Search Results (400)

Background/Objectives: Vitamin D plays an important role in muscle metabolism and recovery, yet its kinetics during and after football-specific physical activity remain poorly understood. Therefore, this study aimed to determine whether physical effort during a football match influences the concentration of vitamin D metabolites and to explore the effect of a single high-dose cholecalciferol supplementation combined with physical exercise on the levels of vitamin D metabolites in professional football players. Methods: Twenty professional football players participated in a three-phase, randomized placebo-controlled pilot study. Baseline fitness and blood samples were collected, followed by pre- and post-match measurements during two games. In the final phase, half of the players received a single 500,000 IU dose of vitamin D₃ before a simulated match. Blood samples were collected before and after each session to analyze vitamin D metabolites using the isotope-dilution liquid chromatography–tandem mass spectrometry (ID-LC-MS/MS) method. Results: Physical exercise during the football match significantly increased serum concentrations of 25-(OH)D₃, 24,25-(OH)₂D₃, and 3-epi-25-(OH)D₃ (by up to 25%, p < 0.001). Following supplementation, these effects were further amplified, with 25-(OH)D₃ rising by 98% and 3-epi-25-(OH)D₃ by 424% (p < 0.001). Significant alterations in vitamin D metabolite ratios after exercise and supplementation suggest enhanced metabolic turnover and dynamic regulation of vitamin D pathways in response to physical effort. Conclusions: Football-specific physical activity appears to stimulate the release of vitamin D metabolites. High-dose cholecalciferol supplementation was well tolerated and may rapidly increase vitamin D status in professional athletes. These findings may have implications for optimizing recovery and performance, though larger trials are needed. Full article

Vitamin D deficiency is associated with the risk of atopic diseases and respiratory infections. The activated vitamin D receptor (VDR) forms a dimer with the retinoid X receptor alpha (RXRA) and binds to VDR/RXRA composite elements (CEs) in enhancers of target genes. However, VDR/RXRA CEs are identified in only 11.5% of cases in ChIP-Seq peaks. Our hypothesis was that VDR could form a VDR-Partner complex with transcription factor for which CEs have not yet been identified. We utilized Web-MCOT to search for novel VDR/Partner CEs in regulatory DNA. The potential formation of the VDR-Partner protein complex was assessed using the AlphaFold machine learning model. Through real-time RT-PCR, we measured the expression of immune system genes in a culture of U937 macrophage-like cells incubated with the active metabolite of vitamin D, calcitriol. We have predicted novel VDR/NR2C2 and VDR/PPARG CEs in the regulatory regions of immune system genes. We found potential synergism of VDR/NR2C2 and VDR/RXRA CEs in relation to the IRF5 gene, as well as potential synergism of VDR/PPARG and VDR/RXRA CEs for MAPK13. Predicting new regulatory relationships through the identification of new potential VDR/Partner CEs may provide insight into the deep mechanisms of vitamin D involvement in the pathogenesis of atopic dermatitis, bronchial asthma, allergic rhinitis, and pulmonary infections. Full article

Vitamin D₃ (VD3) is an essential micronutrient, but its analytical determination in biological matrices is often hindered by structurally related metabolites and the limited selectivity of conventional analytical sorbents. The preparation of a molecularly imprinted polymer (MIP) using VD3 as a template is challenging due to its hydrophobic structure and lack of polar groups. Therefore, in this work, MIPs were prepared using the closely related structure hyodeoxycholic acid methyl ester as a template and tested for their adsorption capacity toward VD3. Several MIPs were first prepared using different functional monomers, and the results showed that 4-vinylpyridine (4VP) monomer in combination with divinylbenzene (DVB) as a crosslinker exhibited a relatively high binding capacity and imprinting factor. UV spectroscopy indicated an optimal VD3–monomer ratio of 1:4, while computational modeling further confirmed favorable interactions between VD3 and 4VP. The effect of incorporating styrene as a co-monomer with 4VP was also investigated, showing an enhancement in adsorption capacity with a slight increase in the imprinting factor. However, TGA analysis revealed that the thermal stability of the MIPs decreased with higher styrene content. Overall, the prepared MIPs demonstrated improved selectivity and recognition of VD3 compared to the non-imprinted polymers, offering a promising approach for its selective extraction and quantification. Full article

