Randomized controlled trial of enteral vitamin D supplementation (ViDES) in infants <28 weeks gestational age or <1000 g birth weight: study protocol.

BACKGROUND: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. METHODS: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. DISCUSSION: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. TRIAL REGISTRATION: ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.

Interplay of interleukins (IL6, IL10) and 25 hydroxycholecalciferol in asthmatic subjects with chronic post-COVID condition (PCC).

The study aimed to compare and correlate serum levels of IL-6, 10, and 25-hydroxycholecalciferol in individuals with asthma with and without post-COVID condition (PCC). The study was designed to investigate the inflammatory response and serum 25-hydroxycholecalciferol status in asthmatics with and without PCC. A cross-sectional study of 252 subjects (128 asthmatics and 124 non-asthmatic subjects) was carried out. Interleukins and 25-hydroxycholecalciferol levels were estimated on ELISA. The principle findings were that IL-6 and 25-hydroxycholecalciferol levels were significantly increased (p<0.001), while IL-10 levels were non-significant in asthmatics with PCC compared to those without PCC. However, 25-hydroxycholecalciferol levels were significantly increased, but no significant change was observed in IL-6, and IL-10 levels in non-asthmatics with and without chronic PCC. A significant positive correlation (r = 0.258) was found between 25-hydroxycholecalciferol and IL-6 but a significant negative correlation (r = -0.227) with IL-10 in asthmatics with PCC. Similarly, a significant negative correlation (r = -0.285) was found between 25-hydroxycholecalciferol and IL-10 but was non-significant with IL-6 in asthmatics without PCC. The correlation of 25-hydroxycholecalciferol with IL-10 was significant (0.683), but IL-6 was non-significant in non-asthmatics with PCC. Multiple regression analysis showed that age, IL-6, gender, and PCC were significantly related in adjusted values to 25-hydroxycholecalciferol. This study sheds light on the complex liaison between 25-hydroxycholecalciferol levels and inflammatory responses in asthmatics, especially those with PCC. The findings suggest that although asthmatics with PCC maintain sufficient levels of 25-hydroxycholecalciferol, they show a substantial increase in the proinflammatory response. This suggests that PCC exacerbates the pro-inflammatory response in asthma. Moreover, the study reveals that asthmatics, whether with or without PCC, display a negative correlation between 25-hydroxycholecalciferol and the anti-inflammatory response. This emphasizes the main influence of asthma on the overall inflammatory response. These findings reveal a complex interplay between vitamin D levels and inflammatory mediators in asthmatic individuals with and without PCC.

Longitudinal analysis of vitamin D levels considering sunshine duration and suggestion for a standardised approach for vitamin D supplementation in children and adolescents with obesity.

BACKGROUND: Children with obesity have low 25 hydroxy-vitamin D (25-OH-D3) levels compared to lean children. Recommendations on when to start vitamin D supplementation differ largely between countries. Longitudinal data on 25-OH-D3 levels to guide treatment decisions are scarce since they are largely influenced by solar radiation and are difficult to compare. METHODS: We carried out a retrospective analysis of multiple 25-OH-D3 and parathyroid hormone (PTH) measurements in a cohort of 543 patients without vitamin D supplementation. All measurements were taken at the local paediatric obesity clinic as documented in the German-Austrian-Swiss APV (Prospective Documentation of Overweight Children and Adolescents) registry from 2009 to 2019. Serial 25-OH-D3 and PTH levels were adjusted for sunshine duration over the last 30 days to account for seasonal variation, as well as for sex and body mass index (BMI). We further performed an exploratory analysis of the association of sunshine duration, sex, BMI SDS (standard deviation score), abnormal lipid levels or dysglycemia with the 25-OH-D3 trend. RESULTS: 229 obese patients (mean BMI SDS: 2,58 (± 0,56), 53% females, mean age: 12 (± 3) years, range: 2-21 years) with two, 115 with three and 96 with four repeated 25-OH-D3 measurements were identified. Mean adjusted 25-OH-D3 (48.2 nmol/l) and PTH (34.9 ng/l) levels remained stable over 120 weeks. 5% of the patients had an elevated PTH > 65 ng/l. High total cholesterol ≥ 200 mg/dl and high triglycerides ≥ 130 mg/dl were associated with higher 25-OH-D3 levels. CONCLUSION: We propose a simple method to include sunshine duration in the analysis of 25-OH-D3 levels to minimise the bias of seasonal variation. Based on our data we established the pragmatic strategy of limiting vitamin D supplementation to patients with biochemical signs of mineralisation disorders such as elevated PTH and alkaline phosphatase (AP). In children with normal PTH and AP we recommend adjustment of calcium intake and increase of outdoor activity instead.

