Search Results (1,143)

Primary hyperparathyroidism (PHPT) and vitamin D deficiency (VD) are two frequent medical conditions in the Western world. Purely by dint of their prevalence, these conditions are commonly comorbid. Moreover, they can interact with one another: VD may stimulate PTH secretion, while PHPT may lead to unregulated vitamin D activation from 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25OH2D), thereby lowering 25OHD levels and further exacerbating VD. Thus, a real conundrum arises: should the careful clinician replete VD in PHPT or not? On the one hand, both conditions could lead to bone mineral density (BMD) loss if untreated, ultimately resulting in osteoporosis and fragility fractures; on the other hand, vitamin D supplementation could lead to further worsening of hypercalcemia and its dreaded complications. To complicate matters, patients undergoing parathyroidectomy (PTX) after long-standing PHPT can also suffer from postoperative hungry-bone syndrome and symptomatic hypocalcemia, which may be further exacerbated by VD. This narrative review aims to summarize the relevant pathophysiological mechanisms underlying these two diseases and their complex interactions. The latest evidence regarding thresholds and targets for vitamin D supplementation in PHPT will be discussed, with a focus on the balance between benefits and risks. Full article

Background: The adverse cardiometabolic outcomes that have been associated with early menopause include obesity, insulin resistance, and metabolic syndrome. Other studies have also linked metabolic dysfunction with vitamin D deficiency. However, the independent association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with metabolic syndrome and type of menopause is unclear. Thus, the present study was designed to assess the association between vitamin D status and metabolic syndrome in women with early menopause compared with those with natural menopause. Methods: A total of 301 postmenopausal women were enrolled. Metabolic syndrome was assessed independently according to the NCEP-ATP III and IDF diagnostic definitions. They were classified into two groups: early menopause (EM, n = 79) and physiological menopause (PHYSM, n = 222). Demographic, anthropometric, biochemical, and lifestyle characteristics were recorded. The criteria for diagnosing metabolic syndrome were those of the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and the International Diabetes Federation (IDF). Serum 25(OH)D was also categorized as deficiency, insufficiency, or sufficiency. Multivariable logistic regression analyses were used to determine independent predictors of metabolic syndrome. Multivariable linear regression analyses were used to determine the association between serum 25(OH)D and individual metabolic parameters. Results: Women with early menopause had a higher body mass index than those with physiological menopause, whereas current smoking was more prevalent among women with physiological menopause. No significant differences were observed between the groups in the prevalence of metabolic syndrome, 25(OH)D concentrations, lipid profile, blood pressure, glycaemic indices, or other biochemical parameters. In multivariable analyses, menopausal status was not independently associated with metabolic syndrome according to either the NCEP-ATP III or IDF criteria. Body mass index was the only independent predictor of metabolic syndrome in the adjusted IDF model (OR 1.2, 95% CI 1.0–1.4; p = 0.047). Serum 25(OH)D concentrations were independently associated only with lower fasting glucose levels and were not independently associated with metabolic syndrome or its other components. Although vitamin D categories showed significant associations with metabolic syndrome in unadjusted analyses, these associations were attenuated after adjustment for demographic, anthropometric, menopausal, and lifestyle-related factors. Conclusions: Menopausal type was not independently associated with the prevalence of metabolic syndrome or vitamin D status. Although metabolic syndrome prevalence differed across vitamin D categories in unadjusted analyses, these associations were attenuated after adjustment for demographic, anthropometric, menopausal, and lifestyle-related factors. Obesity appeared to be the strongest independent predictor of metabolic syndrome within this cohort. Given the retrospective observational design, these findings should be interpreted cautiously, and prospective longitudinal studies are warranted to confirm these associations. Full article

