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Metabolic dysfunction-associated steatotic liver disease (MASLD)—and its worse form, metabolic-associated steatohepatitis (MASH), characterised by inflammation and liver damage—corresponds to the liver's involvement in metabolic syndrome, which constitutes an economic burden for healthcare systems. However, the biomolecular pathways that contribute to steatotic liver disease are not completely clear. Abnormalities of bone metabolism are frequent in people affected by metabolic liver disease, with reduced bone density and an increased risk of fracture. Receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin(OPG) are critical regulators of bone metabolism, performing pleiotropic effects, and may have potential involvement in metabolic disorders like MASLD, resulting in a topic of great interest and intrigue. This narrative review aims to investigate this potential role and its implications in MASLD development and progression and in hepatocellular carcinoma, which represents its worst complication. [ABSTRACT FROM AUTHOR]

This study explores the association of vitamin D-binding protein (VDBP) gene polymorphisms, vitamin D levels, and the severity of COVID-19, including the need for intensive care unit (ICU) hospitalization. We analyzed a cohort of 56 consecutive age- and gender-matched adult COVID-19-positive patients and categorized them into three groups: outpatients with mild illness, inpatients with moderate disease, and ICU patients. We measured levels of free, total, and bioavailable 25-hydroxyvitamin D [25(OH)D], VDBP, and albumin. VDBP polymorphisms rs5488 and rs7041 were identified using real-time PCR. A significant proportion of ICU patients were vitamin D-deficient (56.25%) compared to outpatients (10%) and inpatients (5%) (p = 0.0003). ICU patients also had notably lower levels of VDBP (median: 222 mg/L) and total 25(OH)D (median: 18.8 ng/mL). Most patients carried heterozygous rs7041 (60.7%) and wild-type rs4588 (58.9%) genotypes. The distribution of rs7041 SNP varied significantly among groups (p = 0.0301), while rs4588 SNP distribution did not (p = 0.424). Heterozygous rs4588 patients had significantly lower VDBP levels (p = 0.029) and reduced bioavailable 25(OH)D compared to those with wild-type rs4588 (p = 0.020). Our findings indicate that VDBP gene polymorphisms, particularly rs7041 and rs4588, are associated with vitamin D status and the severity of COVID-19. The lower VDBP levels and bioavailable vitamin D in ICU patients suggest that these genetic variants may influence disease severity and hospitalization needs. These results highlight the potential role of VDBP polymorphisms in COVID-19 severity, suggesting that genetic screening could be valuable in assessing the risk of severe outcomes and guiding personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder in the intestines without a cure. Current therapies suppress inflammation to prevent further intestinal damage. However, healing already damaged intestinal epithelia is still an unmet medical need. Under physiological conditions, Lgr5+ intestinal stem cells (ISCs) in the intestinal crypts replenish the epithelia every 3–5 days. Therefore, understanding the regulation of Lgr5+ ISCs is essential. Previous data suggest vitamin D signaling is essential to maintain normal Lgr5+ ISC function in vivo. Our recent data indicate that to execute its functions in the intestines optimally, 1,25(OH)2D requires high concentrations that, if present systemically, can cause hypercalcemia (i.e., blood calcium levels significantly higher than physiological levels), leading to severe consequences. Using 5-bromo-2′-deoxyuridine (BrdU) to label the actively proliferating ISCs, our previous data suggested that de novo synthesized locally high 1,25(OH)2D concentrations effectively enhanced the migration and differentiation of ISCs without causing hypercalcemia. However, although sparse in the crypts, other proliferating cells other than Lgr5+ ISCs could also be labeled with BrdU. This current study used high-purity Lgr5+ ISC lines and a mouse strain, in which Lgr5+ ISCs and their progeny could be specifically tracked, to investigate the effects of de novo synthesized locally high 1,25(OH)2D concentrations on Lgr5+ ISC function. Our data showed that 1,25(OH)2D at concentrations significantly higher than physiological levels augmented Lgr5+ ISC differentiation in vitro. In vivo, de novo synthesized locally high 1,25(OH)2D concentrations significantly elevated local 1α-hydroxylase expression, robustly suppressed experimental colitis, and promoted Lgr5+ ISC differentiation. For the first time, this study definitively demonstrated 1,25(OH)2D's role in Lgr5+ ISCs, underpinning 1,25(OH)2D's promise in IBD therapy. [ABSTRACT FROM AUTHOR]

Cognitive decline and comorbid conditions commonly co-occur, and these conditions can affect cognitive health. We aimed to estimate the prevalence of cognitive impairment (CI) according to weight status and to evaluate the associations between CI, weight status and comorbid conditions in adults of 55 years and older. The Abbreviated Mental Test Score (AMTS) was used. Logistic regressions were performed. Overall, 415 individuals were included. The mean age was 75.7 ± 10.1 years, and the mean BMI was 26.2 ± 6.9 kg/m2. The prevalence of CI was 20.7% in the whole study group and 31%, 24.8%, 17.7% and 10.2% in underweight, normal weight, overweight and obese individuals, respectively; p < 0.004. The low folate, vitamin D and prealbumin levels were more frequently found in individuals with CI compared with those without CI. Compared with the obese individuals, a higher odds ratio of prevalent CI was noted for underweight individuals OR 3.89 (95% CI 1.54–9.80); p = 0.004. Additionally, male gender, older age, stroke, having three or more comorbid conditions and findings of undernutrition were significantly associated with CI. Being underweight was associated with an increased risk of CI. Prevention strategies including the monitoring of nutritional status may help to prevent cognitive decline and promote healthy aging. [ABSTRACT FROM AUTHOR]

Background/Objectives: The objective of this study was to test the hypothesis that vitamin D deficiency (i.e., serum 25-hydroxyvitamin D (25(OH)D) ≤ 20 ng/mL) associates with the increased occurrence and shortened time to a knee osteoarthritis (OA) diagnosis after anterior cruciate ligament reconstruction (ACLR). Methods: This study consisted of a retrospective, case-control design. The inclusion criteria consisted of (1) patients (≥18 y) who underwent arthroscopic ACLR with (cases; n = 28) and without (controls; n = 56) a subsequent knee OA diagnosis (≥90 d from the date of ACLR) and (2) with a documented serum 25(OH)D concentration after ACLR (and before a knee OA diagnosis for the cases). Controls were matched (2:1) to cases based on sex, age at ACLR, date of ACLR, and body mass index. After matching, patients were separated into two groups: (1) vitamin D deficient (serum 25(OH)D ≤ 20 ng/mL) or (2) non-vitamin D deficient (serum 25(OH)D > 20 ng/mL). Data were extracted from the medical records. Results: Thirty-one percent (n = 26) of patients included were vitamin D deficient. Fifty percent (n = 13) of the vitamin D deficient and twenty-six percent (n = 15) of the non-vitamin D deficient patients were subsequently diagnosed with knee OA (p = 0.03). Time from ACLR to a knee OA diagnosis was significantly (p = 0.02) decreased in the vitamin D deficient (OA-free interval, 95% confidence interval [CI] = 7.9 to 10.9 y) compared to the non-vitamin D deficient group (OA-free interval, 95% CI = 10.5 to 12.5 y). Conclusions: Vitamin D deficiency after ACLR may serve as a prognostic biomarker for knee OA following ACLR. [ABSTRACT FROM AUTHOR]

Objective: In this study, we investigated 25-hydroxyvitamin D (25(OH)D, vitamin D), inflammatory hematologic ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte/HDL-C ratio (MHR) and plasma atherogenic index (PAI) and possible relationships with insulin resistance (IR) in children. Methods: A total of 210 individuals, including 96 children with IR and 114 children without IR, aged 6–18 years, who were admitted to the Pediatric Endocrinology Outpatient Clinic at Medicine Hospital, Istanbul Atlas University were included in our study. Result: Compared to patients without IR, NLR, PLR, SII, and MHR were significantly higher in patients with IR. Fasting insulin, PAI, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-β were significantly higher and quantitative insulin sensitivity check index (QUICKI) was considerably lower in patients with IR compared to those without IR. NLR, SII, and MHR were lower in normal vitamin D groups than the others (p < 0.001). PLR was lower in the group with normal vitamin D levels than the groups with insufficient or deficient levels of vitamin D (D < 21). Conclusions: We found that vitamin D deficiency in childhood is related to increased levels of circulating inflammatory markers (NLR, PLR, MHR, PAI), IR, and decreased insulin sensitivity. According to our results, supplementation of vitamin D may be beneficial in averting IR and enhanced systemic inflammation [ABSTRACT FROM AUTHOR]

