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The association between vitamin D concentrations and the occurrence of diabetic foot ulcers (DFUs) remains a topic of ongoing debate. In order to provide a comprehensive and updated review, we conducted this meta-analysis to further investigate the relationship between vitamin D concentrations and DFUs occurrence. The following databases, including Cochrane Library, EMBASE, Web of Science, PubMed, CBM, CNKI, WANFANG DATA and VIP Database, were systematically searched for studies published up to Dec. 20th, 2023. The combined estimation was calculated using both fixed-effects and random-effects models. The overall effect size was reported as a weighted mean difference (WMD) with a corresponding 95% confidence interval (95%CI). Data analysis was performed utilizing Review Manager 5.4 and Stata 14. The Protocol has been registered in PROSPERO CRD42024503468. This updated meta-analysis, incorporating thirty-six studies encompassing 11,298 individuals with or without DFUs, demonstrated a significant association between vitamin D deficiency/insufficiency and an elevated risk of DFUs occurrence (< 25 nmol/L, OR 3.28, P < 0.00001; < 50 nmol/L, OR 2.25, P < 0.00001; < 75 nmol/L, OR 1.67, P = 0.0003). Vitamin D concentrations were significantly lower in individuals with DFUs compared to those without DFUs (P < 0.00001). Subgroup analyses consistently demonstrated this trend among the older population (> 50 years, P < 0.00001), individuals with long duration of diabetes (> 10 years, P < 0.00001), and those with poor glycemic control (mean HbA1c 8%-9% and > 9%, P < 0.00001)., (© 2024. The Author(s).)

Background: The rate of vitamin D deficiency (VDD) in critically ill children worldwide has been estimated at 50%. These children are at risk of multiple organ dysfunction, chronic morbidity, and decreased health related quality of life (HRQL). Pediatric and adult ICU clinical trials suggest that VDD is associated with worse clinical outcomes, although data from supplementation trials are limited and inconclusive. Our group's phase II multicenter dose evaluation pilot study established the efficacy and safety of an enteral weight-based cholecalciferol loading dose to rapidly restore vitamin D levels in critically ill children., Methods: Our aim is to evaluate the impact of this dosing regimen on clinical outcomes. VITdALIZE-KIDS is a pragmatic, phase III, multicenter, double-blind RCT aiming to randomize 766 critically ill children from Canadian PICUs. Participants are randomized using a 1:1 scheme to receive a single dose at enrollment of enteral cholecalciferol (10,000 IU/kg, max 400,000 IU) or placebo. Eligibility criteria include critically ill children aged newborn (> 37 weeks corrected gestational age) to < 18 years who have blood total 25-hydroxyvitamin D < 50 nmol/L. The primary objective is to determine if rapid normalization of vitamin D status improves HRQL at 28 days following enrollment. The secondary objective is to evaluate the impact of rapid normalization of vitamin D status on multiple organ dysfunction. The study includes additional tertiary outcomes including functional status, HRQL and mortality at hospital discharge and 90 days, PICU and hospital length of stay, and adverse events related to vitamin D toxicity. Additionally, we are performing comprehensive vitamin D speciation and non-targeted metabolite profiling as part of a sub-study for the first 100 participants from whom an enrollment and at least one post-intervention blood and urine sample were obtained., Discussion: The VITdALIZE-KIDS trial is the first phase III, multicenter trial to evaluate whether rapid normalization of vitamin D status could represent a simple, inexpensive, and safe means of improving outcomes following pediatric critical illness. Recruitment was initiated in June 2019 and is expected to continue to March 2026., Trial Registration: Clinicaltrials.gov, NCT03742505. Study first submitted on November 12, 2018 https://clinicaltrials.gov/study/NCT03742505., (© 2024. The Author(s).)

Background: The incidence of vitamin D deficiency among pregnant women remains high and is associated with vitamin D deficiency in infants. In normally breastfed infants, Bifidobacteriaceae and Lactobacillaceae are known to help in maintaining immunotolerance and prevent infection. Vitamin D in the gastrointestinal tract plays a role in determining the composition and function of intestinal bacteria. Preterm infants are vulnerable to intestinal dysbiosis and sepsis due to bacterial translocation. This study aimed to determine the association between vitamin D levels and intestinal dysbiosis., Methods: It was a cohort study conducted in the Neonatal Unit, Cipto Mangunkusumo Hospital, Tertiary hospital in Indonesia, from November 2019 to January 2021. The inclusion criteria in this study were preterm infants with a gestational age of less than 32 weeks or a birth weight of less than 1500 g. Total 25-hydroxyvitamin D (25(OH)D) levels were collected from the umbilical cords of very preterm or very low birth weight infants. A fecal examination was performed on the seventh day of life to assess intestinal bacteria using real-time PCR for four bacterial genera: Bifidobacteriaceae, Lactobacillaceae, Enterobacteriaceae, and Clostridiaceae., Results: A total of 43 infants were included in this study. Among the subjects, 53.4% had vitamin D deficiency. There was no association identified between vitamin D deficiency and intestinal dysbiosis (RR 0.67; 95% CI (0.15-2.82), p-value = 0.531). However, the ratio of Lactobacillacecae to Enterobacteriaceae was lower in those with vitamin D deficiency., Conclusion: Vitamin D deficiency was not associated with dysbiosis in preterm infants. However, this study found that the ratio of Lactobacillaceae to Enterobacteriaceae in those with vitamin D deficiency was lower than in those without vitamin D deficiency. Further research is warranted to confirm this finding., (© 2024. The Author(s).)

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 Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background/objectives: The objective of this study was to test the hypothesis that vitamin D deficiency (i.e., serum 25-hydroxyvitamin D (25(OH)D) ≤ 20 ng/mL) associates with the increased occurrence and shortened time to a knee osteoarthritis (OA) diagnosis after anterior cruciate ligament reconstruction (ACLR)., Methods: This study consisted of a retrospective, case-control design. The inclusion criteria consisted of (1) patients (≥18 y) who underwent arthroscopic ACLR with (cases; n = 28) and without (controls; n = 56) a subsequent knee OA diagnosis (≥90 d from the date of ACLR) and (2) with a documented serum 25(OH)D concentration after ACLR (and before a knee OA diagnosis for the cases). Controls were matched (2:1) to cases based on sex, age at ACLR, date of ACLR, and body mass index. After matching, patients were separated into two groups: (1) vitamin D deficient (serum 25(OH)D ≤ 20 ng/mL) or (2) non-vitamin D deficient (serum 25(OH)D > 20 ng/mL). Data were extracted from the medical records., Results: Thirty-one percent ( n = 26) of patients included were vitamin D deficient. Fifty percent ( n = 13) of the vitamin D deficient and twenty-six percent ( n = 15) of the non-vitamin D deficient patients were subsequently diagnosed with knee OA ( p = 0.03). Time from ACLR to a knee OA diagnosis was significantly ( p = 0.02) decreased in the vitamin D deficient (OA-free interval, 95% confidence interval [CI] = 7.9 to 10.9 y) compared to the non-vitamin D deficient group (OA-free interval, 95% CI = 10.5 to 12.5 y)., Conclusions: Vitamin D deficiency after ACLR may serve as a prognostic biomarker for knee OA following ACLR.

Objective: In this study, we investigated 25-hydroxyvitamin D (25(OH)D, vitamin D), inflammatory hematologic ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte/HDL-C ratio (MHR) and plasma atherogenic index (PAI) and possible relationships with insulin resistance (IR) in children., Methods: A total of 210 individuals, including 96 children with IR and 114 children without IR, aged 6-18 years, who were admitted to the Pediatric Endocrinology Outpatient Clinic at Medicine Hospital, Istanbul Atlas University were included in our study., Result: Compared to patients without IR, NLR, PLR, SII, and MHR were significantly higher in patients with IR. Fasting insulin, PAI, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-β were significantly higher and quantitative insulin sensitivity check index (QUICKI) was considerably lower in patients with IR compared to those without IR. NLR, SII, and MHR were lower in normal vitamin D groups than the others ( p < 0.001). PLR was lower in the group with normal vitamin D levels than the groups with insufficient or deficient levels of vitamin D (D < 21)., Conclusions: We found that vitamin D deficiency in childhood is related to increased levels of circulating inflammatory markers (NLR, PLR, MHR, PAI), IR, and decreased insulin sensitivity. According to our results, supplementation of vitamin D may be beneficial in averting IR and enhanced systemic inflammation.

Introduction/aim: Vitamin D plays a crucial role in immune modulation, which may influence the development of graft-versus-host disease (GvHD) in patients undergoing hematopoietic stem cell transplantation (HSCT). This study aims to evaluate the impact of vitamin D levels and supplementation on the incidence of GvHD in HSCT patients., Methods: A narrative review was conducted across PubMed/Medline, Cochrane Library, CINAHL, and Embase databases., Results: The reviewed studies indicated widespread vitamin D deficiency among HSCT patients, with baseline levels ranging from 12.8 to 29.2 ng/mL. Supplementation protocols varied significantly, with dosages ranging from 1000 IU/day to 60,000 IU/week. Post-supplementation levels improved in some studies. Studies exploring the relationship between vitamin D and GvHD showed mixed results. Lower baseline vitamin D levels were associated with an increased risk of acute GvHD in some studies, while others found no significant correlation. However, a significant association between low levels of vitamin D and the incidence of chronic GvHD was observed., Conclusion: Vitamin D deficiency is prevalent in HSCT patients and may influence the risk of developing chronic GvHD. Future research should focus on larger and more rigorous studies to determine the optimal role of vitamin D as an adjuvant therapy in the context of HSCT.

