Vitamin D deficiency is prevalent and linked to chronic diseases; its association with advanced liver disease progression requires clarification.

To investigate the association between vitamin D levels and risks of liver cirrhosis, hepatocellular carcinoma (HCC), and mortality, and assess risk changes after achieving sufficiency post-supplementation.

This was a retrospective cohort study.

Utilized TriNetX US data (3,905,594 patients, 2000-2024). Adults with vitamin D deficiency (20.00-30.00 ng/mL) were compared with those with sufficient levels (30.01-80.00 ng/mL). Follow-up was initiated from the first vitamin D test or start of supplementation to minimize immortal time bias. Propensity score matching (1:1) balanced >20 baseline confounders.

After matching, 1,204,760 patients with vitamin D deficiency and 1,204,760 with sufficient vitamin D levels were included. Vitamin D deficiency was associated with an increased risk of liver cirrhosis (hazard ratio (HR), 1.30; 95% confidence interval (CI), 1.25-1.36), HCC (HR, 1.22; 95% CI, 1.08-1.37), and all-cause mortality (HR, 1.14; 95% CI, 1.13-1.16). Achieving sufficient vitamin D levels reduced the risk of all-cause mortality (HR, 0.93; 95% CI, 0.88-0.99) and aligned HCC outcomes (HR, 1.16; 95% CI, 0.68-2.00). However, it did not significantly reduce the risk of liver cirrhosis (HR, 2.05; 95% CI, 1.69-2.50). Dose-response analysis showed a U-shaped relationship for liver cirrhosis and HCC, with the lowest risks at 40-60 ng/mL.

Serum vitamin D levels showed a nonlinear association with liver cirrhosis and HCC risk; deficiency independently increased the risks for cirrhosis, HCC, and mortality. Supplementation achieving sufficiency reduced mortality and normalized HCC risk but not cirrhosis risk, potentially reflecting limitations in reversing established disease. The lowest liver disease risk was associated with vitamin D levels of 40-60 ng/mL in this cohort, although causality and the clinical benefit of targeting this specific range require confirmation.

It has been hypothesized but seldom tested that the winter excess in cardiovascular disease (CVD) is related to hypovitaminosis D. The present study examined the association between CVD and (i) seasonality of 25-hydroxyvitamin D (25[OH]D) and (ii) individual 25(OH)D concentrations.

Harmonized 25(OH)D data were obtained from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, including 79,570 participants examined between 1984 and 2010. One 25(OH)D measurement was available per participant. Primary endpoints were CVD incidence (coronary heart disease or stroke; n = 6006) and CVD mortality (n = 2985). To study (i), Poisson regression-derived rate ratios were compared according to two-month categories, ordered by baseline 25(OH)D concentrations. To study (ii), Cox regression-derived hazard ratios were compared according to quarters of baseline 25(OH)D concentrations. With respect to (i), despite a median 25(OH)D concentration ratio of 1:1.79, the trough months of 25(OH)D in March and April had a similar CVD incidence as the peak months of 25(OH)D in August and September (rate ratio: 1.07, 95% CI: 0.98-1.17). CVD mortality was slightly higher in the trough months compared to the peak months (rate ratio: 1.27, 95% CI: 1.12-1.44) but not compared to the other months (despite median 25[OH]D concentration ratios up to 1:1.62; p ≥ 0.077). The CVD mortality peak in January preceded the 25(OH)D trough, not adhering to the temporality criterion of Bradford Hill. With respect to (ii), compared to the lowest quarter, the highest quarter of 25(OH)D was associated with lower CVD incidence (hazard ratio: 0.82, 95% CI: 0.76-0.89) and CVD mortality (hazard ratio: 0.64, 95% CI: 0.57-0.72).

The present study does not support the hypothesis that seasonal increases in CVD are driven by short-term reductions in 25(OH)D. As in most observational studies, higher 25(OH)D concentrations were inversely associated with CVD.

Vitamin D deficiency and sleep disorders may independently contribute to increased mortality, but the combined effects of these two factors on mortality remain unknown. This study aimed to investigate both the separate and joint effects of vitamin D deficiency and sleep disorders on cardiovascular disease mortality, as well as all-cause mortality and cancer mortality.

We analyzed data from 24,566 adults in the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Sleep disorders were assessed using self-report questionnaires, and vitamin D levels were measured through serum total 25-hydroxyvitamin D [25(OH)D]. Cox proportional hazards models were employed to evaluate the associations between separate and joint effects of vitamin D deficiency and sleep disorders with mortality outcomes.

Over a median follow-up of 9.08 years, we included a total of 24,566 individuals, in this study. Among them, 2,776 cases were all-cause deaths, 858 were cardiovascular disease deaths, and 644 were cancer deaths. We found that Vitamin D deficiency was independently associated with an increased risk of all-cause mortality, while sleep disorders were similarly associated with a higher risk of all-cause mortality. Notably, participants with both vitamin D deficiency and sleep disorders exhibited a significantly higher risk of all-cause mortality (HR, 2.31; 95% CI: 1.36-3.91) and cardiovascular mortality (HR, 2.39; 95% CI, 1.03-5.58) compared to those with only one or neither risk factor, even after adjusting for potential confounders.

Our study highlights that the combination of vitamin D deficiency and sleep disorders was associated with an increased risk of all-cause and cardiovascular mortality in adults. These findings might help to refine dietary and lifestyle intervention strategies for this population.

Vitamin D has the potential to therapeutically affect the endocrine parameters of premature ovarian insufficiency (POI) patients. Previous research has indicated that serum vitamin D levels tend to decline with age and in individuals with POI. However, the precise impact of vitamin D deficiency on female fertility, especially their ovarian function, remains unclear. Vitamin D receptor (VDR) deficiency mice provide a model to investigate the possible effect of vitamin D on female reproduction. In this study, we observed abnormal follicular development in the Vdr deficiency mice. This anomaly is associated with reduced expression of anti-Mullerian hormone (AMH) and disrupted aromatase expression that disrupts the hormone secretion. Moreover, our findings indicate that Vdr deficiency disturbs redox balance, resulting in oxidative stress in the ovary, which further suppresses granulosa cell function and accelerates ovarian aging. Mechanistically, loss of Vdr inhibits de novo cholesterol synthesis by transcriptional repression of Hmgcr, and the antioxidant and anti-aging effects of the intermediate product 7-dehydrocholesterol (7-DHC) are also decreased. Treatment with 7-DHC effectively reduces ROS levels and alleviates aging in KGN cells deficient in Vdr. In conclusion, our results show that Vdr deficiency impairs follicle maturation and hormone secretion by accelerating granulosa cell aging, as a result of the reduced antioxidant and anti-aging effect of 7-DHC.