The extracellular matrix of cartilage primarily constitutes of collagen and aggrecan. Cartilage degradation starts with aggrecan loss in osteoarthritis (OA). Vitamin D (VD) plays an essential role in several inflammation-related diseases and can protect the collagen in cartilage during OA. The present study focused on the role of VD in aggrecan turnover of human articular chondrocytes treated with tumor necrosis factor α (TNF-α) and the possible mechanism. Treatment with different doses of VD and different periods of intervention with TNF-α and TGF-β1 receptor (TGFβR1) inhibitor SB525334 were investigated. The viability of human chondrocytes and extracellular secretion of TGF-β1 were measured. The expression of intracellular TGFβR1 and VD receptor was examined. Transcriptional and translational levels of aggrecan and the related metabolic factors were analyzed. The results showed that TNF-α markedly reduced the viability, TGFβR1 expressions and aggrecan levels of human chondrocytes, and increased disintegrin and metalloproteinase with thrombospondin motifs. The alterations were partially inhibited by VD treatment. Furthermore, the effects of VD were blocked by the TGFβR1 inhibitor SB525334 in TNF-α-treated cells. VD may prevent proteoglycan loss due to TNF-α via TGF-β1 signaling in human chondrocytes. [ABSTRACT FROM AUTHOR]

Introduction/Aim: Vitamin D plays a crucial role in immune modulation, which may influence the development of graft-versus-host disease (GvHD) in patients undergoing hematopoietic stem cell transplantation (HSCT). This study aims to evaluate the impact of vitamin D levels and supplementation on the incidence of GvHD in HSCT patients. Methods: A narrative review was conducted across PubMed/Medline, Cochrane Library, CINAHL, and Embase databases. Results: The reviewed studies indicated widespread vitamin D deficiency among HSCT patients, with baseline levels ranging from 12.8 to 29.2 ng/mL. Supplementation protocols varied significantly, with dosages ranging from 1000 IU/day to 60,000 IU/week. Post-supplementation levels improved in some studies. Studies exploring the relationship between vitamin D and GvHD showed mixed results. Lower baseline vitamin D levels were associated with an increased risk of acute GvHD in some studies, while others found no significant correlation. However, a significant association between low levels of vitamin D and the incidence of chronic GvHD was observed. Conclusion: Vitamin D deficiency is prevalent in HSCT patients and may influence the risk of developing chronic GvHD. Future research should focus on larger and more rigorous studies to determine the optimal role of vitamin D as an adjuvant therapy in the context of HSCT. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency is a global problem. Vitamin D, the vitamin D receptor, and its enzymes are found throughout neuronal, ependymal, and glial cells in the brain and are implicated in certain processes and mechanisms in the brain. To investigate the processes affected by vitamin D deficiency in adults, we studied vitamin D deficient, control, and supplemented diets over 6 weeks in male and female C57Bl/6 mice. The effect of the vitamin D diets on proliferation in the neurogenic niches, changes in glial cells, as well as on memory, locomotion, and anxiety-like behavior, was investigated. Six weeks on a deficient diet was adequate time to reach deficiency. However, vitamin D deficiency and supplementation did not affect proliferation, neurogenesis, or astrocyte changes, and this was reflected on behavioral measures. Supplementation only affected microglia in the dentate gyrus of female mice. Indicating that vitamin D deficiency and supplementation do not affect these processes over a 6-week period. [ABSTRACT FROM AUTHOR]

Cancer, the second leading cause of death worldwide, demands the identification of modifiable risk factors to optimize its prevention. Diet has emerged as a pivotal focus in current research efforts. This literature review aims to enhance the ACS guidelines on diet and cancer by integrating the latest findings and addressing unresolved questions. The methodology involved an advanced PubMed search with specific filters relevant to the research topic. Topics covered include time-restricted diet, diet quality, acid load, counseling, exercise and diet combination, Mediterranean diet, vegetarian and pescetarian diets, weight loss, dairy consumption, coffee and tea, iron, carbohydrates, meat, fruits and vegetables, heavy metals, micronutrients, and phytoestrogens. The review highlights the benefits of the Mediterranean diet in reducing cancer risk. Adherence to overnight fasting or carbohydrate consumption may contribute to cancer prevention, but excessive fasting may harm patients' quality of life. A vegetarian/pescetarian diet is associated with lower risks of general and colorectal cancer compared to a carnivorous diet. High heme and total iron intake are linked to increased lung cancer risk, while phytoestrogen intake is associated with reduced risk. Coffee and tea have a neutral impact on cancer risk. Finally, the roles of several preventive micronutrients and carcinogenic heavy metals are discussed. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is one of the most prevalent pregnancy problems, and there is still debate over the relationship between vitamin D and GDM. Objectives: Our objective is to investigate the correlation between vitamin D and GDM by employing Mendelian randomization (MR) with summary data obtained from genome-wide association studies (GWAS). Methods: Data on exposures and outcomes, namely vitamin D, vitamin D insufficiency, and GDM, were acquired from the IEU OpenGWAS Project. Bidirectional MR analysis was performed utilizing the inverse variance weighted (IVW) method as the principal analytical approach. The complementary approaches employed in this study encompassed weighted median, simple mode, weighted mode, and MR-Egger regression. A series of sensitivity analysis were conducted in order to assess the reliability of the obtained results. Results: The data were acquired from the IEU OpenGWAS Project. Following the application of the three assumptions of MR, 13 single nucleotide polymorphisms (SNPs) were included in the MR analysis for vitamin D levels and vitamin D deficiency on GDM, and 10 and 26 SNPs were included for GDM on vitamin D levels and deficiency, respectively. The findings from the IVW analysis revealed a significant positive correlation between vitamin D levels and GDM (OR = 1.057, 95% CI: 1.011–1.104, p = 0.015). Conversely, a negative correlation was seen between vitamin D deficiency and GDM (OR = 0.979, 95% CI: 0.959–0.999, p = 0.039). The results of the reverse MR study revealed no evidence of reverse causation between GDM and vitamin D. The findings from multiple MR approaches were in line with the direction of IVW analysis. Sensitivity analysis revealed no evidence of heterogeneity, pleiotropy, or outliers, suggesting the robustness of the results. Conclusions: There exists a causal association between vitamin D and GDM, whereby vitamin D levels serve as a risk factor for GDM. [ABSTRACT FROM AUTHOR]

Background: Kidney transplantation is followed by immunosuppressive therapy involving calcineurin inhibitors (CNIs) such as cyclosporin A. However, long-term high CNIs doses can lead to vitamin D deficiency, and genetic variations influencing vitamin D levels can indirectly impact the necessary CNIs dosage. This study investigates the impact of genetic variations of vitamin D binding protein (DBP) rs2282679 and CYP2R1 hydroxylase rs10741657 polymorphisms on the cyclosporin A dosage in kidney transplant recipients. Additional polymorphisims of genes that are predicted to influence the pharmacogenetic profile were included. Methods: Gene polymorphisms in 177 kidney transplant recipients were analyzed using data mining techniques, including the Random Forest algorithm and Classification and Regression Trees (C&RT). The relationship between the concentration/dose (C/D) ratio of cyclosporin A and genetic profiles was assessed to determine the predictive value of DBP rs2282679 and CYP2R1 rs10741657 polymorphisms. Results: Polymorphic variants of the DBP (rs2282679) demonstrated a strong predictive value for the cyclosporin A C/D ratio in post-kidney transplantation patients. By contrast, the CYP2R1 polymorphism (rs10741657) did not show predictive significance. Additionally, the immune response genes rs231775 CTLA4 and rs1800896 IL10 were identified as predictors of cyclosporin A response, though these did not result in statistically significant differences. Conclusions:DBP rs2282679 polymorphisms can significantly predict the cyclosporin A C/D ratio, potentially enhancing the accuracy of CNI dosing. This can help identify patient groups at risk of vitamin D deficiency, ultimately improving the management of kidney transplant recipients. Understanding these genetic influences allows for more personalized and effective treatment strategies, contributing to better long-term outcomes for patients. [ABSTRACT FROM AUTHOR]