Background: Irritable bowel syndrome (IBS) is a common disease with unknown etiology. Poor dietary intake with nutritional deficiency and overweight have been described to increase the risk of IBS. The aim of the present study was to compare weight and circulating levels of micronutrients in IBS compared with healthy controls., Design: Cross-sectional study., Methods: Patients diagnosed with IBS and healthy volunteers were recruited. Participants had to complete a dietary diary book and the questionnaires Rome IV, IBS-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). Weight and height were measured, and blood samples were drawn. C-reactive protein (CRP), cobalamin, folate, iron, total iron-binding capacity (TIBC), and 25-hydroxy (25-OH) vitamin D were analyzed. Differences were calculated between groups and generalized linear model for regressions was adjusted for false discovery rate (FDR)., Results: IBS patients (n = 260) were elder than controls (n = 50) (44.00 (33.25-56.00) vs. 37.85 (30.18-45.48) years; p = 0.012). After adjustment for age, both weight (β: 5.880; 95% CI: 1.433-10.327; p = 0.010, FDR = 0.020) and body mass index (BMI) (β: 2.02; 95% CI: 0.68-3.36; p = 0.003, FDR = 0.012) were higher in patients. Among IBS participants, 48.1% were overweight/obese compared with 26.0% in controls (p = 0.007). Diarrhea-predominated IBS had highest weight (p < 0.001) and BMI (p = 0.077). CRP and cobalamin were higher in patients than controls (p = 0.010 vs. p = 0.007), whereas folate was highest in controls (p = 0.001). IBS patients had lower intake of vegetables (p = 0.026), dairy products (p = 0.004), and cereals (p = 0.010) compared with controls. Despite 21.5% of IBS patients were taking vitamin D supplements, 23.65% of them had vitamin D levels below 50 nmol/L, compared with 26.0% observed in the control group (p = 0.720). Vitamin D levels were lower in overweight than in normal weight IBS patients (60 (48-73) nmol/L vs. 65 (53-78) nmol/L, p = 0.022). Vitamin D correlated with cobalamin and folate but correlated inversely with TIBC and BMI. IBS patients had a high degree of gastrointestinal and extraintestinal symptoms, which were inversely associated with iron levels. Extraintestinal symptoms were associated with increased BMI., Conclusion: IBS patients were often overweight or obese, with low vitamin D levels. High burden of extraintestinal symptoms were associated with overweight and lower iron levels., Registration: ClinicalTrials.gov, NCT05192603 (Date of registration 11/29/2021) and NCT03306381 (Date of registration 09/18/2017), respectively., (© 2024. The Author(s).)

Vitamin D deficiency is a global problem. Vitamin D, the vitamin D receptor, and its enzymes are found throughout neuronal, ependymal, and glial cells in the brain and are implicated in certain processes and mechanisms in the brain. To investigate the processes affected by vitamin D deficiency in adults, we studied vitamin D deficient, control, and supplemented diets over 6 weeks in male and female C57Bl/6 mice. The effect of the vitamin D diets on proliferation in the neurogenic niches, changes in glial cells, as well as on memory, locomotion, and anxiety-like behavior, was investigated. Six weeks on a deficient diet was adequate time to reach deficiency. However, vitamin D deficiency and supplementation did not affect proliferation, neurogenesis, or astrocyte changes, and this was reflected on behavioral measures. Supplementation only affected microglia in the dentate gyrus of female mice. Indicating that vitamin D deficiency and supplementation do not affect these processes over a 6-week period.

Background and Aims: Vitamin D is known to influence the risk of cardiovascular disease, which is a recognized risk factor for sudden cardiac arrest (SCA). However, the relationship between vitamin D and SCA is not well understood. Therefore, this study aims to investigate the association between vitamin D and SCA in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls., Methods and Results: Using the Phase II Cardiac Arrest Pursuit Trial with Unique Registration and Epidemiologic Surveillance (CAPTURES II) registry, a 1:1 propensity score-matched case-control study was conducted between 2017 and 2020. Serum 25-hydroxyvitamin D (vitamin D) levels in patients with OHCA (454 cases) and healthy controls (454 cases) were compared after matching for age, sex, cardiovascular risk factors, and lifestyle behaviors. The mean vitamin D levels were 14.5 ± 7.6 and 21.3 ± 8.3 ng/mL among SCA cases and controls, respectively. Logistic regression analysis was used adjusting for cardiovascular risk factors, lifestyle behaviors, corrected serum calcium levels, and estimated glomerular filtration rate (eGRF). The adjusted odds ratio (aOR) for vitamin D was 0.89 (95% confidence interval [CI] 0.87-0.91). The dose-response relationship demonstrated that vitamin D deficiency was associated with SCA incidence (severe deficiency, aOR 10.87, 95% CI 4.82-24.54; moderate deficiency, aOR 2.24, 95% CI 1.20-4.20)., Conclusion: Vitamin D deficiency was independently and strongly associated with an increased risk of SCA, irrespective of cardiovascular and lifestyle factors, corrected calcium levels, and eGFR., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Patients with inflammatory bowel disease (IBD) are more likely to be confirmed with vitamin D deficiency. However, the association between inflammation and vitamin D remains unclear. The purpose of this study was to evaluate the association between inflammation and vitamin D in hospitalized patients with IBD., Methods and Study Design: All the participants were recruited from one teaching hospital from June 2018 to October 2022. Inflammation was evaluated by serum concentration of C-reactive protein (CRP), using an immunoturbidimetric method at admission. We further divided the participants into five groups based on serum CRP levels: <5, 5-9.9, 10-19.9, 20-39.9, and >40mg/L. Serum 25-hydroxy-vitamin D (25-(OH)-D) was assessed by liquid chromatography tandem mass spectrometry. Addi-tional information, including age, sex, body mass index (BMI), IBD (ulcerative colitis vs. Crohn's disease) subtype, was abstracted from medical records., Results: This study included 1,989 patients with IBD (average age was 39.4 years, 33.8% of them were women, 1,365 CD and 624 UC patients). The median CRP was 5.49 mg/L (range of quartiles: 1.64~19.5 mg/L) and the prevalence of 25-(OH)-D deficiency was 69.8%. CRP was significantly associated with serum level of 25-(OH)-D. The difference in 25-(OH)-D was -4.28 ng/ml (-5.27 ng/ml, -3.31 ng/ml) between two extremist CRP groups after adjustment of potential covariates (age, sex, BMI, type of IBD, dietary type, season, and lymphocyte count). Subgroup analysis in sex, type of IBD, and age, were similar to the main analysis results., Conclusions: There was a negative association between CRP levels and vitamin D in hospitalized patients with IBD., Competing Interests: The authors declare no conflict of interest