Depression is a serious global public health issue due to its significant impact on well-being and quality of life. Since vitamin D3 is involved in more than simply bone health, there has been discussion over its potential link to depression. Despite growing evidence that there is a connection between vitamin D3 deficiency and depression, there is a lack of evidence from India. So this study aims to evaluate vitamin D deficiency and depression among patients attending private clinics in Ernakulam, Kerala, India.

The cross-sectional study investigated the association between vitamin D3 levels and depression. This study was approved by the institutional ethical committee of SRM School of Public Health, SRMIST, Kattankulathur, and Tamil Nadu. After getting informed consent from the patients the data regarding socio-demographic profile, Vitamin D and depression was acquired from the patients during their next consecutive follow-up. Participants without significant psychiatric problems or chronic illnesses between the ages of 18 and 49 were enrolled. Serum 25 (OH) D levels were tested, and depression was evaluated using the modified Beck Depression Inventory (BDI-II). Descriptive, Chi-square, and logistic regression analyses were done.

The study was among the 126 participants. Depression was more common in those with low vitamin D3 levels than in those without it (67.2% vs. 32.8%). There is a significant association between depression and demographic variables such as age, gender, and occupation. Under logistic regression, age was found to be a significant predictor, the odds ratios showed that older adults had 12 times the odds of developing depression than younger adults. Males have 2.9 times the odds of developing depression than females.

This study shows that there is an association between vitamin D insufficiency and increased depression in Ernakulam, Kerala, India. The identification and treatment of depression should take into account vitamin D3 status since treating vitamin D3 insufficiency may have an impact on mental health outcomes. Prospective investigations ought to delve into longitudinal associations and encompass a range of demographics to reinforce causal deductions and overall applicability.

Vitamin D is an essential micronutrient for multiple physiological processes, and its deficiency remains a world-wide public health problem that cannot be ignored. Dried blood spot (DBS) is a convenient tool in large-scale epidemiological studies, but its application in evaluating vitamin D status in Chinese population is still scarce. Herein, we aimed to determine the vitamin D status in Chinese pre-school children using DBS coupled with LC-MS/MS method.

We first developed a sensitive and reliable method for the determination of 25-hydroxyvitamin D (25(OH)D) in DBS samples using an ultra-high-performance liquid chromatograph coupled with triple quadrupole mass spectrometer (UHPLC-QQQ-MS/MS). Next, we conducted a pilot study to compare the 25(OH)D concentration in DBS and serum samples. Finally, the assay method was used to evaluate vitamin D status in Chinese pre-school children.

The present method was validated to be reliable and robust for the determination of 25(OH)D in DBS samples. Comparable consistency was observed between the 25(OH)D concentration in DBS and serum samples. A total of 3826 DBS samples collected from children aged 1-7 years were determined. The median concentration of 25(OH)D was 19.57 ng/mL (interquartile range 14.73-24.36 ng/mL), and decreased from 1 to 7 years of age. In addition, 13.51% of male children and 15.12% female children are found to be deficient in 25(OH)D.

DBS coupled with LC-MS/MS is a feasible strategy to evaluate vitamin D status in epidemiological studies. And vitamin D deficiency remains a common health problem in Chinese pre-school children.

Sufficient vitamin D levels are reported to be a factor in reducing various chronic diseases and resulting mortality rates. Well-dried mushrooms and blue-backed fish are known to be rich in vitamin D. In this study, the association between mortality rates and the intake of vitamin D-rich foods was confirmed using data from the Korean Genome and Epidemiological Study (KoGES). Among the KoGES database, we followed up a total of 6844 adults who participated in the Ansung-Ansan cohort study recruited from 2001 to 2002 and continued for an average of 16.7 years until 2018. The main findings were analyzed using Cox regression analysis. During follow-up, 439 cases of all-cause mortality, 149 cases of cancer-related mortality, and 91 cases of cardiovascular mortality were confirmed. In the fully adjusted model, the hazard ratio (HR) for all-cause mortality in quartile 3 of mushroom consumption was 0.709 (95% confidence interval [CI], 0.525-0.958) compared with quartile 1. In addition, the HRs for cardiovascular mortality in quartile 3 of mushroom consumption were 0.348 (95% CI, 0.154-0.787) compared with those in quartile 1. The HRs of cardiovascular mortality for quartiles 3 and 4 of fish consumption were 0.442 (95% CI, 0.226-0.865) and 0.533 (95% CI, 0.285-0.998), respectively, compared with quartile 1. In conclusion, moderate consumption of mushrooms was related to decreased risk of all-cause and cardiovascular mortality, while heightened fish consumption was inversely related to cardiovascular mortality.

Epidemiological evidence indicates that trace elements are significantly associated with cardiovascular health. However, its causality and underlying mechanisms remain unclear. Therefore, this study aimed to investigate the causal relationship between trace elements and cardiovascular disease, as well as their potential mechanism of action.

Two-sample Mendelian randomization (MR) analyses along with mediated and multivariate MR analyses were employed. These analyses utilized 13 trace elements as exposure variables and 20 cardiovascular diseases as outcome variables, with 4907 circulating plasma proteins, 1400 serum metabolites, 731 immune cell phenotypes, and 473 intestinal flora as potential mediators. The Bayesian weighted MR method was used to validate the MR results, and linkage disequilibrium score regression (LDSC) was applied to explore the genetic correlation between trace elements and cardiovascular disease.

Our findings indicated a positive or negative causal relationship between genetically predicted trace elements and cardiovascular disease. An analysis using the Bayesian weighted MR method demonstrated that our causal inference results were reliable. The results of the mediated MR analyses indicate that potassium may reduce the risk of ischemic heart disease by influencing the expression of the plasma proteins BDH2 and C1R. Vitamin B12 may increase the risk of coronary atherosclerosis and cardiovascular death by reducing the levels of VPS29 and PSME1 proteins, while vitamin C may mitigate the risk of cardiac arrest by inhibiting the expression of the TPST2 protein. In addition, potassium can reduce the risk of ischemic heart disease by lowering 4-methoxyphenyl sulfate levels. None of the instrumental variables exhibited pleiotropy in the MR analysis. A sensitivity analysis using the leave-one-out method further confirmed the robustness of our findings. LDSC results indicated a genetic correlation between multiple trace elements and various cardiovascular diseases.

