Serum Vitamin D Level in Overweight Individuals and Its Correlation With the Incidence of Non-alcoholic Fatty Liver Disease.

In this study, we investigated the serum vitamin D level in overweight individuals and its correlation with the incidence of nonalcoholic fatty liver disease (NAFLD). Between May 2020 and May 2021, the Department of Gastroenterology at the People's Hospital of Henan University of Traditional Chinese Medicine treated a total of 321 outpatients and inpatients with NAFLD, who were included in the NAFLD group, while 245 healthy age- and gender-matched individuals were included in the control group. All the data were collected for the relevant indices, including fasting plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine transaminase, and 25-hydroxy vitamin D (25[OH]D. The patients with NAFLD were divided into the normal BMI group, the overweight group, and the obese group, according to the body mass index, and the 25(OH)D levels were compared between the different groups. Spearman's correlation analysis was performed to analyze the correlation between the serum 25(OH)D level and NAFLD. Regarding the serum 25 (OH)D level, it was lower in the NAFLD group than in the control group ([18.36 + 1.41] µg/L vs [22.33 + 2.59] µg/L, t = ?5.15, P<0.001), and was lower in the overweight group than in the normal group ([18.09 ± 5.81] µg/L vs [20.60 ± 4.16] µg/L, t = 0.26, P = 0.041). The serum 25(OH)D level was thus negatively correlated with the incidence of NAFLD in overweight individuals (r = 0.625, P<0.05). In conclusion, the level of 25(OH)D decreased in patients with NAFLD with increasing BMI (normal, overweight, obese). Keywords: Nonalcoholic fatty liver disease, Vitamin D.

Association of 1,25 dihydroxyvitamin D with left ventricular hypertrophy and left ventricular diastolic dysfunction in patients with chronic kidney disease.

Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are highly prevalent predictors of cardiovascular disease in individuals with chronic kidney disease (CKD). Vitamin D, particularly 25-hydroxyvitamin D [25(OH)D], deficiency has been reported to be associated with cardiac structure and function in CKD patients. In the current study, we investigated the association between 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of 25(OH)D, and LVH/LVDD in CKD patients. We enrolled 513 non-dialysis CKD patients. The presence of LVH and LVDD was determined using transthoracic echocardiography. In multivariable analysis, serum 1,25(OH)2D levels, but not serum 25(OH)D, were independently associated with LVH [odds ratio (OR): 0.90, 95% confidential interval (CI): 0.88-0.93, P < 0.001]. Additionally, age, systolic blood pressure, and intact parathyroid hormone levels were independently associated with LVH. Similarly, multivariable analysis demonstrated that serum 1,25(OH)2D levels, but not 25(OH)D levels, were independently associated with LVDD (OR: 0.88, 95% CI: 0.86-0.91, P < 0.001) with systolic blood pressure showing independent association with LVDD. The optimal cut-off values for serum 1,25(OH)2D levels for identifying LVH and LVDD were determined as ≤ 12.7 pg/dl and ≤ 18.1 pg/dl, respectively. Our findings suggest that serum 1,25(OH)2D levels have independent association with LVH and LVDD in CKD patients, underscoring their potential as biomarkers for these conditions in this patient population.

A 3'-pre-tRNA-derived small RNA tRF-1-Ser regulated by 25(OH)D promotes proliferation and stemness by inhibiting the function of MBNL1 in breast cancer.