Research Question: Is low serum 25-hydroxyvitamin D (25(OH)D) associated with an increased risk of miscarriage in women who presented with threatened miscarriage to the Early Pregnancy Assessment Clinic (EPAC)?, Design: This was a secondary retrospective analysis using archived serum samples from a randomized, double-blind, placebo-controlled trial. Stored serum samples from 371 women presenting to the EPAC with threatened miscarriage during the first trimester were assayed for 25(OH)D by liquid chromatography-mass spectrometry., Results: The overall miscarriage rate was 45/371 (12.1%) in the whole cohort. After grouping vitamin D insufficiency and vitamin D sufficiency together into a 'non-deficient' group and excluding participants who underwent termination of pregnancy, there was no difference in the miscarriage rate between those who were vitamin D deficient compared with those who were not (25/205, 12.2% versus 20/157, 12.7%, P= 0.877, odds ratio 0.951, 95% CI 0.507-1.784). When analysed according to the number of gestational weeks, the miscarriage rate was significantly higher in the vitamin D non-deficient group than the vitamin D-deficient group in women who presented at 6 gestational weeks or earlier (13/33 [39.4%] versus 10/58 [17.2%], P= 0.019), but there were no statistically significant differences between the two groups presenting at later gestations. There was no difference in the vitamin D level in women who had a miscarriage compared with those who had a live birth (48 [37-57] versus 47 [37-58] nmol/l, P= 0.725 median [25th-75th percentile])., Conclusions: A low serum vitamin D concentration was not associated with an increased risk of miscarriage in women with threatened miscarriage presenting to the EPAC., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Over the past few years, there has been a surge in interest regarding the connection between sleep duration and quality, sleep disorders, mainly Obstructive sleep apnoea (OSA) and Vitamin D. There is growing evidence to support a new role of Vitamin D in the maintenance and regulation of optimal sleep. Furthermore, a notable link has been identified between OSA and a decrease in serum Vitamin D levels, which appears to intensify as the severity of sleep apnea worsens. Vitamin D status could also potentially serve as a mediator or provide an explanation for the association between OSA and cardiometabolic morbidity, but the current state of research in this area is inadequate. Studies have indicated that the supplementation of Vitamin D can optimize sleep quality, presenting more proof of the connection between insufficient vitamin D levels and sleep disorders. However, it is unclear whether low serum Vitamin D levels are a contributing factor to OSA development or if OSA predisposes individuals to Vitamin D deficiency. As a result, various studies have endeavored to examine the complex relationship between OSA and Vitamin D deficiency. In children and adolescents, while data is limited, there seems also to be a link between sleep disorders and Vitamin D levels. Therefore, the objective of this review is to provide a comprehensive overview of the current evidence on the association between Vitamin D and sleep disorders in both adults and children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Vitamin D deficiency is a global problem, and 13 to 75% of patients undergoing total joint arthroplasty (TJA) have vitamin D deficiency. Several studies have shown that low preoperative vitamin D levels may increase the risk of postoperative complications, including periprosthetic joint infection (PJI), in patients undergoing primary TJA. Most of the studies are underpowered. This study aimed to investigate the relationship between vitamin D deficiency and surgical and medical complications after primary TJA, with a specific focus on PJI., Methods: Prospectively collected institutional multicenter arthroplasty databases were reviewed to identify patients who underwent primary total knee and hip arthroplasty. The study group was defined as patients whose vitamin D level is < 30 ng/dL and who received a single oral dose of 7.5 mg (300,000 IU) D3 within two weeks before index surgery (n = 488; mean age 63 years). Patients in the control group were those whose preoperative vitamin D levels were unknown and who did not receive vitamin D supplementation (n = 592, mean age 66). The groups were compared regarding 90-day medical and surgical complications, including PJI, mortality, and readmission rates., Results: The total number of complications (8.6 and 4.3%; respectively; P = .005), superficial wound infection (2.5 and 0.2%, respectively; P < .001), and postoperative cellulitis (2.2 and 0% respectively; P < .001) were statistically significantly higher in the patient group who did not receive vitamin D supplementation. However, 90-day mortality (P = .524), PJI (P = .23), and readmission rate (P = .683) were similar between the groups., Conclusions: This study demonstrated that preoperative optimization of vitamin D levels may be beneficial in reducing postoperative complications, including superficial wound infection and postoperative cellulitis. Administering an oral 300,000 U single-dose vitamin D regimen to correct vitamin D deficiency can positively impact outcomes following primary TJA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: Polycystic ovary syndrome (PCOS) is a common and complex endocrine disorder in women of reproductive age. Vitamin D supplementation is a promising complementary therapy for PCOS, yet there is no consensus on an optimal dose, leading to a lack of evidence-based supplementation guidelines., Objective: The objective of this study was to conduct a vitamin D dose-response meta-analysis among women with PCOS., Data Sources: MEDLINE, CINAHL, and EMBASE databases from inception to November 2022 were searched for relevant articles., Data Extraction: Study screening and bias assessment were conducted by 2 independent reviewers. Eight relevant studies were identified; data for serum 25(OH)D (nmol/L) at baseline and at 12 weeks in each intervention group (mean ± SD) and vitamin D dose were extracted., Data Analysis: Estimates across studies were used to create a pooled curve, using restricted cubic splines with knots at the 10th, 50th, and 90th percentiles of the distribution of doses, to estimate the mean difference in effect for serum 25(OH)D at each dose compared with 0 IU/day. Sensitivity analyses were conducted fixing knots at 4000 IU/day and 7000 IU/day, which were a priori identified as potentially important thresholds, and to assess model fit and estimate heterogeneity. The pooled analysis demonstrated strong evidence of a dose-response relationship (P < .001), suggesting an increasing effect with increasing dose. An initial increase in serum 25(OH)D was evident until doses of approximately 3000 IU/day; this was followed by a plateau in effect between approximately 3000 IU/day and 5000 IU/day. The effect of supplementation with >5000 IU/day was unclear, given the minimal data at higher doses. The curve produced robust results for moderate doses (3000 IU/day to 4000 IU/day), which were not sensitive to model specification., Conclusion: Women with PCOS are responsive to vitamin D supplementation, but the benefit of providing doses of >3000 IU/day appears minimal. Further data is required to determine dose-response at doses of >5000 IU/day, and whether higher intakes provide a clinically meaningful advantage in this population., Systematic Review Registration: PROSPERO registration no. CRD42021259396., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This retrospective cohort study aimed to determine whether severe calcidiol deficiency [25-hydroxyvitamin (OH)D <30 nmol/L] improvement has a beneficial effect on cardiometabolic parameters in children and adolescents (5-17 years) with or without metabolic syndrome (MetS). Logistic regression analysis was performed to test for multivariate associations between potential confounders and changes in vitamin D (VD) status from baseline to follow-up care when predicting binary categorical outcomes. Of 562 participants, 146 (26%) had MetS. Individuals with severe VD deficiency (VDD) were more likely to have MetS with elevated blood pressure than those with sufficient (≥75 nmol) VD levels (adjusted odds ratio [AOR], 4.46; 1.08-18.43; p < .05) at follow-up. In the logistic regression model, every unit increase in VD across time decreased the odds of MetS (AOR, 0.98; 95% confidence interval: [0.96, 0.99]; p < .05). Improvement in VD status demonstrated a beneficial metabolic effect in children and adolescents with severe VDD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: This study aimed to assess the association between vitamin D and sleep health and to investigate whether depression could mediate this relationship., Methods: A cross-sectional analysis was performed using the 2005-2014 US National Health and Nutrition Examination Survey (NHANES) data. The logistic regression models were conducted to evaluate association of serum vitamin D concentrations with sleep health and depression. Mediation analyses were conducted to investigate the mediated effects of depression on the association of vitamin D with sleep health., Results: In multivariate logistic models, vitamin D was found to be negatively associated with an increased risk of poor sleep health, with an odds ratio (OR) of vitamin D deficiency versus sufficiency was 1.256 (95% CI = 1.084-1.455). Additionally, univariate logistic models showed that vitamin D was also negatively associated with depression risk (vitamin D deficiency vs. sufficiency: OR = 1.699, 95% CI = (1.373-2.103). Further mediation analyses showed that the association of vitamin D with sleep health was mediated by depression, with the mediating effects of depression accounted for 44.56% of the total effects., Conclusion: Vitamin D affects sleep health directly and indirectly through depression. The results suggest that interventions increasing intake of vitamin D should be prioritized to promote sleep health of persons with or at risk of depression.

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women. Dyslipidemia is a prevalent metabolic abnormality in individuals with PCOS. Moreover, vitamin D deficiency is widespread across all societal strata, with a particularly heightened prevalence observed in patients afflicted with PCOS. The present study aimed to investigate the level of vitamin D and its correlation with lipid profiles in Iranian women diagnosed with PCOS., Methods: This cross-sectional study was carried out at the PCOS and infertility clinic of Arash Women's Hospital in Tehran. The study encompassed the medical records of PCOS patients who attended the clinic from March 2021 to December 2023. All patients underwent blood tests, which included assessments of fasting blood sugar levels, lipid profiles, and 25-hydroxyvitamin D (25(OH)D) levels. The investigation focused on evaluating the relationship between vitamin D levels and lipid profiles. Statistical analyses, including the chi-square test and Spearman's correlation coefficient, were employed to analyze the data., Results: A total of 1004 women diagnosed with PCOS were included in the study. The age range of the participants was 14 to 46 years. The majority of the participants had a body mass index (BMI) within the normal range (n = 555, 55.3%). The median vitamin D level among the participants was 26.00 (IQR: 19.00-34.00). The relationship between vitamin D levels and lipid profile parameters was assessed, revealing no significant correlation between vitamin D levels and low-density lipoprotein (LDL) (r = 0.021, p = 0.505), high-density lipoprotein (HDL) (r = 0.011, p = 0.719), or triglyceride (TG) (r = -0.026, p = 0.417) levels, both in non-adjusted and age-adjusted analyses., Conclusion: According to the present study, there was no significant correlation between serum 25(OH)D deficiency and elevated TG or LDL levels or decreased HDL levels in PCOS patients. Nevertheless, further prospective studies are needed to determine whether there is a causal relationship between vitamin D deficiency and lipid profile alterations, specifically among PCOS patients., (© 2024. The Author(s).)