Vitamin D3 is a crucial fat-soluble pro-hormone essential for bolstering bone health and fortifying immune responses within the human body. Orodispersible films (ODFs) serve as a noteworthy formulation strategically designed to enhance the rapid dissolution of vitamin D, thereby facilitating efficient absorption in patients. This innovative approach not only streamlines the assimilation process but also plays a pivotal role in optimizing patient compliance and therapeutic outcomes. The judicious utilization of such advancements underscores a paradigm shift in clinical strategies aimed at harnessing the full potential of vitamin D for improved patient well-being. This study aims to examine the vitamin D3 ODF structure using spectroscopic techniques to analyze interactions with excipients like mannitol. Fourier-transform infrared spectroscopy (FTIR) and ultraviolet–visible (UV–Vis) spectroscopy were utilized to assess molecular composition, intermolecular bonding, and vitamin D3 stability. Understanding these interactions is essential for optimizing ODF formulation, ensuring stability, enhancing bioavailability, and facilitating efficient production. Furthermore, this study involves a translational approach to interpreting chemical properties to develop an administration protocol for ODFs, aiming to maximize absorption and minimize waste. In conclusion, understanding the characterized chemical properties is pivotal for translating them into effective self-administration modalities for Vitamin D films. [ABSTRACT FROM AUTHOR]

Simple Summary: Postoperative hypoparathyroidism (HypoPTH) is the most common complication following total thyroidectomy, but the literature still lacks clear risk and protective factors. This study aimed to evaluate and compare the risk factors for post-surgical HypoPTH in a large series of patients at a tertiary academic high-volume center undergoing total thyroidectomy for both benign and malignant diseases. It also focused on identifying risk and protective factors for persistent HypoPTH. Background: Postoperative hypoparathyroidism (HypoPTH) is the most common complication following total thyroidectomy. Several risk factors have been identified, but data on postoperative follow-up are scarce. Methods: The study focused on 1965 patients undergoing surgery for benign and malignant thyroid diseases at a tertiary-level academic center. Anamnestic, biochemical, surgical, pathological, and follow-up data were evaluated. HypoPTH was defined by a serum concentration of PTH < 10 pg/mL on the first or the second post-operative day. Persistent HypoPTH was defined by the need for calcium/active vitamin D treatment > 12 months after surgery. Results: Postoperative HypoPTH occurred in 542 patients. Multivariate analysis identified the association of central lymph-nodal dissection, reduced preoperative PTH levels, a lower rate of parathyroid glands preserved in situ, and longer duration of surgery as independent risk factors. At a median follow-up of 47 months, HypoPTH regressed in 443 patients (more than 6 months after surgery in 7%) and persisted in 53 patients. Patients receiving a lower dose of calcium/active vitamin D treatment at discharge (HR 0.559; p < 0.001) or undergoing prolonged, tailored, and direct follow-up by the operating endocrine surgeon team had a significantly lower risk of persistent HypoPTH (2.4% compared to 32.8% for other specialists) (HR 2.563; p < 0.001). Conclusions: Various patient, disease, and surgeon-related risk factors may predict postoperative HypoPTH. Lower postoperative calcium/active vitamin D treatment and prolonged, tailored follow-up directly performed by operating endocrine surgeons may significantly reduce the rate of persistent HypoPTH. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in the treatment of acute lymphoblastic leukemia (ALL) have led to a marked improvement in the survival rate of patients. Nevertheless, these patients may develop adverse effects during and after treatment, such as bone abnormalities and vitamin D deficiency. Bone remodeling allows for bone volume and structure to be maintained, which is controlled by the receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system-determining pathway in the balance between bone formation and resorption. Some reports have explored the role of corticosteroids in modulating the RANKL and OPG levels and RANKL/OPG ratio in pediatric patients. Nevertheless, studies evaluating the role of RANKL and OPG in the bone health of pediatric ALL patients during treatment are limited. During remission, we observed an increase in the RANKL/OPG ratio, increased RANKL levels, and decreased OPG levels in ALL patients. These changes may predispose such patients to the development of bone health disorders in their adult lives. Background: The receptor activator of the nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is a determining pathway in the balance between bone formation and resorption, and disruptions in this complex can affect bone metabolism. Methods: This study analyzes the changes in RANKL, OPG, and 25(OH)D levels; the RANKL/OPG ratio; and other bone turnover markers (BTMs) from diagnosis to complete remission in children with acute lymphoblastic leukemia (ALL). This is a prospective observational cohort study, carried out at the Instituto Mexicano del Seguro Social, Mexico City, including 33 patients (4–17 years) with newly diagnosed B-cell ALL. The patients were treated with the HP09 chemotherapy protocol. Children who had previously been treated with corticosteroids were excluded. A peripheral blood sample at diagnosis and remission was collected to determine the 25(OH)D and BTM concentrations. Results: Increased RANKL (p = 0.001) and osteocalcin (p < 0.001) levels and RANKL/OPG ratio (<0.001) and a decreased OPG level (p = 0.005) were observed at remission, predominantly in the high-risk (HR) relapse and vitamin D deficiency groups. A negative association between RANKL and OPG (r = −0.454, p = 0.008) was observed. Conclusions: we suggest that the RANKL/OPG ratio could serve as a bone remodeling marker in ALL patients. [ABSTRACT FROM AUTHOR]

Idiopathic pulmonary fibrosis remains a relevant problem of the healthcare system with an unfavorable prognosis for patients due to progressive fibrous remodeling of the pulmonary parenchyma. Starting with the damage of the epithelial lining of alveoli, pulmonary fibrosis is implemented through a cascade of complex mechanisms, the crucial of which is the TGF-β/SMAD-mediated pathway, involving various cell populations. Considering that a number of the available drugs (pirfenidone and nintedanib) have only limited effectiveness in slowing the progression of fibrosis, the search and justification of new approaches aimed at regulating the immune response, cellular aging processes, programmed cell death, and transdifferentiation of cell populations remains relevant. This literature review presents the key modern concepts concerning molecular genetics and cellular mechanisms of lung fibrosis development, based mainly on in vitro and in vivo studies in experimental models of bleomycin-induced pulmonary fibrosis, as well as the latest data on metabolic features, potential targets, and effects of vitamin D and its metabolites. [ABSTRACT FROM AUTHOR]

Vitamin D plays a role in inflammatory skin disease, but the exact mechanisms and the clinical significance remain unclear. According to the free hormone hypothesis, it is the free concentration of 25-hydroxy vitamin D (25(OH)D) that is biologically active. Vitamin D-binding protein (DBP) acts as the major transporter of vitamin D in the circulation, and DBP concentration defines the free 25(OH)D levels. DBP levels are elevated in various inflammatory conditions, including psoriasis. Narrowband-ultraviolet B (NB-UVB) is the most widely used phototherapy and is an established first-line treatment for psoriasis and atopic dermatitis (AD), often used before proceeding to systemic treatment. The aim of this study was to investigate the influence of NB-UVB phototherapy on DBP and high-sensitivity C-reactive protein (hsCRP) levels, as markers of systemic inflammation, in inflammatory skin disease. Thirty adults (psoriasis (n = 20) and AD (n = 10)) were treated with NB-UVB. Serum DBP, hsCRP, total and free 25(OH)D, and 1,25-dihydroxy vitamin D (1,25(OH)2D) were measured before and after NB-UVB. Disease severity was assessed with Psoriasis Area and Severity Index (PASI), SCORing Atopic Dermatitis (SCORAD), and Visual Analogue Scale (VAS). DBP decreased in psoriasis patients and varied with no clear trend in AD patients. HsCRP decreased in both groups, but this did not reach statistical significance. PASI, SCORAD, and VAS improved, and vitamin D levels increased after NB-UVB. Sub-analysis indicated a better response to NB-UVB for patients with vitamin D deficiency and insufficiency compared to vitamin D-sufficient patients. The decrease in DBP after NB-UVB in psoriasis patients suggests a potential systemic anti-inflammatory effect of phototherapy. Measurement of vitamin D levels may potentially serve as a tool to identify patients who would derive the greatest benefit from NB-UVB phototherapy. [ABSTRACT FROM AUTHOR]