Background: Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy. Vitamin D has been implicated in glucose metabolism; however, its association with GDM remains controversial. Objective: The objective was to evaluate the association between maternal serum 25-hydroxyvitamin D [25(OH)D] concentrations and GDM in pregnant women referred for diagnostic 100 g oral glucose tolerance testing following a positive 50 g glucose challenge test. Methods: This retrospective study included 92 pregnant women (44 with GDM and 48 without GDM) who underwent diagnostic 100 g oral glucose tolerance testing between January 2016 and June 2025 at a tertiary-care hospital. Demographic characteristics and biochemical parameters, including serum 25(OH)D concentrations, were obtained from medical records. Logistic regression analysis was performed to identify factors independently associated with GDM. Results: Women with GDM were significantly older than those without GDM (37.55 ± 6.06 vs. 29.21 ± 4.29 years, p < 0.001) and had lower serum vitamin D concentrations (14.08 ± 9.88 vs. 19.06 ± 10.30 ng/mL, p = 0.003). In multivariable logistic regression analysis, advanced maternal age (OR 1.404, 95% CI 1.217–1.620; p < 0.001) and lower serum vitamin D concentrations (OR 0.933, 95% CI 0.880–0.989; p = 0.020) were independently associated with GDM. Conclusion: Lower maternal serum 25(OH)D concentrations were independently associated with GDM in women referred for diagnostic 100 g oral glucose tolerance testing. These findings should be interpreted as observational and hypothesis-generating. Larger prospective studies are needed to confirm these results. Full article

Background: Vitamin D deficiency is highly prevalent in patients with sickle cell disease (SCD) and may contribute to hematological dysregulation and increased vaso-occlusive crisis (VOC) burden. However, data from Sudan, a region with a substantial SCD burden, remain limited. This study investigated the prevalence and determinants of vitamin D deficiency and its association with hematological parameters and VOC frequency in Sudanese patients with SCD. Methods: A cross-sectional observational study was conducted among 50 patients with confirmed SCD attending a hematology outpatient clinic in Sudan. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using chemiluminescence immunoassay and categorized as deficient (<20 ng/mL), insufficient (20–29 ng/mL), or sufficient (≥30 ng/mL). Clinical and laboratory data, including hemoglobin concentration, annual VOC frequency, genotype, hydroxyurea use, hospitalization frequency, and sun exposure, were collected. Statistical analyses included chi-square tests, independent t-tests, Pearson correlation, and multivariable linear regression. Results: Vitamin D deficiency was identified in 54.0% of participants, whereas only 16.0% demonstrated sufficient vitamin D levels. Mean serum 25(OH)D concentration was 21.23 ± 7.44 ng/mL. HbSS patients exhibited significantly lower vitamin D levels compared with HbAS patients (19.89 ± 6.96 vs. 25.03 ± 7.71 ng/mL, p = 0.031). Serum 25(OH)D levels positively correlated with hemoglobin concentration (r = 0.584, p < 0.001) and inversely correlated with annual VOC frequency (r = −0.692, p < 0.001). Multivariable regression demonstrated that serum vitamin D was independently associated with hemoglobin levels (β = 0.048, p = 0.002) and annual VOC frequency (β = −0.121, p < 0.001) after adjustment for age, sex, genotype, sun exposure, and hydroxyurea use. Sun exposure was significantly associated with vitamin D status (p < 0.001). Conclusions: Vitamin D deficiency is highly prevalent among Sudanese patients with SCD and is significantly associated with anemia severity and increased VOC frequency. Given the single-center design and modest sample size, these findings should be regarded as exploratory and hypothesis-generating. They support routine vitamin D assessment and indicate that targeted supplementation strategies warrant evaluation as potential adjunctive approaches in SCD management in prospective, adequately powered studies. Full article

