Search Results (1,012)

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

Background: Vitamin D (VD) plays a central role in calcium homeostasis during pregnancy and has been implicated in redox-related biological processes. While VD deficiency (VDD) has been consistently associated with adverse pregnancy outcomes, the relationships between VD insufficiency (VDI), maternal antioxidant-related biomarkers, and neonatal outcomes remain incompletely characterized, particularly during the third trimester. Objective: To determines the prevalence of VDI in third-trimester pregnant women and to examine its associations with antioxidant-related markers and selected neonatal outcomes. Methods: A cross-sectional study was conducted among pregnant women in the third trimester attending a tertiary referral hospital in Mexico City. Maternal serum 25-hydroxyvitamin D (25-OHD) concentrations were measured, along with a panel of redox-related markers, including 2,2-diphenyl-2-2picrylhydrazyl (DPPH) radical scavenging activity, reduced glutathione (GSH), glutathione S-transferase (GST), glutathione peroxidase (GPx), and oxygen radical absorbance capacity (ORAC). Neonatal anthropometric parameters were recorded at birth. Associations between maternal VD status, redox-related markers, environmental factors, and neonatal outcomes were evaluated using appropriate statistical analyses. Results: A high prevalence of VDI was observed in the study population. Maternal VDI was associated with lower activities of GSH, GST, and GPx. Passive exposure to tobacco smoke and season of sampling were also associated with lower VD concentrations. Neonates born to women with VDI had higher birth weight compared with those born to women with sufficient VD concentrations. Maternal serum 25-OHD concentrations correlated positively with selected antioxidant enzyme activities. Conclusions: In this cohort of third-trimester pregnant women, VDI co-occurred with environmental factors, differences in maternal redox-related markers, and selected neonatal outcomes. These findings support an associative framework in which suboptimal VD status during the third trimester is accompanied by variations in redox-related markers. Longitudinal and mechanistic studies are needed to clarify the temporal sequence and biological relevance of these associations. Full article

Background: Functional imbalance within the stomatognathic system can develop long before clinical symptoms become evident. Subtle biological changes, such as low-grade inflammation or metabolic disturbance, may precede gingival inflammation, temporomandibular discomfort, or masticatory muscle sensitivity. This study introduces the BioRisk-S (Biological Risk–Stomatognathic System) algorithm, a predictive model designed to identify early systemic alterations associated with the subclinical stage of stomatognathic dysfunction. Methods: A total of 260 clinically healthy adults without apparent stomatognathic disorders were enrolled and evaluated at baseline (T0) and re-examined after six months (T1). Routine laboratory tests were performed to determine high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), and 25-hydroxyvitamin D levels. These biomarkers were integrated into the BioRisk-S algorithm to estimate systemic biological imbalance. Follow-up examinations focused on detecting early functional changes, including gingival inflammation, signs of temporomandibular joint (TMJ) dysfunction, and masticatory muscle tenderness. Results: Participants with higher baseline BioRisk-S scores showed significantly higher hs-CRP and NLR values, as well as lower vitamin D levels, indicating a mild but persistent inflammatory profile. After six months, these individuals exhibited early gingival inflammation, muscle tenderness, or mild TMJ discomfort more frequently than those with low BioRisk-S values (p < 0.01). The predictive model demonstrated good accuracy for detecting early biological imbalance preceding clinical dysfunction, with an area under the curve (AUC) of 0.84 (95% CI: 0.78–0.89). Conclusions: The BioRisk-S algorithm represents a feasible, low-cost tool for early systemic screening of functional imbalance within the stomatognathic system. By integrating routine laboratory parameters, this method may help identify individuals at risk before the onset of visible symptoms, supporting preventive and personalized approaches in oral and systemic health management. Full article

Background: Vitamin D (VD) insufficiency is present in chronic pancreatitis (CP), leading to increased cardiovascular risk, bone complications, impaired quality of life, and increased mortality. This study aimed to determine the prevalence of VD deficiency in patients with CP and to assess its relationship to CP progression and associated cardiovascular complications. Methods: Seventy patients were enrolled and evaluated for pancreatic exocrine insufficiency by fecal elastase-1, CP severity by M-ANNHEIM classification, cardiovascular risk by 10-year risk mortality scores (SCORE and FRS), and for arterial stiffness using pulse wave velocity (PWV) at a. carotis and a. femoralis. Determination of 25-hydroxyvitamin D was performed by an LC-MS/MS method. Resting energy expenditure was calculated using the Harris–Benedict formula. Results: Mean VD levels were 37.86 ± 24.36 nmol/L (range 3.854–99.874 nmol/L); only five patients were in sufficiency status. VD levels correlated significantly with body mass index (BMI) and resting energy expenditure. In patients with severe structural changes, we observed lower VD levels regardless of etiology (p < 0.01). VD levels were lower in patients with pancreatic exocrine insufficiency (PEI), p < 0.05. Patients with mild CP by M-ANNHEIM had lower levels of VD compared to moderate and advanced CP, p < 0.05. At a cut-off of VD 11.95 nmol/L, we verified pancreatic lithiasis with 89.4% sensitivity, 83.3% specificity, and AUC of 0.826 ± 0.113 (95% CI, 0.61–1). VD status worsened with the increase in the 10-year risk mortality by both SCORE and FRS and PWV, p < 0.05. Conclusions: Most of our patients with CP were VD insufficient. Monitoring of nutritional status in patients with CP is mandatory to prevent the development of malnutrition complications and the associated morbidity and mortality. 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: Vitamin D deficiency is recognized as a global public health concern due to its implications for bone health, immune regulation, and chronic disease risk. Despite its significance, comprehensive data on the prevalence of hypovitaminosis D in the Croatian population remain limited. This study aimed to determine the distribution of 25-hydroxyvitamin D (25-OH D) levels in a group of patients who underwent routine clinical examination, evaluate the prevalence of deficiency, and assess potential associations with demographic factors such as age and sex. Methods: This cross-sectional study included 829 individuals aged 19–85 years who underwent routine clinical testing at our institution. Serum 25-OH D concentrations were measured and classified as normal (≥75 nmol/L), deficient (<75 nmol/L, ≥50 nmol/L), or severely deficient (<50 nmol/L). Data on age and sex were extracted, and statistical analyses included descriptive statistics, tests for normality (Kolmogorov–Smirnov), comparisons (Mann–Whitney U, Kruskal–Wallis), and correlation testing (Spearman’s rho). Significance was set at p < 0.05. Results: The cohort consisted of 525 females (63.3%) and 304 males (36.7%), with a mean age of 49.2 ± 15.8 years. The mean and median serum 25-OH D concentrations were 53.5 and 53.0 nmol/L, respectively (IQR: 40.0–65.0). Severe deficiency (<50 nmol/L) was present in 43.7% of participants, while an additional 49.2% exhibited moderate deficiency, leaving only 7.1% with sufficient levels. No statistically significant differences in vitamin D levels were observed between sexes, nor was there a significant correlation between age and vitamin D concentration (p > 0.05). Conclusions: Vitamin D deficiency is highly prevalent in the Croatian population, with more than 90% of individuals showing suboptimal serum levels. The absence of significant associations with age or sex suggests a widespread deficiency pattern, underscoring the need for nationwide preventive strategies, including dietary supplementation and public health education initiatives to improve vitamin D status. Full article