Background: It has been reported that vitamin D deficiency may be associated with the development of oral lichen planus (OLP). Given the high prevalence of vitamin D deficiency in many countries, we sought to determine whether it constitutes a comorbidity of OLP. Methods: One hundred and twenty patients clinically and histologically diagnosed with OLP were evaluated for their serum vitamin D levels. The results were compared to results from a control series of the same number of subjects matched for age and sex. Results: Vitamin D deficiency was diagnosed in 45% (n = 54) of OLP patients and in 26.7% (n = 32) of the control group. Vitamin D supplements were being taken by 32 (26.7%) OLP patients and 15 (12.5%) subjects in the control group. A multivariate logistic regression model showed that OLP was associated with vitamin D deficiency [OR: 2.24 (1.28–3.98, p = 0.005)] and vitamin D supplementation [OR: 2.51 (1.25–5.22, p = 0.011)], even after controlling for confounding variables such as sex, age ≤60>, tobacco, and alcohol. Conclusion: The association between OLP patients and vitamin D deficiency or vitamin D supplementation suggests that further research might explore the benefits of vitamin D supplements in managing OLP patients. [ABSTRACT FROM AUTHOR]

Background: Cancer is a growing public health problem and cancer is linked to vitamin D via several mechanisms. Recent umbrella reviews on the extra-skeletal effects of vitamin D did not turn their attention to cancer. Accordingly, an overview of the current state of research is needed. Materials and methods: An umbrella review was conducted to provide an overview of systematic reviews on the association between vitamin D and incidence or mortality of breast cancer, colorectal cancer, lung cancer, pancreatic cancer, and prostate cancer. Results: Inverse correlations were found between the vitamin D level (measured by circulating 25(OH)D) and mortality for all five types of cancer. For breast cancer, colorectal cancer, lung cancer, and pancreatic cancer, there are also hints of a lower incidence due to higher 25(OH)D levels. Conclusion: As most reviews include observational studies, conclusions on causality cannot be made. Methodological differences between the included reviews and different study designs in the individual studies lead to methodological problems. Despite these problems, the review shows inverse correlations between 25(OH)D levels and mortality, and mostly inverse correlations between 25(OH)D levels and incidence. [ABSTRACT FROM AUTHOR]

Bone fractures are a significant public health issue among elderly subjects. This study examines the impact of diet and vitamin D status on the risk of long bone fractures due to falls in elderly subjects in Vojvodina, Serbia. Conducted at the University Clinical Center of Vojvodina in autumn/winter 2022–2023, the study included 210 subjects >65 years: 105 (F: 80/M: 15) with long bone fractures due to falls and 105 (F: 80/M: 15) controls. Groups were similar regarding age and BMI. Dietary intakes (by two 24-h recalls) and serum vitamin D levels were analyzed. The fracture group had a significantly lower median daily vitamin D intake (1.4 μg/day vs. 5.8 μg/day), intake of calcium, energy, proteins, fats, fibers, dairy products, eggs, fish, edible fats/oils, and a higher intake of sweets (p < 0.001 for all). Serum vitamin D levels were significantly lower in the fracture group (40.0 nmol/L vs. 76.0 nmol/L, p < 0.001). Logistic regression identified serum vitamin D as the most important protective factor against fractures, and ROC curve analysis indicated that serum vitamin D levels > 50.5 nmol/L decreased fracture risk. Nutritional improvements (increased intake of vitamin D and protein sources such as fish, eggs, and dairy), increased sun exposure, and routine vitamin D supplementation during winter are advised. [ABSTRACT FROM AUTHOR]

This study investigated the prognostic impact of vitamin D deficiency and reduced skeletal muscle mass in diffuse large B-cell lymphoma (DLBCL) patients. A retrospective analysis of 186 newly diagnosed DLBCL patients from 2012 to 2022 was conducted, measuring serum 25-hydroxyvitamin D [25(OH)D] levels and the skeletal muscle index (SMI). Decreased vitamin D levels were linked to more severe DLBCL disease, with a median 25(OH)D concentration of 13 (4.0–27) ng/mL. Males in the group with a low SMI had a considerably lower 25(OH)D concentration. The optimal threshold of 25(OH)D levels for overall survival (OS) was 9.6 ng/mL, with lower values associated with a higher likelihood of recurrence and mortality. Multivariable analysis showed hazard ratios for OS of 1.4 [95% CI 0.77–2.5] for a low SMI and 3.2 [95% CI 1.8–5.8] for low 25(OH)D concentration. The combination of a low SMI and low vitamin D concentration resulted in the worst prognosis. Thus, low levels of vitamin D associated with disease progression significantly impact DLBCL prognosis, which can be further stratified by the SMI, providing valuable insights for patient management and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

This narrative review comprehensively explores the cardiometabolic implications of two vital nutrients, magnesium and vitamin D, during gestation. Magnesium, a key regulator of vascular tone, glucose metabolism, and insulin sensitivity, plays a crucial role in mitigating gestational hypertension and diabetes, a point this review underscores. Conversely, vitamin D, critical for immune response and calcium level maintenance, is linked to gestational diabetes and hypertensive disorders of pregnancy. The authors aim to enhance comprehension of the complex interaction between these nutrients and cardiometabolic function in pregnancy, knowledge that is pivotal for optimizing maternal–fetal outcomes. The mother's health during pregnancy significantly influences the long-term development of the fetus. Recognizing the impact of these nutrient deficiencies on the physiology of cardiometabolic cycles underscores the importance of adequate nutritional support during pregnancy. It also emphasizes the pressing need for future research and targeted interventions to alleviate the burden of pregnancy complications, highlighting the crucial role of healthcare professionals, researchers, and policy makers in obstetrics and gynecology in this endeavor. [ABSTRACT FROM AUTHOR]

Background: The prevalence of vitamin D deficiency has been a growing concern in recent years. Vitamin D is important in many of the body's physiological systems, such as the musculoskeletal, cardiovascular and immune functions. A deficiency of vitamin D in athletes may negatively impact both muscle functions and recovery and, thus, affect performance and increase the risk of injury. Many studies assessed the prevalence of vitamin D deficiency in athletes; however, as of today, there are no official recommendations/protocols for screening vitamin D levels in athletes, and only a few studies were performed in male and female elite athletes (i.e., Olympic level), in different sport disciplines. Method: We investigated the prevalence of vitamin D deficiency among athletes entering the Israeli Olympic team. A total of 761 samples of Vitamin D(OH)25 from 334 athletes were analyzed. For this analysis, we used the first test the athlete had performed when joining the Olympic team. The prevalence of vitamin D deficiency (<50 nmol/L, as defined by the Endocrine Society Committee) was investigated according to gender, types of sports and outdoor vs. indoor sports through the different seasons of the Israeli Olympic team athletes. Result: Twenty-five athletes (7.5%) were diagnosed with vitamin D deficiency. One hundred and thirty-one athletes (39.2%) had insufficient levels of vitamin D (50–75 nmol/L). The highest incidence of vitamin D deficiency was found amongst gymnastics and combat sport athletes. A significant difference was also found in vitamin D concentration between seasons. Vitamin D average concentration in the winter was 74.1 nmol/L compared to 86.4 nmol/L in the Summer (p < 0.0005). Conclusions: Due to the importance of vitamin D to athletic performance and the high prevalence of deficiency and insufficiency, we suggest careful and frequent monitoring of groups at risk, including elite athletes, especially in susceptible sports and during the winter. Future studies are necessary to investigate the effectiveness of Vitamin D supplementation in athletes with low baseline vitamin D levels. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have examined whether vitamin D is associated with gestational diabetes mellitus (GDM). Nevertheless, it is still challenging to determine the causality, due to a number of shortcomings in observational research and randomized controlled trials. Objective: Mendelian randomization (MR) with two samples was conducted to investigate the potential causative association between 25-hydroxyvitamin D (25(OH)D), vitamin D binding protein (VDBP) and GDM risk. Methods: Publicly accessible summary data from independent cohorts were used for two-sample MR. For 25(OH)D, we obtained data from UK Biobank, IEU and EBI, then performed a meta-analysis to enhance the statistical power (via METAL); for VDBP, data were obtained from the INTERVAL study; for GDM, data were obtained from FinnGen. The inverse variance weighted (IVW) approach was performed as the main analysis, together with several sensitivity analyses, such as MR–Egger, maximum likelihood, weighted median, and weighted mode. Results: The IVW results revealed a weak negative causal connection between 25(OH)D and GDM risk [OR (95% CI) = 0.71 (0.50, 0.99), p = 0.046]. However, the causal association was unstable according to sensitivity analyses, and Cochran's Q test revealed significant heterogeneity. After removing BMI-related IVs, the causal association between 25(OH)D and GDM disappeared [OR (95% CI) = 0.76 (0.55, 1.06), p = 0.101]. In addition, our study found no proof to support the assumption that VDBP level was related to GDM risk causally [OR (95% CI) = 0.98 (0.93, 1.03), p = 0.408]. Conclusions: According to this study, a weak negative causal association between 25(OH)D and GDM risk was found, while we had little proof to support the link between VDBP and GDM. To further explore whether total or free 25(OH)D levels and GDM are causally related, GWAS data with an emphasis on women of reproductive age and other ethnic groups are required. [ABSTRACT FROM AUTHOR]