Association between serum ferritin and bone turnover marker levels in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease.

OBJECTIVE: To investigate the correlation between serum ferritin (SF) and bone turnover markers in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Seven hundred and forty-two people with T2DM were selected. Serum bone turnover markers: osteocalcin (OC), type I procollagen N-terminal peptide (PINP), ß-I type collagen carboxy-terminal peptide (ß-CTx), and 25-hydroxyvitamin D3 (25-[OH]-D) levels were detected. High SF (HF) was defined as the indicated SF levels above 400 ng/mL in males and more than 150 ng/mL in females. Patients were divided into four groups: T2DM+normal SF (non-HF); T2DM+high SF (HF); T2DM+NAFLD+non-HF; andT2DM+NAFLD+HF. Relationships between SF and bone turnover markers were analyzed. RESULTS: Compared with the T2DM+non-HF group, ß-CTx levels were higher in the T2DM+HFgroup. Compared with the T2DM+NAFLD+non-HF group, ß-CTx levels were increased and 25-(OH)-D levels decreased in the T2DM+NAFLD+HF group (all p < 0.05). SF was positively correlated with ß-CTx [ß = 0.074; 95% CI (0.003, 0.205)] and negatively correlated with 25-(OH)-D [ß=-0.108; 95%CI (-0.006, -0.001)]. Compared with the T2DM+non-HF group, an independent positive correlation was found between ß-CTx and SF in the T2DM+NAFLD+HF group [OR = 1.002; 95% CI (1.001, 1.004)]. Among males, SF was positively correlatedwith ß-CTx [ß = 0.114; 95% CI (0.031, 0.266)]. SF was negatively correlated with 25-(OH)-D levels in both male and female patients [ß=-0.124; 95% CI (0.007,0.001) and ß=-0.168; 95% CI (-0.012, -0.002)]. Among those >50 years of age and postmenopausal females, SF was negatively correlated with 25-(OH)-D levels [ß=-0.117; 95% CI (-0.007, -0.001) and ß=-0.003; 95% CI (-0.013, -0.003)]. CONCLUSION: SF level was positively correlated with ß-CTx in T2DM patients with NAFLD, which may promote bone resorption and increase the risk of bone loss.

Serum 25-hydroxyvitamin D concentrations are inversely associated with all-cause mortality among Koreans: a nationwide cohort study.

Evidence on the association between serum 25-hydroxyvitamin D (25(OH)D) concentration and all-cause and cause-specific mortality in Asians, especially Koreans, is limited. We hypothesized that high concentrations of 25(OH)D are associated with lower all-cause and cause-specific mortality in the general Korean population. This study included 27,846 adults participating in the Fourth and Fifth Korean National Health and Nutrition Examination Survey 2008-2012, followed up through December 31, 2019. Hazard ratios (HR) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and cancer were estimated using multivariable-adjusted Cox proportional hazards regression. The weighted mean serum 25(OH)D of study participants was 17.77 ng/mL; 66.5% had vitamin D deficiency (<20 ng/mL) and 94.2% had insufficient vitamin D (<30 ng/mL). During a median follow-up of 9.4 years (interquartile range, 8.1-10.6 years), 1680 deaths were documented, including 362 CVD deaths and 570 cancer deaths. Serum 25(OH)D levels ≥30 ng/mL were inversely associated with all-cause mortality (HR, 0.57; 95% CI, 0.43-0.75) compared with serum 25(OH)D levels <10 ng/mL. Based on the quartile cutoffs of serum 25(OH)D concentration, the highest quartile of serum 25(OH)D concentration (≥21.8 ng/mL) was associated with the lowest all-cause mortality (HR, 0.72; 95% CI, 0.60-0.85; P trend < .001), and CVD mortality (HR, 0.60; 95% CI, 0.42-0.85; P trend = .006). No association with cancer mortality outcome was found. In conclusion, higher serum 25(OH)D levels were associated with lower all-cause mortality in the general Korean population. An additional association was found between higher quartile of serum 25(OH)D and lower CVD mortality.