BACKGROUND: We explored the potential novel anticancer mechanisms of 25-hydroxyvitamin D (25(OH)D), a vitamin D metabolite with antitumour effects in breast cancer. It is stable in serum and is used to assess vitamin D levels in clinical practice. Transfer RNA-derived small RNAs are small noncoding RNAs that generate various distinct biological functions, but more research is needed on their role in breast cancer. METHODS: Small RNA microarrays were used to explore the novel regulatory mechanism of 25(OH)D. High-throughput RNA-sequencing technology was used to detect transcriptome changes after 25(OH)D treatment and tRF-1-Ser knockdown. RNA pull-down and high-performance liquid chromatography-mass spectrometry/mass spectrometry were used to explore the proteins bound to tRF-1-Ser. In vitro and in vivo functional experiments were conducted to assess the influence of 25(OH)D and tRF-1-Ser on breast cancer. Semi-quantitative PCR was performed to detect alternative splicing events. Western blot assay and qPCR were used to assess protein and mRNA expression. RESULTS: The expression of tRF-1-Ser is negatively regulated by 25(OH)D. In our breast cancer (BRCA) clinical samples, we found that the expression of tRF-1-Ser was higher in cancer tissues than in paired normal tissues, and was significantly associated with tumour invasion. Moreover, tRF-1-Ser inhibits the function of MBNL1 by hindering its nuclear translocation. Functional experiments and transcriptome data revealed that the downregulation of tRF-1-Ser plays a vital role in the anticancer effect of 25(OH)D. CONCLUSIONS: In brief, our research revealed a novel anticancer mechanism of 25(OH)D, unveiled the vital function of tRF-1-Ser in BRCA progression, and suggested that tRF-1-Ser could emerge as a new therapeutic target for BRCA.

Identification of vitamin D-related signature for predicting the clinical outcome and immunotherapy response in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers globally, seriously endangering people health. Vitamin D was significantly associated with tumor progression and patients' prognosis. Integrative 10 machine learning algorithms were used to develop a Vitamin D-related signature (VRS) with one training cohort and 3 testing cohorts. The performance of VRS in predicting the immunology response was verified using several predicting approaches. The optimal VRS was constructed by stepCox + superPC algorithm. VRS acted as a risk factor for HCC patients. HCC patients with high-risk score had a poor clinical outcome and the AUCs of 1-, 3-, and 5-year ROC were 0.786, 0.755, and 0.786, respectively. A higher level of CD8 + cytotoxic T cells and B cells was obtained in HCC patients with low-risk score. There is higher PD1&CTLA4 immunophenoscore and TMB score in low-risk score in HCC patients. Lower TIDE score and tumor escape score was found in HCC cases with low-risk score. The IC50 value of camptothecin, docetaxel, crizotinib, dasatinib, and erlotinib was lower in HCC cases with high-risk score. HCC patients with high-risk score had a higher score of cancer-related hallmarks, including angiogenesis, glycolysis, and NOTCH signaling. Our study proposed a novel VRS for HCC, which served as an indicator for predicting clinical outcome and immunotherapy responses in HCC.

Vitamin Nutritional Status in Patients with Pancreatic Cancer: A Narrative Review.

Due to the high mortality rate in Western countries, pancreatic cancer is considered one of the big killers, leaving patients and their families with little hope upon diagnosis. Although surgical and drug therapies are critical for cancer patients to improve life expectancy and alleviation of suffering, nutrition plays a key role in improving cancer treatment outcomes. This narrative review, conducted as part of the activities of the Italian Society of Human Nutrition (SINU) working group in oncology, focuses on the prevalence of vitamin malnutrition among pancreatic cancer patients. The results of the literature search show that pancreatic cancer patients are at a heightened risk of water-soluble vitamin deficiencies, particularly of vitamins B1, B3, and B6. Additionally, they also face an increased risk of deficiency of fat-soluble vitamins. Among these vitamins, the potential role of vitamin D in pancreatic cancer has garnered the most attention, with its plasma levels being identified as a significant factor in patient survival. Investigating vitamin nutritional status could provide valuable insights for incorporating nutritional approaches into the prevention and treatment of pancreatic cancer, thereby reducing the exacerbation of symptoms associated with the diagnosis.

Is There an Association Between Inflammation and Serum-Vitamin D? - Results of a Retrospective Analysis of Hospitalized Geriatric Patients.

