92; -2.12), and those with AC and CC genotypes for GC-rs2282679 (β = -6.84; 95%CI: -10.09; -3.59; β = -10.63; 95%CI: -17.52; -3.74, respectively). Factors directly associated with serum 25(OH)D included summer (β = 20.14; 95%CI: 14.38; 25.90), intermediate skin type (β = 6.16; 95%CI: 2.52; 9.80), higher sun exposure (β = 0.49; 95%CI: 0.22; 0.75), vitamin D intake (β = 0.48; 95%CI: 0.03; 0.93), and physical activity (β = 4.65; 95%CI: 1.54; 7.76). Besides physical activity, diet, and sun exposure, non-modifiable factors, such as GC genotypes must be considered when evaluating vitamin D insufficiency in mixed-race populations. Moreover, high visceral fat in association with poorer vitamin D status deserve attention given that both conditions are unfavorably related with chronic and acute health outcomes.

Este estudo teve como objetivo investigar fatores associados com as concentrações séricas de 25-hidroxivitamina [25(OH)D] em adultos brasileiros de acordo com fatores sociodemográficos e de estilo de vida, assim como de polimorfismos de nucleotídeo único (SNPs) relacionados à vitamina D. Este é um estudo transversal (n = 491; 34-79 anos; 251 mulheres) aninhado em uma coorte prospectiva (Estudo Pró-Saúde). Associações entre a 25(OH)D sérica e características sociodemográficas, consumo alimentar, uso de suplementos, atividade física, estação do ano na coleta da amostra de sangue, gordura corporal, fototipo de pele, índice de exposição solar e SNPs CYP2R1-rs10741657 e GC-rs2282679, explorados por regressão multilinear. A prevalência de 25(OH)D sérica < 50nmol/L foi 55%. A concentração sérica de 25(OH)D foi menor entre mulheres (β = -4,38; IC95%: -8,02; -0,74), indivíduos com mais gordura visceral (β = -4,02; IC95%: -5,92; -2,12) e genótipos AC e CC para GC-rs2282679 (β = -6,84; IC95%: -10,09; -3,59 e β = -10,63; IC95%: -17,52; -3,74, respectivamente). Os fatores associados diretamente à 25(OH)D sérica incluíram os meses de verão (β = 20,14; IC95%: 14,38; 25,90), fototipo intermediário (β = 6,16; IC95%: 2,52; 9,80), maior exposição solar (β = 0,49; IC95%: 0,22; 0,75), ingestão de vitamina D (β = 0,48; IC95%: 0,03; 0,93) e atividade física (β = 4,65; IC95%: 1,54; 7,76). Além de atividade física, dieta e exposição solar, fatores não modificáveis, tais como variantes do gene GC devem ser considerados na avaliação da deficiência de vitamina D em populações miscigenadas. Além disso, merece atenção a associação entre a gordura visceral elevada e o pior estado de vitamina D, uma vez que ambas as condições implicam em desfechos de saúde desfavoráveis, tanto crônicos quanto agudos.

Nuestro objetivo fue investigar factores asociados con la concentración sérica 25-hidroxivitamina D [25(OH)D] en adultos brasileños, considerando factores sociodemográficos y de vida, así como también los polimorfismos de nucleótido único relacionados con la vitamina D (SNPs). Se trata de un estudio transversal (n = 491; 34-79 años; 251 mujeres), anidado dentro de una cohorte prospectiva (Estudio Pro-Salud). Se investigaron las asociaciones entre concentración sérica 25(OH)D y características sociodemográficas, ingesta alimentaria, uso de suplementos, actividad física, estación del año de recogida de muestras de sangre, grasa corporal, tipo de piel, índice de exposición al sol, y SNPs CYP2R1-rs10741657 y GC-rs2282679 mediante una regresión múltiple lineal. La prevalencia sérica 25(OH)D < 50nmol/L fue 55%. La 25(OH)D sérica fue menor entre las mujeres (β = -4,38; IC95%: -8,02; -0,74), quienes tenían alta grasa visceral (β = -4,02; IC95%: -5,92; -2,12), genotipos AC y CC para GC-rs2282679 (β = -6,84; IC95%: -10,09; -3,59 y β = -10,63; IC95%: -17,52; -3,74, respectivamente). Los factores directamente asociados con la concentración sérica 25(OH)D incluyeron verano (β = 20,14; IC95%: 14,38; 25,90), tipo de piel intermedia (β = 6,16; IC95%: 2,52; 9,80), más alta exposición al sol (β = 0,49; IC95%: 0,22; 0,75), toma de vitamina D (β = 0,48; IC95%: 0,03; 0,93) y actividad física (β = 4,65; IC95%: 1,54; 7,76). Además de la actividad física, dieta y exposición al sol, los factores no modificables, tales como genotipos GC, necesitan tenerse en cuenta cuando se está evaluando la insuficiencia de vitamina D en poblaciones mestizas. Asimismo, las implicaciones de la asociación de una alta grasa visceral con un estatus más pobre de vitamina D merece que se le preste atención, puesto que ambas condiciones de salud están relacionadas desfavorablemente con resultados de salud graves y crónicos.

Racial differences in the relationship between high-normal 25-hydroxy vitamin d and parathyroid hormone levels in early stage chronic kidney disease / Diferenças raciais na relação entre níveis normais-elevados de 25-hidroxivitamina d e hormônio da paratireóide na doença renal crônica em estágio inicial

ABSTRACT Aim: Current guidelines do not address between-person variability in markers of bone and mineral metabolism across subgroups of patients, nor delineate treatment strategies based upon such factors. Methods: A cross sectional study was carried out to analyze data from 20,494 United States Veterans and verify the variability of Vitamin D (25(OH)D) and parathyroid hormone (PTH) levels across race and stage of chronic kidney disease. Results: PTH levels were higher in Black Americans (BA) than White Americans (WA) at all levels of 25(OH)D and across eGFR strata. There was a progressive decline in PTH levels from the lowest (25(OH)D < 20) to highest quartile (25(OH)D >=40) in both BA (134.4 v 90 pg/mL, respectively) and WA (112.5 v 71.62 pg/mL) (p<0.001 for all comparisons). Conclusion: In this analysis, higher than normal 25(OH)D levels were well tolerated and associated with lower parathyroid hormone values in both blacks and whites. Black Americans had higher PTH values at every level of eGFR and 25(OH)D levels suggesting a single PTH target is not appropriate.