Background: Vitamin D is involved in musculoskeletal function, but evidence that supplementation improves athletic performance remains inconsistent, particularly in athletes with sufficient baseline vitamin D status. Methods: In this double-blind randomized controlled trial, 18 professional female soccer players were randomized during the autumn preparatory period (August–September) to receive vitamin D₃ (4000 IU/day; n = 9) or placebo (n = 9) for eight weeks. Outcomes included total serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)₂D] concentrations, hematological variables, RAST total sprint time, 5- and 30-m sprint performance, and countermovement-jump outcomes. Results: At baseline, after summer exposure, 25% of participants had insufficient or deficient 25(OH)D concentrations (≤30 ng/mL). The remaining cohort (75%) had sufficient 25(OH)D concentrations (>30 ng/mL). After eight weeks, no statistically significant between-group differences were observed in vitamin D metabolites, hematological variables, or performance outcomes (Δ25(OH)D: SG +12.4 ± 8.2 ng/mL vs. PG +3.1 ± 6.5 ng/mL; p = 0.12). RAST total sprint time (p = 0.001) and 30-m sprint performance (p = 0.005) improved over time. Conclusions: Vitamin D₃ supplementation at 4000 IU/day for eight weeks was not associated with additional improvements in muscle strength, sprint performance, or countermovement-jump outcomes compared with placebo. Because most participants had sufficient baseline 25(OH)D concentrations, larger trials in female athletes with confirmed vitamin D insufficiency or deficiency are needed to determine whether individualized supplementation or longer intervention periods provide additional physiological or performance-related benefits. The trial was retrospectively registered at ClinicalTrials.gov (NCT07641075) on 8 June 2026. Full article

Euthyroid autoimmune thyroiditis (Hashimoto’s disease) has been shown to negatively affect female sexual health; however, this adverse impact appears to be mitigated by vitamin D therapy. Emerging research suggests that vitamin E may reduce susceptibility to autoimmune thyroiditis and that supplementation could contribute to improved sexual health outcomes. The present study aimed to investigate whether vitamin E status influences the effects of exogenous vitamin D on female sexual function and depressive symptoms in individuals with this condition. This pilot study included three cohorts of young women with Hashimoto’s disease, matched for age, thyroid antibody titers, and 25-hydroxyvitamin D levels, all exhibiting normal TSH and free thyroid hormone concentrations. The cohorts differed in vitamin E intake: below the recommended daily allowance (group 1), adequate intake (group 2), and high intake (exceeding 400 IU daily; group 3). All participants received vitamin D at a daily dose of 100 µg for six months. Serum hormone levels, thyroid antibody titers, and calculated indices of thyroid homeostasis were evaluated at enrollment and at the conclusion of the study. Female sexual function and depressive symptoms were also evaluated at both time points using validated instruments: the Female Sexual Function Index (FSFI) and the Beck Depression Inventory-II (BDI-II). At enrollment, group 2 scored higher than the other cohorts in the sexual desire and arousal domains. Vitamin D supplementation increased serum 25-hydroxyvitamin D in all groups. The decrease in antibody titers was most pronounced in group 2, and only in this group did vitamin D enhance thyroid secretory capacity and increase testosterone levels. In group 2, treatment led to improvements across all FSFI domains and the total score. In group 1, positive effects were limited to the lubrication and lack of pain/discomfort domains, whereas group 3 showed no changes in sexual function. Improvements in female sexual function correlated with vitamin E intake, reductions in antibody titers, and increases in testosterone levels. Significant improvements in depressive symptoms, as measured by the BDI-II, were observed exclusively in group 2. Adequate vitamin E intake is essential to achieve the full effects of vitamin D on female sexual function and mood in young euthyroid patients with Hashimoto’s disease. Full article