Forecasting levels of serum 25-hydroxyvitamin D based on dietary intake, lifestyle and personal determinants in a sample of Southern Europeans.

Vitamin D is an essential nutrient to be consumed in the habitual dietary intake, whose deficiency is associated with various disturbances. This study represents a validation of vitamin D status estimation using a semi-quantitative FFQ, together with data from additional physical activity and lifestyle questionnaires. This information was combined to forecast the serum vitamin D status. Different statistical methods were applied to estimate the vitamin D status using predictors based on diet and lifestyle. Serum vitamin D was predicted using linear regression (with leave-one-out cross-validation) and random forest models. Intraclass correlation coefficients, Lin's agreement coefficients, Bland-Altman plots and other methods were used to assess the accuracy of the predicted v. observed serum values. Data were collected in Spain. A total of 220 healthy volunteers aged between 18 and 78 years were included in this study. They completed validated questionnaires and agreed to provide blood samples to measure serum 25-hydroxyvitamin D (25(OH)D) levels. The common final predictors in both models were age, sex, sunlight exposure, vitamin D dietary intake (as assessed by the FFQ), BMI, time spent walking, physical activity and skin reaction after sun exposure. The intraclass correlation coefficient for the prediction was 0·60 (95 % CI: 0·52, 0·67; P < 0·001) using the random forest model. The magnitude of the correlation was moderate, which means that our estimation could be useful in future epidemiological studies to establish a link between the predicted 25(OH)D values and the occurrence of several clinical outcomes in larger cohorts.

Vitamin D Metabolites Are Associated with Physical Performance in Young Healthy Adults.

PURPOSE: This study aimed to determine vitamin D metabolites and vitamin D receptor (VDR) single-nucleotide polymorphism (SNP) relationships with physical performance. METHODS: In 1205 men and 322 women (94.8% White Caucasian, 22.0 ± 2.8 yr) commencing military training, we measured serum vitamin D metabolites (25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH) 2 D) by high-performance liquid chromatography tandem mass spectrophotometry and 1,25-dihydroxyvitamin D (1,25(OH) 2 D) by immunoassay), VDR SNPs (rs2228570, rs4516035, and rs7139166 by polymerase chain reaction genotyping), and endurance performance by 2.4-km run, muscle strength by maximal dynamic lift, and muscle power by maximal vertical jump. RESULTS: Serum 25(OH)D was negatively associated with 2.4-km run time and positively associated with muscle power ( ß = -12.0 and 90.1), 1,25(OH) 2 D was positively associated with run time and negatively associated with strength and muscle power ( ß = 5.6, -1.06, and -38.4), and 24,25(OH) 2 D was negatively associated with run time ( ß = -8.9; P < 0.01), after controlling for age, sex, smoking, alcohol, physical activity, time outdoors, season, and body mass index. Vitamin D metabolites (25(OH)D, 1,25(OH) 2 D, and 24,25(OH) 2 D) together explained variances of 5.0% in run time, 0.7% in strength, and 0.9% in muscle power (Δ F P < 0.001). All performance measures were superior with low 1,25(OH) 2 D:24,25(OH) 2 D ratio ( P < 0.05). VDR SNPs were not associated with physical performance (Δ FP ≥ 0.306). CONCLUSIONS: Vitamin D metabolites accounted for a small portion of variance in physical performance. Associations between vitamin D metabolites and run time were the most consistent. VDR SNPs explained no variance in performance. Greater conversion of 25(OH)D to 24,25(OH) 2 D, relative to 1,25(OH) 2 D (i.e., low 1,25(OH) 2 D:24,25(OH) 2 D ratio), was favorable for performance, indicating 24,25(OH) 2 D may have a role in optimizing physical performance.