Dysmobility Syndrome (DMS), is a combination, that is analogous to the approach taken with metabolic syndrome, The diagnosis of DMS is complex. So this study aimed to explore the relationship between 25-(OH) Vit D with Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients. This is a cross-sectional study, including 330 patients (67.0 ± 8.8 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. Selected independent variables include grip strength, six-meter gait speed, level of 25-(OH) vitamin D, and bone mineral density (BMD) measured by Dual-energy X-ray (DXA). DMS includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, occurrences of falls in the past year ≥ 1, and obesity, having three or more of these conditions were diagnosed with DMS. Patients were classified based on DMS. The detection rate of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. The 25-(OH) Vit D deficiency was defined based on the 25th percentile into two groups; < 36.2 nmol/L. The vitamin D levels in Group DMS were significantly lower than that in Group Non-DMS (41.74 ± 14.60 vs. 47.19 ± 13.01, P < 0.05). After adjusting confounder factors including sex, age, vitamin D levels, HbA1c, ALB, HDLC, eGFR, diabetes microvascular complications and macrovascular, there was an independent association between risk of DMS and age (OR value = 1.160, 95% CI 1.091-1.234, P = 0.000), HbA1c(OR value = 1.262, 95% CI 1.046-1.532, P = 0.015), and vitamin D deficiency (< 36.2 nmol/L) (OR value = 2.990, 95% CI 1.284-6.964, P = 0.011). Our findings suggest that low levels of vitamin D are a predictor of DMS in middle-aged and elderly patients with poor control of type 2 diabetes., (© 2024. The Author(s).)

Background: Gestational diabetes mellitus (GDM) is one of the most prevalent pregnancy problems, and there is still debate over the relationship between vitamin D and GDM., Objectives: Our objective is to investigate the correlation between vitamin D and GDM by employing Mendelian randomization (MR) with summary data obtained from genome-wide association studies (GWAS)., Methods: Data on exposures and outcomes, namely vitamin D, vitamin D insufficiency, and GDM, were acquired from the IEU OpenGWAS Project. Bidirectional MR analysis was performed utilizing the inverse variance weighted (IVW) method as the principal analytical approach. The complementary approaches employed in this study encompassed weighted median, simple mode, weighted mode, and MR-Egger regression. A series of sensitivity analysis were conducted in order to assess the reliability of the obtained results., Results: The data were acquired from the IEU OpenGWAS Project. Following the application of the three assumptions of MR, 13 single nucleotide polymorphisms (SNPs) were included in the MR analysis for vitamin D levels and vitamin D deficiency on GDM, and 10 and 26 SNPs were included for GDM on vitamin D levels and deficiency, respectively. The findings from the IVW analysis revealed a significant positive correlation between vitamin D levels and GDM (OR = 1.057, 95% CI: 1.011-1.104, p = 0.015). Conversely, a negative correlation was seen between vitamin D deficiency and GDM (OR = 0.979, 95% CI: 0.959-0.999, p = 0.039). The results of the reverse MR study revealed no evidence of reverse causation between GDM and vitamin D. The findings from multiple MR approaches were in line with the direction of IVW analysis. Sensitivity analysis revealed no evidence of heterogeneity, pleiotropy, or outliers, suggesting the robustness of the results., Conclusions: There exists a causal association between vitamin D and GDM, whereby vitamin D levels serve as a risk factor for GDM.

Vitamin D contains 2 related fat-soluble substances, D3 and D2, that are essential for bone health and overall well-being. The burden of vitamin D deficiency within the active component of the armed forces is unknown. This study describes trends of vitamin D deficiency diagnoses in the active component of the U.S. Armed Forces. Risk factors for vitamin D, such as military occupation, were examined to see if preventive measures and targeted vitamin D screening would be beneficial, as the United States Preventive Task Force does not recommend universal screening for vitamin D, nor does TRICARE cover screening for asymptomatic individuals. The surveillance period covered January 1, 2018 through December 31, 2022. The data were derived from the Defense Medical Surveillance System (DMSS). Vitamin D deficiency was measured using ICD-9-CM and ICD-10-CM diagnoses recorded in inpatient and outpatient medical encounters. Incidence rate and average annual prevalence were calculated. A logistic regression was performed to obtain adjusted odds ratios. The rates of vitamin D deficiency diagnoses among active component service members (ACSMs) remained steady during the study period, with an incidence rate of 16.4 per 1,000 person-years and an average annual prevalence of 2.2%. Female service members, those of older age groups, and indoor workers demonstrated higher rates of vitamin D deficiency. Previously described demographic risk factors such as indoor work and history of obesity or malabsorption syndrome were also associated in this study with vitamin D deficiency in ACSMs, although older age groups in this study were not associated with vitamin D deficiency. Pilots and air crew had the lowest rates of vitamin D deficiency, while health care workers had the highest, when evaluating by occupation.

Background: It has been reported that vitamin D deficiency may be associated with the development of oral lichen planus (OLP). Given the high prevalence of vitamin D deficiency in many countries, we sought to determine whether it constitutes a comorbidity of OLP., Methods: One hundred and twenty patients clinically and histologically diagnosed with OLP were evaluated for their serum vitamin D levels. The results were compared to results from a control series of the same number of subjects matched for age and sex., Results: Vitamin D deficiency was diagnosed in 45% ( n = 54) of OLP patients and in 26.7% ( n = 32) of the control group. Vitamin D supplements were being taken by 32 (26.7%) OLP patients and 15 (12.5%) subjects in the control group. A multivariate logistic regression model showed that OLP was associated with vitamin D deficiency [OR: 2.24 (1.28-3.98, p = 0.005)] and vitamin D supplementation [OR: 2.51 (1.25-5.22, p = 0.011)], even after controlling for confounding variables such as sex, age ≤60>, tobacco, and alcohol., Conclusion: The association between OLP patients and vitamin D deficiency or vitamin D supplementation suggests that further research might explore the benefits of vitamin D supplements in managing OLP patients.

Background: Glaucoma is the second leading cause of blindness worldwide, with intraocular pressure as the only known modifiable risk factor. Vitamin D has been proposed to influence intraocular pressure and decrease retinal ganglion cell degeneration. Based on these findings, vitamin D has been suggested to prevent or reduce the severity of primary open-angle glaucoma (POAG), which is the most common form., Methods: We applied two-sample Mendelian randomisation (MR) analyses to data from the SUNLIGHT consortium and the UK Biobank to assess the causal effect of vitamin D levels and vitamin D deficiency on primary open-angle glaucoma (POAG). MR analysis, including sensitivity tests using other GWAS summary statistics from FinnGen, was also performed. We also investigated the association between single nucleotide polymorphisms (SNPs) on genes involved in vitamin D metabolic pathways and POAG., Results: We found no statistical evidence that vitamin D levels (OR = 1.146, 95% CI 0.873 to 1.504, p = 0.326) or vitamin D deficiency (OR = 0.980 (95% CI 0.928 to 1.036, p = 0.471) causally affect the risk of developing POAG. Sensitivity analyses, including the use of a more relaxed p -value threshold, and use of winter-measured samples only, replication in the FinnGen dataset, and exploration of specific genetic markers also showed no evidence of association between SNPs for genes involved in key steps of vitamin D metabolism and POAG., Conclusions: These results indicate that vitamin D may not be a significant factor in modifying POAG risk, challenging the hypothesis that vitamin D supplementation could be effective in reducing POAG risk. Further research should focus on identifying other potential risk factors for POAG prevention strategies.

Vitamin D, a steroid hormone, acts via the vitamin D receptor expressed in various tissues, including bones, muscles, and the cardiovascular system and is associated with well-being of individuals and vitamin D deficiency is considered as a prevalent public health problem. Menopause is an important cornerstone for women, where the hormonal changes may lead to adverse health effects. Vitamin D deficiency during menopausal transition or in postmenopausal period may aggravate the health risks such as osteoporosis, sarcopenia, and cardiovascular diseases associated with menopause. This manuscript aims to provide a review of the complex interaction between vitamin D deficiency and the well-being of postmenopausal women, focusing on musculoskeletal and cardiovascular implications. Clinical studies highlight the importance of maintaining optimal vitamin D levels to decrease the risk of musculoskeletal disorders and cardiovascular diseases in postmenopausal women. However, conflicting findings regarding the effectiveness of vitamin D supplementation in reducing cardiovascular risk suggest the need for further research and a personalized approach for the chemical form of Vitamin D, dose, duration of deficiency, individual variations, and accompanying conditions. The use of vitamin D supplementation in well-evaluated patients is desirable, and help to optimize health status in postmenopausal women., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Vitamin D deficiency is increasingly common in systemic lupus erythematosus (SLE) patients and is associated with the disease activity and proteinuria. Recently, alterations in metabolism have been recognized as key regulators of SLE pathogenesis. Our objective was to identify differential metabolites in the serum metabolome of SLE with vitamin D deficiency. In this study, serum samples from 31 SLE patients were collected. Levels of 25(OH)D3 were assayed by ELISA. Patients were divided into two groups according to their vitamin D level (20 ng/ml). Untargeted metabolomics were used to study the metabolite profiles in serum by high-performance liquid chromatography-tandem mass spectrometry. Subsequently, we performed metabolomics profiling analysis to identify 52 significantly altered metabolites in vitamin D deficient SLE patients. The area under the curve (AUC) from ROC analyses was calculated to assess the diagnostic potential of each candidate metabolite biomarker. Lipids accounted for 66.67% of the differential metabolites in the serum, highlighted the disruption of lipid metabolism. The 52 differential metabolites were mapped to 27 metabolic pathways, with fat digestion and absorption, as well as lipid metabolism, emerging as the most significant pathways. The AUC of (S)-Oleuropeic acid and 2-Hydroxylinolenic acid during ROC analysis were 0.867 and 0.833, respectively, indicating their promising diagnostic potential. In conclusion, our results revealed vitamin D deficiency alters SLE metabolome, impacting lipid metabolism, and thrown insights into the pathogenesis and diagnosis of SLE., (© 2024. The Author(s).)

