The role of vitamin D in outcomes of critical care in COVID-19 patients: evidence from an umbrella meta-analysis of interventional and observational studies.

OBJECTIVES: Several meta-analyses have suggested the beneficial effect of vitamin D on patients infected with severe acute respiratory syndrome coronavirus-2. This umbrella meta-analysis aims to evaluate influence of vitamin D supplementation on clinical outcomes and the mortality rate of COVID-19 patients. DESIGN: Present study was designed as an umbrella meta-analysis. The following international databases were systematically searched till March 2023: Web of Science, PubMed, Scopus, and Embase. SETTINGS: Random-effects model was employed to perform meta-analysis. Using AMSTAR critical evaluation tools, the methodological quality of the included meta-analyses was evaluated. PARTICIPANTS: Adult patients suffering from COVID-19 were studied. RESULTS: Overall, 13 meta-analyses summarising data from 4 randomised controlled trial and 9 observational studies were identified in this umbrella review. Our findings revealed that vitamin D supplementation and status significantly reduced mortality of COVID-19 [Interventional studies: (ES = 0·42; 95 % CI: 0·10, 0·75, P < 0·001; I2 = 20·4 %, P = 0·285) and observational studies (ES = 1·99; 95 % CI: 1·37, 2·62, P < 0·001; I2 = 00·0 %, P = 0·944). Also, vitamin D deficiency increased the risk of infection and disease severity among patients. CONCLUSION: Overall, vitamin D status is a critical factor influencing the mortality rate, disease severity, admission to intensive care unit and being detached from mechanical ventilation. It is vital to monitor the vitamin D status in all patients with critical conditions including COVID patients.

Accumulated LPS induced by colitis altered the activities of vitamin D-metabolizing hydroxylases and decreased the generation of 25-hydroxyvitamin D.

It is generally accepted that low vitamin D (VD) levels are associated with a high prevalence factor for Inflammatory bowel disease (IBD). IBD patients have observed higher levels of lipopolysaccharide (LPS), ALT, and AST than healthy people. Gut-derived LPS causes inflammatory injury in the liver and kidney. The VD-metabolizing mechanism is involved in the liver and kidney, which means IBD might impact VD metabolism. However, whether IBD affects VD metabolism has not been studied. In vitro LPS resulted in decreased CYP2R1 in liver cells as well as decreased CYP27B1 and increased CYP24A1 in kidney cells, revealing that LPS changed the activities of several hydroxylases. Mice with acute colitis had an increased LPS in serum and liver with mild hepatic injuries, while mice with chronic colitis had a significant elevation of LPS in serum, liver, and kidney with hepatorenal injuries. Thus, the liver hydroxylase for VD metabolism would be the first to be affected in IBD. Consequently, serum 25-hydroxyvitamin D declined dramatically with a significant elevation of 24,25-dihydroxyvitamin D and 1,24,25-trihydroxyvitamin D. Unchanged serum levels of 1,25-dihydroxyvitamin D might be the result of other factors in vivo. In acute colitis, a small dosage (4 IU/day) of cholecalciferol could protect the colon, decrease the serum level of LPS, and finally increase serum 25-hydroxyvitamin D. However, this improvement of cholecalciferol was fading in chronic colitis. These results suggested that VD supplementations for preventing and curing IBD in the clinic should consider hepatorenal hydroxylases and be employed as soon as possible for a better outcome.

Vitamin D and Cutaneous Melanoma Risk: An Umbrella Review of Systematic Reviews and Meta-Analyses.

Background: Vitamin D (VitD) properties can impact cancer cells. Despite the documented link between VitD levels and prevalence of several cancer types, conflicting findings have been reported for cutaneous melanoma (CM). Objective: This overview aims to compile the evidence from existing systematic reviews and meta-analyses, emphasizing the relationships between VitD serum levels, intake, receptor (VDR) gene polymorphisms, and CM risk. Methods: A literature search in electronic databases was conducted, based on certain inclusion criteria. Results: Twenty-one studies were included. Conflicting evidence between high VitD serum levels, dietary/supplementary intake, and CM risk is highlighted. VDR polymorphisms may play a role in the intricate CM pathogenesis. Also, high serum levels of VitD are associated with improved CM prognosis. Conclusions: This overview showed that the impact of VitD on CM is not clear, and thus further research is suggested to explore its true effect size on CM risk.