The genus Plukenetia includes lianas or vines with oleaginous seeds rich in omega-3 and omega-6 fatty acids, proteins, and vitamin E, and the presence of flavonoids, steroids, and terpenoids has also been reported in leaves. Several species of Plukenetia have traditionally been cultivated in their native distribution areas, and their propagation is usually by seed. The aim of this work was to establish callus and cell suspension cultures of P. carabiaseae, an endemic species of Mexico, for the evaluation of the in vitro antioxidant and anti-inflammatory potential of its extracts. Three light conditions were evaluated for the establishment of P. carabiaseae callus lines from leaf explants. Friable calluses obtained under constant light were used to initiate a cell suspension cultures in Gamborg basal (B5) medium supplemented with 2,4-dichlorophenoxyacetic acid (2,4-D) and kinetin (CIN), as growth regulators. After 35 days of cultivation, different polarity extracts from biomass were obtained, showing that the acetone extract had the highest antioxidant activity and a high total phenolic content (30.57 mg of gallic acid equivalent (GAE)/g dry weight). The anti-inflammatory activity of the methanolic extract, evaluated in murine macrophages induced with bacterial lipopolysaccharides, was dose-dependent, without cytotoxic effects. This is the first report of the establishment of P. carabiasiae cell suspension culture and demonstrates its potential as a biotechnological source of antioxidant and anti-inflammatory metabolites. Full article

Humans with chronic biliary tract disease (CBTD) have low serum liposoluble vitamins (A, D, E). Few studies have been performed in veterinary medicine to evaluate whether vitamins vary in canine CBTD. This study aimed to compare liposoluble vitamin between CBTD and healthy dogs. A total of 84 client-owned dogs with CBTD and 50 healthy dogs were included. CBTD diagnosis was based on clinical, blood biochemistry and abdominal ultrasound. Dogs with CBTD were divided into subgroups according to their cholestasis ultrasound severity. To measure vitamin concentrations, leftover serum samples were used. The 25-hydroxyvitamin D, α-tocopherol, and retinol, respectively, vitamin D, E, and A metabolites, were measured with HPLC. Both, 25-hydroxyvitamin D and α-tocopherol were significatively lower in CBTD than in healthy dogs. In contrast, retinol was higher in CBTD dogs. In CBTD dogs, no significant differences in vitamin concentrations considering ultrasound severity were found. Presence of biliary disease in dogs results in lower blood vitamins D and E, and higher vitamin A concentration. Lower vitamins D and E concentration could reflect a possible lipid malabsorption. The higher concentration of vitamin A could be in line with recent human studies, where retinol increases as an expression of dysregulated homeostasis during chronic liver disease. Full article

