Search Results (1,019)

Background/Objective: Vitamin D plays an important role in musculoskeletal health; however, its association with skeletal muscle microvascular perfusion has not been clearly defined using quantitative imaging techniques. To investigate the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and skeletal muscle microvascularity using an advanced ultrasound-based microvascular imaging method. Methods: In this cross-sectional study a total of 141 healthy adults were stratified into two groups according to serum 25(OH)D concentration (<20 ng/mL, n = 71; ≥20 ng/mL, n = 70). Ultra-Micro-Angiography was used to quantitatively assess the vascular index (VI), while cross-sectional area (CSA) measurements were obtained for the flexor carpi radialis, biceps brachii, and tibialis anterior muscles. Group comparisons and receiver operating characteristic (ROC) analyses were performed to evaluate the discriminative performance of microvascular parameters. Results: CSA values did not differ significantly between the groups. In contrast, VI values were significantly higher in participants with higher serum 25(OH)D levels across all examined muscles (p < 0.001). Among the evaluated parameters, the biceps brachii VI demonstrated excellent diagnostic performance in distinguishing between groups (AUC = 0.992; optimal cut-off = 1.25). Conclusions: Serum 25(OH)D levels are strongly associated with skeletal muscle microvascularity independent of muscle size. These findings demonstrate a strong association between serum 25-hydroxyvitamin D concentration and skeletal muscle microvascularity and highlight the potential of ultra-micro-angiography as a non-invasive imaging approach for detecting microvascular differences related to vitamin D status. Full article

Background/Objectives: Vitamin D is a nutrient involved not only in bone metabolism but also in metabolic functions, and deficiency is common during adolescence. This study aimed to describe the distribution of serum 25-hydroxyvitamin D levels among Korean adolescents and to examine their associations with metabolic syndrome and its individual components. Methods: We analyzed data from the 2022–2023 Korea National Health and Nutrition Examination Survey. Adolescents aged 10–18 years with serum 25-hydroxyvitamin D measurements were included (unweighted N = 880). Weighted analyses were performed by categorizing serum 25-hydroxyvitamin D levels into quartiles. Associations between vitamin D quartiles and anthropometric and metabolic parameters were examined using complex-sample general linear models, and odds ratios for metabolic syndrome and its individual components according to vitamin D deficiency were estimated using complex-sample logistic regression models. Results: Weighted prevalence of vitamin D deficiency (<20 ng/mL) was 62.4%, higher in females than males. Higher 25(OH)D quartiles were inversely associated with obesity-related indices, including BMI, waist circumference, and waist-to-height ratio, after full adjustment (p for trend < 0.05). No significant associations were observed for blood pressure, fasting glucose, or lipid parameters. In dichotomous analyses (<20 vs. ≥20 ng/mL), vitamin D deficiency was associated with higher odds of waist circumference ≥ 90th percentile (OR 2.59), waist-to-height ratio > 0.5 (OR 2.63), and BMI ≥ 95th percentile (OR 1.89), while metabolic syndrome was not significant. Conclusions: Vitamin D appears to play an important role in metabolic health in adolescents and was particularly associated with general and central obesity. Full article