RESUMO Objetivo: as diretrizes atuais não abordam a variabilidade entre as pessoas nos marcadores do metabolismo ósseo e mineral em subgrupos de pacientes, nem traçam estratégias de tratamento com base em tais fatores. Métodos: realizamos um estudo transversal para analisar dados de 20.494 veteranos de guerra dos Estados Unidos e verificar a variabilidade nos níveis de vitamina D (25 (OH) D) e hormônio da paratireóide (PTH) entre a raça e o estágio da doença renal crônica. Resultados: os níveis de PTH foram maiores em americanos negros (AN) do que em americanos brancos (AB) em todos os níveis de 25 (OH) D e em todos os estratos de TFGe. Houve um declínio progressivo nos níveis de PTH do quartil mais baixo (25 (OH) D <20) para o quartil mais alto (25 (OH) D> = 40) em AN (134,4 v 90 pg/mL, respectivamente) e AB (112,5 v 71,62 pg/mL) (p <0,001 para todas as comparações). Conclusão: Nesta análise, níveis de 25 (OH) D acima do normal foram bem tolerados e associados a valores mais baixos do hormônio da paratireóide em negros e brancos. Os americanos negros tinham valores de PTH mais altos em todos os níveis de TFGe e 25 (OH) D, sugerindo que uma única meta de PTH não é apropriado.

Relationship of serum 25- hydroxy vitamin D and systemic lupus erythematosus / 北京大学学报(医学版)

OBJECTIVE@#To investigate the application value of serum 25-hydroxy vitamin D [25(OH)D] in systemic lupus erythematosus (SLE).@*METHODS@#Data of 158 patients with SLE in Department of Rheumatology and Immunology in the People's Hospital of Xinjiang Uygur Autonomous Region from July 2016 to July 2019. All the SLE patients were divided into two groups by SLE scores of the disease activity index (SLEADI): 59 cases of active group (SLEADI > 4), 99 cases of non-active group (SLEDAI ≤4). Fifty healthy people were selected as healthy control group. The patients' general information and their laboratory data including serum 25(OH)D levels were collected. Statistical methods used were t-test, Spearman's correalation analysis and Logistic regression analysis.@*RESULTS@#(1) A total of 208 cases were included in this study. The level of 25(OH)D in SLE group [10.4(5.6, 15.8) μg/L] was significantly lower than that in healthy control group [25.5(22.8, 32.3) μg/L, P < 0.01]. 25(OH)D level in active SLE patients [6.2(3.7, 13.8) μg/L] was significantly lower than that in remission SLE patients [12.3(7.2, 16.7) μg/L, P < 0.01]. The serum 25(OH)D level in lupus nephritis [6.7 (4.4, 12.9) μg/L] was significantly lower than that in SLE without renal involvement [13.3 (7.4, 18.7) μg/L, P < 0.01]. (2) A significant negative correlation was demonstrated between the serum level of 25(OH)D and SLEDAI (r=-0.35, P < 0.01), and the 24h urinary protein excretion (r=-0.39, P < 0.01).Positive correlation was demonstrated between the serum level of 25(OH)D and C3 that decreased (r=0.249, P < 0.05). (3) Univariate analysis showed anti- dsDNA antibodies(ds-DNA), anti-Sm antibodies(Sm), IgG, C3, C4, erythrocyte sedimentation rate (ESR), 24h urinary protein quantification(24h-pro) and 25(OH)D were associated with disease activity in the SLE patients; Multivariate Logistic regression analysis showed that 25(OH)D was associated with the disease activity of the lupus patients.@*CONCLUSION@#The decrease of vitamin D level is related to the disease activity of SLE patients, and may be related to lupus nephritis, which plays an important role in the occurrence and development of SLE.

Negative association between 25-hydroxyvitamin D and inflammatory markers in rheumatologic diseases / Asociación negativa entre 25-hidroxi vitamina D y los marcadores inflamatorios en enfermedades reumatológicas

Objective: The main purpose of this study was to evaluate serum 25-hydroxyvitamin D (25OHD) levels and its association with in"ammatory markers in patients with rheumatologic diseases (RD). Methods: A cross-sectional study in 154 women with RD (rheumatoid arthritis, spondyloarthritis and other connective tissue diseases) and 112 healthy individuals as a control group (CG) was carried out. Results: No differences in serum and urine calcium, serum phosphate, and urinary deoxypyridinoline were found. RD group had lower 25OHD and higher PTH compared to CG. RD group had higher C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) compared to CG. The overall mean level of 25OHD (ng/ml) was 26.3±12.0 in the CG and 19.4±6.8 in the RD group (p<0.0001). Moreover, CG had lower percentage of individuals with 25OHD de!ciency compared to RD (29.9% vs 53.2%). The femoral neck BMD was signi!cantly lower in postmenopausal RD women compared to CG. 25OHD levels signi!cantly correlated with ESR and CRP as in"ammatory markers. Age, BMI, presence of RD, and CRP were signi!cantly and negatively associated with 25OHD levels through linear regression analysis. According to univariate logistic regression analysis for 25OHD deficiency (<20 ng/ml), a significant and negative association with BMI, presence of RD, ESR and CRP were found. Conclusion: Patients with RD had lower 25OHD levels than controls and the presence of a RD increases by 2.66 the risk of vitamin D de!ciency. In addition, 25OHD has a negative correlation with ESR and CRP as in"ammatory markers. (AU)