Purpose: Vitamin D deficiency is a common finding in geriatric patients. The ESPEN micronutrient guideline states that vitamin D serum levels significantly decrease in the presence of inflammation and should be interpreted with caution. This is of great interest for hospital care and would imply a significant change to the current approach to hospitalized patients with suspected vitamin D deficiency. Patients and methods: To evaluate the association of vitamin D and inflammation, we reanalyzed the data set of serum 25(OH)D-Levels of 687 consecutive geriatric hospitalized patients of a previously published study. Results: We found that vitamin D deficiency (<20 ng/dl) was prevalent in 78.0% and vitamin D insufficiency (20-30 ng/dl) in 9.9% of patients. Sperman's correlation showed a significant but very weak correlation (R = -0.100, P < 0.01) of serum vitamin D and C-reactive protein. However, linear regression with the inclusion of age and gender revealed no significant association (beta-coefficient -0.070; p=0.067). Conclusion: In this study, we could not confirm a significant and clinically relevant association between serum vitamin D levels and inflammation, contrasting with a previous study. However, longitudinal studies need to be performed to draw a final conclusion.

Monitoring the utilization and effectiveness of Iron and Vitamin D supplementations program and its predictive factors in high schools' girls in Qom, Iran.

Background: Iron and Vitamin D3 deficiency is one of the major global health problems in teenagers and adolescent population. This study was aimed to monitor the utilization and predictive factors of Iron and Vitamin D Supplementations Program (IVDSP) in high schools' girls. Methods: In a cross sectional study, the pattern of Iron and D3 consumption based on IVDSP on 400 high schools' girl in Qom, Iran assesses. Data collection was used by a reliable and standard researcher based questionnaire and daily, weekly, monthly and seasonally consumption of complementary minerals in schools were gathered. Data analysis conducted using SPSS version 20 (SPSS Inc., Chicago, IL, USA) by chi square, independent t-test and multivariate logistic regression. Results: The mean age of subjects was 15.14 ± 1.52 years and ranged from 12 to 18 years old. The total weekly prevalence of D3 and Iron consumption in high schools' girls was calculated 36.73% and the weekly prevalence of Iron and monthly prevalence of Vitamin D3 consumption was 33.75% and 40.5%, respectively. The most common causes of non-consumption were bad taste 49.31%, Iranian made drug 20.27%, drug sensitivity 19.82% and drug interaction 10.60%, respectively. Conclusions: The inadequate and incomplete rate of IVDSP in Qom was high and more than 60% of distributed supplementations have been wasted. Results showed that students who were participated in educational orientation classes were more successful and eager in Iron and Vitamin D3 consumption. Therefore, more educational explanatory interventions for both students and her parents recommended to increase the efficiency of the program.

Vitamin D and reproductive disorders: a comprehensive review with a focus on endometriosis.

Vitamin D is a fat-soluble steroid hormone that was initially known only for regulating calcium and phosphorus levels and maintaining bone health. However, it was later discovered that many organs express vitamin D metabolizing enzymes and have a ligand for vitamin D, which regulates the expression of an extensive assortment of genes. As a result, vitamin D is indispensable for the proper function of organs, and its deficiency is believed to be a critical factor in symptoms and disorders such as cardiovascular diseases, autoimmune diseases, and cancers. The significance of vitamin D in reproductive tissues was recognized later, and studies have revealed its crucial role in male and female fertility, as well as proper reproductive function during pregnancy. Vitamin D deficiency has been identified as a risk factor for infertility, gonadal cancers, pregnancy complications, polycystic ovary syndrome, and endometriosis. However, data investigating the association between vitamin D levels and reproductive disorders, including endometriosis, have encountered inconsistencies. Therefore, the present study aims to review existing research on the effect of vitamin D on proper reproductive function, and the role of deficiency in reproductive diseases and specifically focuses on endometriosis.