Background/Objectives: One of the main reasons for discrepancies in the role of vitamin D in ART could be the measurement of the conventional biomarker 25(OH)D₃. It is known that this value is affected by multiple factors, such as tissue origin, assay variability, classification criteria, and potential storage-related degradation. In this study, we investigate 24,25(OH)₂D₃ as a new biomarker to improve vitamin D assessment in women’s reproductive health, particularly regarding oocyte development. Methods: A prospective cohort study including 35 oocyte donors undergoing controlled ovarian stimulation, who were recruited between October and November 2017, was conducted. Vitamin D metabolites were measured at the baseline and after seven months of storage at −80 °C. Paired serum and pooled follicular fluid (FF) samples were collected at oocyte retrieval. 25(OH)D₃ and 24,25(OH)₂D₃ were quantified by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). Statistical analyses included paired tests (serum vs. FF; baseline vs. stored) and Pearson’s correlations (two-sided α = 0.05). Results: At the baseline, the mean serum 25(OH)D₃ concentration was 91.56 ± 39.01 nmol/L and the mean FF concentration was 58.13 ± 19.55 nmol/L (p < 0.0001). Serum 24,25(OH)₂D₃ averaged 15.62 ± 10.99 nmol/L, compared with 11.26 ± 6.09 nmol/L in FF (p = 0.004). In both fluids, 25(OH)D₃ and 24,25(OH)₂D₃ were strongly correlated (serum R² = 0.92; FF R² = 0.91). Across fluids, the serum–FF correlation was stronger for 24,25(OH)₂D₃ (R² = 0.77, p <0.0001) than for 25(OH)D₃ (R² = 0.69, p < 0.0001). After seven months of storage, 25(OH)D₃ concentrations decreased significantly (serum −32%; FF −38%; both p < 0.0001), whereas 24,25(OH)₂D₃ levels remained stable (serum p = 0.24; FF p = 0.36). Conclusions: Serum 24,25(OH)₂D₃ is a more reliable and minimally invasive biomarker for assessing ovarian vitamin D status than the current gold standard, 25(OH)D₃. Incorporating this metabolite into research studies and storage quality control may improve the reliability of retrospective analyses based on cryopreserved material, contributing to a better understanding of the role of vitamin D in human reproduction. Full article

Background: Vitamin D is increasingly recognized as a key immunomodulatory nutrient, influencing innate and adaptive immune responses. While 25-hydroxyvitamin D [25(OH)D] is widely used to assess vitamin D status, the active form, 1,25-dihydroxyvitamin D [1,25(OH)₂D], may exert distinct effects on immune function. This study investigates the concentration-dependent and sex-specific relationships of both vitamin D metabolites with systemic inflammatory markers in a large clinical cohort. Objectives: To characterize the associations of 25(OH)D and 1,25(OH)₂D with total white blood cell (WBC) count and leukocyte subtypes, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils. Methods: We conducted a retrospective cross-sectional analysis of 125,537 adults (37.9% male; age 18–89 years) from routine laboratory diagnostics collected between 2014 and 2020 in Germany. Serum 25(OH)D and 1,25(OH)₂D were measured using standardized chemiluminescent immunoassays. Inflammatory markers were assessed via automated hematology. Multivariable-adjusted linear and non-linear regression models were used to assess associations, adjusting for age, sex, and season. Results: Neutrophils and Monocytes: Displayed U-shaped associations with both 25(OH)D and 1,25(OH)₂D. Neutrophil counts were lowest at 25(OH)D levels of ~40–60 nmol/L and increased significantly at both lower and higher extremes (p < 0.001). Lymphocytes: Inverse relationship with 25(OH)D (p < 0.001), and an inverse U-shaped relationship with 1,25(OH)₂D, peaking at ~90 pmol/L, with counts decreasing at both lower and higher levels (p < 0.001). Sex-specific analysis revealed that the relationship between 1,25(OH)₂D and lymphocyte count remained independent only in men, Eosinophils and Basophils: Demonstrated consistently negative correlations with both forms of vitamin D across all concentration ranges (p < 0.001). Conclusions: Our findings reveal distinct, concentration-dependent associations between vitamin D metabolites and leukocyte profiles, with evidence for nonlinear and sex-specific immunological effects. Both low and high levels of 25(OH)D and 1,25(OH)₂D were linked to increased neutrophil and monocyte counts, suggesting that vitamin D excess, like deficiency, may be linked to low-grade inflammation. These data are hypothesis-generating and suggest that personalized monitoring of vitamin D status may be relevant for future research on immune health, particularly in populations at risk for inflammatory or metabolic disease, but they do not provide a basis for clinical decision-making. Full article

The interaction between the gut microbiota and the skeletal system has evolved into a new research focus. Studies underscore the role of bioactive metabolites in sustaining systemic balance via the “gut microbiota–endocrine–skeleton” axis, where they modulate metabolic processes and organ morphology through intracellular signaling. A key bidirectional relationship exists with the gut: shifts in gut microbiota affect host metabolism and subsequent metabolite profiles, while these metabolites can, in turn, reshape the intestinal microenvironment. This review explores how short-chain fatty acids (SCFAs), estrogen, and vitamin D modulate osteoporosis via the gut–bone axis. It synthesizes evidence of their signaling pathways and metabolic roles, identifies research gaps from recent clinical studies, and evaluates gut microbiota-targeted therapeutic strategies for potential clinical translation. Full article