Background: Pediatric hypertension is an increasingly recognized health concern and is commonly influenced by modifiable factors such as dietary sodium intake and obesity and non-modifiable factors like family history of hypertension. Urinary sodium excretion provides an objective surrogate marker of sodium consumption and may be associated with blood pressure severity. This study aimed to evaluate urinary sodium excretion in children with primary hypertension (PH) and to test the hypothesis that higher sodium excretion is associated with less favorable clinical, biochemical, and blood pressure parameters. Methods: This retrospective, cross-sectional, single-center study analyzed data from 369 hypertensive patients and 59 healthy children. Patients with a confirmed diagnosis of PH and ambulatory blood pressure monitoring results were included in the study group. Clinical, anthropometric, laboratory, echocardiographic, and blood pressure data were examined, and sodium excretion was evaluated using both the spot urine sodium-to-creatinine ratio and 24-h urinary sodium per kilogram of body weight. Results: Children with hypertension exhibited higher urinary sodium excretion compared to the control group. Sodium excretion of the hypertensive group, measured using the sodium/creatinine ratio and 24 h urinary sodium excretion per kilogram, was positively correlated with 25-hydroxyvitamin D, the urinary potassium/creatinine ratio, and the urinary uric acid/creatinine ratio. Moreover, negative correlations were observed for both parameters with age, body weight, serum uric acid, and left ventricular mass. In the multivariate analysis, weighted Z-score (beta = −0.393), age (beta = −0.293), 25-OHD (beta = 0.182), and arterial hypertension in the father (beta = 0.166) predicted 24 h urinary sodium excretion. Children with excessive sodium excretion had a significantly higher systolic blood pressure load over 24 h. Conclusions: Urinary sodium excretion is elevated in children with PH. Children with a lower weight for their age, who are younger, and who have a father with arterial hypertension might be at higher risk of excessive urine excretion. Our findings underscore the clinical importance of dietary sodium reduction as a non-pharmacological therapeutic target, especially in these patient populations. Prospective studies are needed to evaluate its impact on long-term cardiovascular outcomes in this population. Full article

Background/Objectives: Erectile dysfunction (ED) is a common sexual disorder in men, frequently linked to endothelial dysfunction affecting penile vasculature. Accumulating evidence suggests that vitamin D (VD) status may influence endothelial function and, consequently, erectile function. VD deficiency has also been associated with cardiovascular risk factors, which are well-known contributors to ED. Methods: A systematic review following PRISMA guidelines was conducted, analyzing studies from PubMed and Cochrane databases published between 2010 and 2025. Randomized controlled trials, observational studies, and pilot clinical trials examining the relationship between VD levels and ED in the general male population were included. Results: Out of 1335 identified articles, 10 studies met inclusion criteria, encompassing over 13,000 men. Observational studies consistently showed that men with moderate-to-severe or arteriogenic ED had significantly lower serum VD levels and poorer erectile function scores compared to those with mild ED. VD deficiency was independently associated with higher ED prevalence, irrespective of lifestyle, cardiovascular risk, or sex hormone levels. Although several observational studies suggested a potential optimal vitamin D threshold, definitive recommendations cannot be established due to the heterogeneity of available evidence and conflicting findings from randomized controlled trials. The latter demonstrated inconsistent effects of vitamin D supplementation on erectile dysfunction outcomes, with the largest trial reporting no significant reduction in disease prevalence. These findings underscore the critical need for rigorously designed trials targeting populations with severe VD deficiency and arteriogenic ED. Conclusions: This systematic review highlights an association between vitamin D status and erectile dysfunction, particularly in men with moderate-to-severe or arteriogenic ED. However, most of the evidence is derived from low-certainty observational studies. While observational data suggest potential benefits of adequate VD levels for sexual health, well-designed randomized controlled trials are essential to delineate causal relationships and potential for therapeutic efficacy. Full article