Effects of Vitamin D Supplementation on Central Hemodynamic Parameters and Autonomic Nervous System in Obese or Overweight Individuals. / Efeitos da Suplementação de Vitamina D sobre Parâmetros Hemodinâmicos Centrais e Sistema Nervoso Autônomo em Indivíduos com Obesidade ou Sobrepeso.

BACKGROUND: Previous studies have been inconsistent in demonstrating beneficial cardiovascular effects of vitamin D supplementation. OBJECTIVE: To evaluate the effects of vitamin D3 supplementation on central hemodynamic parameters and autonomic activity in obese/overweight individuals with low vitamin D levels (<30ng/dl). METHODS: Adults 40-65 years old with body mass index ≥25<40 kg/m2 were enrolled in this prospective, randomized, double-blind clinical trial (NCT05689632). Central hemodynamics was assessed using the oscillometric method (Mobil-O-Graph®), and heart rate variability using a Polar heart rate monitor (Kubios® software). Patients (n=53) received a placebo in the control group (CO, n=25) or vitamin D3 (VD, n=28) 7000 IU/day, and were evaluated before (W0) and after 8 weeks (W8) with a significance level of 0.05. RESULTS: The groups were homogeneous regarding age (51±6 vs 52±6 years, p=0.509) and vitamin D levels (22.8±4.9 vs 21.7±4.5ng/ml, p=0.590). At W8, the VD group had significantly higher levels of vitamin D (22.5 vs 35.6ng/ml, p<0.001). Only the VD group showed a significant reduction in systolic blood pressure (SBP; 123±15 vs 119±14mmHg, p=0.019) and alkaline phosphatase (213±55 vs 202±55mg/dl, p=0.012). The CO group showed an increase in augmentation pressure (AP: 9 vs 12 mmHg, p=0.028) and augmentation index (AIx: 26 vs 35%, p=0.020), which was not observed in the VD group (AP: 8 vs 8 mmHg, AIx: 26 vs 25%, p>0.05). VD group showed an increase in the parasympathetic nervous system index (PNSi) (-0.64±0.94 vs -0.16±1.10, p=0.028) and the R-R interval (866±138 vs 924±161 ms, p= 0.026). CONCLUSION: In this sample, eight weeks of daily vitamin D supplementation resulted in an improvement in blood pressure levels and autonomic balance.

FUNDAMENTO: Estudos prévios têm sido inconsistentes em demonstrar efeitos cardiovasculares benéficos da suplementação de vitamina D. OBJETIVO: Avaliar efeitos da suplementação de vitamina D3 sobre parâmetros hemodinâmicos centrais e atividade autonômica em indivíduos obesos/sobrepeso e baixos níveis de vitamina D (<30ng/dl). MÉTODOS: Ensaio clínico prospectivo, randomizado, duplo-cego (NCT05689632), adultos 40-65 anos com índice de massa corporal ≥25<40 kg/m2. Hemodinâmica central avaliada por método oscilométrico (Mobil-O-Graph®), variabilidade da frequência cardíaca utilizando frequencímetro Polar (software Kubios®). Os pacientes (n=53) receberam placebo no grupo controle (CO, n=25) ou vitamina D3 (VD, n=28) 7000 UI/dia, avaliados antes (S0) e após 8 semanas (S8) com nível de significância de 0,05. RESULTADOS: Os grupos foram homogêneos na idade (51±6 vs. 52±6 anos, p=0,509) e níveis de vitamina D (22,8±4,9 vs. 21,7±4,5ng/ml, p=0,590). Na S8, o grupo VD apresentou níveis significativamente maiores de vitamina D (22,5 vs. 35,6ng/ml, p<0,001). Apenas o grupo VD mostrou redução significativa da pressão arterial sistólica (PAS; 123±15 vs. 119±14mmHg, p=0,019) e fosfatase alcalina (213±55 vs. 202±55mg/dl, p=0,012). O grupo CO mostrou elevação da pressão de aumento (AP: 9 vs. 12mmHg, p=0,028) e do índice de incremento (Aix: 26 vs. 35%, p=0,020), o que não foi observado no grupo VD (AP: 8 vs. 8mmHg, Aix: 26 vs. 25%, p>0,05). Grupo VD apresentou aumento no índice do sistema nervoso (iSN) parassimpático (-0,64±0,94 vs. -0,16±1,10, p=0,028) e no intervalo R-R (866±138 vs. 924±161ms, p=0,026). CONCLUSÃO: Nesta amostra, a suplementação diária de vitamina D durante oito semanas resultou em melhora dos níveis pressóricos, parâmetros hemodinâmicos centrais e do equilíbrio autonômico.