Objective: This study's objective was to identify the factors and impact of serums calcium 25-Hydroxy vitamin D, ferritin, uric acid, and sleeping disorders on benign paroxysmal positional vertigo (BPPV) patients. Methods: This is a case and control design study. The consecutive patients' visits (age, older than 25 years) with idiopathic BPPV were recruited in the present study. For each patient, 3:1 sex and age-matched healthy people were assigned as the control. The study comprised 177 patients with BPPV and 656 controls. The study included biochemical, clinical, physical examinations, PSQI sleep quality, supine roll test, and Dix–Hallpike test for the diagnosis of all patients, and pure-tone audiometry (PTA) was used to assess hearing. Univariate and multivariate stepwise regression analyses were used for statistical analysis. Results: The study comprised 833 patients with 295 males (35.4%) and 538 females (64.6%) who were between 25 and 70 years old. Of a total of 833 participants, 177 were BPPV patients, and 656 subject were normal. The results shown that there were significant differences between the BPPV and the normal group in terms of BMI (p = 0.039), physical activity (p = 0.003), cigarette smoking (p = 0.035), nargile-waterpipe use (p < 0.001), diabetes (p < 0.001), hypertension (p < 0.001), congestive heart failure (CHF) (p < 0.001), neurology (p < 0.001), tinnitus (p < 0.001), dizziness (p < 0.001), headache (p < 0.001), vitamin D (p = 0.004), calcium (p = 0.004), magnesium (p < 0.001), potassium (p = 0.019), phosphorus (p < 0.001), haemoglobin (p < 0.001), serum glucose (p < 0.001), HbA1c (p < 0.001), triglyceride (p < 0.001), systolic BP (p = 0.004), diastolic BP (p = 0.008), and microalbuminuria (p = 0.005); ATP III metabolic syndrome (p = 0.038), IDF metabolic syndrome (p = 0.034), and poor sleep (p = 0.033). In terms of the type of BPPV, the posterior canal was the most commonly affected (n = 126, 71.2%), followed by the horizontal (n = 43, 24.3%) and anterior canal (n = 8, 4.5%). The analysis indicated that serum ferritin (p < 0.001), uric acid (p < 0.001), blood pressure (p < 0.001), dizziness (p < 0.001), cigarette–water-pipe smokers (p = 0.004), headaches/migraines (p = 0.005), calcium (p = 0.007), vitamin D deficiency (p = 0.008), sleepiness (p = 0.016), physical activity (p = 0.022), CHF (p = 0.024), and tinnitus (p = 0.025) were considered as risk predictors for BPPV. Conclusions: The results revealed that the serum levels of vitamin D, ferritin, uric acid, and calcium are low among the study population and supplementation could be considered as prevention in BPPV patients. [ABSTRACT FROM AUTHOR]

Although vitamin D insufficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH)D) and atherogenic indices predictive of CVD. This study investigated the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred women aged 18 to 50 years from Meknes were included. Fasting 25(OH)D and lipid concentrations were assayed by a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (atherogenic index of plasma (AIP), atherogenic coefficient (AC), non-HDL cholesterol (non-HDL-C), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH)D levels associated with high atherogenic indices. 25(OH) D below 20 ng/mL was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856–12.959), 3.637 (2.149–6.158), 3.589 (1.673–7.700), 2.074 (1.215–3.540), and 2.481 (1.481–4.123), respectively. According to the ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/mL, ≤17.5 ng/mL, ≤19.8 ng/mL, ≤20.1 ng/mL, and ≤19.5 ng/mL, respectively, all p < 0.01. Based on the atherogenic indices, this study indicates that vitamin D below 20 ng/mL may increase the risk of cardiovascular disease in adult women. Additional health measures are essential to raise awareness among women and health professionals of preventing and controlling cardiovascular risk factors, particularly among young individuals. [ABSTRACT FROM AUTHOR]

Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions. [ABSTRACT FROM AUTHOR]

Background: The perioperative impact of calcium and vitamin D on left ventricular (LV) performance during major cardiac surgery remains unexplored. We aimed to assess the relation of calcium and vitamin D measured at different time points with the LV ejection fraction (EF), and to investigate whether changes in EF correlate with postoperative outcomes. Methods: We enrolled 83 patients, in whom ionized calcium was measured before, during, and after surgery (until discharge), vitamin D preoperatively, and EF pre- and postoperatively at 24 h. The postoperative outcomes were cardiopulmonary bypass (CPB) time, aortic cross-clamp time, mechanical ventilation time, vasoactive inotropic score (VIS) (intraoperative, day 0, day 1), and ICU stay time. Results: The mean age was 64.9 ± 8.5 years, with 21 of the patients (25%) having an EF < 50%. The median change from preoperative to postoperative EF was −2.0 (−10.0–0.0) % (p < 0.001). At the baseline, the EF < 50% group had significantly lower preoperative vitamin D levels than the EF ≥ 50% group (p = 0.048). The calcium trend did not differ across the groups. Preoperative EF was significantly associated with CPB time (r = 0.22, p = 0.044) and aortic cross-clamp time (r = 0.24, p = 0.031). Postoperative EF was significantly and inversely associated with intraoperative VIS (r = −0.28, p = 0.009), VIS day 0 (r = −0.25, p = 0.020), VIS day 1 (r = −0.23, p = 0.036), and ICU length of stay (r = −0.22, p = 0.047). Finally, the change in ejection fraction was significantly and inversely associated with CPB time (r = −0.23, p = 0.037), aortic cross-clamp time (r = −0.22, p = 0.044), intraoperative VIS (r = −0.42, p < 0.001), VIS day 0 (r = −0.25, p = 0.024), mechanical ventilation time (r = −0.22, p = 0.047), and ICU length of stay (r = −0.23, p = 0.039). Conclusions: The fluctuations in perioperative ionized calcium levels were not associated with the evolution of LVEF, although preoperative vitamin D levels may affect those with low EF. Correspondingly, a reduced EF significantly impacted all the studied postoperative outcomes. Further investigation into biomarkers affecting cardiac inotropic function is warranted to better understand their significance. [ABSTRACT FROM AUTHOR]

A total hip arthroplasty (THA) can improve quality of life, but loosening of the hip prosthesis is a complex problem in which vitamin D may also play a role. The Vitamin D Receptor (VDR) is involved in the response of cells to the action of vitamin D, and its genetic variability raises the question of whether individual differences could influence the risk of prosthesis loosening. The aim of this study was to investigate the relationship between VDR single nucleotide polymorphisms (SNPs) (ApaI, BsmI, FokI and TaqI) and the serum VDR and 25(OH)D levels in three groups of patients: (1) arthroscopy patients after THA without loosening of the prosthesis (CA—Control Arthroplasty), (2) patients after THA with loosened hip prostheses (L—Loosening) and (3) the control group (C—Control). Our results suggest that the genotypes tt of TaqI, BB of BsmI, and FF of FokI may influence the VDR effect in patients with loosened protheses. Our results showed that the ACAC haplotype (AtBF) was over two times more frequent in the L group than in CA + C: OR =2.35 [95% CI 1.44–3.83; p = 0.001]. There was no significant correlation between the VDR and serum 25(OH)D levels, but there were differences between studied groups. [ABSTRACT FROM AUTHOR]