This study uncovered the true causal relationship between trace elements and cardiovascular disease risk using genetic methods, and revealed the significant mediating role of specific plasma proteins and metabolites in this relationship.

Light enhances or disrupts circadian rhythms, depending on the timing of exposure. Circadian disruption contributes to poor health outcomes that increase mortality risk. Whether personal light exposure predicts mortality risk has not been established. We therefore investigated whether personal day and night light, and light patterns that disrupt circadian rhythms, predicted mortality risk. UK Biobank participants (N = 88,905, 62.4 ± 7.8 y, 57% female) wore light sensors for 1 wk. Day and night light exposures were defined by factor analysis of 24-h light profiles. A computational model of the human circadian pacemaker was applied to model circadian amplitude and phase from light data. Cause-specific mortality was recorded in 3,750 participants across a mean (±SD) follow-up period of 8.0 ± 1.0 y. Individuals with brighter day light had incrementally lower all-cause mortality risk (adjusted-HR ranges: 0.84 to 0.90 [50 to 70th light exposure percentiles], 0.74 to 0.84 [70 to 90th], and 0.66 to 0.83 [90 to 100th]), and those with brighter night light had incrementally higher all-cause mortality risk (aHR ranges: 1.15 to 1.18 [70 to 90th], and 1.21 to 1.34 [90 to 100th]), compared to individuals in darker environments (0 to 50th percentiles). Individuals with lower circadian amplitude (aHR range: 0.90 to 0.96 per SD), earlier circadian phase (aHR range: 1.16 to 1.30), or later circadian phase (aHR range: 1.13 to 1.20) had higher all-cause mortality risks. Day light, night light, and circadian amplitude predicted cardiometabolic mortality, with larger hazard ratios than for mortality by other causes. Findings were robust to adjustment for age, sex, ethnicity, photoperiod, and sociodemographic and lifestyle factors. Minimizing night light, maximizing day light, and keeping regular light-dark patterns that enhance circadian rhythms may promote cardiometabolic health and longevity.

Vitamin D plays important role in inflammatory rheumatic diseases, which in turn rose an interest for investigating association of its deficiency with disease activity. In this research we aimed to evaluate this matter in the context of spondyloarthritis (SpA), together with treatment modalities and bone density in people diagnosed with axial or peripheral SpA in real-life setting. In our study we enrolled 99 patients with diagnosis of SpA treated at the tertiary level rheumatology department. Serum 25(OH)D levels, treatment modality (NSAIR or DMARDs), disease activity, tobacco smoking habits, mineral density of bone, supplementation and seasonal variations were assessed. We used standardized questionnaires such as ASDAS-CRP, BASFI and joint count, among many others, to evaluate some of the mentioned parameters. Sixty-five percent of patients had vitamin D deficiency. We found marginaly higher activity of disease in subjects with low vitamin D. In cases of peripheral SpA, there was a significant association of higher number of swollen joints and lower vitamin D levels. Additionally, the significant correlation was seen between normal serum vitamin D and supplementation. In our real-life study of patients with SpA we found a significant percentage of vitamin D deficit, with a tendency of slightly higher disease activity in those patients.In order to clarify the impact of the vitamin on disease activity in SpA and the supplementation recommendations for patients with these conditions, the conduction of further studies is required.

Little is known about the role of vitamin D receptor polymorphisms and their interaction with vitamin D status in hepatocellular carcinoma (HCC) prognosis.

We evaluated the association of TaqI, BsmI, Cdx-2, and ApaI polymorphisms, individually and in combination, with liver cancer-specific (LCSS) and overall survival (OS) among 967 patients with newly diagnosed HCC. Subsequently, we examined whether these polymorphisms modified the association between serum bioavailable 25-hydroxyvitamin D (25OHD) concentrations and survival. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).

During a median follow-up of 1017 days, 393 deaths occurred, with 360 attributed to HCC. Having TaqI G allele (HRper allele = 1.30, 95% CI = 1.08 to 1.57) or BsmI T allele (HRper allele = 1.41, 95% CI = 1.01 to 1.99) was associated with worse LCSS. Carrying increasing numbers of protective alleles was associated with superior LCSS (HR6-8 vs 0-3 = 0.52, 95% CI = 0.34 to 0.80). The inverse association of bioavailable 25OHD with LCSS was statistically significant only in patients with TaqI AA (HRQuartile 4 vs Quartile 1 = 0.63, 95% CI = 0.44 to 0.92), BsmI CC (HRQuartile 4 vs Quartile 1 = 0.62, 95% CI = 0.44 to 0.88), and 6 to 8 protective alleles (HRQuartile 4 vs Quartile 1 = 0.45, 95% CI = 0.23 to 0.87). Similar associations were observed for OS.

Patients carrying wild-type TaqI, BsmI, or more protective alleles had improved survival and might benefit from optimizing bioavailable 25OHD status.

Epidemiological and observational studies suggest that vitamin D has potential for the chemoprevention of ovarian cancer. The anticancer effect of vitamin D in the fallopian tube epithelium (FTE), which is now thought to harbor the precursor cells for high grade ovarian cancer, is not known. The purpose of this study was to investigate whether vitamin D can inhibit carcinogenesis in the mogp-TAg fallopian tube (FT) ovarian cancer mouse model and examine underlying mechanisms. To test this hypothesis, 3 groups of 40 5-week-old female mogp-TAg mice were divided equally into two cohorts of 20 mice, treated with either vehicle (vitamin D solvent) or the active 1,25(OH)2D3 analogue EB1089, delivered via mini-pump or IP injection or cholecalciferol delivered in the feed. The FTs were characterized histologically and pathologically after 3 and 7 weeks of treatment. The effect of vitamin D on cultured human FTE cells was also examined. After 3 weeks, vitamin D, delivered as either cholecalciferol or EB1089 significantly inhibited FT carcinogenesis. After 7 weeks, cholecalciferol significantly reduced p53 signatures, serous tubal epithelial carcinoma, FT cancer, and plasma CA125 while increasing apoptosis in the FTE. EB1089 had no significant effect on FT carcinogenesis at 7 weeks. Cholecalciferol significantly reduced proliferation and increased apoptosis in vitro in p53-altered FTE cells. In conclusion, vitamin D inhibited FT carcinogenesis by clearing cells with p53 alterations. These data suggest that vitamin D has merit for the chemoprevention of fallopian tube/ovarian cancer. The optimal chemopreventive effect may be dependent on the route of vitamin D administration.