CYP24A1, a mitochondrial cytochrome P450 enzyme, plays a critical role in the catabolism of active vitamin D metabolites and is a key regulator of local vitamin D signaling in the small intestine. While traditionally studied in the context of renal physiology, increasing evidence highlights its distinct regulatory mechanisms and functional significance within the intestinal epithelium. This review explores the molecular architecture, tissue-specific expression patterns, and multifactorial regulation of CYP24A1 in enterocytes, encompassing nuclear receptor signaling, epigenetic and post-transcriptional control, and environmental influences such as inflammation, diet, and the gut microbiota. We discuss how intestinal CYP24A1 modulates the expression of vitamin D target genes involved in transcellular calcium absorption and epithelial barrier function, and how its dysregulation contributes to gastrointestinal disorders including inflammatory bowel diseases, celiac disease, microbiota dysbiosis, and colorectal cancer. In addition, we examine preclinical and translational evidence supporting CYP24A1 as a potential therapeutic target. Emerging strategies such as selective enzyme inhibitors, microbiota modulation, RNA-based technologies, and personalized supplementation approaches are considered in the context of restoring local vitamin D bioactivity and mineral homeostasis. Together, this review underscores the clinical importance of intestinal CYP24A1 and highlights novel opportunities for targeted interventions in vitamin D-responsive gastrointestinal pathologies. Full article

Background/Objectives: Vitamin C plays a vital role in human health, functioning as a powerful antioxidant and enzymatic cofactor. Although vitamin C bioavailability from food versus supplements has been debated, few studies have examined how intake form affects absorption and physiological markers. Methods: This randomized, controlled, crossover trial aimed to compare the bioavailability of vitamin C consumed as a supplement, through raw fruits and vegetables, or through fruit and vegetable juice. Twelve healthy adults underwent three 1-day crossover trials, each separated by a 2-week washout. Participants consumed 101.7 mg of vitamin C via powder, raw fruits and vegetables (186.8 g), or juice (200 mL). Plasma and urinary vitamin C concentrations, urinary metabolites (¹H NMR), and antioxidant activity (ORAC and TRAP) were assessed over 24 h. Results: All interventions elevated plasma vitamin C levels, with juice yielding the highest AUC (25.3 ± 3.2 mg/dL·h). Urinary vitamin C increased in all groups. Metabolomics revealed increased urinary excretion of mannitol, glycine, taurine, dimethylglycine (DMG), and asparagine, and decreased choline and dimethylamine (DMA). Notably, urinary mannitol increased only in the morning. Choline significantly decreased after powder intake (p = 0.001), with similar trends observed in the other groups. DMG and glycine increased following raw and juiced vegetable intake. Antioxidant activity showed transient ORAC elevation post-powder but no sustained improvements. Conclusions: Vitamin C is bioavailable from all intake forms, with juice providing the most efficient absorption. Urinary metabolite changes suggest microbiota-related modulation, while antioxidant activity improvements were limited. Full article

Corneal fibrosis, a significant source of visual impairment, can result from keratocyte-to-myofibroblast transdifferentiation during wound healing. This study investigated the antifibrotic role of 1,25-dihydroxyvitamin D₃ (1,25 Vit D) and the lesser-known vitamin D, 24,25-dihydroxyvitamin D₃ (24,25 Vit D), in human and mouse corneal stromal cells (HSCs and MSCs) and in a Vit D receptor knockout (VDR KO) mouse model. Cells were treated with TGF-β1 ± Vit D metabolites and the expression of fibrotic and antifibrotic genes and proteins was evaluated. Both metabolites significantly reduced α-smooth muscle actin levels in HSCs, MSCs and organ-cultured mouse corneas (p < 0.05). They also upregulated the mRNA expression of BMP2, BMP6, BMPR2, and TGF-β3, as well as the protein expression of BMP6 and TGF-β3. VDR KO corneas subjected to alkali injury exhibited increased fibrotic responses and reduced CD45+ immune cell infiltration compared to wild-type controls. Notably, 24,25 Vit D exerted antifibrotic effects even in VDR KO cells, and the alternative 24,25 Vit D receptor FAM57B was expressed in all corneal cell layers. These results reveal consistent antifibrotic effects of both 1,25 and 24,25 Vit D across species, support the existence of VDR-independent mechanisms in the cornea, and offer new insights into potential therapeutic strategies for preventing corneal fibrosis. Full article