Correlation between maternal and umbilical cord 25-hydroxy-vitamin D levels over a range of values. A prospective observational study from the United Arab Emirates.

Worldwide vitamin D insufficiency is remarkably prevalent in both children and adults, including pregnant women. The total amount of the vitamin is best measured by 25-hydroxy-vitamin D (25(OH)D), which is a measurement of total serum cholecalciferol 25(OH)D3 and ergocalciferol 25(OH)D2. There is a known correlation between maternal and umbilical cord blood (UCB) 25(OH)D; however, whether specific maternal demographics or comorbidities influence the correlation remains uncertain. This prospective observational study was designed to study if maternal 25(OH)D levels, maternal age and BMI, amount of supplementation, mode of delivery, diabetes, hypertension/preeclampsia, or sunlight exposure had an impact on the correlation. Women were enrolled in the study at admission to the labor ward. If they agreed to participate, venous blood was directly collected and analyzed for 25(OH)D. The UCB was sampled after delivery from the unclamped cord and immediately analyzed for 25(OH)D. ANOVA, Fisher's exact test, Pearson's correlation, and test of the differences between correlations using Fisher's z-transformation with Bonferroni correction were used accordingly. Of the 298 women enrolled, blood from both the mother and umbilical cord was analyzed successfully for 25(OH)D in 235 cases. The crude correlation between maternal and UCB 25(OH)D was very strong over all values of 25(OH)D (r = 0.905, R2 = 0.821, p <0,001) and remained strong independently of maternal demographics or co-morbidities (r ≥ 0.803, R2 ≥ 0.644, p <0.001). For women who delivered by caesarean section in second stage the correlation was strong (r ≥ 0.633, R2 ≥ 0.4, p <0.037). Test of differences between correlations showed significant stronger correlation in women with unknown 25(OH)D3 supplementation compared to women receiving 10.000 IU/week (p = 0.02) and 20.000IU/week (p = 0.01) and that the correlation was significantly stronger for women with a BMI of 25-29.9 compared to women with a BMI of <24.9 (p = 0.004) and 30-34.9 (p = 0.002). 213 (91%) women had lower 25(OH)D compared to the neonate, with a mean difference of -13.7nmol/L (SD = 15.6). In summary, the correlation between maternal and UCB 25(OH)D is very strong throughout low to high maternal levels of 25(OH)D with lower levels in maternal blood. Typical maternal demographics and comorbidities did not affect the transition.

Secondary hyperparathyroidism: Predictors and relationship with vitamin D status, bone turnover markers and bone mineral density.

INTRODUCTION: Secondary hyperparathyroidism (SHPT) has adverse implications for bone health but is relatively understudied. In this study we examine the prevalence and determinants of SHPT and describe the relationship of SHPT with bone turnover markers and bone mineral density (BMD) in older Irish adults. METHOD: Eligible participants (n = 4139) were identified from the Trinity-Ulster-Department of Agriculture (TUDA) study, a cohort of Irish adults aged ≥60 years. Exclusion criteria included an estimated glomerular filtration rate (eGFR) <30 ml/min and serum calcium >2.5 mmol/l to remove hyperparathyroidism due to advanced chronic kidney disease (CKD) and primary hyperparathyroidism respectively. The relationship between SHPT and bone turnover markers and BMD (measured by densitometry) was examined in a subsample (n = 1488). Vitamin D deficiency was defined as 25-hydroxyvitamin D [25 (OH)D] <30 nmol/l. RESULTS: Participants had a mean age of 73.6 ± 7.9 years, 65.1 % were female and 19.4 % were found to be vitamin D deficient. The prevalence of SHPT decreased as vitamin D increased, from 30.6 % in those deficient to 9.8 % in those with 25(OH)D ≥ 50 nmol/l and increased with declining kidney function. In non­calcium supplement users, principal determinants of SHPT were vitamin D deficiency (OR 4.18, CI 3.05-5.73, p < 0.001), eGFR 30-44 ml/min (OR 3.69, CI 2.44-5.57, p < 0.001), loop diuretic use (OR 3.52, CI 2.59-4.79, p < 0.001) and to a lesser extent body mass index (p = 0.001), eGFR 45-59 ml/min (p < 0.001) and 25(OH)D level 30-49 nmol/l (p = 0.002). Similar findings were observed in calcium supplement users, though proton pump inhibitors were also associated with SHPT (OR 1.55, CI 1.08-2.22, p = 0.018) while vitamin D 30-49 nmol/l was not. In participants with SHPT versus those without, bone turnover markers were higher: bone alkaline phosphatase (p = 0.017) and tartrate-resistant acid phosphatase (p = 0.033), whilst there was lower BMD at the neck of femur (0.880 vs. 0.903 g/cm2, p = 0.033) and total hip (0.968 vs. 0.995 g/cm2, P = 0.017). DISCUSSION: The results show that up to one in six older Irish adults had SHPT and this was associated with lower BMD and higher concentrations of bone turnover markers. Both vitamin D deficiency and 25(OH)D level 30-49 nmol/l were important predictors of SHPT. Loop diuretics and PPIs may also increase the risk of SHPT, and their use may need to be carefully considered in this population. Further studies examining the potential impact of these factors on bone health in similar populations to our study sample are warranted.