Objetivo El objetivo principal de este estudio fue evaluar los niveles séricos de 25-hidroxivitamina D (25OHD) y su asociación con marcadores inflamatorios en enfermedades reumatológicas. Materiales y métodos: Se realizó un estudio transversal en 154 mujeres con enfermedades reumatológicas (artritis reumatoide, espondiloartritis y otras enfermedades del tejido conectivo) y 112 individuos sanos como grupo control (GC). Resultados: No se encontraron diferencias en el calcio sérico y urinario, el fosfato sérico y la desoxipiridinolina urinaria entre el GC y los sujetos con enfermedades reumatológicas. El grupo de pacientes con enfermedades reumatológicas tenía 25OHD más bajo y PTH más alto en comparación con el GC. Asimismo, el grupo de individuos con enfermedades reumatológicas tenía proteína C reactiva (PCR) y velocidad de eritrosedimentación (VES) más altas en comparación con el GC. El nivel de 25OHD (ng/ml) fue 26,3±12,0 en el GC y 19,4±6,8 en el grupo con enfermedades reumatológicas (p<0,0001). Además, el GC presentó un porcentaje menor de deficiencia de 25OHD en comparación con el grupo con enfermedades reumatológicas (29,9% vs 53,2%). La DMO del cuello femoral fue significativamente menor en las mujeres posmenopáusicas con enfermedades reumatológicas en comparación con el GC. La 25OHD correlacionó significativamente con la VES y la PCR como marcadores inflamatorios. El análisis de regresión lineal mostró que la edad, el IMC, la presencia de una enfermedad reumatológica y la PCR se asociaron significativa y negativamente con los niveles de 25OHD. Mientras que el análisis de regresión logística univariada mostró que la deficiencia de 25OHD (<20 ng/ml), se asoció significativa y negativamente con el IMC, la presencia de una enfermedad reumatológica, la VES y los niveles de PCR. Conclusiones: Los pacientes con enfermedades reumatológicas tenían niveles de 25OHD más bajos que los controles y la presencia de una enfermedad reumatológica aumenta en 2.66 el riesgo de deficiencia de vitamina D. Además, la 25OHD mostró correlación negativa con la VES y la PCR como marcadores inflamatorios. (AU)

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.

Efecto de la suplementación con vitamina D en dosis única sobre el estado nutricional de vitamina D / Effect of vitamin D supplementation as a single dose on the nutritional status of vitamin D

INTRODUCCIÓN: El primer año de vida es un periodo de riesgo de deficiencia de vitamina D (VD). La administración de 400 UI diarias de VD no tiene una adherencia del 100%, en cambio dosis únicas de 100.000 UI de VD oral son seguras en recién nacidos. OBJETIVO: Comparar el efecto de la suplementación oral de VD en dosis única de 100.000 UI al mes de edad vs dosis diarias de 400 UI sobre las concentraciones séricas de VD, a los 6 meses de vida. SUJETOS Y MÉTODOS: Ensayo clínico aleatorizado, sin enmascaramiento. Se incluyeron 84 lactantes sanos de 1 mes de vida, asignados al azar al grupo de estudio (GE) que recibió una dosis única de VD de 100.000 UI oral o al grupo control (GC), que recibió dosis diarias de VD de 400 UI oral del 1er al 6to mes de vida. A los 6 meses de edad se determinó la concentración sérica de VD. RESULTADOS: 65 lactantes terminaron el estudio, 36 en GE y 29 en GC. No se encontró deficiencia de VD. La insuficiencia de VD fue de 5,5% y 6,8% en el GE y GC, respectivamente. La concentración sérica de VD a los 6 meses de vida, fue de 38,8 ± 5,2 ng/ml y 39,7 ± 6,3 ng/ml para GE y GC, respectivamente (NS). CONCLUSIONES: La suplementación con 100.000 UI de VD única al mes de edad logra concentraciones séricas de VD a los 6 meses de vida, similares a dosis diarias de 400 UI de VD, del 1er al 6to mes.

INTRODUCTION: Infants are a group at risk of vitamin D (VD) deficiency. The administration of 400 IU of VD per day during the first year of life does not achieve 100% adherence. A single dose of 100,000 IU of oral VD is safe in newborns. OBJECTIVE: To compare the effect of oral administration of VD between a single dose of 100,000 IU at one month of age vs daily doses of 400 IU on serum concentrations of VD, at 6 months of age. SUBJECTS AND METHOD: Randomized clinical trial, without masking. 84 healthy infants were included at 1 month of age, randomized to the study group (SG) receiving a single oral dose of 100,000 IU or to the control group (CG), who received daily oral doses of VD of 400 IU from the 1st to the 6th month of life. At 6 months of life, the serum concentration of VD was determined. RESULTS: 65 infants completed the study, 36 in SG and 29 in CG. No VD deficiency was found. VD insufficient was 5.5% and 6.8% in the SG and CG, respectively. The serum concentration of VD at six months of age was 38.8 ± 5.2 ng/ml and 39.7 ± 6.3 ng/ml for the SG and CG, respectively (NS). CONCLUSIONS: Supplementation of 100,000 IU of VD at one month age achieves serum concentrations of VD at 6 months of life similar to the administration of daily doses of 400 IU of VD from the 1st to the 6th month.