Background/Objectives: Observational studies have found inverse associations between 25-hydroxyvitamin D concentration and risk of hypertension, hypercholesterolemia and type 2 diabetes (T2D). More robust evidence from large-scale randomized controlled trials, however, is limited or inconclusive. Methods: The D-Health Trial (N = 21,315) is a randomized, double-blind, placebo-controlled trial of supplementation with monthly doses of 60,000 international units of oral vitamin D₃, conducted in Australians aged 60–84 years. Commencing treatment with anti-hypertensive, lipid-modifying, or anti-diabetic drugs was used as a surrogate for incident hypertension, hypercholesterolemia, and T2D, respectively. Outcomes were ascertained via linkage with the Australian Pharmaceutical Benefits Scheme database. Follow-up began 6 months after randomization; we excluded participants without linked data, and those who were prevalent cases or who died prior to start of follow-up. Flexible parametric survival models were used to estimate the effect of vitamin D supplementation on each outcome. Results: We included 10,964 participants (vitamin D, n = 5456 [49.8%]; placebo, n = 5508 [50.2%]) in the analysis of hypertension, 12,126 participants (vitamin D, n = 6038 [49.8%]; placebo, n = 6088 [50.2%]) in the analysis of hypercholesterolemia, and 17,846 (vitamin D, n = 8931 [50.0%]; placebo, n = 8915 [50.0%]) in the analysis of T2D. Over a median follow-up of 4.6 years, 2672 (24.4%), 2554 (21.1%), and 779 (4.4%) participants developed hypertension, hypercholesterolemia, and T2D, respectively. Vitamin D supplementation had no material effect on the incidence of any of hypertension (HR 1.00; 95% CI 0.93 to 1.08), hypercholesterolemia (HR 1.05; 95% CI 0.97 to 1.13), or T2D (HR 0.97; 95% CI 0.84 to 1.12). Conclusions: Monthly supplements of vitamin D did not alter the incidence of any of the three conditions in older, largely vitamin D-replete Australians. Full article

Background: Vitamin D deficiency has been implicated in breast cancer pathogenesis and prognosis. However, the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and molecular breast cancer subtypes remains incompletely understood. Methods: This cross-sectional study included 168 women (89 breast cancer patients, 79 healthy controls) from Poland. Serum 25(OH)D was measured by electrochemiluminescence immunoassay. Blood samples were collected year-round, with 54% obtained during winter/spring months (October–March). Molecular subtypes (luminal A, luminal B, HER2-enriched, triple-negative) were classified by immunohistochemistry. Results: Mean 25(OH)D was 30 ± 13 ng/mL, with 55% showing insufficiency (<30 ng/mL). No significant differences were observed between patients and controls (p = 0.93). A borderline non-significant trend was observed across molecular subtypes (p = 0.055). HER2-enriched tumors showed descriptively higher concentrations (37.6 ng/mL, 95% CI: 29.5–45.8) compared to luminal A (31.0 ng/mL), luminal B (26.4 ng/mL), and triple-negative (25.9 ng/mL). A significant subtype × season interaction was detected (p = 0.015), though interpretation is limited by the absence of a main seasonal effect (p = 0.64). Age (OR = 1.06, p = 0.023) and BMI (OR = 1.06, p = 0.090) predicted vitamin D deficiency. Conclusions: Vitamin D insufficiency is prevalent in breast cancer patients and healthy women. In this exploratory analysis with limited statistical power, no definitive associations between 25(OH)D and molecular subtype were established. The descriptive trend suggesting higher vitamin D in HER2-enriched tumors requires validation. Limitations: Small sample sizes (n = 11–35 per subtype) and post-surgical blood collection limit interpretation; findings require validation in larger cohorts. Full article

Seventy 28-day-old weaned barrow piglets (Duroc × Landrace × Large White; 7.2 ± 0.20 kg) were used to determine the effects of 25-hydroxyvitamin D₃ (25-OH-VD₃) combined with phytase and probiotics on calcium and phosphorus metabolism and bone development. Five dietary groups were tested: basal diet + 50 µg/kg 25-OH-VD₃ (CON); basal diet with 17% reduced calcium and phosphorus + 50 µg/kg 25-OH-VD₃ (LCP); LCP + 50 mg/kg phytase (LH); LCP + 10 mg/kg probiotics (LC); LCP + 50 mg/kg phytase + 10 mg/kg probiotics (LHC). The experiment lasted for 31 days, including 3 days adaptation period. Apparent phosphorus digestibility was higher in the LH and LHC groups than in the CON group (p < 0.05). Bone mineral density and calcium content in metacarpal and rib bones were also higher in the LHC group compared with the CON, LCP, LC, and LH groups (p < 0.05). The jejunal mRNA expression of solute carrier family 34 members (SLC34A1, SLC34A2, and SLC34A3) members was higher in the LHC group than the CON, LCP, LC, and LH groups (p < 0.05), while the relative protein expression of the calcium-sensing receptor in the kidneys was lower in the CON group than in the LCP, LH, LC, and LHC groups (p < 0.05). Additionally, supplementation with 25-OH-VD₃, either alone or in combination with phytase and probiotics, was associated with an increased abundance of beneficial gut bacteria. Overall, combined supplementation of 25-OH-VD₃, phytase and probiotics enhanced bone development in weaned piglets fed a low-calcium, low-phosphorus diet by improving calcium and phosphorus utilization and calcium–phosphorus metabolic regulation. Full article