To analyze the impact of different methods of Vitamin D administration on the prognosis of COVID-19 patients.

A comprehensive literature search was conducted across four databases: PubMed, Embase, Web of Science, and Cochrane, up to January 5, 2024. Eligible studies included randomized controlled trials and cohort studies that compared Vitamin D supplementation with control groups in COVID-19 patients. Outcomes of interest were mortality rate, ICU (Intensive Care Unit) admission rate, length of hospital stay, and endotracheal intubation rate. Subgroup analyses were performed based on the dosing regimen (single-dose vs. continuous-dose), total Vitamin D intake within 14 days (≥100,000 IU vs. <100,000 IU), and baseline serum Vitamin D levels (deficient group: 25OHD < 30 ng/mL vs. non-restricted group). A random-effects model was employed for meta-analysis to account for heterogeneity among studies.

A total of 21 studies involving 4,553 participants were included. In terms of mortality, Vitamin D supplementation significantly reduced the mortality rate (RR = 0.72, 95% CI: 0.54-0.94, I 2 = 54%, p = 0.02), with continuous dosing being more effective (RR = 0.53, 95% CI: 0.34-0.83, I 2 = 55%, p = 0.006) compared to single-dose (RR = 0.88, 95% CI: 0.69-1.12, I 2 = 21%, p = 0.3), and lower total doses (<100,000 IU) showing greater benefit (RR = 0.30, 95% CI: 0.21-0.44, I 2 = 0%, p < 0.0001). Mortality was significantly reduced in the Vitamin D-deficient group (25OHD < 30 ng/mL) (RR = 0.73, 95% CI: 0.59-0.89, I 2 = 0%, p = 0.002) but not in the non-restricted group. Regarding ICU admission, supplementation reduced ICU admission rates (RR = 0.58, 95% CI: 0.38-0.88, I 2 = 74%, p = 0.01), with continuous dosing (RR = 0.44, 95% CI: 0.22-0.90, I 2 = 74%, p = 0.02) being more effective than single-dose (RR = 0.79, 95% CI: 0.61-1.03, I 2 = 22%, p = 0.08), and lower doses (<100,000 IU) providing more significant reduction (RR = 0.31, 95% CI: 0.21-0.47, I 2 = 0%, p = 0.001). ICU admission rates were significantly reduced in the Vitamin D-deficient group (RR = 0.63, 95% CI: 0.42-0.93, I 2 = 0%, p = 0.02) but not in the non-restricted group (RR = 0.59, 95% CI: 0.32-1.11, I 2 = 86%, p = 0.1). For length of hospital stay, no significant differences were observed between Vitamin D and control groups (MD = -1, 95% CI: -2.16 to 0.16, p = 0.13), and subgroup analyses by dosing regimen, total dose, and baseline Vitamin D levels also showed no significant differences. Similarly, for endotracheal intubation, there was no significant difference in intubation rates between groups (RR = 0.78, 95% CI: 0.56-1.08, p = 0.13), and subgroup analyses confirmed no significant effect of different dosing strategies or baseline Vitamin D status on intubation rates.

Vitamin D supplementation improves clinical outcomes in COVID-19 patients by reducing mortality and ICU admission rates, particularly when administered continuously with a total dose of less than 100,000 IU over 14 days, and among those with baseline Vitamin D deficiency (25OHD < 30 ng/mL). However, there were no significant effects on the length of hospital stay or endotracheal intubation rates, regardless of the dosing regimen or baseline Vitamin D levels. These findings emphasize the importance of considering both the total dose over 14 days and baseline Vitamin D status to optimize therapeutic benefits.

The 6th International Conference, "Controversies in Vitamin D," was convened to discuss controversial topics, such as vitamin D metabolism, assessment, actions, and supplementation. Novel insights into vitamin D mechanisms of action suggest links with conditions that do not depend only on reduced solar exposure or diet intake and that can be detected with distinctive noncanonical vitamin D metabolites. Optimal 25-hydroxyvitamin D (25(OH)D) levels remain debated. Varying recommendations from different societies arise from evaluating different clinical or public health approaches. The lack of assay standardization also poses challenges in interpreting data from available studies, hindering rational data pooling and meta-analyses. Beyond the well-known skeletal features, interest in vitamin D's extraskeletal effects has led to clinical trials on cancer, cardiovascular risk, respiratory effects, autoimmune diseases, diabetes, and mortality. The initial negative results are likely due to enrollment of vitamin D-replete individuals. Subsequent post hoc analyses have suggested, nevertheless, potential benefits in reducing cancer incidence, autoimmune diseases, cardiovascular events, and diabetes. Oral administration of vitamin D is the preferred route. Parenteral administration is reserved for specific clinical situations. Cholecalciferol is favored due to safety and minimal monitoring requirements. Calcifediol may be used in certain conditions, while calcitriol should be limited to specific disorders in which the active metabolite is not readily produced in vivo. Further studies are needed to investigate vitamin D effects in relation to the different recommended 25(OH)D levels and the efficacy of the different supplementary formulations in achieving biochemical and clinical outcomes within the multifaced skeletal and extraskeletal potential effects of vitamin D.

The circulating vitamin D level that is optimal for health is unknown. This study aimed to examine the association between circulating vitamin D level and risk of all-cause and cause-specific mortality.

This prospective cohort study included 18,797 Korean adults aged 40 years or older, living in rural areas, with no history of cancer or cardiovascular disease (CVD) at baseline. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at baseline. Participants were followed-up from the survey date (2005-2012) until December 31, 2021. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality by baseline vitamin D level. Restricted cubic splines were used to explore the nonlinearity.