Background and Objectives: Previous studies have shown that the levodopa treatment of Parkinson's disease (PD) elevates circulating homocysteine levels, which are associated with an increased risk of cardiovascular and neurological disorders, or thrombosis. The present trial aimed to examine whether the intake of vitamin B12, folic acid, and vitamin D3 supplements improved homocysteine level and quality of life (QoL). Materials and Methods: An interventional prospective trial was conducted in multiple centers across Romania. Participants with clinically established PD taking at least 300 mg/day of levodopa for more than 1 year received a daily tablet of a supplement containing 800 UI of vitamin D3, 1000 µg of folic acid, and 15 µg of vitamin B12. They were followed for 6 months and their serum homocysteine, vitamin B12, vitamin D, and QoL scores were measured at baseline and at 6 months of treatment. QoL was measured using a 15D questionnaire, which assesses mobility, vision, hearing, breathing, sleeping, eating, speech, excretion, usual activities, mental function, discomfort and symptoms, depression, distress, vitality, and sexual activity. Results: Twenty-four PD patients with a mean age of 71 ± 5.04 years (54.2% male and 45.8% female) finished the study. After the intervention, the mean score of speech, mental function, discomfort and symptoms, depression, and QoL significantly increased (p < 0.05 for all). Also, the serum homocysteine and vitamin D were significantly enhanced (p < 0.0001 and p = 0.025, respectively). Changes in vitamin B12 were not statistically significant at 6 months of treatment (p = 0.996). No gender differences were found among the changes that we have demonstrated for homocysteine, vitamin B12, vitamin D, and QoL levels (p < 0.05 for all). Conclusions: The findings of this study showed that the dietary intake of vitamin B12, folic acid, and vitamin D3 remarkably decreased the dimensions of homocysteine and finally increased the total score of QoL in PD patients. We have successfully captured the potential benefits of the supplementation regimen over time and provided insights into the broader implications for managing PD with a focus on nutritional support. [ABSTRACT FROM AUTHOR]

Background: Glaucoma is the second leading cause of blindness worldwide, with intraocular pressure as the only known modifiable risk factor. Vitamin D has been proposed to influence intraocular pressure and decrease retinal ganglion cell degeneration. Based on these findings, vitamin D has been suggested to prevent or reduce the severity of primary open-angle glaucoma (POAG), which is the most common form. Methods: We applied two-sample Mendelian randomisation (MR) analyses to data from the SUNLIGHT consortium and the UK Biobank to assess the causal effect of vitamin D levels and vitamin D deficiency on primary open-angle glaucoma (POAG). MR analysis, including sensitivity tests using other GWAS summary statistics from FinnGen, was also performed. We also investigated the association between single nucleotide polymorphisms (SNPs) on genes involved in vitamin D metabolic pathways and POAG. Results: We found no statistical evidence that vitamin D levels (OR = 1.146, 95% CI 0.873 to 1.504, p = 0.326) or vitamin D deficiency (OR = 0.980 (95% CI 0.928 to 1.036, p = 0.471) causally affect the risk of developing POAG. Sensitivity analyses, including the use of a more relaxed p-value threshold, and use of winter-measured samples only, replication in the FinnGen dataset, and exploration of specific genetic markers also showed no evidence of association between SNPs for genes involved in key steps of vitamin D metabolism and POAG. Conclusions: These results indicate that vitamin D may not be a significant factor in modifying POAG risk, challenging the hypothesis that vitamin D supplementation could be effective in reducing POAG risk. Further research should focus on identifying other potential risk factors for POAG prevention strategies. [ABSTRACT FROM AUTHOR]

Evidence is increasing that vitamin D and CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites play a significant antioxidant role beyond its classical functions in bone health and calcium metabolism. Several recent studies have linked these elements to reduced oxidative stress as well as improved immune, cardiovascular, and neurological functions as a result of chronic kidney disease and cancer. Additionally, supplementation with this vitamin has been shown to be one of the most cost-effective micronutrient interventions worldwide, highlighting its potential as a therapeutic approach. The underlying mechanisms and implications of this antioxidant function of vitamin D or CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites are not well understood. This comprehensive and narrative review is aimed at summarizing the current evidence regarding the molecular mechanisms implicated in this antioxidant function of vitamin D, as well as to provide a general overview and to identify key research areas for the future, offering an extensive perspective that can guide both researchers and clinicians in the management of diseases associated with oxidative stress and/or insufficient vitamin D status. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is a severe psychiatric disorder marked by extreme weight control behaviors and significant impacts on physical and psychosocial health. This study explores the relationship between vitamin D (Vit-D) levels and impulsivity in women with AN. Forty-six cisgender White women participants were assessed upon admission and before discharge from a specialized eating disorder treatment center, with an average duration of 2.5 ± 0.10 months. Methods included self-reported questionnaires and behavioral tasks to measure impulsivity, alongside serum Vit-D levels. Our results showed significant improvements in Vit-D levels and certain impulsivity measures, such as faster reaction times and fewer errors on the go/no-go task, correlating with higher Vit-D levels. However, no significant correlations were found between Vit-D levels and self-reported impulsivity. These findings suggest that adequate Vit-D levels may enhance cognitive functions related to impulse control in AN. Given this study's limitations, including its exclusive focus on women and small sample size, future research should involve larger, more diverse populations and randomized clinical trials to better understand the causal relationships and therapeutic potential of Vit-D in managing AN-related impulsivity. [ABSTRACT FROM AUTHOR]

Exercise-induced inflammation can influence iron metabolism. Conversely, the effects of vitamin D3, which possesses anti-inflammatory properties, on ultramarathon-induced heart damage and changes in iron metabolism have not been investigated. Thirty-five healthy long-distance semi-amateur runners were divided into two groups: one group received 150,000 IU of vitamin D3 24 h prior to a race (n = 16), while the other group received a placebo (n = 19). Serum iron, hepcidin (HPC), ferritin (FER), erythroferrone (ERFE), erythropoietin (EPO), neopterin (NPT), and cardiac troponin T (cTnT) levels were assessed. A considerable effect of ultramarathon running on all examined biochemical markers was observed, with a significant rise in serum levels of ERFE, EPO, HPC, NPT, and cTnT detected immediately post-race, irrespective of the group factor. Vitamin D3 supplementation showed a notable interaction with the UM, specifically in EPO and cTnT, with no other additional changes in the other analysed markers. In addition to the correlation between baseline FER and post-run ERFE, HPC was modified by vitamin D. The ultramarathon significantly influenced the EPO/ERFE/HPC axis; however, a single substantial dose of vitamin D3 had an effect only on EPO, which was associated with the lower heart damage marker cTnT after the run. [ABSTRACT FROM AUTHOR]

With the emergence of the COVID-19 pandemic, the absence of established evidence-based treatment protocols led healthcare professionals and the public to explore experimental treatments, including high doses of vitamin D supplements. This study aimed to assess changes in serum 25-hydroxyvitamin D levels during the pandemic, employing a retrospective cohort analysis of data from Charleston Area Medical Center (CAMC). The study analyzed serum 25-hydroxyvitamin D levels in a cohort of 35,556 patients treated at CAMC in 2019, a representative pre-pandemic period, to 2021, a representative pandemic period. Our findings revealed a significant increase in mean serum 25-hydroxyvitamin D levels as compared with 2019 (37 ± 21 vs. 31 ± 15 ng/mL, p ≤ 0.001). Additionally, in 2021, there were significantly more patients exhibiting serum levels in the highest quintiles, specifically >100 ng/mL (1.6% vs. 0.2%), 75–100 ng/mL (4.6% vs. 1.2%), and 50–75 ng/mL (16.0% vs. 8.4%), p ≤ 0.001. This upsurge suggests increased intake of vitamin D supplements, potentially fueled by widespread discussions that were taking place largely on the internet regarding the efficacy of vitamin D against COVID-19. Our findings underscore the critical need for evidence-based public health messaging, especially during health crises, to prevent unnecessary health risks and ensure patient safety. [ABSTRACT FROM AUTHOR]

Low serum vitamin D levels have been associated with a variety of health conditions which has led the medical community but also the general population to evaluate vitamin D status quite liberally. Nevertheless, there remain questions about the efficacy and cost-effectiveness of such a broad and untargeted approach. This review therefore aims to summarize the current evidence and recommendations on when and how to evaluate vitamin D status in human health and disease. For the general population, most guidelines do not recommend universal screening but suggest a targeted approach in populations at risk. Also, some guidelines do not even recommend evaluating vitamin D status when vitamin D substitution is indicated anyway, such as in children or patients receiving anti-osteoporosis drugs. In those guidelines that recommend the screening of vitamin D status, serum 25(OH)D levels are universally proposed as the preferred screening tool. However, little attention is given to analytical considerations and almost no guidelines discuss the timing and frequency of screening. Finally, there is the known variability in diagnostic thresholds for defining vitamin D insufficiency and deficiency. Overall, the existing guidelines on the evaluation of vitamin D status differ broadly in screening strategy and screening implementation, and none of these guidelines discusses alternative screening modes, for instance, the vitamin metabolic ratio. Efforts to harmonize these different guidelines are needed to enhance their efficacy and cost-effectiveness. [ABSTRACT FROM AUTHOR]