Background: Irisin, a muscle-derived hormone, enhances the energy metabolism by activating the brown adipose tissue and acts as a bone-forming agent across the entire life span. No consistent clinical data in humans have been published so far to highlight if blood irisin as glucose/bone biomarker should be refined based on the vitamin D status (deficient or sufficient). Therefore, we aimed to objectively assess the level of irisin in female adults with abnormal and normal vitamin D status, as reflected by the level of 25-hydroxyvitamin (25OHD) in relationship with glucose and bone metabolic parameters. Methods: This pilot, prospective, exploratory study included eighty-nine menopausal women aged over 50. We excluded subjects with malignancies, bone and metabolic disorders, insulin treatment, and active endocrine disorders. Fasting profile included glycaemia, insulin, and glycated haemoglobin A1c (HbA1c). Then, 75 g oral glucose tolerance test (OGTT) included glycaemia and insulin assay after 60 and 120 min. Bone status involved bone turnover markers and central dual-energy X-ray absorptiometry providing bone mineral density (BMD) and trabecular bone score. Results: Eighty-nine subjects were included in the following two groups depending on 25OHD: vitamin D-deficient (VDD) group (N = 48; 25OHD < 30 ng/mL) and vitamin D-sufficient (VDS) group (N = 41; 25OHD ≥ 30 ng/mL). The two groups had similar age and menopausal period (62.29 ± 10.19 vs. 63.56 ± 8.16 years, respectively; 15.82 ± 9.55 vs. 16.11 ± 9.00 years, p > 0.5 for each). A statistically significant higher body mass index (BMI) was found in VDD vs. VDS group (32.25 ± 5.9 vs. 28.93 ± 4.97 kg/m², p = 0.006). Circulating irisin was similar between the groups as follows: median (IQR) of 91.85 (44.76–121.76) vs. 71.17 (38.76–97.43) ng/mL, p = 0.506. Fasting profile and OGTT assays showed no between-group difference. Median HOMA-IR in VDD group pointed out insulin resistance of 2.67 (1.31–3.29). Lowest mean/median T-scores at DXA for both groups were consistent with osteopenia category, but they were confirmed at different central sites as follows: femoral neck in both groups [VDD versus VDS group: −1.1 (−1.20–−0.90) vs. −1.1 (−1.49–−0.91), p = 0.526, respectively], only at lumbar spine for VDS group (T-score of −1.18 ± 1.13). The correlations between irisin and the mentioned parameters displayed a different profile when the analysis was performed in the groups with different 25OHD levels. In VDD group, irisin levels statistically significantly correlated with serum phosphorus (r = −0.32, p = 0.022), osteocalcin (r = −0.293, p = 0.038), P1NP (r = −0.297, p = 0.04), HbA1c (r = 0.342, p = 0.014), and BMI (r = 0.408, p = 0.003). Conclusions: This pilot study brings awareness in the analysis of irisin in relationship with glucose and bone-related biomarkers correlates, showing a distinct type of association depending on 25OHD level, which might represent an important crossroad in the multitude of irisin-activated signal transduction pathways. Full article