The median (interquartile range) of 25(OH)D level was 55.8 (40.8-71.8) nmol/L. During a median follow-up of 14.3 years, 2250 deaths were recorded. Compared with participants with a 25(OH)D level <30 nmol/L, higher vitamin D levels (30 to < 50, 50 to < 75, and ≥75 nmol/L) were associated with a lower risk of all-cause mortality: HR (95% CI) of 0.82 (0.69-0.98), 0.74 (0.62-0.88), and 0.69 (0.57-0.84), respectively. A nonlinear relationship between vitamin D level and all-cause mortality was observed, with the risk plateauing between 50 and 60 nmol/L (p for nonlinearity = 0.009). The association was more pronounced for cancer-related mortality. HR 0.55 (95% CI: 0.39-0.77) for a 25(OH)D level ≥75 nmol/L compared with <30.0 nmol/L. Low vitamin D levels were associated with increased CVD mortality in men.

Vitamin D level was inversely associated with all-cause and cause-specific mortality in middle-aged and older adults. Maintaining a serum 25(OH)D level of approximately 50-60 nmol/L may contribute to longevity and warrants further investigation.

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

We aimed to probe the association of serum 25-hydroxyvitamin D [25(OH)D] concentrations with all-cause and cause-specific mortality among patients with gout and hyperuricemia (HUA).

The study included 1169 gout patients and 7029 HUA patients from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 and 2001-2018, respectively. The association between serum 25(OH)D and mortality was evaluated by Cox proportional hazard and restricted cubic spline models.

Among participants with gout and HUA, the weighted mean concentrations of serum 25(OH)D were 71.49 ± 30.09 nmol/L and 64.81 ± 26.92 nmol/L, respectively. Vitamin D deficiency occurred in 29.68% of gout patients and 37.83% of HUA patients. During 6783 person-years of follow-up among gout patients, 248 all-cause deaths occurred, among which 76 died from cardiovascular disease (CVD) and 49 died from cancer. 1375 HUA patients were recorded for all-cause mortality during 59,859 person-years of follow-up, including 427 CVD deaths and 232 cancer deaths. After multifactorial adjustment, per one-unit increment in natural log-transformed 25(OH)D was associated with lower risk of 55% all-cause mortality and 61% CVD mortality among gout patients, and a 45% reduced risk of cancer mortality among HUA patients. Restricted cubic splines showed a U-shaped relationship with all-cause and CVD mortality among HUA patients, with inflection points of 72.7 nmol/L and 38.0 nmol/L, respectively. The results were robust in subgroup and sensitivity analyses.

Serum 25(OH)D was negatively linearly correlated with mortality among gout patients, whereas U-shaped correlated with mortality in HUA patients. These results indicate that adequate vitamin D status could prevent premature death.

To investigate vitamin-D levels effect on the survival/success and on marginal bone levels of dental implants.

Patients with peri-implant disease and healthy control patients with functionally loaded dental implants were included in this retrospective case-control study. Forty patients with 201 implants were in the diseased-cohort, while thirty-three patients with 90 implants were in the control-cohort. Patient blood 25(OH)D levels were assessed through quantitative blood test. The correlation between abnormal 25(OH)D levels and disease status of each patient was assessed using Fisher's exact tests. The correlation of each implant's outcomes with vitamin-D status was assessed using Kaplan-Meier survival analysis and Mann-Whitney U tests.

Patients with blood 25(OH)D levels >70 ng/mL (hypervitaminosis-D) had a 21.1-fold increase in the risk of implant failure or severe peri-implant bone loss regarding patients with intermediate (>30, ≤70 ng/mL) levels. Kaplan-Meier survival analysis revealed that implants in the hypervitaminosis-D cohort had a survival probability of 73.7 % (95 % CI:56.5-84.5 %) at 19-years after surgery, compared to 95 % for implants in patients with intermediate 25(OH)D levels (95 % CI:88.3-97.9 %). Additionally, implants in the hypervitaminosis-D cohort lost bone faster than implants in the intermediate cohort. These results were specific to the patient cohort with elevated blood 25(OH)D levels and not observed in patients taking vitamin-D supplementation. The impact of hypervitaminosis-D was enriched for implants in the maxilla, and not as apparent for implants in the mandible.

Blood 25(OH)D levels >70 ng/mL were correlated with adverse implant outcomes, including implant failure and peri-implant bone loss, especially in the maxilla.

These results suggest that hypervitaminosis D may be a previously unidentified risk factor for dental implant complications and should be further investigated to elucidate the underlying mechanism.

Vitamin D deficiency is widespread across the globe. Numerous reports have linked vitamin D deficiency to certain non-skeletal diseases such as cardiovascular diseases. According to recent studies, there is evidence indicating a possible link between 25-hydroxyvitamin D deficiency and dyslipidemia. The main aim of this study is to investigate the relationship between vitamin D levels and lipid profile and to identify people who may benefit from vitamin D supplementation.

In this observational study, a total of 154 patients were included, 98 women and 56 men, aged between 19 and 82 years, in which serum vitamin D levels, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and blood sugar were analyzed.

The serum levels of vitamin D showed some differences, being lower in patients with dyslipidemia, with a positive correlation between vitamin D levels and total cholesterol (F ratio = 7.3247, p=0.008), and also with LDL cholesterol (F ratio = 5.0023, p=0.027). The HDL-C fraction and triglycerides showed no significant correlation with the serum levels of vitamin D. Further on, we divided the patients according to the fraction that had pathological values and compared the levels of vitamin D between these categories. We observed that the lowest levels of vitamin D were present in patients with all lipid parameters modified (HIGH-TC/LOW-HDL/HIGH-LDL/HIGH-TG), and also the highest levels of low HDL-C and high LDL-C.

Our research provides additional evidence to the unfavorable lipid profile found in people with vitamin D deficiency.

This study aimed to investigate the association between serum 25-hydroxyvitamin D (25(OH)D) concentrations and mortality in long-term prescription opioid users.

The study included 1856 long-term prescription opioid users from the National Health and Nutrition Examination Survey (NHANES, 2001-2018). Mortality status were determined by matching with the National Death Index (NDI) records until December 31, 2019. Multivariable Cox proportional hazard models were constructed to assess the association.