(1) Colorectal cancer is a major cause of cancer-related death, with colorectal adenomas (CRAs) serving as precursors. Identifying risk factors such as vitamin D deficiency and the insulin-like growth factor (IGF) axis is crucial for prevention. (2) This case–control study included 85 participants (53 CRA patients and 32 controls) who underwent colonoscopy. We measured serum vitamin D3 (cholecalciferol), calcidiol (vitamin D metabolite), calcitriol (active vitamin D metabolite), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) to explore their associations with CRA risk. (3) Results: We found that lower cholecalciferol levels were a significant risk factor for CRA (OR = 4.63, p = 0.004). Although no significant differences in calcidiol and calcitriol levels were observed between CRA patients and controls, calcidiol deficiency was common in the study population. IGF-1 levels inversely correlated with age, calcitriol, and IGFBP-3 in CRA patients. (4) This study highlights the potential of lower cholecalciferol levels to detect patients at risk of CRA when calcidiol values cannot, suggesting the importance of evaluating different vitamin D metabolites in cancer prevention research. Our findings underscore the need to further investigate the interactions between calcitriol, the active form of vitamin D, and the IGF axis in colorectal cancer development. [ABSTRACT FROM AUTHOR]

Autoimmune thyroiditis (Hashimoto's thyroiditis) is the most common autoimmune disease. It most often manifests itself as hypothyroidism but may also present with euthyroidism or even hyperthyroidism. The etiopathogenesis of autoimmune thyroiditis is still unclear. However, in addition to genetic and epigenetic factors, many environmental factors are known to increase the risk of developing AIT. In this review, we aimed to collect and analyze data connected with environmental factors and autoimmune thyroiditis development. Our review indicates iodine intake, vitamin D deficiency, selenium deficiency, viral infections caused by Epstein–Barr Virus (EBV), Human parvovirus B19 (PVB19), Human herpesvirus 6A (HHV-6A) and Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), bacterial infection caused by Helicobacter pylori, microbiome disruption, medications such as interferon-alpha and tyrosine kinase inhibitors, as well as stress, climate, and smoking can influence the risk of the occurrence of autoimmune thyroiditis. Having knowledge of risk factors allows for making changes to one's diet and lifestyle that will reduce the risk of developing the disease and alleviate the course of autoimmune thyroiditis. [ABSTRACT FROM AUTHOR]

Anomalies in lipid metabolism involve multifactorial pathogenesis, among other factors, being associated with an inflammatory state and disturbances in vitamin D status. The literature has focused on the binary relationships between inflammation and dyslipidemia, vitamin D and dyslipidemia, or vitamin D and inflammation. Our study aimed to explore the link between all these three factors: 25-OH vitamin D serum levels, the presence of inflammation assessed through serum C-reactive protein (CRP), and serum lipid profile in 2747 hospitalized patients. Our results showed a positive correlation of HDL-C with 25 (OH) vitamin D and a negative correlation of HDL-C with CRP. This relationship had different patterns in the statistical network analysis. The network analysis patterns are preserved for males and females, except for the relationship between CRP and vitamin D, which is present in male cases and absent in females. The same triangular relationship between all three—CRP, vitamin D, and HDL-C was found with different strengths of partial correlation in obese and non-obese patients. This pattern was similar in patients with and without fatty liver. A shifted pattern was found in the network analysis of hypertensive patients. The CRP was negatively correlated with vitamin D and HDL-C, and vitamin D was positively correlated with HDL-C in non-hypertensive patients. Castelli's Risk indexes I and II were positively associated with CRP, suggesting that increased cardiovascular risk is proportional to an inflammatory state. The triad formed by altered serum lipid levels, inflammation, and vitamin D represents a complex relationship marked by specific dynamics between lipidic fractions such as HDL-C and C-reactive protein and vitamin D. [ABSTRACT FROM AUTHOR]

Human beta-defensins are host defense peptides with broad antimicrobial and inflammatory functions. In the oral cavity, these peptides are produced mainly by the keratinocytes of the epithelium; however, fibroblasts, monocytes, and macrophages also contribute to oral human beta-defensin expressions. The resident and immune cells of the oral cavity come into contact with various microbe-associated molecular patterns continuously and simultaneously. The overall antimicrobial cellular response is highly influenced by local and environmental factors. Recent studies have produced evidence showing that not only systemic chronic diseases but also systemic factors like hyperglycemia, pregnancy, the long-term use of certain vitamins, and aging can modulate oral cellular antimicrobial responses against microbial challenges. Therefore, the aim of this narrative review is to discuss the role of systemic factors on oral human beta-defensin expressions. [ABSTRACT FROM AUTHOR]

Simple Summary: This case report highlights two wild juvenile American black bears that were admitted to a rehabilitation facility but were euthanized due to severe immobility and joint laxity. Known musculoskeletal diseases of young bears are usually caused by trauma in the wild, or potentially rickets (a form of malnutrition) if raised in captivity. However, Case 1 was diagnosed with abnormal cartilage development (chondrodysplasia), likely of genetic origin, and Case 2 had osteoporosis and unidentified collagen abnormalities which are both unique to the current literature. With growing black bear populations, and increasing wildlife–human interface, we advise wildlife biologists and veterinarians to monitor and evaluate similar cases to help us further understand these uncommon diseases. Severe musculoskeletal disease characterized by marked joint laxity was the cause of euthanasia in two wild juvenile American black bears (Ursus americanus) admitted to a rehabilitation facility in eastern Tennessee in 2023. Previously, almost all reported musculoskeletal diseases in this population were of traumatic etiology, even in malnourished yearlings. Case 1 was an orphaned 11-month-old male cub exhibiting disproportionate dwarfism, progressive immobility, and joint laxity. Necropsy findings suggested either chondrodysplasia or rickets, and imaging findings supported a skeletal dysplasia. Case 2 was a 14-month-old emaciated male yearling exhibiting joint laxity and immobility. Necropsy findings showed osteoporosis and serous atrophy of fat, and imaging findings were inconsistent with a skeletal dysplasia. Both cases were clinically inconsistent with rickets based on normal calcium, phosphorous, and parathyroid hormone concentrations; however, Case 1 had hypovitaminosis D (9 nmol/L) compared to healthy juvenile black bears. We hypothesize that Case 1 had a genetic chondrodysplasia while the osteoporosis of Case 2 was due to chronic malnutrition. The goal of this case report is to inform wildlife agencies and facilities to monitor for similar, non-trauma-related debilitating musculoskeletal disease in free-ranging bears and evaluate cases that allow us to further understand the disease processes involved. [ABSTRACT FROM AUTHOR]

Vitamin D plays an important pleiotropic role in maintaining global homeostasis of the human body. Its functions go far beyond skeletal health, playing a crucial role in a plethora of cellular functions, as well as in extraskeletal health, ensuring the proper functioning of multiple human organs, including the skin. Genes from the Grainyhead-like (GRHL) family code for transcription factors necessary for the development and maintenance of various epithelia. Even though they are involved in many processes regulated by vitamin D, a direct link between vitamin D-mediated cellular pathways and GRHL genes has never been described. We employed various bioinformatic methods, quantitative real-time PCR, chromatin immunoprecipitation, reporter gene assays, and calcitriol treatments to investigate this issue. We report that the vitamin D receptor (VDR) binds to a regulatory region of the Grainyhead-like 1 (GRHL1) gene and regulates its expression. Ectopic expression of VDR and treatment with calcitriol alters the expression of the GRHL1 gene. The evidence presented here indicates a role of VDR in the regulation of expression of GRHL1 and correspondingly a role of GRHL1 in mediating the actions of vitamin D. [ABSTRACT FROM AUTHOR]