Background: Glaucoma is an age-related optic neuropathy frequently accompanied by systemic comorbidities. Vitamin D deficiency (VDD) has been associated with cardiovascular and renal diseases in the general population, yet its relationship with long-term systemic outcomes in glaucoma remains unclear. This study evaluated the association between baseline vitamin D status and subsequent mortality and cardiorenal events in patients with primary glaucoma. Methods: We conducted a retrospective cohort study using deidentified electronic health records from the TriNetX U.S. Collaborative Network, a federated network of participating healthcare organizations. Adults (≥18 years) with incident primary glaucoma (2005–2020) and a serum 25-hydroxyvitamin D (25(OH)D) test within 12 months prior to diagnosis were categorized as VDD (<30 ng/mL) or vitamin D adequacy (VDA; ≥30 ng/mL). After 1:1 propensity score matching across 47 demographic, clinical, medication, and laboratory variables, 11,855 patients per group were followed for up to 5 years. Outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), and renal function decline (eGFR < 60 mL/min/1.73 m²). Analyses incorporated Kaplan–Meier curves, Cox models, landmark tests, sensitivity analyses, and competing risk methods. Results: Among the 35,100 eligible patients, the matched cohorts demonstrated higher 5-year risks associated with VDD for all-cause mortality (HR 1.104; 95% CI 1.001–1.217), MACE (HR 1.151; 95% CI 1.078–1.229), and AKI (HR 1.154; 95% CI 1.056–1.261), whereas the risks of renal function decline did not differ (HR 0.972; 95% CI 0.907–1.042). Risk divergence emerged within the first year of follow-up and persisted through the 5-year observation period. Conclusions: In patients with primary glaucoma, vitamin D deficiency was associated with higher long-term risks of mortality and cardiorenal complications, but not renal function decline. Taken together, the results are consistent with vitamin D status serving as a marker of broader systemic vulnerability in glaucoma and highlight the need for prospective studies to further clarify its prognostic significance. Full article

Background: Although total 25-hydroxyvitamin D (25(OH)D) measurements may not accurately reflect functional vitamin D status, vitamin D deficiency is common in hepatocellular carcinoma (HCC). The contribution of altered vitamin D-binding protein (VDBP) and albumin to impaired bioavailability is poorly characterized in liver cancer. Methods: We measured total, free, and bioavailable 25(OH)D, VDBP, and albumin in 46 HCC patients and 87 healthy controls during winter and summer. Correlations with Child–Pugh score, Barcelona Clinic Liver Cancer (BCLC) stage, and disease aetiology were evaluated. Results: HCC patients exhibited significantly lower VDBP (177.3 ± 237.0 vs. 239.9 ± 141.9 mg/L, p < 0.001) and albumin (35.9 ± 5.4 vs. 48.0 ± 3.9 g/L, p < 0.001) compared to winter controls. Total 25(OH)D was lower in HCC (39.3 ± 22.1 nmol/L) versus summer controls (75.0 ± 22.8 nmol/L, p < 0.001) but comparable to winter controls (p = 0.061). HCC patients lacked seasonal variation in vitamin D fractions, unlike the controls. VDBP negatively correlated with free (ρ = −0.606, p < 0.001) and bioavailable 25(OH)D (ρ = −0.541, p < 0.001). Child–Pugh score correlated positively with BCLC stage (ρ = 0.378, p = 0.012) and inversely with albumin (ρ = −0.565, p < 0.001). Conclusions: Free and bioavailable vitamin D are profoundly compromised in HCC, reflecting impaired hepatic synthetic function and systemic inflammation. These fractions may serve as novel metabolic biomarkers superior to total 25(OH)D for assessing vitamin D deficiency and guiding individualized supplementation strategies in patients with liver cancer. Full article