Over a median follow-up period of 7.75 years, there were 443 cases of all-cause mortality, including 135 cardiovascular disease (CVD) deaths and 94 cancer deaths. After multivariable adjustment, participants with serum 25(OH)D concentrations within 50.00 to <75.00 nmol/L and ≥ 75 nmol/L had a lower risk of all-cause mortality, with hazard ratios (HRs) of 0.50 (95% confidence interval [CI] 0.29, 0.86) and 0.54 (95% CI 0.32, 0.90), respectively. Nevertheless, no significant association was found between serum 25(OH)D concentrations and the risk of CVD or cancer mortality. The RCS analysis revealed a non-linear association of serum 25(OH)D concentration with all-cause mortality (p for non-linear = 0.01). Per 1-unit increment in those with serum 25(OH)D concentrations <62.17 nmol/L corresponded to a 2% reduction in the risk of all-cause mortality (95% CI 0.97, 1.00), but not changed significantly when 25(OH)D concentrations ≥62.17 nmol/L.

In conclusion, a non-linear association existed between serum 25(OH)D concentrations and all-cause mortality in long-term prescription opioid users. Maintaining serum 25(OH)D concentrations ≥62.17 nmol/L may be beneficial in preventing all-cause mortality in this population.

Colorectal cancer (CRC) is one of the most life-threatening neoplasias in terms of incidence and mortality worldwide. Vitamin D deficiency has been associated with an increased risk of CRC. 1α,25-Dihydroxyvitamin D3 [1,25(OH)2D3], the most active vitamin D metabolite, is a pleiotropic hormone that, through its binding to a transcription factor of the nuclear receptor superfamily, is a major regulator of the human genome. 1,25(OH)2D3 acts on colon carcinoma and stromal cells and displays tumor protective actions. Here, we review the variety of molecular mechanisms underlying the effects of 1,25(OH)2D3 in CRC, which affect multiple processes that are dysregulated during tumor initiation and progression. Additionally, we discuss the epidemiological data that associate vitamin D deficiency and CRC, and the most relevant randomized controlled trials of vitamin D3 supplementation conducted in both healthy individuals and CRC patients.

On March 28, 2024, the Council of Experts "High-dose vitamin D (Devilam) in the practice of obstetrician-gynecologist, gynecologist and endocrinologist" was held in Moscow with the participation of leading experts gynecologists, endocrinologists and obstetricians-gynecologists, during which new possibilities for the use of high-dose vitamin D in patients of various ages who need correction of existing vitamin D deficiency or insufficiency.

Calcium and vitamin D have well-established roles in maintaining calcium balance and bone health. Decades of research in human subjects and animals have revealed that calcium and vitamin D also have effects on many other organs including male reproductive organs. The presence of calcium-sensing receptor, vitamin D receptor, vitamin D activating and inactivating enzymes and calcium channels in the testes, male reproductive tract and human spermatozoa suggests that vitamin D and calcium may modify male reproductive function. Functional animal models have shown that vitamin D deficiency in male rodents leads to a decrease in successful mating and fewer pregnancies, often caused by impaired sperm motility and poor sperm morphology. Human studies have to a lesser extent validated these findings; however, newer studies suggest a positive effect of vitamin D supplementation on semen quality in cases with vitamin D deficiency, which highlights the need for initiatives to prevent vitamin D deficiency. Calcium channels in male reproductive organs and spermatozoa contribute to the regulation of sperm motility and capacitation, both essential for successful fertilisation, which supports a need to avoid calcium deficiency. Studies have demonstrated that vitamin D, as a regulator of calcium homoeostasis, influences calcium influx in the testis and spermatozoa. Emerging evidence suggests a potential link between vitamin D deficiency and male infertility, although further investigation is needed to establish a definitive causal relationship. Understanding the interplay between vitamin D, calcium and male reproductive health may open new avenues for improving fertility outcomes in men.

We summarized the current evidence on vitamin D and major health outcomes from Mendelian randomization (MR) studies. PubMed and Embase were searched for original MR studies on vitamin D in relation to any health outcome from inception to September 1, 2022. Nonlinear MR findings were excluded due to concerns about the validity of the statistical methods used. A meta-analysis was preformed to synthesize study-specific estimates after excluding overlapping samples, where applicable. The methodological quality of the included studies was evaluated according to the STROBE-MR checklist. A total of 133 MR publications were eligible for inclusion in the analyses. The causal association between vitamin D status and 275 individual outcomes was examined. Linear MR analyses showed genetically high 25-hydroxyvitamin D (25(OH)D) concentrations were associated with reduced risk of multiple sclerosis incidence and relapse, non-infectious uveitis and scleritis, psoriasis, femur fracture, leg fracture, amyotrophic lateral sclerosis, anorexia nervosa, delirium, heart failure, ovarian cancer, non-alcoholic fatty liver disease, dyslipidemia, and bacterial pneumonia, but increased risk of Behçet's disease, Graves' disease, kidney stone disease, fracture of radium/ulna, basal cell carcinoma, and overall cataracts. Stratified analyses showed that the inverse association between genetically predisposed 25(OH)D concentrations and multiple sclerosis risk was significant and consistent regardless of the genetic instruments GIs selected. However, the associations with most of the other outcomes were only pronounced when using genetic variants not limited to those in the vitamin D pathway as GIs. The methodological quality of the included MR studies was substantially heterogeneous. Current evidence from linear MR studies strongly supports a causal role of vitamin D in the development of multiple sclerosis. Suggestive support for a number of other health conditions could help prioritize conditions where vitamin D may be beneficial or harmful.

With the analysis of nationwide health claim data, treatment with the composite agent of SERMs and vitamin D reduces the risk of osteoporotic fracture and hip fracture better compared to SERMs treatment in women with osteoporosis aged ≥ 50 years.

This study compared the potential of the composite agent of selective estrogen receptor modulators (SERMs) and vitamin D (SERM + VitD) with that of SERMs-only for fracture prevention and mortality reduction in women aged ≥ 50 years.

The incidence of osteoporotic fracture (fractures of the vertebrae, hip, wrist, or humerus) and all-cause death after treatment with SERM + VitD and SERMs were characterized using the Korean National Health Insurance Service database 2017-2019. The participants were divided into two groups (SERM + VitD vs SERMs). After exclusion and propensity score matching, 2,885 patients from each group were included in the analysis. Fracture incidence was compared between groups. Kaplan-Meier curves were used to compare mortality. Cox proportional hazards regression analysis was used to compare the risks of fracture occurrence and mortality between the groups.