Reference values of 25-hydroxyvitamin D revisited: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC)

ABSTRACT Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL

Chronic kidney disease is a main confounding factor for 25-vitamin D measurement / A doença renal crônica é um importante fator de confusão para a dosagem de 25-hidroxivitamina D

Abstract Background: Current guidelines recommend assessment of 25-vitamin D status in patients with chronic kidney disease (CKD). Although significant differences among assays have been described, the impact of CKD on this variability has never been tested. Methods: We tested the variability between two 25-vitamin D assays in patients with CKD (eGFR < 60 mL/min/1.73m2) who had consecutive 25-vitamin D measurements in 2015 (Assay 1 - Diasorin LIASON 25 TOTAL - D assay®) and 2016 (Assay 2 - Beckman Coulter Unicel Xl 800®). The cohort consisted of 791 adult patients (122 with normal renal function and 669 with CKD - 33, 30, and 37% in stages 3, 4, and 5 on dialysis, respectively). Results: Levels of 25-vitamin D were lower and the prevalence of hypovitaminosis D using assay 1 was higher than using assay 2 in patients with CKD, regardless of similar levels of calcium, phosphate, and parathyroid hormone. As kidney function decreased, the percentage of disagreement between the assays increased. Conclusion: There is a noteworthy variability between assays in patients with CKD such that the diagnosis of hypovitaminosis D is modified. The mechanism behind this result is still unclear and might be due to a possible interference in the analytical process. However, the clinical significance is unquestionable, as the supplementation of vitamin D can be erroneously prescribed to these patients.

Resumo Antecedentes: As diretrizes atuais recomendam a avaliação do estado da 25-hidroxivitamina D em pacientes com doença renal crônica (DRC). Embora significativas diferenças entre os ensaios tenham sido descritas, o impacto da nesta variabilidade DRC nunca foi testado. Métodos: Testamos a variabilidade entre dois ensaios de 25-hidroxivitamina D em pacientes com DRC (TFGe < 60 mL/min/1,73 m2) que realizaram medidas consecutivas de 25-hidroxivitamina D em 2015 (Ensaio 1 - Diasorin LIASON 25 TOTAL - D assay® ) e 2016 (Ensaio 2 - Beckman Coulter Unicel Xl 800®). A coorte consistiu de 791 pacientes adultos (122 com função renal normal e 669 com DRC - 33, 30 e 37% nos estágios 3, 4 e 5 em diálise, respectivamente). Resultados: Os níveis de 25-hidroxivitamina D foram menores e a prevalência de hipovitaminose D foi maior utilizando o ensaio 1 do que com o ensaio 2 em pacientes com DRC, independentemente dos níveis similares de cálcio, fosfato e paratormônio. Quando a função renal diminuiu, a porcentagem de discordância entre os ensaios aumentou. Conclusão: Existe uma notável variabilidade entre os ensaios em pacientes com DRC, de modo a modificar o diagnóstico de hipovitaminose D. O mecanismo por trás desse resultado ainda não está claro e pode ser devido a uma possível interferência no processo analítico. Entretanto, o significado clínico é inquestionável, pois a suplementação de vitamina D pode ser erroneamente prescrita a esses pacientes.

Association of vitamin d with mild cognitive impairment and alzheimer's dementia in older mexican adults

ABSTRACT Background It has been proposed that Vitamin D helps reduce the accumulation of cerebral β-amyloid-42 by innate immune stimulation and phagocytosis activation. An association between low Vitamin D levels and Alzheimer’s dementia (AD) has been established. We determined the association between Vitamin D, mild cognitive impairment (MCI), and AD in older Mexican adults (> 65 years) Methods Cross-sectional study conducted at the memory clinic in a tertiary-level hospital in Mexico City. We evaluated subjects with MCI, AD, and normal cognition (NC) with available serum Vitamin D [25(OH)D] levels (past 6 months). Three categories were assigned according to 25(OH)D levels: sufficiency (> 30 ng/mL), insufficiency (21-29 ng/mL), and deficiency (≤ 20 ng/mL). Descriptive statistics, means and standard deviations were used. Logistic regression analyses adjusted by age, sex, and educational level were performed Results We evaluated 208 patients. Mean age was 79 ± 1 year, 65% (n = 136) were female; and mean educational level was 6.7 ± 2.3 years. Thirty-one subjects (14%) had NC; 42% (n = 88) had MCI; and 43% (n = 89) had AD. Prevalence of Vitamin D deficiency was 54%, more frequent in the AD group (64%) followed by the MCI (59%) and NC (13%) (p < 0.001) groups. In the multivariate logistic regression analysis, Vitamin D deficiency was associated with MCI (HR 25.02 [confidence interval 95% 4.48-139]; p < 0.001) and AD (HR 41.7 [5.76-301]; p < 0.001) after adjusting for confounders Conclusions Serum Vitamin D deficiency was associated with MCI and dementia; low levels produced a greater effect over executive functions.

Niveles de vitamina D en médicos: ¿son los anestesiólogos el único grupo de riesgo? / Vitamin D levels among anesthesiologists and other physicians

Background Sun exposure is the main source of 25-hydroxy-vitamin D. Since anesthesiologists work inside operating rooms, they are identified as a deficiency risk group. As medical activity in general occurs indoors, added to the work excess and sedentary lifestyle, physicians in general have low sun exposure. Aim To investigate the determinants of vitamin D levels in physicians. Material and Methods Anesthesiologists and physicians not working in operating rooms were included. A survey that comprised working hours, diet, skin color, sunscreen use and outdoor activities was also applied. Measurements of vitamin D and parathormone levels in blood were performed. Results We analyzed samples from 81 volunteers. Median vitamin D values of the whole sample were in the range of insufficiency (25.3 [interquartile range 12.4] ng/ml). Multiple linear regression analysis detected no differences between anesthesiologists and non-anesthesiologists. A higher body mass index was a risk factor for vitamin D deficiency, (p = 0.025). The only protective factor was the intake of a vitamin D supplement (p < 0.01). Conclusions Anesthesiologists and other specialists were both at risk for vitamin D deficiency. Obesity was a risk factor and the use of a vitamin D supplement was the only protective factor.