Background/Objectives: Chronic low-grade inflammation and nutritional deficiencies, particularly vitamin D deficiency, have emerged as important contributors to Metabolic syndrome (MetS) pathogenesis but remain underexplored. This study aimed to comprehensively evaluate the associations between dietary intake, vitamin D status, and inflammatory biomarkers (high-sensitivity C-reactive protein -CRP- and ferritin) in patients with MetS. Methods: A cross-sectional observational study was conducted on 141 adult MetS patients at a Mexican hospital. Clinical, anthropometric, dietary (using a validated food frequency questionnaire), and biochemical data including serum 25-hydroxyvitamin D, CRP, ferritin, and neutrophil-to-lymphocyte ratio (NLR) were collected. Vitamin D deficiency was defined as serum 25(OH)D < 20 ng/mL, and high inflammation as CRP ≥ 3 mg/L. Logistic regression models adjusted for confounders were used to analyze associations. Mediation analysis assessed whether vitamin D deficiency mediated the link between dietary intake and high CRP or ferritin. Results: Patients with elevated CRP had significantly lower serum vitamin D levels (14.0 ± 5.1 vs. 22.1 ± 7.0 ng/mL; p < 0.001). Multivariable analysis showed vitamin D deficiency (adjusted OR 7.1; 95% CI 2.5–19.4; p < 0.001) and hyperferritinemia (ferritin ≥ 200 μg/L; aOR 8.0, 95% CI 3.5–18.2, p < 0.001) as predictors of high CRP. Conversely, hyperferritinemia was predicted by vitamin D deficiency (aOR 24.69; 95% CI 3.76–162.16; p = 0.001), elevated CRP (aOR 5.06; p = 0.014), Hb (aOR 63.23; p < 0.001), and inversely by grade 2 obesity (aOR 0.11; 95% CI 0.02–0.60; p = 0.03), confirming bidirectional CRP-ferritin associations and hyperferritinemia as an inflammation marker rather than iron overload indicator. Although Hb > 14.3 g/dL associated with hyperferritinemia, it did not independently predict CRP in multivariate analyses. Frequent consumption of vitamin D-rich foods (milk, fish, Manchego and Oaxaca cheese) was associated with lower inflammation. Mediation analysis confirmed that vitamin D deficiency mediated dietary intake-CRP and dietary intake-ferritin links (Sobel test p < 0.05). Conclusions: Vitamin D deficiency is a key mediator linking inadequate dietary vitamin D intake to systemic inflammation in MetS. Nutritional strategies emphasizing vitamin D repletion and consumption of vitamin D fortified foods may effectively reduce chronic inflammation and improve metabolic outcomes. Full article

Vitamin D is involved in immune regulation through effects on innate and adaptive immune responses mediated by vitamin D receptor activation within immune cells. Experimental and translational studies support its role in promoting regulatory T-cell activity, modulating Th1/Th17 responses, and influencing autoantibody production. At the population level, low serum 25-hydroxyvitamin D concentrations are consistently associated with an increased risk of autoimmune diseases, including autoimmune thyroid disorders such as Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), suggesting a potential preventive association. In contrast, clinical evidence from interventional studies in patients with established disease is heterogeneous. Although vitamin D supplementation has been associated with reductions in thyroid autoantibody titers in some studies—particularly in patients with HT and baseline vitamin D deficiency—consistent effects on thyroid function, disease progression, or relapse prevention have not been demonstrated. Overall, current evidence supports vitamin D deficiency as a potentially modifiable risk marker rather than a confirmed disease-modifying therapeutic target in autoimmune thyroid diseases, highlighting the need for further studies focused on clinically meaningful outcomes. Full article

Background: Interindividual differences in statin efficacy and tolerability are partly determined by genetic and metabolic factors. The SLCO1B1 c.521T>C polymorphism affects hepatic statin transport, while vitamin D deficiency may influence lipid metabolism and muscular tolerance. This study aimed to assess the impact of SLCO1B1 genotype and vitamin D status on lipid-lowering response and adverse events in postmenopausal women treated with atorvastatin or rosuvastatin. Methods: A total of 145 Croatian postmenopausal women were prospectively followed for 16 weeks. Participants received atorvastatin or rosuvastatin with dose titration to achieve low-density lipoprotein cholesterol (LDL-C) targets. Serum lipids, liver enzymes, and creatine kinase were monitored monthly. Serum levels of 25-hydroxyvitamin D were quantified by LC–MS/MS, while SLCO1B1 c.521T>C genotyping was performed using real-time PCR. Results: Rosuvastatin achieved a higher LDL-C target attainment rate compared with atorvastatin (81.1% vs. 67.6%, p = 0.02). The SLCO1B1 genotype was not associated with lipid response but was significantly associated with adverse effects. In multivariable regression analysis, patients with the T/C genotype had a significantly higher risk of developing adverse effects compared with those with the T/T genotype (OR 7.4, 95% Cl 2.1–26.7, p = 0.002). Vitamin D status showed no significant association with lipid outcomes or adverse events, although participants with severe deficiency exhibited a weaker LDL-C response. Conclusions: Rosuvastatin demonstrated superior lipid-lowering efficacy and tolerability compared with atorvastatin in postmenopausal women. The SLCO1B1 c.521T>C variant primarily affected safety rather than efficacy, while severe vitamin D deficiency might contribute to diminished statin response. Integrating pharmacogenetic and endocrine profiling could enhance individualized statin therapy and cardiovascular prevention in women. Full article