The incidence rate (138.6/10,000 vs. 192.4/10,000 person-years), and risk of osteoporotic fractures (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.97; p = 0.024) were lower in the SERM + VitD group than in the SERMs group. Analysis for specific fractures showed a lower hazard of hip fracture in the SERM + VitD group (HR, 0.25; 95% CI, 0.09-0.71; p = 0.009). No difference was observed between the groups regarding mortality.

The risk of osteoporotic fractures, especially hip fractures, was lower in the SERM + VitD group than in the SERMs group. Therefore, the composite agent of SERMs and vitamin D can be considered as a viable option for postmenopausal women with a relatively low fracture risk.

Cancer survivors have a high risk of mortality, and vitamin D (VD) is associated with the risk of mortality. This study is aim to examine the impact of VD on mortality in cancer survivors.

A prospective study was conducted using data from the National Health and Nutrition Examination Survey. Participants were obtained information on their baseline characteristics, dietary habits, comorbidities, lifestyle, and serum 25-hydroxy VD [25(OH)D] concentrations. The weighted Cox proportional hazard and competing risk regression models were used to estimate the hazard ratio and 95% confidence intervals (HR, 95% CI) of mortality for different serum 25(OH)D concentrations. Restricted cubic spline (RCS) curves were utilized to illustrate the dose-response relationship between serum 25(OH)D concentrations and mortality.

The study encompassed 2,495 participants with cancer diagnoses. Multivariate models indicated that, compared to serum 25(OH)D concentrations below 58.5 nmol/L, concentrations exceeding 81.6 nmol/L were associated with reduced HRs for all-cause mortality (HR = 0.70; 95% CI: 0.56-0.87), cardiovascular mortality (HR = 0.53; 95% CI: 0.32-0.86), and cancer-specific mortality (HR = 0.66; 95% CI: 0.45-0.99). RCS curves revealed "L-shaped" associations between serum 25(OH)D concentration and both all-cause and cancer-specific mortality, with threshold effects at 87.9 nmol/L and 84.6 nmol/L, respectively. Conversely, the relationship between serum 25(OH)D concentration and cardiovascular mortality exhibited a more linear pattern, with a threshold at 88.7 nmol/L. Subgroup analyses highlighted a gender-specific interaction that elevated serum 25(OH)D concentrations were significantly more protective against mortality in males than in females, especially regarding cancer-specific mortality (P-interaction = 0.009).

Elevated serum 25(OH)D concentrations were correlated with decreased risks of all-cause, cardiovascular, and cancer-specific mortality in cancer survivors, with benefit thresholds at 87.9, 88.7, and 84.6 nmol/L, respectively. These findings suggested that cancer survivors might benefit from higher vitamin D recommendations than the general population.

Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with β-hydroxy-β-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care.

A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes.

During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring.

The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS.

Vitamin D is a promising anticancer agent for the prevention and treatment of several cancers, including melanoma. Low 25-hydroxyvitamin D levels, a routinely used marker for vitamin D, have been suggested as one of the factors in the development and progression of melanoma. The parent vitamin D needs activation by cytochrome P450 (CYP) enzymes to exert its actions via the vitamin D receptor (VDR). This review discusses the role of vitamin D in melanoma and how CYP-mediated metabolism can potentially affect the actions of vitamin D. Through interacting with the retinoid X receptor, VDR signaling leads to anti-inflammatory, antioxidative, and anticancer actions. Calcitriol, the dihydroxylated form of vitamin D3, is the most active and potent ligand of VDR. CYP27A1, CYP27B1, and CYP2R1 are involved in the activation of vitamin D, whereas CYP24A1 and CYP3A4 are responsible for the degradation of the active vitamin D. CYP24A1, the primary catabolic enzyme of calcitriol, is overexpressed in melanoma tissues and cells. Several drug classes and natural health products can modulate vitamin D-related CYP enzymes and eventually cause lower levels of vitamin D and its active metabolites in tissues. Although the role of vitamin D in the development of melanoma is yet to be fully elucidated, it has been proposed that melanoma prevention may be significantly aided by increased vitamin D signaling. Furthermore, selective targeting of the catabolic enzymes responsible for vitamin D degradation could be a plausible strategy in melanoma therapy. Vitamin D signaling can be improved by utilizing dietary supplements or by modulating CYP metabolism. A positive association exists between the intake of vitamin D supplements and improved prognosis for melanoma patients. Further investigation is required to determine the function of vitamin D supplementation and specific enzyme targeting in the prevention of melanoma.

Activation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos.

We analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD). Western blot, ELISA, ChIP, and dual-luciferase reporter assays were performed to determine the mechanism of VDR regulating CCL20. Migration assay and immunofluorescence were used to investigate the role of CCL20 in M2 macrophage polarization and recruitment. We employed multiplexed immunohistochemical staining and mouse models to validate the correlation of VDR on macrophages infiltration in PAAD. Flow cytometry analysis of M2/M1 ratio in subcutaneous graft tumors.

VDR is extensively expressed in PAAD, and patients with elevated VDR levels exhibited a significantly reduced overall survival. VDR expression in PAAD tissues was associated with increased M2 macrophages infiltration. PAAD cells overexpressing VDR promote macrophages polarization towards M2 phenotype and recruitment in vitro and vivo. Mechanistically, VDR binds to the CCL20 promoter and up-regulates its transcription. The effects of polarization and recruitment on macrophages can be rescued by blocking CCL20. Finally, the relationship between VDR and M2 macrophages infiltration was evaluated using clinical cohort and subcutaneous graft tumors. A positive correlation was demonstrated between VDR/CCL20/CD163 in PAAD tissues and mouse models.

High expression of VDR in PAAD promotes M2 macrophage polarization and recruitment through the secretion of CCL20, which activates tumor progression. This finding suggests that the combination of anti-macrophage therapy may improve the efficacy of VDR activation therapy in PAAD.

Although calcium and vitamin D (CaD) supplementation may affect chronic disease in older women, evidence of long-term effects on health outcomes is limited.

To evaluate long-term health outcomes among postmenopausal women in the Women's Health Initiative CaD trial.

Post hoc analysis of long-term postintervention follow-up of the 7-year randomized intervention trial of CaD. (ClinicalTrials.gov: NCT00000611).

A multicenter (n = 40) trial across the United States.