Background: Vitamin D deficiency, a common occurrence among pregnant women, is an emerging public health concern worldwide. According to research, prenatal vitamin D deficiency is associated with various complications. This study assessed the vitamin D status of pregnant women in Yanbian, Jilin Province, as well as the correlation and predictive value of their vitamin D levels in relation to gestational length (weeks) and fetal weight, aiming to provide a basis for clinical diagnosis and treatment., Methods: We conducted a population-based retrospective study involving 510 pregnant women from August 2019 to October 2022. Blood samples were collected at 16-20 weeks of gestation for the detection of serum vitamin D levels. Statistical analyses were performed using SPSS 28.0 and R 4.1.0 software. Multifactorial logistic regression analysis was employed to establish whether each variable was a risk factor for deliveries at ≤ 38 gestational weeks and low fetal weight. These results were used to construct a risk prediction model, and the model's predictive efficacy was evaluated. Results or differences with p < 0.05 were considered statistically significant., Results: Multifactorial logistic regression analysis revealed that vitamin D ≤ 14.7 ng/mL(OR: 1.611; 95% CI: 1.120-2.318; P = 0.010), Bone Mineral Density (BMD) T-value ≤-1(OR: 1.540; 95%CI: 1.067-2.223; P = 0.021), and gestational hypertension(OR: 7.173; 95% CI: 1.482-34.724; P = 0.014) were the independent risk factors for deliveries at ≤ 38 gestational weeks. Additionally, vitamin D ≤ 14.7 ng/mL(OR: 1.610; 95%CI: 1.123-2.307; P = 0.009), BMD T-value ≤ -1(OR: 1.560; 95%CI: 1.085-2.243; P = 0.016), and gestational hypertension(OR: 4.262; 95% CI: 1.058-17.167; P = 0.041) were the independent risk factors for low fetal weight (< 3400 g)., Conclusion: This study revealed that low vitamin D levels are an independent risk factor for a short gestational length and low fetal weight. Prenatal low BMD T-value and comorbid hypertensive disorders were also found to increase the risk of a short gestational length and low fetal weight., (© 2024. The Author(s).)

Background: Liver cirrhosis is a chronic and progressive liver disease with significant global health implications. Recent evidence suggests an association between serum vitamin D levels and the severity of liver cirrhosis, potentially serving as a therapeutic target. This study aimed to investigate the relationship between serum vitamin D status and the severity of liver cirrhosis in a population of Nigerian patients., Methods: This analytical, cross-sectional study involved 201 participants, including 103 with liver cirrhosis and 98 age- and sex-matched controls. Serum vitamin D was measured using ELISA, with deficiency defined as < 20 ng/ml. Cirrhosis severity was assessed using Child-Pugh and MELD scores. Spearman's correlation was used to assess the relationship between vitamin D and severity of liver cirrhosis while ordinal regression analysis assessed its performance as an indicator of the disease severity., Result: Among cirrhotic patients, 36.9% were deficient, 31.1% insufficient, and 32.0% had sufficient vitamin D levels. Serum vitamin D showed strong negative correlations with Child-Pugh and MELD scores (r = -0.696, p < 0.001; r = -0.734, p < 0.001, respectively). Ordinal regression showed that higher vitamin D levels were associated with lower severity scores (Child-Pugh: OR = 0.856, 95% CI: 0.815-0.900, p < 0.001; MELD: OR = 0.875, 95% CI: 0.837-0.915, p < 0.001)., Conclusion: Lower serum vitamin D levels correlated with increased liver cirrhosis severity, suggesting its potential as both a prognostic marker and therapeutic target. Further studies should investigate the efficacy of vitamin D supplementation in improving cirrhosis outcomes., (© 2024. The Author(s).)

This study investigated the prognostic impact of vitamin D deficiency and reduced skeletal muscle mass in diffuse large B-cell lymphoma (DLBCL) patients. A retrospective analysis of 186 newly diagnosed DLBCL patients from 2012 to 2022 was conducted, measuring serum 25-hydroxyvitamin D [25(OH)D] levels and the skeletal muscle index (SMI). Decreased vitamin D levels were linked to more severe DLBCL disease, with a median 25(OH)D concentration of 13 (4.0-27) ng/mL. Males in the group with a low SMI had a considerably lower 25(OH)D concentration. The optimal threshold of 25(OH)D levels for overall survival (OS) was 9.6 ng/mL, with lower values associated with a higher likelihood of recurrence and mortality. Multivariable analysis showed hazard ratios for OS of 1.4 [95% CI 0.77-2.5] for a low SMI and 3.2 [95% CI 1.8-5.8] for low 25(OH)D concentration. The combination of a low SMI and low vitamin D concentration resulted in the worst prognosis. Thus, low levels of vitamin D associated with disease progression significantly impact DLBCL prognosis, which can be further stratified by the SMI, providing valuable insights for patient management and potential therapeutic interventions.

Background: The prevalence of vitamin D deficiency has been a growing concern in recent years. Vitamin D is important in many of the body's physiological systems, such as the musculoskeletal, cardiovascular and immune functions. A deficiency of vitamin D in athletes may negatively impact both muscle functions and recovery and, thus, affect performance and increase the risk of injury. Many studies assessed the prevalence of vitamin D deficiency in athletes; however, as of today, there are no official recommendations/protocols for screening vitamin D levels in athletes, and only a few studies were performed in male and female elite athletes (i.e., Olympic level), in different sport disciplines., Method: We investigated the prevalence of vitamin D deficiency among athletes entering the Israeli Olympic team. A total of 761 samples of Vitamin D(OH)25 from 334 athletes were analyzed. For this analysis, we used the first test the athlete had performed when joining the Olympic team. The prevalence of vitamin D deficiency (<50 nmol/L, as defined by the Endocrine Society Committee) was investigated according to gender, types of sports and outdoor vs. indoor sports through the different seasons of the Israeli Olympic team athletes., Result: Twenty-five athletes (7.5%) were diagnosed with vitamin D deficiency. One hundred and thirty-one athletes (39.2%) had insufficient levels of vitamin D (50-75 nmol/L). The highest incidence of vitamin D deficiency was found amongst gymnastics and combat sport athletes. A significant difference was also found in vitamin D concentration between seasons. Vitamin D average concentration in the winter was 74.1 nmol/L compared to 86.4 nmol/L in the Summer ( p < 0.0005)., Conclusions: Due to the importance of vitamin D to athletic performance and the high prevalence of deficiency and insufficiency, we suggest careful and frequent monitoring of groups at risk, including elite athletes, especially in susceptible sports and during the winter. Future studies are necessary to investigate the effectiveness of Vitamin D supplementation in athletes with low baseline vitamin D levels.

Cardiometabolic risk factors increase the chance of developing cardiovascular disease (CVD) and type 2 diabetes. Most CVD risk factors are influenced by total and regional obesity. A higher risk of developing CVD may be linked to vitamin D deficiency, which is more prevalent in the older population. With the goal of evaluating the association between vitamin D and cardiometabolic risk factors and total and regional obesity in older adults, this research included 25 (OH) vitamin D3 concentrations and biochemical markers associated with cardiometabolic diseases, as well as total and regional adiposity, which was measured by DXA. A total of 1991 older participants in the PoCOsteo study were included. Overall, 38.5% of participants had vitamin D deficiency. After adjusting for confounders, the results of multiple linear and logistic regression suggested an inverse association between vitamin D and body mass index (P = 0.04), waist circumference (P = 0.001), total fat (P = 0.02), android fat (P = 0.001), visceral fat (P < 0.001), subcutaneous fat (P = 0.01), trunk fat (P = 0.006), arm fat (P = 0.03), high systolic blood pressure (P = 0.004), high total cholesterol (P < 0.001), high LDL-cholesterol (P < 0.001), high serum triglycerides (P = 0.001), and high fasting glucose (P < 0.001). Additionally, higher vitamin D concentrations decreased the risk of dyslipidemia by 2%. Our results showed a significant association between serum vitamin D and a number of cardiometabolic risk factors, including total and regional obesity., (© 2024. The Author(s).)

Background: Diabetic retinopathy (DR) is one of the most common complications of diabetes worldwide. The aim of this study was to assess the prevalence of DR in hospitalized patients with type 2 diabetes (T2DM) in Tibet and to identify risk factors that may influence the occurrence of DR., Methods: This was a cross-sectional study conducted in a third-class hospital in the Tibet Autonomous Region. The prevalence of DR in hospitalized patients with T2DM was measured. Univariate and multivariate logistic regression, restricted cubic spline (RCS) analysis and receiver-operating characteristic curve analysis were used to investigate the risk factors for DR., Results: The prevalence of DR was 29.3%. The duration of diabetes; concentrations of 25-OH-VitD3, hemoglobin, fasting insulin, alanine aminotransferase, total bilirubin, and creatinine; and HOMA-IR were significantly different between DR patients and non-DR patients (all P < 0.05). Univariate and multivariate logistic regression revealed that a longer duration of diabetes and lower 25-OH-VitD3 levels were associated with increased DR risk. RCS analysis suggested overall positive associations of the duration of diabetes and 25-OH-VitD3 concentrations with DR risk (P nonlinearity < 0.05). The turning points for the duration of diabetes and 25-OH-VitD3 concentrations were 5.1 years and 10.6 ng/mL, respectively. The sensitivity, specificity, and area under the receiver-operating characteristic curve for the combination of the duration of diabetes and 25-OH-VitD3 levels were 79.4%, 69.4% and 0.764, respectively., Conclusions: Given the high prevalence of DR in hospitalized patients with T2DM in Tibet, vitamin D supplementation seems to be important in the prevention of DR to some degree., (© 2024. The Author(s).)