Osteoporosis management in Australian aged care facilities: a mixed method study.

Osteoporosis is a common but sub-optimally managed disease amongst aged care residents. Pharmacists undertaking comprehensive medication reviews is one strategy to improve osteoporosis management. Analysis of pharmacist medication review recommendations has identified common clinical practice issues that can be addressed to optimise osteoporosis management for aged care residents. PURPOSE: This study investigates the prevalence of osteoporosis medicine use amongst Australian aged care residents and explores drug-related problems (DRPs) identified during medication reviews and pharmacist recommendations to resolve them. METHODS: Resident demographics, medications, diagnoses, osteoporosis related DRPs, and recommendations to resolve them were extracted from medication review reports. A mixed methods approach was taken to analysis, involving descriptive statistical analysis and content analysis. RESULTS: Medication review reports relating to 980 residents were collected. Antiresorptive therapies were used by 21.7% of residents, of which 87.2% were prescribed denosumab. Osteoporosis related DRPs represented 14.0% of all DRPs identified by pharmacists. Vitamin D was involved in 55.4% of these DRPs, the remainder concerned antiresorptive therapies (23.4%), medications contributing to osteoporosis (16.3%), and calcium (4.9%). Frequent deviations in practice from aged care clinical guidelines and consensus recommendations concerning vitamin D and calcium were found. DRPs and accompanying recommendations relating to denosumab revealed inadequate monitoring and inadvertent therapy disruptions. CONCLUSION: Pharmacist identified DRPs and recommendations revealed common aspects of clinical practice that can be addressed to improve osteoporosis management for aged care residents. A need to raise awareness of aged care-specific consensus recommendations concerning vitamin D and calcium is evident. Facility protocols and procedures must be developed and implemented to ensure safe and effective use of denosumab.

Association between urinary arsenic species and vitamin D deficiency: a cross-sectional study in Chinese pregnant women.

Background: An increasing number of studies suggest that environmental pollution may increase the risk of vitamin D deficiency (VDD). However, less is known about arsenic (As) exposure and VDD, particularly in Chinese pregnant women. Objectives: This study examines the correlations of different urinary As species with serum 25 (OH) D and VDD prevalence. Methods: We measured urinary arsenite (As3+), arsenate (As5+), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) levels and serum 25(OH)D2, 25(OH)D3, 25(OH) D levels in 391 pregnant women in Tianjin, China. The diagnosis of VDD was based on 25(OH) D serum levels. Linear relationship, Logistic regression, and Bayesian kernel machine regression (BKMR) were used to examine the associations between urinary As species and VDD. Results: Of the 391 pregnant women, 60 received a diagnosis of VDD. Baseline information showed significant differences in As3+, DMA, and tAs distribution between pregnant women with and without VDD. Logistic regression showed that As3+ was significantly and positively correlated with VDD (OR: 4.65, 95% CI: 1.79, 13.32). Meanwhile, there was a marginally significant positive correlation between tAs and VDD (OR: 4.27, 95% CI: 1.01, 19.59). BKMR revealed positive correlations between As3+, MMA and VDD. However, negative correlations were found between As5+, DMA and VDD. Conclusion: According to our study, there were positive correlations between iAs, especially As3+, MMA and VDD, but negative correlations between other As species and VDD. Further studies are needed to determine the mechanisms that exist between different As species and VDD.