Single bout of exercise triggers the increase of vitamin D blood concentration in adolescent trained boys: a pilot study.

Vitamin D is necessary for musculoskeletal health, however, the supplementation of vitamin D above the sufficiency level does not bring additional bone mass density (BMD), unlike physical exercise which enhances the bone formatting process. Regular physical activity has been shown to upregulate VDR expression in muscles and to increase circulating vitamin D. Here we investigate whether a single bout of exercise might change 25(OH)D3 blood concentration and how it affects metabolic response to exercise. Twenty-six boys, 13.8 years old (SD ± 0.7) soccer players, participated in the study. The participants performed one of two types of exercise: the first group performed the VO2max test until exhaustion, and the second performed three times the repeated 30 s Wingate Anaerobic Test (WAnT). Blood was collected before, 15 min and one hour after the exercise. The concentration of 25(OH)D3, parathyroid hormone (PTH), interleukin-6 (IL-6), lactate, non-esterified fatty acids (NEFA) and glycerol were determined. 25(OH)D3 concentration significantly increased after the exercise in all boys. The most prominent changes in 25(OH)D3, observed after WAnT, were associated with the rise of PTH. The dimensions of response to the exercises observed through the changes in the concentration of 25(OH)D3, PTH, NEFA and glycerol were associated with the significant increases of IL-6 level. A single bout of exercise may increase the serum's 25(OH)D3 concentration in young trained boys. The intensive interval exercise brings a more potent stimulus to vitamin D fluctuations in young organisms. Our results support the hypothesis that muscles may both store and release 25(OH)D3.

Vitamin D Receptor Gene Polymorphisms and Risk of Knee Osteoarthritis: Possible Correlations with TNF-α, Macrophage Migration Inhibitory Factor, and 25-Hydroxycholecalciferol Status.

Osteoarthritis (OA) etiology and pathogenesis not yet fully understood. We studied the role of vitamin D receptor single-nucleotide polymorphisms (VDR-SNPs), vitamin D3, serum and synovial macrophage migration inhibitory factor (MIF), and tumor necrosis factor-α (TNF-α) in the development and progression of knee OA (KOA). This study included 205 Egyptian subjects (105 patients with KOA and 100 unrelated, healthy matched subjects selected as controls). The patient group was divided into three groups according to KOA severity (mild, moderate, and severe), with 35 patients in each group. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for the ApaI and TaqI SNPs. Vitamin D, serum and synovial TNF-α, and MIF assays were performed using ELISA kits. There were significantly lower serum levels of 25-hydroxycholecalciferol with significant increasing TNF-α and MIF levels in relation to disease severity among the cases (all: p˂0.05).Wild homozygous and heterozygous mutant genotypes (GG+GT) and G allele of ApaI demonstrated risk for KOA development, with odds ratio OR = 6.313 (95% confidence interval (CI) 2.074-19.210) and OR = 1.532 (95%CI 1.013-2.317), respectively. Homozygous mutant CC genotype and C allele of TaqI could be considered a risk factor associated with KOA development, with OR = 2.667 (95%CI 1.270-5.601) and OR = 0.737 (95%CI 0.496-1.095), respectively. VDR-SNPs, vitamin D3, TNF-α, and MIF could play an essential role in the pathogenesis and progression of KOA with mechanistic associations.

Association of Serum Parathyroid Hormone Levels With All-Cause and Cause-Specific Mortality Among U.S. Adults.