Background/Objectives: Osteoarthritis (OA) remains a global health problem, as it can cause permanent joint damage, leading to irreversible disability. Therefore, there is a need for accessible and non-invasive alternative examinations, such as USG, serum COMP, and 25-hydroxyvitamin D [25(OH)D] assessment. This study aims to analyze the correlation between serum COMP and 25(OH)D levels and the degree of articular cartilage degradation in patients with knee OA, based on findings from USG and MRI examinations. Methods: A cross-sectional analytical study was conducted at Mohammad Hoesin Hospital, Palembang, from December 2024 to August 2025. 31 patients diagnosed with knee OA based on the 1990 American College of Rheumatology (ACR) classification criteria were enrolled. Serum COMP and 25(OH)D levels were measured. All patients underwent standardized USG and MRI examinations of the knee. Spearman’s rank correlation coefficient was used for statistical analysis. Results: The majority of the study subjects were female, comprising 23 (74.2%). The mean age was 63.90 ± 7.77 years with a body mass index of 25.46 ± 5.51 kg/m². Most subjects were engaged in heavy physical activity 17 (54.8%). Laboratory examination showed serum COMP levels with a median of 869 ng/mL and a range of 136–3302 ng/mL. Meanwhile, the 25(OH)D level demonstrated a mean value of 24.84 ± 7.33 ng/mL. The analysis revealed a strong and statistically significant positive correlation between serum COMP levels and the degree of articular cartilage degradation in knee OA. This correlation was observed in both USG (r = 0.61; p < 0.001) and MRI assessments (r = 0.72; p < 0.001). In contrast, serum 25(OH)D levels showed no significant correlation with cartilage degradation. The correlation coefficient between 25(OH)D levels and USG-assessed cartilage degradation was r = −0.12 (p = 0.51), and for MRI assessment, it was r = 0.17 (p = 0.92). Conclusions: A strong and significant positive correlation exists between serum COMP levels and the degree of articular cartilage degradation based on USG (r = 0.61; p < 0.001) and MRI (r = 0.72; p < 0.001). In contrast, serum 25(OH)D levels showed no significant correlation with cartilage degradation, implying that 25(OH)D may not directly reflect the extent of structural cartilage damage in knee osteoarthritis. This finding proves that an increase in serum COMP levels is associated with an increase in the degree of articular cartilage degradation in knee OA as measured by both USG and MRI. Full article

Background and aims: Low vitamin D₃ levels are common in cancer patients, and these patients might benefit from vitamin D₃ level normalization in parallel with the conventional oncology treatment. This study aimed to examine the molecular effects of moderate–high-dose vitamin D₃ supplementation in vitamin D-deficient cancer patients. Methods: Eight patients under oncological treatment (5 lung cancer, 2 colorectal cancer, and 1 urothelial carcinoma) received 30,000 IU of vitamin D₃ per week for two months. Blood samples were collected before and after supplementation, and peripheral blood mononuclear cells (PBMCs) were isolated. With the aim of assessing further potential epigenetic alterations, global DNA methylation level was estimated on the basis of LINE-1 bisulfite-sequencing experiments on cfDNA and PBMC cells. In order to explore the chromatin accessibility alterations after the treatment in PBMCs, an assay for transposase-accessible chromatin with sequencing (ATAC-Seq) was performed using the (10x Genomics, Pleasanton, CA, USA) on a NextSeq 550 instrument using High Output Sequencing kit (Illumina, San Diego, CA, USA). DNA integrity was assessed by the alkaline Comet-assay and telomere qPCR was also performed. Results: After serum 25-hydroxy-vitamin D levels were normalized, DNA integrity in mononuclear cells improved significantly (p = 0.01), while no significant changes were found in granulocytes. Vitamin D₃ supplementation also led to significant changes in telomere length in mononuclear cells (p = 0.007). No significant differences were observed in cfDNA levels or DNA methylation in PBMCs and cfDNA after supplementation. ATAC-Seq revealed changes in PBMC composition, including an increased number of NK, pDC cells, and monocytes, especially in patients treated with Pembrolizumab in parallel with vitamin D supplementation. Conclusions: These exploratory findings suggest that the observed immune cell and chromatin changes after vitamin D₃ level normalization are compatible with immunomodulatory effects and warrant confirmation in larger, controlled cohorts. Full article