The role of vitamin D in pediatric systemic lupus erythematosus - a double pawn in the immune and microbial balance.

Having increased popularity during the Covid-19 pandemic, vitamin D3 is currently impressing thanks to the numerous researches aimed at its interactions with the body's homeostasis. At the same time, there is a peak in terms of recommendations for supplementation with it. Some of the studies focus on the link between autoimmune diseases and nutritional deficiencies, especially vitamin D3. Since the specialized literature aimed at children (patients between 0-18 years old) is far from equal to the informational diversity of the adult-centered branch, this review aims to bring up to date the relationship between the microbial and nutritional balance and the activity of pediatric systemic lupus erythematosus (pSLE). The desired practical purpose resides in a better understanding and an adequate, individualized management of the affected persons to reduce morbidity. The center of the summary is to establish the impact of hypovitaminosis D in the development and evolution of pediatric lupus erythematosus. We will address aspects related to the two entities of the impact played by vitamin D3 in the pathophysiological cascade of lupus, but also the risk of toxicity and its effects when the deficiency is over supplemented (hypervitaminosis D). We will debate the relationship of hypovitaminosis D with the modulation of immune function, the potentiation of inflammatory processes, the increase of oxidative stress, the perfusion of cognitive brain areas, the seasonal incidence of SLE and its severity. Finally, we review current knowledge, post-pandemic, regarding the hypovitaminosis D - pSLE relationship.

Interaction between MARK3 (rs11623869), PLCB4 (rs6086746) and GEMIN2 (rs2277458) variants with bone mineral density and serum 25-hidroxivitamin D levels in Mexican Mestizo women.

Introduction: Understanding the genetic factors contributing to variations in bone mineral density (BMD) and vitamin D could provide valuable insights into the pathogenesis of osteoporosis. This study aimed to evaluate the association of single nucleotide variants in MARK3 (rs11623869), PLCB4 (rs6086746), and GEMIN2 (rs2277458) with BMD in Mexican women. Methods: The gene-gene interaction was evaluated in these variants in serum 25(OH)D levels and BMD. A genetic risk score (GRS) was created on the basis of the three genetic variants. Genotyping was performed using predesigned TaqMan assays. Results: A significant association was found between the rs6086746-A variant and BMD at the total hip, femoral neck, and lumbar spine, in women aged 45 years or older. However, no association was observed between the variants rs11623869 and rs2277458. The rs11623869 × rs2277458 interaction was associated with total hip (p=0.002) and femoral neck BMD (p=0.013). Similarly, for vitamin D levels, we observed an interaction between the variants rs6086746 × rs2277458 (p=0.021). GRS revealed a significant association with total hip BMD (p trend=0.003) and femoral neck BMD (p trend=0.006), as well as increased vitamin D levels (p trend=0.0003). These findings provide evidence of the individual and joint effect of the MARK3, PLCB4, and GEMIN2 variants on BMD and serum vitamin D levels in Mexican women. Discussion: This knowledge could help to elucidate the interaction mechanism between BMD-related genetic variants and 25OHD, contributing to the determination of the pathogenesis of osteoporosis and its potential implications during early interventions.

ED-71 Improves Bone Mass in Ovariectomized Rats by Inhibiting Osteoclastogenesis Through EphrinB2-EphB4-RANKL/OPG Axis.