OBJECTIVE: To examine whether parathyroid hormone (PTH) is associated with mortality among U.S. adults. METHODS: This study included 8286 U.S. adults aged ≥20 years with a measurement of serum intact PTH from the National Health and Nutrition Examination Survey 2003-2006 linked to national mortality data through 2015. Multivariable Cox proportional hazard regression models were employed to estimate the adjusted hazard ratio (aHR) of all-cause and cause-specific (cardiovascular and cancer) mortality according to intact PTH levels (low or low-normal, <38; middle-normal, 38-56; high-normal, 57-74; high, >74 pg/mL). We also stratified the analyses by serum albumin-adjusted calcium and 25-hydroxy vitamin D (25OHD) levels. RESULTS: During a median follow-up of 10.1 years, the mean age was 49 years, and 48% were men. After adjusting for potential confounders, both the high-normal and high PTH groups showed higher risks of all-cause mortality than the low or low-normal PTH group (high-normal PTH, aHR, 1.28; 95% confidence interval [CI], 1.10-1.48; high PTH, aHR, 1.42; 95% CI, 1.19-1.69]. When stratified by calcium and 25OHD levels, the association between high PTH and mortality was also found among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL (aHR, 1.53; 95% CI, 1.17-2.01) and those with 25OHD levels of ≥20 ng/mL (aHR, 1.46, 95% CI, 1.17-1.82). We found no evidence of the increased cause-specific mortality risks in the high PTH group. CONCLUSION: Higher PTH levels were associated with an increased risk of all-cause mortality, particularly among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL or 25OHD levels of ≥20 ng/mL.

Association Between Serum Vitamin D Level and Ménière's Disease.

OBJECTIVES: Ménière's disease (MD) is a well-known inner ear disease; however, the etiopathogenesis is unknown. Several factors may be involved. Meanwhile, vitamin D is reported to have an important role in inner ear physiology. The aim of this study is to evaluate the relation between vitamin D deficiency and MD. STUDY DESIGN: This matched case-control study compared serum vitamin D levels between patients with definite MD and those without it. SETTING: The study was done between August 2018 and December 2019 at Ghaem University Hospital in Mashhad, Iran. METHODS: Twenty-eight patients with definite MD were matched with a group of 84 healthy individuals, regarding age, sex, body mass index, and occupation (indoor vs outdoor). The serum level of vitamin D (25-hydroxyvitamin D3) was measured in both groups. RESULTS: The mean ± SD vitamin D level was 18.9 ± 9.7 ng/mL in the case group and 25.2 ± 13.7 ng/mL in the control group (P = .027). There was a significant difference between the case and control groups according to the results of the conditional logistic regression model (P = .03; adjusted odds ratio, 0.96). In the MD group, 17 (60.7%) patients were vitamin D deficient, 6 (21.4%) insufficient, and only 5 (17.9%) sufficient. CONCLUSIONS: The results of this study show that serum vitamin D level in MD is significantly lower than that of the control group. However, the role of vitamin D supplementation in the management of MD needs further study. LEVEL OF EVIDENCE: 4.

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

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

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

Fat-Soluble Vitamin Supplementation Using Liposomes, Cyclodextrins, or Medium-Chain Triglycerides in Cystic Fibrosis: A Randomized Controlled Trial.

Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of ß-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients (n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).

A revised action spectrum for vitamin D synthesis by suberythemal UV radiation exposure in humans in vivo.

Action spectra are important biological weighting functions for risk/benefit analyses of ultraviolet (UV) radiation (UVR) exposure. One important human benefit of exposure to terrestrial solar UVB radiation (∼295 to 315 nm) is the cutaneous synthesis of vitamin D3 that is initiated by the photoconversion of 7-dehydrocholesterol to previtamin D3 An action spectrum for this process that is followed by other nonphotochemical steps to achieve biologically active vitamin D3 has been established from ex vivo data and is widely used, although its validity has been questioned. We tested this action spectrum in vivo by full- or partial-body suberythemal irradiation of 75 healthy young volunteers with five different polychromatic UVR spectra on five serial occasions. Serum 25-hydroxyvitamin D3 [25(OH)D3] levels, as the most accurate measure of vitamin D3 status, were assessed before, during, and after the exposures. These were then used to generate linear dose-response curves that were different for each UVR spectrum. It was established that the previtamin D3 action spectrum was not valid when related to the serum 25(OH)D3 levels, as weighting the UVR doses with this action spectrum did not result in a common regression line unless it was adjusted by a blue shift, with 5 nm giving the best fit. Such a blue shift is in accord with the published in vitro action spectra for vitamin D3 synthesis. Thus, calculations regarding the risk (typically erythema) versus the benefit of exposure to solar UVR based on the ex vivo previtamin D3 action spectrum require revision.