Purpose: Both vitamin C and D deficiencies are extremely common in clinical practice, especially in elderly population. Unfortunately, the role of vitamin C deficiency in osteoporosis related consequences is often neglected. The aim of the present study is to analyse if combined vitamin C and D deficiency would have an association with bone mineral density (BMD) and osteoporotic vertebral fracture (OVF)., Methods: Ninety-nine post-menopausal female patients admitted in the department of spine surgery of third affiliated hospital of Sun Yat-sen University were enrolled in the study. The participants were divided into four groups; vitamin D deficiency alone (comparator group), vitamin C deficiency alone and combined vitamin C and D deficiency as experimental group. The levels of vitamin C, vitamin D, calcium, phosphorous, BMD and condition of OVF were analysed., Results: There were statistically significant differences between the groups in terms of vitamin C and D levels. In terms of lumbar BMD, significant differences were observed between vitamin D deficiency alone and combined vitamin C and D deficiency. Only the combined vitamin C and D deficiency had a significant negative association with lumbar BMD and T-score. Similarly, combined vitamin C and D deficiency had a significant positive association with lumbar osteoporosis. None of the groups had any significant association with OVF. Combined vitamin C and D deficiency was found to be significantly associated with lower lumbar BMD and osteoporosis., Conclusion: Combined vitamin C and D deficiency results in lower bone mineral density and higher risk of osteoporosis. We believe that existence of deficiencies of both vitamins could have a synergistic effect. Therefore, we recommend that vitamin C and D should be routinely measured in clinical practice., (© 2024. The Author(s).)

Background: To study the relationship of Vitamin D with innate and adaptive immune response parameters in chronic hepatitis B and C patients., Methods: The laboratory data between January 1, 2013 and February 1, 2023, for patients with chronic hepatitis B (CHB), and chronic hepatitis C (CHC) were extracted. Serum 25-hydroxyl vitamin D, hepatitis B virus serological markers, complements, and subsets of T lymphocytes were determined. Study cohorts were divided into groups based on serum 25-hydroxyl vitamin D levels with further evaluation of laboratory data., Results: In CHB and CHC patients the percentage of CD4+ T lymphocytes and the CD4+/CD8+ ratio significantly decreased (P < 0.05), but the percentage of CD8+ increased (P < 0.05) compared to the control group. In CHB patients Vitamin D decrease was significant (P < 0.001) but not in CHC patients. Vitamin D showed a moderate negative influence on the CD8 cell count in CHB patients. The positive ratio of HBV DNA and HBsAg decreased with increasing serum vitamin D levels. The vitamin D deficient group showed significantly lower antibody production compared to the normal group, and exhibited significantly decreased CD4 numbers and increased CD8 numbers (P < 0.05 and P < 0.001, respectively), while the CD4/CD8 ratio was also significantly decreased in the insufficiency group (P < 0.001). Complement C3 levels were not associated with CD4 and CD8, but had an inverse relation with Vitamin D. Vitamin D levels were significantly associated with complement C3, CD8+, CD4+, CD19+ cells, and HBV DNA levels., Conclusions: Vitamin D may be a modulator of immune function not only via CD8+ and CD4+ cells but also via CD19+ cells in the course of chronic HBV infection. The negative relationship between vitamin D and complement C3 needs elucidation. Moreover, the increased proportion of B cells and decreased CD4+ cells in Vitamin D deficiency disrupt the immune response against HBV since the expected antibody response was not obtained despite the increase in B cell ratio. This indicates an influence of CD4+ cells for B cell functionality. In summary, sufficient levels of Vitamin D may lead to a sustained virological response that is debatable by artificially correcting the deficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Medical Faculty Mannheim of the University of Heidelberg. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the possible association of periorbital melanosis (POM) with insulin resistance (IR) and vitamin D serum levels., Methods: In this pilot, case-control study, we included 100 adult patients with POM and 100 age- and sex-matched healthy control subjects. Vitamin D levels and IR indices (i.e., homeostatic model assessment-insulin resistance [HOMA-IR], triglycerides/high-density lipoprotein cholesterol (TG/HDL-c) ratio, adiponectin/leptin (A/L) ratio) were compared between cases and controls., Results: Compared with controls, POM cases had significantly higher values of HOMA-IR and TG/HDL-c ratio, and significantly lower values of A/L and vitamin D. HOMA-IR and TG/HDL-c ratio were statistically significantly positively correlated with POM severity while Vitamin D and A/L ratio were statistically significantly negatively correlated., Conclusion: POM was associated with indices of IR and vitamin D deficiency. However, the exact causal link among POM, IR, and vitamin D needs to be established. However, the results of this pilot study suggest that POM may have potential as a cutaneous non-invasive marker of these metabolic disorders which would assist in detecting and treating them at an early stage., Competing Interests: Declaration of conflicting interestsThe authors declare there are no conflicts of interest.

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background: The emerging role of vitamin D has drawn the attention of researchers around the world, including its involvement in cardiovascular complications among individuals with diabetes., Aim: This study aimed to obtain comprehensive evidence on the association between serum vitamin D level and the risk of cardiovascular disease among patients with diabetes., Methods: Systematic search was performed on July 1st, 2023, to identify and screen published literature reporting the association between vitamin D and cardiovascular disease among diabetic patients in six databases. Each eligible study was appraised for its quality using modified Newcastle Ottawa Scale for cross-sectional and cohort studies. Meta-analysis was performed using Dersimonian-Laird random effect model or fix-effect model. The heterogeneity and publication bias were judged based on percentage of I 2 and the symmetry of Begg's funnel plot, respectively., Results: As many as 22 studies were found eligible for the systematic review. A meta-analysis from 13 studies comprising of 3850 and 1797 (control and exposure groups, respectively) revealed that serum vitamin D level was significantly lower in patients with diabetes and cardiovascular diseases (Z = 4.89; p-total<0.001; SMD = 0.68 [95%CI: 0.41-0.95]), yet the heterogeneity was high. Following the adjustment of removing the potential outliers, the same results were still observed (Z = 6.19; p-total<0.001; SMD = 0.35 [95%CI: 0.24-0.46]). Though decreased, high heterogeneity could not be resolved, resulting in moderate level of this evidence. Another pooled analysis of 7 studies with 4211 patients in control group and 2381 patients in exposure group revealed that lower level of serum vitamin D is a risk factor for cardiovascular disease incidence among diabetic patients (Z = 4.89; p-total<0.001; OR: 1.76 [95%CI: 1.4-2.2])., Conclusion: Serum vitamin D level status is a risk factor for developing cardiovascular diseases among diabetic patients, hence should be carefully monitored and maintained., Prospero Registration: CRD42023437698., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Purpose: Executive function (EF) impairment and vitamin D deficiency are common clinical features among children with epilepsy (CWE). Recently, vitamin D has become a potential modification factor that affects cognitive status in individuals with neurological disorders. In this study, we investigated the association between EF status and vitamin D levels in patients with CWE., Methods: In total, 79 CWE patients and 39 healthy controls (HCs) were recruited in this study. Each participant's EF was assessed using the Behavior Rating Inventory of Executive Function-Parent form (Brief-P), and the serum level of 25-OH vitamin D was measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS)., Results: Compared with those in the HC group, the CWE group had higher T scores of Brief-P scale, including global executive composite (GEC) (51.01(45.12, 60.69) vs. 44.08(39.24, 49.96), p＜0.001), behavioral regulation index (BRI) (51.29(45.67, 59.13) vs. 45.67(40.06, 51.29), p＜0.001), metacognition index (MI) (51.83(46.77, 59.43) vs. 46.13(40.44, 51.83), p＜0.001), and lower serum vitamin D (14.85(10.24,23.2) vs. 22.5(16.91,30), p＜0.001) levels. After adjustment for covariates, multivariate linear regression models suggested that for every 1 ng/ml increase in vitamin D, the GEC, BRI, and MI would decrease by 0.52 (Coeff = -0.48; 95 % CI = -0.69, -0.26; p = 0.000), 0.45 (Coeff = -0.45; 95 % CI = -0.69, -0.20; p = 0.000), and 0.47 (Coeff = -0.45; 95 % CI = -0.67, -0.22; p = 0.000), respectively., Conclusion: There may be an association between decreased vitamin D levels and EF impairment in CWE. Future research should consider longitudinal variations in EF related to improving vitamin D deficiency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Vitamin D is amongst the most important biomolecules to regularize and help in sustainable health, however, based on the studies, deficiency of this multifunctional vitamin is common. Vitamin D, besides playing a role in the form of vitamins, also acts as a multifunctional hormone (steroid). Vitamin D is synthesized inside the body through various steps starting from ultraviolet radiation exposure and comes from limited food sources, however, vitamin D-fortified food products are still among the major sources of vitamin D. Current review, focused on how vitamin D acts as a multifunctional molecule by effecting different functions in the body in normal or specific conditions and how it is important in fortification and how it can be managed from the available literature till date. During the Covid pandemic, people were aware of vitamin D and took supplementation, fortified foods, and sat under sunlight. As COVID prevalence decreases, people start forgetting about vitamin D. Vitamin D is very crucial for overall well-being as it has protective effects against a broad range of diseases as it can reduce inflammation, cancer cell growth and helps in controlling infection, increase metabolism, muscle, and bone strength, neurotransmitter expression, etc. Therefore, the present review is to provoke the population, and fulfillment of the vitamin D recommended dietary allowance daily must be confirmed., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Backgrounds: Restless legs syndrome (RLS) is an unpleasant condition that affects the quality of life of patients. Its prevalence in increased in women with premenstrual syndrome (PMS). Vitamin D plays a key role in female reproduction through its impact on calcium homeostasis and neurotransmitters. We aimed to evaluate the effect of dairy products fortified with Vitamin D 3 on RLS in women with PMS., Materials and Methods: We conducted a 2.5-month, randomized, total-blinded clinical trial to evaluate the effectiveness of low-fat milk and yogurt fortified with vitamin D on RLS in women with PMS. Among 141 middle-aged women with abdominal obesity, 71 and 70 cases received fortified and non-fortified low-fat dairy products, respectively. All subjects completed a Symptoms Screening Tool (PSST) and RLS questionnaires., Results: The results showed that in the women with severe PMS (PSST > 28), serum levels of vitamin D increased significantly following vitamin D fortification. The mean restless legs score in the severe PMS subgroup (PSST > 28) was significantly lower after the intervention (p < 0.05. Serum Vitamin D levels significantly differed between intervention and control groups in all individuals (PSST < 19, PSST 19-28, and PSST > 28) (p < 0.05), but no significant differences were found between RLS scores of the intervention and control groups in the three PMS subgroups (p > 0.05)., Conclusion: Fortifying dairy products with vitamin D 3 can increase the serum levels of vitamin D and reduce the RLS severity in women with severe PMS, but not in other groups., (© 2024. The Author(s).)