Adiposity, inflammation and fat-soluble vitamins in adolescents / Adiposidade, inflamação e vitaminas lipossolúveis em adolescentes

Abstract Objective: Evaluate the association between inflammatory process, adiposity, and vitamins A, D, and E in adolescents, according to gender. Methods: Cross-sectional study with adolescents aged 12-19 years old of both genders attending public schools in Recife. A questionnaire was used to collect data on socioeconomic level, lifestyle, and food intake of adolescents. Then, an anthropometric evaluation and a blood sampling were performed to analyze serum concentrations of α-1-acid glycoprotein, retinol, β-carotene, α-tocopherol, and 25-hydroxy-vitamin D. Results: The levels of α-1-acid glycoprotein were higher for abdominal obesity in both genders. Male adolescents with insufficient serum α-tocopherol levels had low levels of α-1-acid glycoprotein (p = 0.03) and an increased risk of 25-hydroxy-vitamin D and β-carotene deficiency in relation to total and abdominal fat; female adolescents had an increased risk of insufficient β-carotene with abdominal obesity (PR: 1.33; 95% CI: 1.2-1.5). Conclusion: Abdominal adiposity implies a higher risk of inflammation and causes different changes to the levels of fat-soluble vitamins according to gender.

Resumo: Objetivo: Avaliar a associação entre processo inflamatório, adiposidade e as vitaminas A, D e E em adolescentes, segundo o sexo. Métodos: Estudo transversal com adolescentes de 12 a 19 anos de ambos os sexos de escolas públicas de Recife. Foi utilizado um questionário para coleta de dados socioeconômicos, de estilo de vida e de consumo alimentar dos adolescentes. Em seguida, realizou-se a avalição antropométrica e coleta de sangue para análise das concentrações séricas de α-1-glicoproteína ácida, retinol, β-caroteno, α-tocoferol e 25-hidroxivitamina D. Resultados: Os níveis de α-1-glicoproteína ácida foram maiores na obesidade abdominal de ambos os sexos. Os meninos com níveis séricos insuficientes de α-tocoferol expressaram níveis reduzidos de α-1-glicoproteína ácida (p = 0,03) e apresentaram um maior risco de deficiência de 25-hidroxivitamina D e β-caroteno na adiposidade total e abdominal, enquanto as meninas mostraram maior risco de insuficiência de β-caroteno com a obesidade abdominal (RP 1,33; IC 95% 1,2-1,5). Conclusão: A adiposidade abdominal reflete maior risco de inflamação e causa alterações distintas nas concentrações das vitaminas lipossolúveis, de acordo com o sexo.

A higher circulating concentration of 25-hydroxyvitamin-D decreases the risk of renal cell carcinoma: a case-control study

ABSTRACT Objective: To investigate the relationship between vitamin D status, using circulating 25-hydroxyvitamin D [25 (OH) D], and renal cell carcinoma (RCC) risk in a case-control study, because the association between the two is unclear in China. Materials and Methods: A total of 135 incident RCC cases were matched with 135 controls by age and sex. The blood samples were collected on the first day of hospitalization before surgery to measure plasma 25 (OH) D. Logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) with adjustment for several confounders (e.g. age, gender, smoking and season of blood draw). Furthermore, the association of RCC with 25 (OH) D in units of 10 ng / mL as a continuous variable were also examined. Results: The average plasma 25 (OH) D concentrations in RCC were significantly lower compared with those of the controls (21.5 ± 7.4 ng / mL vs. 24.1 ± 6.6 ng / mL, respectively; P = 0.003). In the adjusted model, inverse associations were observed between circulating 25 (OH) D levels and RCC risk for 25 (OH) D insufficiency (20-30 ng / mL) with OR of 0.50 (95% CI: 0.29-0.88; P = 0.015) and a normal 25 (OH) D level (≥ 30 ng / mL) with OR of 0.30 (95% CI: 0.13-0.72; P = 0.007), compared with 25 (OH) D deficiency (< 20 ng / mL). Furthermore, results with 25 (OH) D as a linear variable indicated that each 10 ng / mL increment of plasma 25 (OH) D corresponded to a 12% decrease in RCC risk. Conclusions: This case-control study on a Chinese Han population supports the protective effect of a higher circulating concentration of 25 (OH) against RCC, whether the confounding factors are adjusted or not.

Low serum vitamin D is associated with an increased likelihood of acquired premature ejaculation

Abstract Purpose: To investigate the relationship between 25-hydroxyvitamin D (25 (OH) D) levels and acquired premature ejaculation (PE). Materials and Methods: A total of 97 patients with acquired PE and 64 healthy men as a control group selected from volunteers without PE attending our Andrology Outpatient Clinic between November 2016 and April 2017 were included the study. All patients were considered to have acquired PE if they fulfilled the criteria of the second Ad Hoc International Society for Sexual Medicine Committee. Premature ejaculation diagnostic tool questionnaires were used to assessment of PE and all participants were instructed to record intravaginal ejaculatory latency time. Vitamin D levels were evaluated in all participants using high performance liquid chromatography method included in the study. Results: Compared to men without PE, the patients with acquired PE had significantly lower 25 (OH) D levels (12.0 ± 4.5 ng/mL vs. 18.2 ± 7.4 ng/mL, p < 0.001). In the logistic regression analysis, 25 (OH) D was found to be an independent risk factor for acquired PE, with estimated odds ratios (95% CI) of 0.639 (0.460-0.887, p = 0.007) and the area under curve of the ROC curve of 25 (OH) D diagnosing acquired PE was 0.770 (95% CI: 0.695 to 0.844, p < 0.001). The best cut-off value was 16 ng/mL with a sensitivity of 60.9%, specificity of 83.5%, PPV of 70.9%, and NPV of 76.4% to indicate acquired PE. Conclusions: This study demonstrates that lower vitamin D levels are associated with the acquired PE. The result of our study showed that the role of serum vitamin D levels should be investigate in the etiology of acquired PE. Perhaps supplementation of vitamin D in men with acquired PE will ameliorate the sexual health of these patients.