Purpose: Estrogen deficiency is the main reason of postmenopausal osteoporosis. Eldecalcitol (ED-71) is a new active vitamin D analogue clinically used in the treatment of postmenopausal osteoporosis. We aimed to investigate whether EphrinB2-EphB4 and RANKL/RANK/OPG signaling cooperate in mediating the process of osteoporosis by ED-71. Methods: In vivo, the ovariectomized (OVX) rats were administered orally with 30 ng/kg ED-71 once a day for 8 weeks. HE staining, Masson staining and Immunofluorescence staining were used to evaluate bone mass, bone formation, osteoclastogenesis associated factors and the expression of EphrinB2, EphB4, RANKL and OPG. In vitro, H2O2 stimulation was used to simulate the cell environment in osteoporosis. Immunofluorescence, quantitative real time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western Blot were applied to detect the expression of EphrinB2, EphB4, RANKL and OPG. In osteoblasts, EphB4 was knocked down by EphB4 small-interfering RNA (siRNA) transfection. LY294002 (PI3K inhibitor) or ARQ092 (AKT inhibitor) was used to block PI3K/AKT pathway. An indirect co-culture system of osteoblasts and osteoclasts was established. The mRNA and protein expression of osteoclastogenes is associated factors were tested by qRT-PCR and Western Blot. Results: ED-71 increased bone mass and decreased the number of osteoclasts in OVX rats. Moreover, ED-71 promoted the expression of EphrinB2, EphB4, and decreased the RANKL/OPG ratio in osteoblasts. Osteoclastogenesis was restrained when osteoclasts were indirectly co-cultured with ED-71-treated osteoblasts. After silencing of EphB4 expression in osteoblasts, ED-71 inhibited the expression of P-PI3K and P-AKT and increased the ratio of RANKL/OPG. This reversed the inhibitory effect of ED-71 on osteoclastogenes. Therefore, in ED-71-inhibited osteoclastogenes, EphB4 is a key factor affecting the secretion of RANKL and OPG by osteoblasts. EphB4 suppressed the RANKL/OPG ratio through activating PI3K/AKT signaling in osteoblasts. Conclusion: ED-71 inhibits osteoclastogenesis through EphrinB2-EphB4-RANKL/OPG axis, improving bone mass in ovariectomized rats. PI3K/AKT pathway is involved this process.

Causal association between low vitamin D and polycystic ovary syndrome: a bidirectional mendelian randomization study.

BACKGROUND: Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain. OBJECTIVE: We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms. METHODS: We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms. RESULTS: TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process. CONCLUSION: Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.

Vitamin D effects on Chlamydia trachomatis infection: a case-control and experimental study.

Introduction: Vitamin D deficiency is the most common nutritional deficiency worldwide. Chronic vitamin D deficiency causes immune system dysfunction, which increases susceptibility to pathogens such as bacteria, especially intracellular parasites, and viruses. Chlamydia trachomatis (C. t) is an obligate intracellular parasitic bacterium that causes a variety of sequelae. We speculated that vitamin D might be associated with C. t infection. This study aimed to address this gap in knowledge by investigating the relationship between vitamin D and C. t infection using both in vitro and in vivo models. Methods and results: The addition of calcitriol to McCoy cell culture in vitro delayed and reduced the quantity and volume of inclusions compared to the control group. Macrophages of peritoneally lavaged mice co-cultured with McCoy decreased the infection rate and delayed the appearance of inclusions. In mice models of vitamin D deficiency, mice in the VD-group exhibited more severe genital tract inflammation and a longer duration of infection after inoculation with C. t in the genital tract. Supplementing these mice with vitamin D3 during treatment enhanced the therapeutic effect of antibiotics. We also conducted a case-control study involving 174 C. t-positive patients (95 males and 79 females) and 380 healthy volunteers (211 males and 169 females) aged 20-49 from January 2016 to March 15, 2017. Serum 25-(OH)D concentration was measured by assessing morning fasting blood samples of healthy volunteers and C. t-positive patients 1 day before antibiotic treatment and the next day after one course of treatment. The patients were followed up for 1 month and evaluated for recovery. The results showed that vitamin D deficiency was a risk factor for C. t infection and treatment failure. Conclusion: In summary, findings from experimental and clinical studies indicate a close association between vitamin D levels and C. t infection and treatment outcomes. Given the affordability and safety of vitamin D, both healthy individuals and patients should focus on vitamin D intake. Vitamin D supplementation could enhance treatment success and should be used as an adjunctive therapy alongside antibiotic therapy for C. t infections, pending confirmation in larger, prospective, randomized controlled trials.