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease in which environmental factors modulate genetically determined immune dysregulation. Vitamin D has emerged as a plausible modifier of disease expression because its active metabolite signals through the vitamin D receptor on innate and adaptive immune cells and influences antigen presentation, cytokine balance, and lymphocyte differentiation. This narrative review synthesizes current evidence on vitamin D status and supplementation in SLE with attention to organ-specific domains. Observational studies consistently report high rates of hypovitaminosis D in SLE and associations with less favorable clinical profiles, including higher global and renal disease activity, adverse cardiometabolic features, greater infection vulnerability, and neuropsychiatric manifestations. Preclinical models demonstrate neuroprotective and barrier-stabilizing actions of vitamin D analogs, supporting biological plausibility. Interventional trials indicate that supplementation safely corrects deficiency and shows signals of benefit for selected outcomes (e.g., modest activity reductions or fatigue in specific contexts), although effects on interferon signatures, complement, and autoantibodies are heterogeneous and often limited. Overall, current evidence supports optimization of vitamin D status as a low-risk adjunct in comprehensive SLE care while highlighting the need for adequately powered, organ-focused randomized trials using standardized measurements and prespecified endpoints to define causality, therapeutic targets, and long-term safety. Full article

Broiler chickens are commonly reared in closed housing systems with limited exposure to sunlight, thereby relying entirely on dietary sources of vitamin D. The hydroxylated metabolite 25-hydroxycholecalciferol [25(OH)D₃] has been proposed as a more potent form than native vitamin D₃ (cholecalciferol). This study evaluated the effects of dietary supplementation with vitamin D₃ alone or in combination with 25(OH)D₃ on growth performance, bone characteristics, and cecal microbiota in Ross 308 broilers. A total of 952 one-day-old male chicks were allocated to four treatments: a negative control (no vitamin D₃), a positive control (vitamin D₃ according to Ross 308 specifications), and a positive control supplemented with 25(OH)D₃ at 1394 or 2788 IU/kg, in a randomized design with 17 replicates per treatment and 14 birds per replicate. Over a 40-day feeding trial, diets containing vitamin D₃ (positive control) or supplemented with 25(OH)D₃ significantly improved final body weight, weight gain, average daily gain, and feed conversion ratio compared with the negative control (p < 0.01), with no significant differences among the positive control and 25(OH)D₃-supplemented groups, with a clear linear dose-dependent response. Although tibia ash and bone-breaking strength were not significantly affected, linear responses indicated a slight numerical trend toward improved skeletal mineralization with increasing 25(OH)D₃. Microbiota analysis indicated that 25(OH)D₃ affected cecal microbial ecology: low-dose inclusion showed reduced species richness and evenness, whereas high-dose inclusion restored richness to levels comparable to the positive control and enriched taxa associated with fiber fermentation and bile acid metabolism while reducing Lactobacillus dominance. In conclusion, supplementation with 25(OH)D₃ in addition to vitamin D₃ enhanced growth performance and selectively shaped the cecal microbiota of broilers, with suggestive benefits for bone mineralization. These findings highlight 25(OH)D₃ as a more potent source of vitamin D than cholecalciferol alone and support its practical use in modern broiler nutrition to improve efficiency, skeletal health, and microbial balance. Full article