Prevalence of hypovitaminosis D in postmenopausal women: a systematic review

SUMMARY BACKGROUND: Hypovitaminosis D is considered a global public health issue. Knowledge of its true dimensions will allow us to design interventions and plan preventive measures that can have a significant impact on human health. OBJECTIVES: The aim of this study was to evaluate the prevalence of hypovitaminosis D, defined as a serum 25-hydroxyvitamin D concentration < 30 ng/ml, in postmenopausal women around the world, as well as to identify the potential associated factors. METHODS: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses recommendations. Specific search terms were consulted in Medline, Excerpta Medica, and Latin-American and Caribbean Health Sciences Literature databases, with no restriction for the year or language of publication. RESULTS: Of 451 studies initially identified, 32 were selected for analysis. Collectively, those 32 studies evaluated 21,236 postmenopausal women, of whom 16,440 (77.4%) had serum 25-hydroxyvitamin D concentrations < 30 ng/ml. The reported prevalence of hypovitaminosis D ranged from 29% (in the United States) to 99.4% (in China). In six of the studies, the prevalence was above 90%. CONCLUSIONS: If the criterion is the 30 ng/ml cut-off point, the majority of postmenopausal women in the world could be classified as having hypovitaminosis D. Among the studies evaluated, the lowest prevalence reported was nearly 30%. Neither latitude, region of the world, nor laboratory methodology were found to be associated with the prevalence of hypovitaminosis D.

RESUMO INTRODUÇÃO: A hipovitaminose D é considerada um problema de saúde pública global. O conhecimento de suas verdadeiras dimensões nos permitirá projetar intervenções e planejar medidas preventivas que possam ter um impacto significativo na saúde humana. OBJETIVO: O objetivo deste estudo foi avaliar a prevalência de hipovitaminose D, definida como concentração sérica de 25-hidroxivitamina D <30 ng/ml, em mulheres na pós-menopausa em todo o mundo, bem como identificar os potenciais fatores associados. MÉTODOS: Uma revisão sistemática foi realizada de acordo com as recomendações de Itens de Relatórios Preferenciais para Revisão Sistemática e Meta-Análises. Os termos de pesquisa específicos foram consultados nas bases de dados Medline, Excerpta Medica e Literatura Latino-Americana e do Caribe em Ciências da Saúde, sem restrição para o ano ou idioma de publicação. RESULTADOS: Dos 451 estudos inicialmente identificados, 32 foram selecionados para análise. Coletivamente, esses 32 estudos avaliaram 21.236 mulheres na pós-menopausa, das quais 16.440 (77,4%) apresentavam concentrações séricas de 25-hidroxivitamina D <30 ng/ml. A prevalência relatada de hipovitaminose D variou de 29% (nos Estados Unidos) a 99,4% (na China). Em seis dos estudos, a prevalência foi superior a 90%. CONCLUSÕES: Se o critério é o ponto de corte de 30 ng/ml, a maioria das mulheres na pós-menopausa no mundo poderia ser classificada como tendo hipovitaminose D. Entre os estudos avaliados, a menor prevalência relatada foi de quase 30%. Nem latitude, região do mundo, nem metodologia laboratorial foram encontrados para ser associados com a prevalência de hipovitaminose D.

On the synthesis of vitamin d in the darkness / Sobre la síntesis de vitamina D en la oscuridad

Published evidence reports the existence of two routes for the transformation of 7-dehydrocholecalciferol into previtamin D3: a photochemical route with the participation of UVB photons and another route that occurs in the darkness. Several reports appears to support the presence of these two routes in some mammals, birds, nonvascular plants (e.g.: mosses), vascular plants (e.g.: angiosperms) and lichens. The reviewed evidence suggests that in the darkness, the synthesis of vitamin D3 follows the same scheme of the photochemical pathway, but at a reduced rate respect to the synthesis under UVB radiation. The process of vitamin D synthesis in the dark, then, may be taken as an insurance for survival, at least for mammals and birds. The low rate of the synthesis of vitamin D3 in the absence of light produce low concentrations of vitamin D3 metabolites in plasma. Long term survival under these circumstances might be possible through upregulation of vitamin D receptors (VDRs). In mole rats (South African rodents that live in the dark in underground tunnels), the reduced rate of vitamin D3 synthesis produce low levels of plasma vitamin D3 and their metabolites 25(OH) D3 and 1α,25OH2 D3 . The fact that Kd and ßmax of the complex 1α,25(OH)2 D3 -VDR from the intestinal mucosa, kidneys and the Harderian glands of the mole rat Heterocephalus glaber are significantly different in each one of these tissues, is interpreted as an indicator that the VDRs are, in each tissue, adapted to the maintenance of normal physiological functions. (AU)

Varios trabajos publicados han informado que existen dos mecanismos para la transformación de 7-dehidrocolecalciferol en previtamina D3 : uno iniciado con el auxilio de fotones UVB y un segundo que ocurre en la oscuridad, sin el auxilio de radiación ultravioleta. Una serie de publicaciones contienen información que apoya la presencia de estos dos mecanismos en mamíferos, pájaros, plantas no vasculares (musgos), vasculares (angiospermas) y líquenes. La evidencia revisada sugiere que, en la oscuridad, la síntesis de vitamina D3 sigue el mismo esquema que la ruta fotoquímica y generalmente ocurre a una tasa reducida respecto de la síntesis bajo irradiación ultravioleta. La operación de la síntesis de vitamina D3 en la oscuridad, por lo menos para mamíferos y pájaros, puede tomarse como un reaseguro de sobrevida. La reducida tasa de síntesis de vitamina D en ausencia de luz produce bajas concentraciones en plasma de los metabolitos de la vitamina. La sobrevida saludable en estas condiciones sería posible mediante upregulation de los receptores. En las ratas topo Heterocephalus glaber (roedores sudafricanos que viven en permanente oscuridad, en túneles subterráneos), la reducida tasa de síntesis de vitamina D3 es la causa de los bajos niveles plasmáticos de la vitamina y sus metabolitos: 25(OH)D3 y 1α,25OH2 D3 . El hecho de que el Kd y ßmax del complejo 1α,25(OH)2 D3 -Vitamina-D-Receptor del intestino, riñón y glándulas de Harder de Heterocephalus glaber sean significativamente diferentes entre sí indicaría que los receptores se han modificado para mantener funciones fisiológicas normales en cada tejido. (AU)