Vitamin D, traditionally regarded as a nutrient, is increasingly recognized as a pharmacologically active secosteroid with pleiotropic effects extending beyond calcium homeostasis and bone integrity. Together with vitamin K2, it participates in the fine-tuning of mineral metabolism and vascular health, potentially modulating cardiometabolic risk through intertwined endocrine and paracrine pathways. Despite widespread fortification and supplementation, vitamin D deficiency remains a major global health concern, driven by limited sun exposure, obesity, and metabolic dysfunction. Observational and mechanistic studies consistently link low serum 25(OH)D concentrations with hypertension, insulin resistance, heart failure, and increased cardiovascular mortality. At the molecular level, vitamin D exerts pharmacological actions—modulating the renin–angiotensin–aldosterone system, exerting anti-inflammatory and antifibrotic effects, and influencing endothelial and cardiomyocyte signaling. While experimental and epidemiological evidence suggests potential cardiovascular benefits, large randomized controlled trials (RCTs) provide conflicting results, particularly regarding hypertension and heart failure. However, these often-neutral results do not preclude a targeted action. On the contrary, clinical efficacy is strongly dependent on baseline deficiency status and the presence of metabolic cofactors. In this context, high-dose supplementation of Vitamin D, in combination with Vitamin K2 to prevent vascular calcification, elevates the supplement to a genuine pharmacological agent, with a distinct therapeutic potential for modulating cardiometabolic risk in selected patient subgroups. Emerging evidence supports the concept that vitamin D, when appropriately dosed and combined with K2, may act more as a low-potency pharmacological modulator than a simple nutritional supplement. This review synthesizes current mechanistic, observational, and interventional evidence, aiming to clarify whether vitamin D should be reclassified—from a micronutrient to a pharmacologically relevant agent—in cardiometabolic prevention and therapy, proposing a paradigm shift toward personalized and targeted dosing strategies, characteristic of precision pharmacology. Full article

Background: Maternal vitamin D status during pregnancy has been hypothesized to influence offspring neurodevelopment; however, the evidence remains inconsistent. Methods: We studied 66 mother–child pairs from the KLOTHO cohort with serum 25-hydroxyvitamin D [25(OH)D] measurements at delivery (maternal and umbilical cord). At 10 years of age, neurodevelopment was assessed using standardized questionnaires, generating composite z-scores for cognitive (cognitive, communication, motor) and psychosocial (social–sentimental, special interests) domains. Multivariable models were adjusted for sex, maternal body mass index and education, and neonatal birth weight and gestational age. Results: Maternal 25(OH)D deficiency (<50 nmol/L) was not associated with cognitive composite scores (p = 0.77). The psychosocial composite scores showed a non-significant negative trend (p = 0.29). Neonatal deficiency showed no consistent association with cognition (p = 0.99) or psychosocial outcomes (p = 0.30). Exploratory partial correlations suggested a positive association between maternal 25(OH)D and psychosocial development (r = 0.60, p = 0.038, n = 12). Seasonal variation in maternal vitamin D was observed (autumn: 56.0 ± 24.6 vs. winter: 32.0 ± 18.3 nmol/L; p < 0.0001), but did not translate into differences in 10-year outcomes. Conclusions: In this cohort of 66 pairs, perinatal vitamin D status was not a determinant of global cognition at 10 years of age. A potential link with psychosocial development requires replication in larger longitudinal studies. Due to the limited sample size, all findings should be interpreted as exploratory. Full article