Background/Objectives: Children with autoimmune gastrointestinal diseases are at increased risk of impaired bone health due to chronic inflammation, nutritional deficiencies, growth disturbances, and treatment-related factors. While dual-energy X-ray absorptiometry (DXA) is the standard method for assessing bone mineral density (BMD), it provides limited information on bone microarchitecture. The trabecular bone score (TBS), derived from lumbar spine DXA images, has emerged as a complementary marker of bone quality. This study aimed to evaluate bone mass and TBS in children with autoimmune gastrointestinal diseases and to assess the clinical utility of TBS in comparison with children with a history of fractures and healthy controls. Methods: This study included 152 children aged 5–18 years: 45 with autoimmune gastrointestinal diseases (Crohn’s disease, ulcerative colitis, or celiac disease), 37 with a history of fractures, and 70 healthy controls. Anthropometric measurements, serum 25-hydroxyvitamin D [25(OH)D] concentrations, DXA-derived parameters, and TBS values were analyzed. Bone mineral density was assessed at the lumbar spine and total body less head (TBLH), with additional adjustment for height-for-age Z-score (HAZ). TBS values were expressed as sex- and pubertal stage-adjusted Z-scores. Results: Low bone mass (aBMD_{for age} Z-score ≤ −2) was observed in 30.3% of participants at TBLH and 11.1% at the lumbar spine, whereas a TBS Z-score ≤ −2 was identified in 5.2% of children. No significant differences in TBS or TBS Z-scores were found among the study groups. In multivariable analysis, fracture history was independently associated with lower absolute TBS, whereas no independent predictors of TBS Z-score were identified. Children with fractures had significantly lower HAZ-adjusted lumbar spine aBMD Z-scores than children with autoimmune gastrointestinal diseases and controls. TBS Z-scores correlated positively with age-adjusted and HAZ-adjusted aBMD values but showed no association with BMI or serum 25(OH)D concentrations. Conclusions: In this cross-sectional study, TBS did not distinguish children with autoimmune gastrointestinal diseases from those with fractures or healthy controls in the unadjusted analyses. Although TBS was associated with selected DXA-derived measures of bone mineral density and fracture history was independently associated with lower absolute TBS after multivariable adjustment, no independent predictors of TBS Z-score were identified. These findings suggest that the clinical role of TBS in the assessment of pediatric bone health remains to be established. Larger prospective studies are crucial to determine whether TBS provides clinically meaningful information complementary to conventional DXA for the assessment of skeletal health and fracture risk in children. Larger prospective studies are needed to clarify the clinical value of TBS for fracture risk assessment in pediatric autoimmune gastrointestinal diseases. Full article

Objective: Vitamin D has been reported to act as a tissue-protective regulator by suppressing Matrix Metalloproteinases (MMPs) and upregulating Tissue Inhibitors of Metalloproteinases (TIMPs), though changes may be body mass index (BMI)-dependent; however, the relationship between vitamin D metabolism and matrix remodeling pathways in Polyendocrine Metabolic Ovarian Syndrome (PMOS) remains poorly understood. Methods: In women with PMOS (n = 28) and controls (n = 28), 12 MMPs and 3 TIMPs were determined by Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement and correlated to 25-hydroxyvitamin D₃ (25(OH)D₃) and its metabolites (active 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) and 24,25-dihydroxyvitamin D₃ (24,25(OH)₂D₃)) measured by gold standard isotope-dilution liquid chromatography tandem mass spectrometry. Results: Insulin resistance and systemic inflammation (normal C-reactive protein) were comparable between PMOS and control women, though PMOS had higher free androgen index and anti-Mullerian hormone levels. Vitamin D and its metabolites did not differ between groups. Only MMP16 was lower in PMOS than controls (549.6 ± 58.3 vs. 678.0 ± 304.1 Relative Fluorescent Units, p = 0.037) but did not pass the false discovery rate. In women with PMOS, 25(OH)D₃ and 24,25(OH)₂D₃ demonstrated significant inverse correlations with TIMP3 (r = −0.60, p = 0.005 and r = −0.58, p = 0.007, respectively). Multivariable regression confirmed independent inverse associations between TIMP3 and both 25(OH)D₃ (β = −51.1, p = 0.031) and 24,25(OH)₂D₃ (β = −858.7, p = 0.028) after adjustment for age, body mass index and Homeostatic Model Assessment-Insulin Resistance, and the association remained stable following bootstrap internal validation. Additional moderate associations were observed between vitamin D metabolites and membrane-type MMPs (MMP14, MMP16, MMP17). Conclusions: Exploratory analyses suggested potential inverse associations between vitamin D metabolites and TIMP3, together with weaker associations involving MMP14, MMP16 and MMP17, suggesting the novel hypothesis that vitamin D may influence extracellular matrix remodeling and ovarian stromal biology through regulation of TIMP3-dependent pathways independently of obesity and insulin resistance, rather than through MMPs directly. Full article