Serum PTH reference values in an adult Brazilian population: implications for the diagnosis of hyperparathyroidism

ABSTRACT Objective: To define serum parathyroid hormone (PTH) reference values in carefully selected subjects following the recommended pre-analytical guidelines. Subjects and methods: First, 676 adults who would be submitted to thyroidectomy were evaluated. Patients using interfering medications or with malabsorption syndrome, hypomagnesemia, hyper- or hypophosphatemia, hypo- or hypercalcemia, 25-hydroxyvitamin D < 30 ng/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, urinary calcium/creatinine ratio ≥ 0.25, thyroid dysfunction, parathyroid adenoma detected during surgery were excluded. The sample consisted of 312 subjects. Results: The median, minimum, maximum, and 2.5th and 97.5th percentiles of the PTH values obtained were 30, 7.2, 78, 10.1, and 52 pg/mL, respectively. Thus, the reference range was 10 to 52 pg/mL. PTH > 65 pg/mL, the upper limit of normal according to the manufacturer of the kit, was observed in only one subject (0.3%). Considering the upper limit proposed by the kit's manufacturer, 1/6 hypercalcemic patients and 4/8 normocalcemic patients with PHPT had normal PTH. Using the upper limit established in this study, only one normocalcemic patient had normal PTH. Thus, the sensitivity of PTH in detecting asymptomatic primary hyperparathyroidism (PHPT) using the values recommended by the kit and established in this study was 64% and 93%, respectively (50% versus 87.5% for normocalcemic PHPT). Conclusion: The upper reference limit of PTH obtained for a rigorously selected sample was 20% lower than that provided by the assay, which increased its sensitivity in detecting PHPT.

Evaluation of bone disease in patients with cystic fibrosis and end-stage lung disease / Avaliação de doença óssea em pacientes com fibrose cística e doença pulmonar terminal

ABSTRACT Objective: Bone disease is a common comorbidity in patients with cystic fibrosis (CF). We sought to determine risk factors and identify potential biochemical markers for CF-related bone disease (CFBD) in a unique cohort of CF patients with end-stage lung disease undergoing lung transplantation (LTx) evaluation. Methods: All of the CF patients who were evaluated for LTx at our center between November of 1992 and December of 2010 were included in the study. Clinical data and biochemical markers of bone turnover, as well as bone mineral density (BMD) at the lumbar spine and femoral neck, were evaluated. Spearman's rho and multivariate logistic regression analysis were used. Results: A total of 102 adult CF patients were evaluated. The mean age was 28.1 years (95% CI: 26.7-29.5), and the mean body mass index was 17.5 kg/m2 (95% CI: 17.2-18.2). Mean T-scores were −2.3 and −1.9 at the lumbar spine and femoral neck, respectively, being lower in males than in females (−2.7 vs. −2.0 at the lumbar spine and −2.2 vs. −1.7 at the femoral neck). Overall, 52% had a T-score of < −2.5 at either skeletal site. The homozygous Phe508del genotype was found in 57% of patients without osteoporosis and in 60% of those with low BMD. Mean T-scores were not particularly low in patients with severe CFTR mutations. Although the BMI correlated with T-scores at the femoral neck and lumbar spine, serum 25-hydroxyvitamin D and parathyroid hormone levels did not. Conclusions: CFBD is common in CF patients with end-stage lung disease, particularly in males and patients with a low BMI. It appears that CF mutation status does not correlate with CFBD. In addition, it appears that low BMD does not correlate with other risk factors or biochemical parameters. The prevalence of CFBD appears to have recently decreased, most likely reflecting increased efforts at earlier diagnosis and treatment.

RESUMO Objetivo: A doença óssea é uma comorbidade comum em pacientes com fibrose cística (FC). Nosso objetivo foi determinar os fatores de risco e identificar possíveis marcadores bioquímicos de doença óssea relacionada à FC (DOFC) em uma coorte única de pacientes com FC e doença pulmonar terminal submetidos a avaliação para transplante de pulmão (TxP). Métodos: Todos os pacientes com FC avaliados para TxP em nosso centro entre novembro de 1992 e dezembro de 2010 foram incluídos no estudo. Foram avaliados dados clínicos e marcadores bioquímicos de remodelação óssea, bem como a densidade mineral óssea (DMO) na coluna lombar e colo do fêmur. Foram usados rô de Spearman e análise de regressão logística multivariada. Resultados: Foram avaliados 102 pacientes adultos com FC. A média de idade foi de 28,1 anos (IC95%: 26,7-29,5), e a média do índice de massa corporal foi de 17,5 kg/m2 (IC95%: 17,2-18,2). A média do escore T foi de −2,3 e −1,9 na coluna lombar e colo do fêmur, respectivamente, sendo menor nos homens que nas mulheres (−2,7 vs. −2,0 na coluna lombar e −2,2 vs. −1,7 no colo do fêmur). No geral, 52% apresentaram escore T < −2,5 em um dos dois sítios esqueléticos. O genótipo homozigoto para Phe508del foi encontrado em 57% dos pacientes sem osteoporose e em 60% daqueles com DMO baixa. A média do escore T não foi particularmente baixa em pacientes com mutações graves do gene CFTR. Embora o IMC tenha se correlacionado com o escore T no colo do fêmur e coluna lombar, os níveis séricos de 25-hidroxivitamina D e paratormônio não o fizeram. Conclusões: A DOFC é comum em pacientes com FC e doença pulmonar terminal, particularmente em homens e pacientes com IMC baixo. O estado de mutação da FC aparentemente não se correlaciona com a DOFC. Além disso, aparentemente não há correlação entre DMO baixa e outros fatores de risco ou parâmetros bioquímicos. A prevalência de DOFC parece ter diminuído recentemente, o que provavelmente é reflexo do aumento dos esforços para antecipar o diagnóstico e tratamento.