Skin pigmentation is negatively associated with circulating vitamin D (VD) concentration. Therefore, genetic factors involved in skin pigmentation could influence the risk of vitamin D deficiency (VDD). We evaluated the impact genetic variants related to skin pigmentation on VD in Mexican population. This cross-sectional analysis included 848 individuals from the Health Worker Cohort Study (ratio males to females ~ 1:3). Eight genetic variants: rs16891982 (SLC45A2), rs12203592 (IRF4), rs1042602 and rs1126809 (TYR), rs1800404 (OCA2), rs12913832 (HERC2), rs1426654 (SLC24A5), and rs2240751 (MFSD12); involved in skin pigmentation were genotyped. Skin pigmentation was assessed by self-report. Linear and logistic regression were used to assess the association between the variants of interest and VD and VDD, as appropriate. In our study, eight genetic variants were associated with skin pigmentation. A genetic risk score built with the variants rs1426654 and rs224075 was associated with lower VD levels (β = - 1.38, 95% CI - 2.59, - 0.17, p = 0.025). Nevertheless, when examining gene-gene interactions, we observed that rs2240751 × rs12203592 were associated with VD levels (P interaction = 0.021). Whereas rs2240751 × rs12913832 (P interaction = 0.0001) were associated with VDD. Our results suggest that skin pigmentation-related gene variants are associated with lower VD levels in Mexican population. These results underscore the importance of considering genetic interactions when assessing the impact of genetic polymorphisms on VD levels., (© 2024. The Author(s).)

With the emergence of the COVID-19 pandemic, the absence of established evidence-based treatment protocols led healthcare professionals and the public to explore experimental treatments, including high doses of vitamin D supplements. This study aimed to assess changes in serum 25-hydroxyvitamin D levels during the pandemic, employing a retrospective cohort analysis of data from Charleston Area Medical Center (CAMC). The study analyzed serum 25-hydroxyvitamin D levels in a cohort of 35,556 patients treated at CAMC in 2019, a representative pre-pandemic period, to 2021, a representative pandemic period. Our findings revealed a significant increase in mean serum 25-hydroxyvitamin D levels as compared with 2019 (37 ± 21 vs. 31 ± 15 ng/mL, p ≤ 0.001). Additionally, in 2021, there were significantly more patients exhibiting serum levels in the highest quintiles, specifically >100 ng/mL (1.6% vs. 0.2%), 75-100 ng/mL (4.6% vs. 1.2%), and 50-75 ng/mL (16.0% vs. 8.4%), p ≤ 0.001. This upsurge suggests increased intake of vitamin D supplements, potentially fueled by widespread discussions that were taking place largely on the internet regarding the efficacy of vitamin D against COVID-19. Our findings underscore the critical need for evidence-based public health messaging, especially during health crises, to prevent unnecessary health risks and ensure patient safety.

Low serum vitamin D levels have been associated with a variety of health conditions which has led the medical community but also the general population to evaluate vitamin D status quite liberally. Nevertheless, there remain questions about the efficacy and cost-effectiveness of such a broad and untargeted approach. This review therefore aims to summarize the current evidence and recommendations on when and how to evaluate vitamin D status in human health and disease. For the general population, most guidelines do not recommend universal screening but suggest a targeted approach in populations at risk. Also, some guidelines do not even recommend evaluating vitamin D status when vitamin D substitution is indicated anyway, such as in children or patients receiving anti-osteoporosis drugs. In those guidelines that recommend the screening of vitamin D status, serum 25(OH)D levels are universally proposed as the preferred screening tool. However, little attention is given to analytical considerations and almost no guidelines discuss the timing and frequency of screening. Finally, there is the known variability in diagnostic thresholds for defining vitamin D insufficiency and deficiency. Overall, the existing guidelines on the evaluation of vitamin D status differ broadly in screening strategy and screening implementation, and none of these guidelines discusses alternative screening modes, for instance, the vitamin metabolic ratio. Efforts to harmonize these different guidelines are needed to enhance their efficacy and cost-effectiveness.

Background and Objectives : Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods : A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: "vitamin D, muscle, rheumatic diseases." Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020-2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results : Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (<30 ng/mL) in patients with idiopathic inflammatory myopathies (IIMs) and polymyalgia rheumatica, as well as other autoimmune connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Of note, vitamin D insufficiency may be associated with reduced muscle strength (2 studies on RA, 2 in SLE and 1 in SSc), increased pain (1 study on SLE), fatigue (2 studies on SLE), and higher disease activity (3 studies on IIMs and 1 on SLE) although there is much heterogeneity in the quality of evidence and different associations for the different investigated diseases. Therefore, linked to the multilevel biological intervention exerted by vitamin D, several translational and clinical studies suggest that active metabolites of this secosteroid hormone, play a role both in reducing inflammation, but also in enhancing muscle regeneration, intra-cellular metabolism and mitochondrial function, although interventional studies are limited. Conclusions : Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold.

Introduction: Most research examining vitamin D and dental caries focuses on children and younger adults. This study investigated the association between vitamin D levels and dental caries in older adults using data from the United States National Health and Nutrition Examination Survey from 2011 to 2016., Methods: Data were analyzed from 2723 participants aged 65 years and older who completed both dental examinations and serum 25(OH)D tests. Dental caries assessments included the decayed, missing, and filled teeth (DMFT) index and the presence of untreated dental caries. Vitamin D levels were measured as serum 25(OH)D concentrations and categorized as severely deficient (<25 nmol/L), deficient (25-49.9 nmol/L), insufficient (50-74.9 nmol/L), and normal (≥75 nmol/L). Logistic regression and Poisson regression models were used to assess the association between vitamin D levels and dental caries, adjusting for demographic factors., Results: The mean DMFT score was 17.73 ± 8.34, with 35.1% of participants having untreated dental caries. Vitamin D deficiency was associated with a 1.44 times higher likelihood of untreated caries (95% CI: 1.15, 1.81), which weakened after adjustment for demographic factors (adjusted OR: 1.23, 95% CI: 0.97, 1.55). Severe vitamin D deficiency correlated with a 1.13 times higher DMFT score (95% CI: 1.06, 1.20), with the association remaining similar after adjustment (adjusted RR: 1.12, 95% CI: 1.05, 1.20). Significant differences in vitamin D levels were observed across gender, race/ethnicity, and country of birth., Conclusions: This study suggests the potential importance of adequate vitamin D levels for maintaining dental health among older adults. Vitamin D deficiency is associated with a higher risk of poorer DMFT scores. Public health strategies that include vitamin D screening and supplementation, particularly for high-risk groups, may improve oral health outcomes in the older adult population. Further research is needed to elucidate the mechanisms by which vitamin D influences dental health and the potential for vitamin D supplementation to reduce the burden of dental caries in older adults.