Aging is driven by progressive epigenetic alterations—DNA methylation drift, aberrant histone modifications, chromatin remodeling, and non-coding RNA dysregulation. Vitamin D, acting through its nuclear receptor vitamin D receptor (VDR), modulates the epigenetic landscape to potentially counteract these age-related changes. This review first describes age-related epigenetic alterations, then outlines vitamin D signaling and its interface with the epigenetic machinery. Next, tissue-specific epigenetic actions of vitamin D in the immune, musculoskeletal, and nervous systems are discussed. Finally, clinical trial evidence is examined, interindividual variability is highlighted, and future research directions are proposed. However, large randomized controlled trials (RCTs) consistently show limited benefits of vitamin D monotherapy, with measurable anti-aging effects observed when combined with exercise and nutritional interventions. Its efficacy is constrained by interindividual variability, J-shaped dose–response, and tissue-specific barriers. For deficient individuals (serum 25-hydroxyvitamin D (25(OH)D) < 50 nmol/L), guided supplementation—typically 800–2000 international units (IU)/day—is warranted to achieve tentative target serum concentrations of 75–125 nmol/L, the range linked to favorable epigenetic and immune effects. For those already sufficient (e.g., serum 25(OH)D ≥ 50 nmol/L), indiscriminate supplementation without biochemical indication is not supported. Therefore, promoting healthy aging through vitamin D requires serum-monitored, individually titrated, and multimodal regimens, with supplementation reserved primarily for documented deficiency and integrated with lifestyle interventions. Full article

Background: Classical phenylketonuria (PKU) requires the lifelong dietary restriction of phenylalanine-containing foods. In this study, we aimed to evaluate the effects of a phenylalanine-restricted diet on carnitine, amino acid, vitamin, and mineral status in children with classical PKU. Methods: This case–control study included 30 children with classical PKU and 30 age- and sex-matched healthy controls. Dietary adherence was categorized as good, moderate, or poor according to blood phenylalanine concentrations during the preceding year. Dried blood spot amino acid and acylcarnitine profiles combined with serum micronutrient and hematological parameters were analyzed. Results: No significant differences were observed between the PKU and control groups regarding tyrosine, free carnitine (C0), acetyl carnitine (C2), valine, or methionine concentrations (p > 0.05). Arginine levels were significantly lower in the PKU group than in controls (40.14 ± 29.89 vs. 48.25 ± 16.08 µmol/L, p = 0.008). Vitamin B12, folate, 25-hydroxyvitamin D, and mean corpuscular volume were significantly higher in patients with PKU (all p < 0.05). Dietary adherence exhibited a strong negative correlation with phenylalanine concentrations (r = −0.86, p < 0.001), a moderate negative correlation with the phenylalanine-to-tyrosine ratio (r = −0.56, p = 0.001), and a moderate negative correlation with body mass index (r = −0.55, p = 0.002). Conclusions: Children with classical PKU receiving long-term dietary treatment maintained adequate carnitine and micronutrient status. Reduced arginine concentrations observed in treated children with classical PKU warrant further investigation, although their clinical significance remains uncertain. Full article

Background and Objectives: Vitamin D deficiency has been implicated in muscle weakness and functional decline among older adults. However, its association with sarcopenia-related impairment, particularly when evaluated using readily available nutritional and functional indicators in routine clinical practice, remains incompletely understood. Materials and Methods: This retrospective cross-sectional study included 148 adults aged ≥65 years who attended a Physical Medicine and Rehabilitation outpatient clinic. Sarcopenia-related risk was classified using an EWGSOP2-informed operational framework based on handgrip strength together with nutritional and functional indicators available in the retrospective dataset. Serum 25-hydroxyvitamin D [25(OH)D] concentrations were measured using a chemiluminescent microparticle immunoassay. Group comparisons, correlation analyses, and multivariable logistic regression analyses were performed. Results: The prevalence of probable sarcopenia and probable sarcopenia with nutritional/functional risk indicators was significantly higher among participants with vitamin D deficiency. Serum 25(OH)D levels differed significantly across the three study groups (p < 0.001). Post-hoc Tukey analysis demonstrated significantly lower serum 25(OH)D concentrations in the probable sarcopenia with nutritional/functional risk indicators group than in both the no sarcopenia and probable sarcopenia groups (both p < 0.001). Serum 25(OH)D levels were moderately and inversely correlated with sarcopenia-related risk severity (r = −0.48, p < 0.001). Lower vitamin D levels were also associated with reduced serum albumin levels and a higher prevalence of falls and assistive walking device use. In multivariable logistic regression analysis, vitamin D deficiency remained independently associated with sarcopenia-related risk after adjustment for age and sex. Conclusions: Vitamin D deficiency was significantly associated with greater sarcopenia-related risk severity and poorer functional status in older adults. Assessment of vitamin D status may therefore represent a simple, inexpensive, and readily available tool for identifying individuals at increased risk of sarcopenia-related impairment in routine geriatric practice. Prospective studies incorporating direct measures of muscle quantity and standardized physical performance assessments are needed to confirm these findings. Full article