Correlation between PCT, 25(OH)D, PTX-3, AMS levels and the severity of diabetic ketoacidosis complicated by pancreatitis.

BACKGROUND: This study aims to explore the correlation between procalcitonin (PCT), 25-hydroxyvitamin D3 (25(OH)D), pentraxin-3 (PTX-3), amylase (AMS) levels and severity of diabetic ketoacidosis complicated by pancreatitis. METHODS: A retrospective analysis of 198 patients with diabetic ketoacidosis admitted to our hospital from January 2015 to February 2020 were included. According to whether the patients with pancreatitis, subjects were divided into diabetic ketoacidosis with pancreatitis (DKA-AP) group and diabetic ketoacidosis (DKA) group. Healthy controls admitted to the hospital for physical examinations were included as a control group. Clinical outcomes were collected. RESULTS: On the first day after admission, the levels of PCT, PTX-3, and AMS in DKA-AP group were significantly higher than those in DKA group and control group, and 25(OH)D levels in DKA-AP group were lower than those in DKA group and control group. PCT, PTX-3, and AMS levels were significantly increased, and 25(OH)D levels were decreased in the DKA group compared with the control group. Furthermore, the levels of PCT, 25(OH)D, PTX-3, and AMS in the DKA-AP group were correlated with the disease severity of of diabetic ketoacidosis complicated by pancreatitis. The levels of PCT, PTX-3, and AMS in the DKA-AP group on day 1 were significantly higher and 25(OH)D levels were significantly lower than those on days 3-7 after admission. The levels of PCT, PTX-3, and AMS in the DKA group on day 1 were significantly higher and 25(OH)D levels were significantly lower than those on days 2-7 after admission. The levels of these indicators returned to normal levels on day 3 or day 7 in DKA or DKA-AP group, respectively. PCT, PTX-3, and AMS levels in the DKA-AP group were significantly increased, while 25(OH)D levels in the DKA-AP group were decreased compared with DKA group on days 1-6 after admission. The duration of hospital stay, patients of ICU care, duration of ICU stay, and cost in DKA-AP group were all higher than those in the DKA group. CONCLUSION: Blood levels of PCT, 25(OH)D, PTX-3, and AMS were correlated with diabetic ketoacidosis complicated by pancreatitis, and have certain application value in assessment of the disease severity.

Calcitriol Attenuates HRV-Induced Respiratory Injury through the AMPK-mTOR-ER Stress Signaling Pathway.

Human rhinovirus (HRV) infection is one of the main causes of respiratory injury. Recently, calcitriol has been reported to have protective effect against respiratory infections. In this paper, we aimed to explore the effects and mechanisms of calcitriol on HRV-induced respiratory infection. Participants including pediatric patients diagnosed with HRV-induced respiratory infection (n = 50) and paired healthy controls (n = 40) were recruited at the Weifang People's Hospital between May 2019 and May 2020. The serum 25(OH)D3 level was measured in participants using ELISA kit. The HRV-induced respiratory infection model in human nasal mucosal epithelial cells (hNECs) was adapted, in vitro. HRV infection was measured by real-time PCR analysis of HRV expression. After HRV infection and treatment with calcitriol, the changes of cell viability were detected by MTT assay, the expression of ER stress-induced apoptosis and AMPK-mTOR related proteins by western blot, and the cell apoptosis by flow cytometry assay. In order to confirm whether AMPK-mTOR signal pathway was involved in the ER stress-induced apoptosis of hNECs, cells were pretreated with compound C which was a AMPK inhibitor. The 25-(OH)D3 concentration in serum collected in HRV-infected children was lower than that in controls. In vitro experiments showed that HRV infection decreased cell viability, and this effect was reversed when treated with calcitriol. Additionally, HRV increased levels of apoptosis and ER stress markers (including cleaved-caspase3, Bax, CHOP, nATF6, and BiP), while calcitriol significantly reversed these effects. Furthermore, calcitriol played a protective role by increasing p-AMPK and decreasing p-mTOR level. However, the protective effects of calcitriol could be abolished by compound C. Calcitriol protected HRV-infected hNECs by inhibiting the ER stress-induced apoptosis through the AMPK-mTOR signaling pathway. These protective effects of calcitriol against HRV-induced respiratory infection may provide an experimental basis for the clinical application.