36 282 postmenopausal women with no history of breast or colorectal cancer.

Random 1:1 assignment to 1000 mg of calcium carbonate (400 mg of elemental calcium) with 400 IU of vitamin D3 daily or placebo.

Incidence of colorectal, invasive breast, and total cancer; disease-specific and all-cause mortality; total cardiovascular disease (CVD); and hip fracture by randomization assignment (through December 2020). Analyses were stratified on personal supplement use.

For women randomly assigned to CaD versus placebo, a 7% reduction in cancer mortality was observed after a median cumulative follow-up of 22.3 years (1817 vs. 1943 deaths; hazard ratio [HR], 0.93 [95% CI, 0.87 to 0.99]), along with a 6% increase in CVD mortality (2621 vs. 2420 deaths; HR, 1.06 [CI, 1.01 to 1.12]). There was no overall effect on other measures, including all-cause mortality (7834 vs. 7748 deaths; HR, 1.00 [CI, 0.97 to 1.03]). Estimates for cancer incidence varied widely when stratified by whether participants reported supplement use before randomization, whereas estimates on mortality did not vary, except for CVD mortality.

Hip fracture and CVD outcomes were available on only a subset of participants, and effects of calcium versus vitamin D versus joint supplementation could not be disentangled.

Calcium and vitamin D supplements seemed to reduce cancer mortality and increase CVD mortality after more than 20 years of follow-up among postmenopausal women, with no effect on all-cause mortality.

National Heart, Lung, and Blood Institute of the National Institutes of Health.

A meta-analysis suggested that marine n-3 polyunsaturated fatty acids (PUFAs), e.g., eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), might reduce cancer mortality. However, a randomized clinical trial of marine n-3 PUFA and vitamin D supplementation failed to verify this benefit. This study aimed to investigate the potential interaction between vitamin D supplementation and serum EPA and DHA levels. This post hoc analysis of the AMATERASU trial (UMIN000001977), a randomized controlled trial (RCT), included 302 patients with digestive tract cancers divided into two subgroups stratified by median serum levels of EPA + DHA into higher and lower halves. The 5-year relapse-free survival (RFS) rate was significantly higher in the higher half (80.9%) than the lower half (67.8%; hazard ratio (HR), 2.15; 95% CI, 1.29-3.59). In the patients in the lower EPA + DHA group, the 5-year RFS was significantly higher in the vitamin D (74.9%) than the placebo group (49.9%; HR, 0.43; 95% CI, 0.24-0.78). Conversely, vitamin D had no effect in the higher half, suggesting that vitamin D supplementation only had a significant interactive effect on RFS in the lower half (p for interaction = 0.03). These results suggest that vitamin D supplementation may reduce the risk of relapse or death by interacting with marine n-3 PUFAs.

The relationship between vitamin D status and mortality among adults with hypertension remains unclear.

This prospective cohort study involved a sample of 19,500 adults with hypertension who participated in the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. We utilized a weighted COX proportional hazard model to assess the association between vitamin D status and mortality. This statistical model calculates hazard ratios (HR) and their corresponding 95% confidence intervals (95% CI).

The study indicated that lower serum 25(OH)D concentration was associated with an increased risk of all-cause mortality among individuals with hypertension. Specially. Those with concentrations between 25.0 and 49.9 nmol/L (HR = 1.71, 95%CI = 1.22-2.40) and less than 25.0 nmol/L (HR = 1.97, 95%CI = 1.15-3.39) had higher hazard ratios for all-cause mortality. Individuals with hypertension who took vitamin D supplements had a lower risk of all-cause mortality, but not the risk of CVD mortality (HR 0.75, 95%CI 0.54-1.03), compared to those who did not supplement (HR = 0.76, 95%CI = 0.61-0.94). Subgroup analysis further revealed that vitamin D supplementation was associated with a reduced risk of all-cause mortality among individuals without diabetes (HR = 0.65, 95%CI = 0.52-0.81) and individuals without CVD (HR = 0.75, 95%CI = 0.58-0.97), and a decreased risk of CVD mortality among individuals without diabetes (HR = 0.63, 95%CI = 0.45-0.88) and without CVD (HR = 0.61, 95%CI = 0.40-0.92). Furthermore, higher-dose vitamin D supplementation was also associated with a greater reduction in all-cause mortality among hypertensive individuals, and there was the potential synergistic effect of combining normal-dose calcium and vitamin D supplementation, showing a superior effect on mortality compared to low-dose supplementation in adults with hypertension.

This prospective cohort study demonstrated a significant association between lower serum 25 (OH)D concentration and increased all-cause mortality among adults with hypertension. Furthermore, the study found that vitamin D supplementation had a strong and significantly positive correlation with reduced all-cause and CVD mortality among hypertensive individuals without diabetes or CVD. This positive correlation suggests that vitamin D supplementation could potentially be an effective strategy to reduce the risk of mortality in this specific group of people.

Acute pancreatitis (AP) is a serious and complex disorder with varying disease course and severity. Early and prompt interventions are crucial in management of AP. Vitamin D, being a prominent actor in calcium metabolism, also takes part in immunity and thus in immune-system related disorders, ranging from infections to cancer. In this study, the role of vitamin D status of a patient on the severity of AP was investigated. This study was conducted between June 2021 to August 2022 with a total of 315 patients. Blood samples were obtained upon admission. A 25-(OH)D3 level less than 10 ng/ml was defined as vitamin D deficiency. 10-19 ng/ml was defined as vitamin D insufficiency whereas 20 ng/ml or above was considered to be sufficient. Scoring systems (Ranson score, CTSI, BISAP, Revised Atlanta Classification (RAC) were applied. Serum 25-(OH)D3 levels of patients with AP were found to be negatively correlated with severity of the disease according to RAC (p < 0.001). In concordance to this finding, both Ranson score and BISAP were found to be statistically significantly related to 25-(OH)D3 levels. Both scoring systems revealed higher scores in patients with insufficient or deficient levels of 25-(OH)D3. Serum 25-(OH)D3 levels were not found to be related to intensive care unit admission or mortality. This study revealed that serum 25-(OH)D3 level is related to the severity of AP. In the future, interventional studies with vitamin D therapy in otherwise serum 25-(OH)D3 deficient AP patients might reveal a new potential therapeutic agent in this mechanically complex, burdensome disorder.