Background: We compared biochemical, micronutrient-related and complete blood count (CBC)-derived inflammatory profiles among children with obesity, undernutrition and normal weight, and explored the discriminatory performance of selected routine laboratory markers for the obesity phenotype. Methods: In this single-centre retrospective comparative study, medical records of children aged 2–17 years evaluated between January 2023 and December 2025 were reviewed. Participants were classified as obese, undernourished or normal weight using World Health Organization (WHO) body mass index-for-age (BMI-for-age) references. Liver enzymes, lipid parameters, iron-related indices, micronutrient levels, zinc, insulin and CBC-derived inflammatory indices were compared across groups using non-parametric omnibus tests. Exploratory receiver operating characteristic (ROC) analyses were performed for selected markers. Results: A total of 690 children were included: 100 with obesity, 90 with undernutrition and 500 with normal weight. The obesity group was significantly older than the normal-weight group (median 11.0 vs. 7.5 years; p < 0.001). Obesity was characterised by higher alanine aminotransferase (ALT), insulin, triglycerides, neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI), together with lower high-density lipoprotein (HDL) cholesterol, 25-hydroxyvitamin D [25(OH)D] and aspartate aminotransferase-to-alanine aminotransferase (AST/ALT) ratio (all p < 0.05). In exploratory, age-unadjusted ROC analyses, the AST/ALT ratio yielded the highest AUC among the evaluated biomarkers (AUC 0.859; 95% CI 0.823–0.895; optimal cut-off ≤ 1.52; sensitivity 77.0%; specificity 77.6%), followed by SIRI (AUC 0.751; 95% CI 0.700–0.802). Conclusions: Pediatric obesity was associated with a distinct liver enzyme-metabolic-inflammatory laboratory profile, whereas undernutrition exhibited a different micronutrient-biochemical pattern. Because the study was retrospective and age-unadjusted, these findings should be interpreted as exploratory and hypothesis-generating. Prospective studies with age-balanced sampling, pubertal staging and liver imaging are required before clinical implementation. Full article

Background: Vitamin D deficiency is common in patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). Whether vitamin D status influences tumor aggressiveness and clinical outcomes remains uncertain. This review examines current evidence on the prevalence, determinants, clinical associations, and clinical relevance of vitamin D deficiency in GEP-NENs. Methods: A narrative and critical review of the literature was conducted using the PubMed/MEDLINE, Scopus, and Web of Science databases. Clinical studies, observational cohorts, translational research, selected mechanistic studies, and current clinical guidelines addressing vitamin D metabolism and neuroendocrine neoplasms were evaluated. Results: Vitamin D deficiency has been reported in approximately 60–80% of patients with GEP-NENs. Low serum 25-hydroxyvitamin D concentrations likely reflect multiple disease-related factors, including malabsorption, pancreatic exocrine insufficiency, chronic diarrhea, previous gastrointestinal surgery, and nutritional impairment. Several observational studies have linked lower vitamin D status with markers of more aggressive disease, including higher Ki-67 proliferation index values and shorter progression-free survival. Nevertheless, the available data are heterogeneous, predominantly observational, and do not support a causal relationship between vitamin D deficiency and tumor progression. At present, the main clinical rationale for assessing vitamin D status is to support metabolic care, preserve bone health, and prevent osteoporosis. Conclusions: Vitamin D deficiency is a frequent and clinically relevant comorbidity in patients with GEP-NENs. Although lower vitamin D status has been associated with markers of more aggressive disease, current findings do not support vitamin D supplementation as an anticancer treatment strategy. Prospective clinical and translational studies are needed to clarify the biological and clinical significance of vitamin D signaling in GEP-NENs. Full article