Vitamin D status in active and inactive noninfectious uveitis - data from a reference university hospital in Rio de Janeiro, Brazil.

PURPOSE: This study aimed to investigate the correlation between serum vitamin D levels and disease activity in patients with noninfectious uveitis. METHODS: We conducted a prospective case-control study, assessing 51 patients with noninfectious uveitis, categorized into active (n=22) and inactive (n=29) groups, along with 51 healthy controls. Serum 25-hydroxy vitamin D [25(OH)D] levels were measured. The uveitis group also completed a questionnaire regarding sunlight exposure habits and vitamin D supplementation. RESULTS: Patients with inflammation-related uveitis exhibited low serum 25(OH)D levels in 68% of cases. The median 25(OH)D level in patients with active uveitis was 17.8 ng/mL (interquartile range [IQR], 15-21 ng/mL), significantly lower compared to the 31.7 ng/mL (IQR, 25-39 ng/mL) in patients with inactive uveitis (p<0.001) and the 27 ng/mL (IQR, 23-31 ng/mL) in the Control Group (p<0.001). Significantly, nearly all patients with uveitis taking vitamin D supplementation were in the Inactive Group (p<0.005). Moreover, reduced sunlight exposure was associated with active uveitis (p<0.003). Furthermore, patients with 25(OH)D levels below 20 ng/mL had ten times higher odds of developing active uveitis (p=0.001). CONCLUSIONS: This study revealed a prevalent 25(OH)D deficiency among patients with noninfectious uveitis and suggested a link between low 25(OH)D levels and disease activity. To prevent future episodes of intraocular inflammation, vitamin D supplementation and controlled sunlight exposure could be viable options.

Association between vitamin D deficiency and benign paroxysmal positional vertigo (BPPV) incidence and recurrence: a systematic review and meta-analysis.

OBJECTIVES: The objective of this study is to determine the relationship between serum vitamin D level and the risk of developing benign paroxysmal positional vertigo (BPPV) incidence and recurrence in countries in the Northern Hemisphere. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Scopus and Web of Science databases were searched for studies published between January 2000 and February 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Participants located in the Northern Hemisphere aged 18 or over with at least one episode of BPPV, serum 25-hydroxyvitamin D levels measured and reported, no comorbidities or history of vitamin D supplementation. DATA EXTRACTION AND SYNTHESIS: Data extraction and synthesis were performed by a single reviewer and checked by a second reviewer. Inclusion and exclusion criteria and risk of bias were assessed by two independent reviewers using the Newcastle Ottawa Tool for Cohort studies and Risk of Bias Assessment Tool for Nonrandomised Studies checklist for case-control studies. Meta-analysis was conducted using random effects models. Standard mean difference with a 95% CI was used to measure the relationship between vitamin D level and BPPV. RESULTS: The 35 articles identified by the literature search reported data of 9843 individuals. 19 studies (7387 individuals) were included in the BPPV incidence meta-analysis while 7 studies (622 individuals) were included in the BPPV recurrence meta-analysis. Lower serum vitamin D levels were found in BPPV incidence compared with controls, but the relationship between vitamin D levels in recurrent BPPV compared with non-recurrent disease remained uncertain. CONCLUSION: Results of this systematic review and meta-analysis demonstrated a negative correlation between serum vitamin D and BPPV incidence, while any relationship between serum vitamin D and BPPV recurrence remained uncertain. Risk of bias analysis revealed evidence of variable quality. There were insufficient data available to evaluate seasonal relationships between serum vitamin D and BPPV. Given the potential for this as a confounding factor, future research should aim to investigate this further. PROSPERO REGISTRATION NUMBER: CRD42021271840.