Vitamin D possesses a crucial role in preserving bone health, modulating the immune system responses, and supporting various physiological functions throughout the body. Chronic atrophic autoimmune gastritis (CAAG) constitutes an autoimmune condition marked by inflammation and damage to the stomach cells, often resulting in a decreased ability to absorb certain nutrients, including vitamin B12 and iron. Although, vitamin D is not directly affected by this condition, the sufficiency of this micronutrient seems to have important implications for overall health and management of the disease. The aim of the current review was to assess the incidence and related features of vitamin D deficiency in patients with CAAG and to elucidate the complex regulatory role of this nutrient, in an effort to improve patient outcomes. Vitamin D greatly contributes to the regulation of the immune system. In patients with CAAG, the immune system attacks the stomach lining; thus, the maintenance of a healthy and balanced immune response is important. In autoimmune conditions such as CAAG, where inflammation plays a decisive role in disease progression, vitamin D could potentially exert a role in managing and controlling the associated symptoms. Adequate vitamin D levels may help in regulating the immune response and reducing inflammation. In addition, patients with CAAG are at risk of nutrient deficiencies, including vitamin B12 and iron, which can lead to anemia and bone health issues. As vitamin D is critical for calcium absorption and bone health, assurance of sufficient levels of this micronutrient can be beneficial in preventing or mitigating bone-related complications. In conclusion, regular monitoring of vitamin D levels, among other nutrients, and appropriate supplementation, when necessary, can help improve overall health and well-being in these patients., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Vitamin D, obtained from diet or synthesized internally as cholecalciferol and ergocalciferol, influences bodily functions through its most active metabolite and the vitamin D receptor. Recent research has uncovered multiple roles for vitamin D in the central nervous system, impacting neural development and maturation, regulating the dopaminergic system, and controlling the synthesis of neural growth factors. This review thoroughly examines these connections and investigates the consequences of vitamin D deficiency in neurological disorders, particularly neurodegenerative diseases. The potential benefits of vitamin D supplementation in alleviating symptoms of these diseases are evaluated alongside a discussion of the controversial findings from previous intervention studies. The importance of interpreting these results cautiously is emphasised. Furthermore, the article proposes that additional randomised and well-designed trials are essential for gaining a deeper understanding of the potential therapeutic advantages of vitamin D supplementation for neurological disorders. Ultimately, this review highlights the critical role of vitamin D in neurological well-being and highlights the need for further research to enhance our understanding of its function in the brain.

An adequate vitamin D level is essential for optimal bone mass formation during growth. The present study aimed to assess (i) the sex-specific, age-specific, and potential seasonal (spring, summer, winter) influences on the pediatric circulating levels of 25-hydroxyvitamin D (25(OH)D); (ii) determine the frequency of pediatric patients with vitamin D deficiency (VDD) or insufficiency (VDI); and (iii) quantify the association between age category, sex, and season types and susceptibility to VDD and VDI, respectively. Laboratory data were collected on serum 25(OH)D levels in children aged between 2 and 18 years (n = 1674) who underwent blood sampling following admission to a university pediatric hospital in Cluj-Napoca (Romania) between January and June 2023. VDD (<20 ng/mL) was observed in 27% of pediatric patients. Among toddlers and preschoolers (2-5 years), VDD was 11%, while it was 33% among school-aged children (6-11 years) and 39% among adolescents (12-18 years). We found a significant difference in the frequencies of vitamin D status between females and males ( p = 0.006). Also, we found significant associations of vitamin D status with age categories ( p < 0.0001) and seasonal variations ( p = 0.03). After adjusting for season of blood collection, the multinomial logistic regression model showed that children aged 6-11 years old (adjusted OR = 7, 95% CI: (4.9, 9.4)), children aged 12-18 years old (adjusted OR = 14, 95% CI: (9.3, 19.6)), and females (adjusted OR = 1.43, 95% CI: (1.10, 1.86)) were significantly associated with higher odds of VDD. In conclusion, the study revealed a significant difference in the frequency of VDD and VDI among pediatric patients older than six years, with a significant difference according to sex and season, being more pronounced among girls and during the winter and spring seasons.

A long-held precept is that vitamin D supplementation primarily, if not exclusively, benefits individuals with low circulating 25-hydroxyvitamin D (25[OH]D) concentrations at baseline. However, the most appropriate 25(OH)D threshold to distinguish unacceptably low vs reliably adequate concentrations remains controversial. Such threshold proposals have largely been based on observational studies, which provide less robust evidence compared to randomized clinical trials (RCTs). Since the Endocrine Society's first vitamin D-related guideline was published in 2011, several large vitamin D-related RCTs have been published, and a newly commissioned guideline development panel (GDP) prioritized 4 clinical questions related to the benefits and harms of vitamin D supplementation in generally healthy individuals with 25(OH)D levels below a threshold. The GDP determined that available clinical trial evidence does not permit the establishment of 25(OH)D thresholds that specifically predict meaningful benefit with vitamin D supplementation. The panel noted important limitations in the available evidence, and the panel's overall certainty in the available evidence was very low. Nonetheless, based on the GDP's analyses and judgments, the Endocrine Society no longer endorses its previously proposed definition of vitamin D "sufficiency" (ie, at least 30 ng/mL [75 nmol/L]) or its previously proposed definition of vitamin D "insufficiency" (ie, greater than 20 ng/mL [50 nmol/L] but lower than 30 ng/mL [75 nmol/L]). The Endocrine Society's rationale for such is the subject of this Guideline Communication., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Background: Numerous studies demonstrate associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and a variety of common disorders, including musculoskeletal, metabolic, cardiovascular, malignant, autoimmune, and infectious diseases. Although a causal link between serum 25(OH)D concentrations and many disorders has not been clearly established, these associations have led to widespread supplementation with vitamin D and increased laboratory testing for 25(OH)D in the general population. The benefit-risk ratio of this increase in vitamin D use is not clear, and the optimal vitamin D intake and the role of testing for 25(OH)D for disease prevention remain uncertain., Objective: To develop clinical guidelines for the use of vitamin D (cholecalciferol [vitamin D3] or ergocalciferol [vitamin D2]) to lower the risk of disease in individuals without established indications for vitamin D treatment or 25(OH)D testing., Methods: A multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 14 clinically relevant questions related to the use of vitamin D and 25(OH)D testing to lower the risk of disease. The panel prioritized randomized placebo-controlled trials in general populations (without an established indication for vitamin D treatment or 25[OH]D testing), evaluating the effects of empiric vitamin D administration throughout the lifespan, as well as in select conditions (pregnancy and prediabetes). The panel defined "empiric supplementation" as vitamin D intake that (a) exceeds the Dietary Reference Intakes (DRI) and (b) is implemented without testing for 25(OH)D. Systematic reviews queried electronic databases for publications related to these 14 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and guide recommendations. The approach incorporated perspectives from a patient representative and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. The process to develop this clinical guideline did not use a risk assessment framework and was not designed to replace current DRI for vitamin D., Results: The panel suggests empiric vitamin D supplementation for children and adolescents aged 1 to 18 years to prevent nutritional rickets and because of its potential to lower the risk of respiratory tract infections; for those aged 75 years and older because of its potential to lower the risk of mortality; for those who are pregnant because of its potential to lower the risk of preeclampsia, intra-uterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality; and for those with high-risk prediabetes because of its potential to reduce progression to diabetes. Because the vitamin D doses in the included clinical trials varied considerably and many trial participants were allowed to continue their own vitamin D-containing supplements, the optimal doses for empiric vitamin D supplementation remain unclear for the populations considered. For nonpregnant people older than 50 years for whom vitamin D is indicated, the panel suggests supplementation via daily administration of vitamin D, rather than intermittent use of high doses. The panel suggests against empiric vitamin D supplementation above the current DRI to lower the risk of disease in healthy adults younger than 75 years. No clinical trial evidence was found to support routine screening for 25(OH)D in the general population, nor in those with obesity or dark complexion, and there was no clear evidence defining the optimal target level of 25(OH)D required for disease prevention in the populations considered; thus, the panel suggests against routine 25(OH)D testing in all populations considered. The panel judged that, in most situations, empiric vitamin D supplementation is inexpensive, feasible, acceptable to both healthy individuals and health care professionals, and has no negative effect on health equity., Conclusion: The panel suggests empiric vitamin D for those aged 1 to 18 years and adults over 75 years of age, those who are pregnant, and those with high-risk prediabetes. Due to the scarcity of natural food sources rich in vitamin D, empiric supplementation can be achieved through a combination of fortified foods and supplements that contain vitamin D. Based on the absence of supportive clinical trial evidence, the panel suggests against routine 25(OH)D testing in the absence of established indications. These recommendations are not meant to replace the current DRIs for vitamin D, nor do they apply to people with established indications for vitamin D treatment or 25(OH)D testing. Further research is needed to determine optimal 25(OH)D levels for specific health benefits., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)