Relationship Between Maternal Bone Biomarkers and Fetal Adiposity Through Normal Pregnancy.

PURPOSE: To examine the association of maternal bone markers [sclerostin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteocalcin, 25-hydroxyvitamin D3] with fetal intra-abdominal and subcutaneous adipose tissue deposition and birthweight during normal pregnancy. METHODS: One hundred pregnant women (aged 30.4 ±â€…5.6 years, mean ±â€…SD) with prepregnancy body mass index = 24.1 ±â€…4.6 kg/m2 were seen prospectively during each trimester. At each visit they were submitted to anthropometric measurements, a fasting blood sampling, a 75-g oral glucose tolerance test, and a fetal ultrasonogram. At birth, neonates had birth weight measurement. RESULTS: In the second trimester, maternal sclerostin concentrations correlated positively with fetal abdominal circumference and birth weight; maternal sRANKL concentrations correlated positively with fetal abdominal subcutaneous fat thickness, sagittal abdominal diameter, and abdominal circumference. Fetuses born to mothers with greater (>254 ng/mL), compared to fetuses born to mothers with lower (≤254ng/mL), sRANKL concentrations had greater abdominal circumference, sagittal diameter, and abdominal subcutaneous fat thickness. Maternal serum sclerostin concentrations were the best positive predictors of birth weight. In the third trimester maternal sclerostin concentrations correlated positively with fetal sagittal abdominal diameter; maternal sRANKL concentrations positively correlated with fetal abdominal circumference and fetal abdominal sagittal diameter. CONCLUSIONS: Maternal bone markers sclerostin and sRANKL may relate to fetal intra-abdominal adipose tissue deposition through as yet unknown direct or indirect mechanisms, thus contributing to birthweight.

Evaluation of Serum 25-Hydroxyvitamin D3 and Bone Mineral Density in 268 Patients with Hip Fractures.

OBJECTIVE: The aim of the present study was to evaluate the relationship among vitamin D nutritional status, bone mineral density, and other factors in elderly patients with brittle hip fractures. METHODS: The present study was a retrospective analysis of 268 patients, 102 men (38.06%) and 166 women (61.94%), with brittle hip fractures admitted to the Hip Joint Center of Tianjin Hospital from February 2016 to June 2018. The median age of the patients was 74 years (range, 50-93 years). The patients were divided into three groups based on age: ≤69 years, 70-79 years, and ≥80 years. Serum 25-hydroxyvitamin D3 (25(OH) D3 ), parathyroid hormone (PTH), body mass index (BMI), and bone mineral density (BMD) of the lumbar spine, femoral neck, and hip were measured and statistically analyzed. RESULTS: The median serum 25(OH)D3 level of patients was 9.90 (range, 2.60-42.70) ng/mL; the proportion of deficiency was 89.18% and the deficiency was severe in 136 cases (49.25%). The proportion of vitamin D deficiency was significantly lower in men than in women (P = 0.013). With the increase of age, 25(OH)D3 levels gradually decreased (P = 0.044) and PTH levels gradually increased (P < 0.001). There was significantly negative correlation (P < 0.001) between the levels of serum 25(OH)D3 and PTH. There were 200 cases (74.63%) in which T-values of BMD were less than -2.5 in any part of the lumbar vertebrae, femoral neck, and hip. T-values in 74 cases (27.61%) were less than -2.5 in all three parts. The T-values of BMD in men were significantly higher than those in men (P < 0.001). With the increase of age, the femoral neck BMD in men gradually decreased (P = 0.016), and the femoral neck and hip BMD in female gradually decreased (P-value was 0.001 and 0.003, respectively). Multivariate analysis suggested that gender and BMI were independent risk factors for BMD, and vitamin D deficiency affected BMD. CONCLUSION: Vitamin D deficiency is common in patients with brittle hip fractures, especially in women. With the increase of age, vitamin D continues to decrease and PTH increases. The decrease of BMD in patients with hip fractures is the result of a combination of age, gender, BMI, and vitamin D content.