Effect of vitamin D, calcium, or combined supplementation on fall prevention: a systematic review and updated network meta-analysis.

BACKGROUND: The association between vitamin D supplementation and the risk of falls in older adults has been controversial. This systematic review and network meta-analysis aims to assess the efficacy of vitamin D, calcium, and combined supplementation in the prevention of falls. METHODS: Randomized controlled trials (RCTs) on the efficacy of vitamin D in fall prevention were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 9, 2023. The network meta-analysis was performed using a random effects model in R4.1.3 and Stata15.0. Heterogeneity was evaluated by the I2 statistic, and publication bias was assessed using funnel plots, Begg's test, and Egger's tests. Data were pooled and expressed as relative risk (RR) and 95% confidence interval (CI). RESULTS: A total of 35 RCTs involving 58,937 participants were included in this study, among which 11 RCTs (31.4%) applied calcium combined with vitamin D. There was low heterogeneity (I2 = 11%) among the included studies. Vitamin D supplementation at 800-1000 International Unit (IU)/d resulted in a lower risk of falls than placebo or no treatment (RR = 0.85, 95%CI: 0.74-0.95). In addition, 800-1000 IU/d of vitamin D with or without calcium were more effective in preventing falls than calcium alone. High-dose vitamin D (> 1000 IU/day) increased the risk of falls compared with 800-1000 IU/d of vitamin D. According to the subgroup analysis, daily administration of 800-1000 IU/d vitamin D was associated with a 22% reduction in the risk of falls (RR = 0.78, 95%CI:0.64-0.92), whereas intermittent vitamin D administration had no preventive effect. Furthermore, 800-1000 IU/d of vitamin D also significantly decreased the risk of falls in old adults with ≤ 50 nmol/L 25-hydroxyvitamin D [25(OH)D] (RR = 0.69, 95%CI:0.52-0.86) but not in individuals with > 50 nmol/L 25(OH)D. CONCLUSION: Vitamin D supplementation at 800-1000 IU/d is associated with a lower risk of falls among older adults. 800-1000IU/d of vitamin D has a benefit on prevention of falls in population received daily dose regimens and in population with vitamin D deficiency.

Diagnosis, treatment, and management of rickets: a position statement from the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology.

Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.

Vitamin D Inadequacy and Its Relation to Body Fat and Muscle Mass in Adult Women of Childbearing Age.

To assess the correlation between vitamin D status and body composition variables in adult women of childbearing age, a cross-sectional study was conducted involving women aged 20-49 years. The participants were categorized based on their vitamin D status and further divided according to body mass index (BMI). Anthropometric and biochemical data were collected to compute body composition indices, specifically body fat and muscle mass. The sample included 124 women, with 63.70% exhibiting vitamin D inadequacy. Women with inadequate vitamin D status demonstrated a higher waist-to-height ratio (WHtR) and body adiposity index (BAI), along with a lower BMI-adjusted muscle mass index (SMI BMI), compared to those with adequate levels of vitamin D (p = 0.021; p = 0.019; and p = 0.039, respectively). A positive correlation was observed between circulating concentrations of 25(OH)D and SMI BMI, while a negative correlation existed between circulating concentrations of 25(OH)D and waist circumference (WC), WHtR, conicity index (CI), fat mass index (FMI), body fat percentage (% BF), and fat-to-muscle ratio (FMR). These findings suggest that inadequate vitamin D status may impact muscle tissue and contribute to higher body adiposity, including visceral adiposity. It is recommended that these variables be incorporated into clinical practice, with a particular emphasis on WHtR and SMI BMI, to mitigate potential metabolic consequences associated with vitamin D inadequacy.