Background and Objectives: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which persistent synovial inflammation and joint damage are influenced not only by immune dysregulation but also by environmental, genetic, and epigenetic factors. Vitamin D is a secosteroid hormone and has emerged as a key immunomodulatory hormone, with reported effects on innate and adaptive immune responses, with potential relevance to RA clinical activity and treatment. This narrative review synthesizes mechanistic and clinical evidence enlightening vitamin D’s immunomodulatory role in RA pathogenesis and management. Methods: A comprehensive literature search was carried out on PubMed and MEDLINE databases using Medical Subject Headings (MeSH) terms: “Vitamin D”, “Cholecalciferol”, “Arthritis, Rheumatoid”, “Seasons”, “Epigenomics”, “DNA Methylation”, and “Therapy”. The narrative review highlights evidence published mainly in the last 5 years on the link between vitamin D and RA, focusing on epigenetic interactions, circannual rhythms, and therapeutic implications. Results: Emerging data suggest that vitamin D-related epigenetic mechanisms (e.g., DNA methylation, histone acetylation, and microRNA regulation) and genetic polymorphisms have been associated with disease susceptibility and treatment outcomes. Latitude and seasonal fluctuations in serum 25-hydroxyvitamin D levels correlate with variations in RA disease activity, although results remain heterogeneous across studies. Overall, the available evidence supports an association between vitamin D deficiency and greater RA disease activity, while its adequate supplementation has been associated with improvements in inflammatory markers and selected clinical outcomes, especially when tailored to baseline status and individual risk factors, such as limited dietary intake and sunlight exposure. Conclusions: Current evidence emphasizes the need for further studies using standardized methods and larger, geographically diverse cohorts to define how best to leverage seasonal vitamin D variations in RA management, considering also the range of concomitant epigenetic modifiers that may influence the effects of vitamin D on the management of RA patients. Full article

Background/Objectives: Lower serum 25-hydroxyvitamin D [25(OH)D] is common in pediatric overweight and obesity, but it remains unclear whether direct adiposity assessment adds information beyond an age- and sex-adjusted model containing BMI z-score and season. We tested whether DXA-derived total body fat percentage is associated with 25(OH)D and whether it adds explanatory power to that model. Methods: We analyzed cross-sectional data from 768 children/adolescents (10–18 years) with overweight/obesity. Anthropometry was available for all; DXA data for 489. The primary analysis used complete-case DXA data (n = 485). Vitamin D supplementation status was not available. Results: Participants with and without DXA were similar in age, sex, BMI z-score, and serum 25(OH)D, but blood sampling season differed (p < 0.001). Adding DXA-derived body fat percentage to the age- and sex-adjusted base model increased R² from 0.0498 to 0.0657 (ΔR² = 0.0159). Within the complete-case DXA subgroup (n = 485), DXA-derived total body fat percentage was inversely associated with 25(OH)D after adjustment for BMI z-score, season, age, and sex (B = −0.265; 95% CI, −0.448 to −0.082; p = 0.005). BMI z-score was significant in the base model but not after adjustment for DXA fat percentage. Conclusions: DXA-derived total body fat percentage added explanatory value for serum 25(OH)D beyond BMI z-score and season, but the incremental gain was small (ΔR² = 0.0159). The findings are consistent with BMI z-score acting as a less direct proxy for the adiposity compartment that DXA quantifies more specifically. Causal interpretation is precluded by the cross-sectional design, unknown supplementation status, and non-random DXA availability. Full article