Latent toxoplasmosis and vitamin D concentration in humans: three observational studies.

Numerous recent studies show that vitamin D deficiency potentiates various chronic physical and psychiatric disorders and diseases. It has been shown that a similar range of disorders is also associated with latent infection with Toxoplasma gondii (Nicolle et Manceaux, 1908). For instance, among cancer, diabetes and schizophrenia patients, we find a higher prevalence of both toxoplasmosis and vitamin D deficiency. Theoretically, therefore, vitamin D deficiency could be the missing link between toxoplasmosis and these disorders. We tested this hypothesis by searching for decreased vitamin D levels in the serum of subjects infected with T. gondii (furthermore called Toxoplasma-infected subjects) in two cross-sectional and one case-control study. Results of the first cross-sectional study (N = 72) suggest that Toxoplasma-infected neurasthenic patients have non-significantly lower levels of calcidiol than Toxoplasma-free patients (study A: P = 0.26 in women, P = 0.68 in men). However, two other studies (study B: N = 400; study C: N = 191) showed a non-significantly higher concentration of vitamin D in Toxoplasma-infected subjects than in Toxoplasma-free subjects both in men (study B: P = 0.70, study C: P = 0.55) and in women (study B: P = 0.64, study C: P = 0.12). Taken together, our preliminary results thus do not support the hypothesis that toxoplasmosis could be associated with vitamin D decrease.

Anti-Thymocyte Globulin Treatment Augments 1,25-Dihydroxyvitamin D3 Serum Levels in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Application of anti-thymocyte globulin (ATG) is a widely used strategy for the prevention of graft-versus-host disease (GvHD). As vitamin D3 serum levels are also discussed to affect hematopoietic stem cell transplantation (HSCT) outcome and GvHD development, we analysed a possible interplay between ATG treatment and serum levels of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 in 4 HSCT cohorts with different vitamin D3 supplementation. ATG is significantly associated with higher serum level of 1,25-dihydroxyvitamin D3 around HSCT (day -2 to 7, peri-transplant), however only in patients with adequate levels of its precursor 25-hydroxyvitamin D3. ATG exposure had no impact on overall survival in patients supplemented with high dose vitamin D3, but was associated with higher risk of one-year treatment-related mortality (log rank test p=0.041) in patients with no/low vitamin D3 supplementation. However, the difference failed to reach significance applying a Cox-model regression without and with adjustment for baseline risk factors (unadjusted P=0,058, adjusted p=0,139). To shed some light on underlying mechanisms, we investigated the impact of ATG on 1,25-Dihydroxyvitamin D3 production by human dendritic cells (DCs) in vitro. ATG increased gene expression of CYP27B1, the enzyme responsible for the conversion of 25-hydroxyvitamin D3 into 1,25-dihydroxyvitamin D3, which was accompanied by higher 1,25-dihydroxyvitamin D3 levels in ATG-treated DC culture supernatants. Our data demonstrate a cooperative effect of 25-hydroxyvitamin D3 and ATG in the regulation of 1,25-dihydroxyvitamin D3 production. This finding may be of importance in the context of HSCT, where early high levels of 1,25-dihydroxyvitamin D3 levels have been shown to be predictive for lower transplant related mortality and suggest that vitamin D3 supplementation may especially be important in patients receiving ATG for GvHD prophylaxis.