Introduction: Chronic spontaneous urticaria (CSU), vitiligo, and Hashimoto’s thyroiditis (HT) frequently co-occur in the same patients, suggesting a shared autoimmune pathogenesis. These conditions are increasingly recognized as components of polyautoimmunity, with overlapping clinical, immunological, and pathogenetic features. Among the proposed common mechanisms, vitamin D deficiency and oxidative stress (OS) have emerged as key contributors. We aimed to explore the shared immunopathogenic pathways linking these conditions, with a focus on the interplay between vitamin D status and redox imbalance. Methods: An extensive narrative review of the current literature regarding the associations among CSU, vitiligo, and HT, focusing on the role of vitamin D status, OS, and nitrosative stress, and shared immunological pathways was conducted. Discussion: Vitamin D deficiency was consistently observed across all three conditions and is associated with increased disease activity and poorer clinical outcomes. Several polymorphisms in the vitamin D receptor (VDR) and binding protein genes correlate with disease susceptibility. OS and nitrosative stress markers, such as malondialdehyde (MDA) and nitric oxide (NO) metabolites, are elevated in patients with CSU, vitiligo, and HT, and are linked to tissue-specific immune activation, apoptosis, and loss of self-tolerance. Evidence suggests that vitamin D and antioxidant supplementation may provide clinical benefit. In vitiligo, narrowband ultraviolet B (NB-UVB) phototherapy not only promotes repigmentation through melanocyte stimulation but also reduces ROS production and modulates local immune responses. Conclusions: The coexistence of CSU, vitiligo, and HT reflects a broader systemic autoimmune tendency, with vitamin D deficiency and redox imbalance serving as potential unifying mechanisms. Routine assessment of vitamin D levels and OS parameters may enhance diagnostic precision and inform therapeutic strategies. Antioxidant-based interventions represent promising avenues in the integrated management of autoimmune skin and endocrine disorders. Full article

Objective: Vitamin D deficiency (VDD) is common in pregnancy and may affect lipid metabolism. The underlying mechanisms are multifactorial, but most evidence so far comes from non-pregnant populations. This study aims to identify metabolites and metabolic patterns associated with VDD in early pregnancy and to evaluate their relationships with maternal lipid profiles. Methods: A nested case–control research was carried out in the Zhoushan Pregnant Women Cohort (ZPWC). Cases were defined as women with VDD (25(OH)D < 20 ng/mL), and controls (≥20 ng/mL) were matched 1:1 using propensity scores based on age, pre-pregnancy BMI, gestational week, and calendar year at blood sampling. The untargeted metabolomics of first-trimester maternal plasma were measured. Metabolic profiles were analyzed using partial least squares-discriminant analysis (PLS-DA). Principal component analysis (PCA) was applied to visualize group separation, and metabolite set enrichment analysis (MSEA) was performed to reveal biologically relevant metabolic patterns. Associations between VDD-related metabolite components in early pregnancy and lipid levels in mid-pregnancy were assessed using linear regression models. Results: 44 cases and 44 controls were selected for the study. There were 60 metabolites identified as being connected to VDD. Among these, 26 metabolites, primarily glycerophospholipids and fatty acyls, exhibited decreased levels in the VDD group. In contrast, 34 metabolites showed increased levels, mainly comprising benzene derivatives, carboxylic acids, and organooxygen compounds. PCA based on these metabolites explained 52.8% of the total variance (R²X = 0.528) across the first six principal components (PC1: 16.4%, PC2: 10.6%, PC3: 9.2%, PC4: 6.3%, PC5: 5.7%, PC6: 4.6%). PC2, dominated by lineolic acids and derivatives, was negatively associated with total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) (all p < 0.01). PC3, dominated by glycerophosphocholines, was negatively associated with TC, TG, and high-density lipoprotein cholesterol (HDL-C) (all p < 0.05). MSEA revealed significant enrichment of the pantothenate and CoA biosynthesis pathway after multiple testing correction (FDR < 0.05). Conclusions: This study reveals distinct metabolic alterations linked to VDD and suggests potential mechanisms underlying its association with maternal lipid metabolism in early pregnancy. Full article