Vitamin D, obtained from diet or synthesized internally as cholecalciferol and ergocalciferol, influences bodily functions through its most active metabolite and the vitamin D receptor. Recent research has uncovered multiple roles for vitamin D in the central nervous system, impacting neural development and maturation, regulating the dopaminergic system, and controlling the synthesis of neural growth factors. This review thoroughly examines these connections and investigates the consequences of vitamin D deficiency in neurological disorders, particularly neurodegenerative diseases. The potential benefits of vitamin D supplementation in alleviating symptoms of these diseases are evaluated alongside a discussion of the controversial findings from previous intervention studies. The importance of interpreting these results cautiously is emphasised. Furthermore, the article proposes that additional randomised and well-designed trials are essential for gaining a deeper understanding of the potential therapeutic advantages of vitamin D supplementation for neurological disorders. Ultimately, this review highlights the critical role of vitamin D in neurological well-being and highlights the need for further research to enhance our understanding of its function in the brain. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide with coronary artery disease (CAD) being the first culprit in this group. In terms of CAD, not only its presence but also its severity plays a role in the patient's treatment and prognosis. CAD complexity can be assessed with the indicator named the SYNTAX score (SS). A higher SS is associated with major adverse cardiovascular event (MACE) occurrence in short- and long-term observations. Hence, the risk factors affecting CAD severity based on SS results may help lower the risk among patients with already developed CAD to reduce their impact on coronary atherosclerosis progression. The well-established risk factors of CAD are consistent with those associated with the coronary plaque burden. However, recently, it was shown that new indicators exist, which we present in this paper, that significantly contribute to CAD complexity such as inflammatory parameters, C-reactive protein (CRP), ratios based on blood smear results, and uric acid. Moreover, microbiota alteration, vitamin D deficiency, and obstructive sleep apnea (OSA) also predicted CAD severity. However, sometimes, certain indicators were revealed as significant only in terms of chronic coronary syndromes (CCSs) or specific acute coronary syndromes (ACSs). Importantly, there is a need to apply the interdisciplinary and translational approach to the novel CAD severity risk assessment to maximize the impact of secondary prevention among patients at risk of coronary atherosclerosis progression. [ABSTRACT FROM AUTHOR]

There is increasing evidence that vitamin D (VitD) supplementation may reduce inflammation in individuals with multiple sclerosis (MS). The aim of this study was to evaluate the effect of different doses of VitD on selected markers of inflammation in patients with relapsing–remitting MS (RRMS). Participants were divided depending on the supplemented dose of VitD into a high-dose (2000 IU/d; HD) group and a low-dose (15,960 IU/month; LD) group (n = 23 and n = 29, respectively). The concentration of 25(OH)D and the levels of CXCL16, PTX3, ALCAM, IL-1RA, and OPG were measured initially and after six months of VitD supplementation in blood serum. A significant increase in the concentrations of CXCL16, PTX3, and OPG was observed during the study (p = 0.02, p = 0.01, and p < 0.01, respectively). Furthermore, a higher increase in PTX3 and OPG in the LD group was observed (p = 0.04 and p = 0.03, respectively). A significant positive correlation was observed between the 25(OH)D serum concentration and PTX3 (R = 0.28, p < 0.05) and OPG (R = 0.28, p < 0.05) only at the beginning of the study. In patients with RRMS, such doses of VitD might be too low to induce obvious beneficial effects on the pro-inflammatory and inflammatory balance. [ABSTRACT FROM AUTHOR]

Sarcopenia refers to the progressive loss and atrophy of skeletal muscle function, often associated with aging or secondary to conditions involving systemic inflammation, oxidative stress, and mitochondrial dysfunction. Recent evidence indicates that skeletal muscle function is not only influenced by physical, environmental, and genetic factors but is also significantly impacted by nutritional deficiencies. Natural compounds with antioxidant properties, such as resveratrol and vitamin D, have shown promise in preventing mitochondrial dysfunction in skeletal muscle cells. These antioxidants can slow down muscle atrophy by regulating mitochondrial functions and neuromuscular junctions. This review provides an overview of the molecular mechanisms leading to skeletal muscle atrophy and summarizes recent advances in using resveratrol and vitamin D supplementation for its prevention and treatment. Understanding these molecular mechanisms and implementing combined interventions can optimize treatment outcomes, ensure muscle function recovery, and improve the quality of life for patients. [ABSTRACT FROM AUTHOR]

The hepatoprotective effects of natural products have been a significant focus in recent decades due to the growing demand for the help in the treatment of hepatic impairments. This review specifically delves into the findings of clinical trials involving 13 selected natural products, namely plants and their derived compounds (e.g., artichoke, berberine, and turmeric), algae (e.g., spirulina), probiotics, and other products like phospholipids and vitamin D. A literature search was performed in the Scopus database, PubMed, and Google Scholar, covering all articles found up to June 2024. Artichoke, berberine, chlorella, chicory, green tea, probiotics, phospholipids, schisandra, silymarin, spirulina, and vitamin D caused a decrease in liver enzymes, while for cinnamon and turmeric such an effect was either not observed or not convincing. The presented results indicate that some natural products might satisfactorily improve hepatic outcomes in NAFLD, NASH, and other liver disorders; however, further studies and metanalyses are needed to clearly demonstrate their effectiveness. [ABSTRACT FROM AUTHOR]

Recently, there has been a growing interest in relation to the female athlete, especially in widespread disciplines such as football. Concerns about vitamin D deficiency status have recently been considered due to its effects on the performance and health status of female footballers. However, its relationship to body composition and muscle damage in female football athletes remains unclear to date. The purpose of the present study was to analyse the association of the vitamin D status of Spanish elite female football players with anthropometric variables and markers of muscle damage. Ethical consent was obtained from a total of 21 players from a Spanish elite women's football team (20–33 years). Anthropometric analysis was carried out according to the standardised protocol of the International Society for the Advancement of Kineanthropometry (ISAK). The clinical analyses, based on urine and blood samples, were carried out by the club's medical staff at the start of the season in the early morning in a fasting state. The athletes were also asked about the regularity of their menstrual cycle and some dietary habits. Thirty-three percent of the female athletes had vitamin D levels below the reference values. Significantly higher FM values were observed in athletes with low vitamin D status (p < 0.05), as well as statistically significant negative correlations between vitamin D levels and FM (p < 0.05) in the group of female players with vitamin D levels below the baseline values. No significant associations were observed between markers of muscle damage and the other variables. Complementing an assessment of body composition with a biochemical analysis of vitamin D levels may be an interesting strategy in the process of monitoring the elite female football player throughout the season. [ABSTRACT FROM AUTHOR]

Vitamin D, a crucial fat-soluble vitamin, is primarily synthesized in the skin upon exposure to ultraviolet radiation and is widely recognized as a bone-associated hormone. However, recent scientific advancements have unveiled its intricate association with gut health. The intestinal barrier serves as a vital component, safeguarding the intestinal milieu and maintaining overall homeostasis. Deficiencies in vitamin D have been implicated in altering the gut microbiome composition, compromising the integrity of the intestinal mucosal barrier, and predisposing individuals to various intestinal pathologies. Vitamin D exerts its regulatory function by binding to vitamin D receptors (VDR) present in immune cells, thereby modulating the production of pro-inflammatory cytokines and influencing the intestinal barrier function. Notably, numerous studies have reported lower serum vitamin D levels among patients suffering from intestinal diseases, including inflammatory bowel disease, irritable bowel syndrome, and celiac disease, highlighting the growing significance of vitamin D in gut health maintenance. This comprehensive review delves into the latest advancements in understanding the mechanistic role of vitamin D in modulating the gut microbiome and intestinal barrier function, emphasizing its pivotal role in immune regulation. Furthermore, we consolidate and present relevant findings pertaining to the therapeutic potential of vitamin D in the management of intestinal diseases. [ABSTRACT FROM AUTHOR]

Athletes are characterized by special nutritional needs. Meeting their dietary needs associated with intensive exercise is a prerequisite for effective training and success in sports competitions. Hence, it is important to supply key performance nutrients, such as macronutrients, antioxidants, calcium, vitamin D, or iron, in adequate quantities. The increased need for these nutrients makes it necessary to look for food products on the market that more fully cover these needs. Such products may include organic foods. According to research, they have unique properties and are richer in selected nutrients, such as antioxidants. Hence, the aim of this review was to analyze the available literature as to whether organic foods have the potential to more fully cover the increased nutritional requirements of athletes for selected nutrients compared to conventionally produced foods. A narrative review of current literature was carried out. As the analysis showed, organic foods are characterized by a higher content of antioxidant bioactive compounds, a higher content of n-3 fatty acids, a better n:3/n:6 ratio, and a more optimal amino acid composition, which may result in an appropriate dietary ration design for athletes. In conclusion, organic food appears to be an interesting alternative to meet the special nutritional needs of professional and amateur athletes. [ABSTRACT FROM AUTHOR]