BsmI polymorphism in the vitamin D receptor gene is associated with 25-hydroxy vitamin D levels in individuals with cognitive decline / Polimorfismo BsmI no gene do receptor de vitamina D está associado aos níveis de 25-hidroxi vitamina D em indivíduos com declínio cognitivo

ABSTRACT Elderly people are at a high risk of developing vitamin D (VitD) deficiency due to both decreased intake and cutaneous synthesis. Most of the biological actions of VitD are mediated by the vitamin D receptor (VDR), which is present in neurons and glial cells of the hippocampus, and in the cortex and subcortical nuclei, essential areas for cognition. It is known that VDR gene polymorphisms may decrease the VDR affinity for VitD. Objective: The present study aimed to investigate the influence of VitD levels on cognitive decline in patients with dementia due to Alzheimer's disease (AD, n = 32) and mild cognitive impairment (MCI, n = 15) compared to cognitively healthy elderly (n = 24). We also evaluated the association of VDR gene polymorphisms with cognitive disturbance. Methods: Four polymorphisms on the VDR gene were studied, namely, BsmI, ApaI, FokI and TaqI, by polymerase chain reaction-restriction fragment length polymorphism. Serum levels of 25-hydroxy vitamin D (25(OH)D) were determined by high performance liquid chromatography. Results: No significant difference in 25(OH)D levels or genotypic/allelic frequencies was observed between the groups. Deficiency of 25(OH)D was more frequently observed in women. The AA/AG genotypes of the BsmI polymorphism was associated with sufficient 25(OH)D levels, while the GG genotype of this same polymorphism was associated to insufficient levels in the cognitively-impaired group (individuals with AD or MCI). Conclusions: The data obtained do not confirm the relationship between reductions of VitD levels, polymorphisms in the VDR gene, and altered cognitive function in this sample. However, the data indicate that BsmI polymorphism in the VDR gene is associated with the VitD levels in individuals with cognitive decline.

RESUMO Idosos apresentam risco elevado de desenvolverem deficiência de Vitamina D (VitD) devido à diminuição da ingestão e da síntese na pele. A maioria das ações biológicas da VitD é mediada pelo receptor da vitamina D (VDR), que está presente nos neurônios e células gliais do hipocampo, e no córtex e em núcleos subcorticais, áreas essenciais para a cognição. Sabe-se que polimorfismos do gene VDR podem diminuir a afinidade do VDR pela VitD. Objetivo: O presente estudo teve como objetivo investigar a influência dos níveis de VitD no declínio cognitivo em pacientes com demência devida à doença de Alzheimer (DA, n = 32) e comprometimento cognitivo leve (CCL, n = 15) em comparação a um grupo de idosos cognitivamente saudáveis (n = 24). Nós também avaliamos a associação entre polimorfimos no gene do receptor de VitD e as alterações cognitivas. Métodos: Quatro polimorfismos no gene VDR foram estudados, sendo BsmI, ApaI, FokI e TaqI, por PCR-RFLP. Os níveis séricos de 25-hidroxi vitamina D (25(OH)D) foram determinados por HPLC. Resultados: Não houve diferença significativa nos níveis de 25(OH)D ou nas frequências genotípicas / alélicas entre os grupos. Níveis deficientes de 25(OH)D foram mais frequentes nas mulheres. Os genótipos AA / AG do polimorfismo BsmI foram associados a níveis suficientes de 25(OH)D, enquanto o genótipo GG deste mesmo polimorfismo foi associado a níveis insuficientes no grupo com comprometimento cognitivo (em indivíduos com DA ou CCL). Conclusões: Os resultados obtidos não confirmam a relação entre redução dos níveis de VitD, polimorfismos no gene VDR e função cognitiva alterada nesta amostra. No entanto, os dados indicam que o polimorfismo BsmI no gene VDR está associado aos níveis de VitD em indivíduos com declínio cognitivo.

Low serum 25-hydroxy vitamin D levels are associated with aggressive breast cancer variants and poor prognostic factors in patients with breast carcinoma

ABSTRACT Objective: This study was conducted to assess the serum 25-hydroxy (OH) vitamin D levels in patients with breast cancer compared to healthy controls and to identify its association with aggressive breast cancer phenotypes. Materials and methods: Serum 25-OH vitamin D levels of 78 breast cancer patients and 78 matched healthy controls were estimated using ELISA. The cases and controls were matched with respect to age, menopausal status, parity, weight, height and co-morbidities. Prognostic factors like grade of tumour, hormone receptor status, HER2 neu status and lymphovascular invasion were compared with 25-OH vitamin D levels. Results: The mean serum 25-OH vitamin D levels of cases were significantly lower compared to the controls (22.33 ± 8.19 vs. 37.41 ± 12.9 ng/mL; p = 0.0001). Patients with higher grades of tumour, non-luminal types of breast cancer and breast cancers with estrogen receptor negativity had significantly lower serum 25-OH vitamin D levels than their opposing groups. Patients with excellent and good Nottingham's prognostic Index (NPI) had significantly higher serum 25-OH vitamin D levels than the moderate and poor NPI groups. Conclusion: Newly diagnosed breast cancer patients have significantly lower serum 25-OH vitamin D levels than healthy controls. Lower level of serum 25-OH vitamin D correlates with aggressive breast cancer phenotypes.