Association of vitamin D with disease severity in infants with bronchiolitis.

Vitamin D's role in immune system regulation and its contribution to host defenses against respiratory infections may have implications for bronchiolitis pathophysiology. This cross-sectional study aimed to determine the association between the clinical severity of bronchiolitis and serum vitamin D levels in infants. Infants aged 1 month to 12 months, diagnosed with bronchiolitis, and healthy controls attending routine immunization were enrolled. Baseline characteristics were recorded, including clinical details, bronchiolitis severity, and course during hospital stay. Bronchiolitis severity score (BSS) was used to score the severity. A 1-2 ml serum sample was obtained for vitamin D levels estimation. The median age of cases (n = 64; 65.6% male) was 5 [3, 8] months, and that of the control group (n = 30) was 3 [2, 9] months. No statistically significant differences were observed between the two groups in age, gender, weight, mode of delivery, family history of atopy/asthma, feeding pattern, smoke exposure, and daily vitamin D supplementation. The median vitamin D levels were not significantly different between the groups (p = 0.68). Among infants with bronchiolitis, 62.5% had vitamin D insufficiency (≤ 20 ng/ml). A significantly higher median BSS indicates that infants with vitamin D insufficiency exhibited more severe disease (p = 0.019). Although a negative correlation between BSS and vitamin D levels was noted, it did not reach statistical significance [rs = (-)0.17; p = 0.16]. CONCLUSION:  Infants with Vitamin D insufficiency experienced more severe bronchiolitis with elevated BSS scores. It highlights the potential role of vitamin D deficiency in severe bronchiolitis. WHAT IS KNOWN: • Vitamin D level is low in infants with bronchiolitis. WHAT IS NEW: • Infant with low vitamin D level experienced more severe bronchiolitis.

Vitamin D and behavioral disorders in older adults: results from the CLIP study.

OBJECTIVES: Vitamin D is involved in brain health and function. Our objective was to determine whether vitamin D deficiency was associated with behavioral disorders in geriatric patients. DESIGN: The observational cross-sectional CLIP (Cognition and LIPophilic vitamins) study. The report followed the STROBE statement. SETTING: Geriatric acute care unit in a tertiary university hospital in France for 3 months at the end of winter and beginning of spring. PARTICIPANTS: 272 patients ≥65 years consecutively hospitalized or seen in consultation. MEASUREMENTS: Participants were separated into two groups according to vitamin D deficiency (i.e., serum 25-hydroxyvitamin D ≤25 nmol/L). Behavior was assessed using the reduced version of the Neuropsychiatric Inventory Scale (NPI-R) score and subscores. Age, sex, BMI, education level, comorbidities, MMSE and GDS scores, use psychoactive drugs and vitamin D supplements, and serum concentrations of calcium, parathyroid hormone, TSH and estimated glomerular filtration rate (eGFR) were used as potential confounders. RESULTS: Participants with vitamin D deficiency (n = 78) had similar NPI-R score (17.4 ± 20.3 versus 17.2 ± 16.1, p = 0.92) but higher (i.e., worse) subscore of agitation and aggressiveness (2.0 ± 3.3 versus 1.2 ± 2.4, p = 0.02) and higher (i.e., worse) subscore of disinhibition (0.99 ± 2.98 versus 0.38 ± 1.42, p = 0.02) than those without vitamin D deficiency (n = 194). In multiple linear regressions, vitamin D deficiency was inversely associated with the subscore of agitation and aggressiveness (ß = 1.37, p = 0.005) and with the subscore of disinhibition (ß = 0.96, p = 0.008). CONCLUSION: Vitamin D deficiency was associated with more severe subscores of agitation and aggressiveness and of disinhibition among older adults. This provides a scientific basis to test the efficacy of vitamin D supplementation on behavioral disorders in older patients with vitamin D deficiency.

Forgetting the Frail: National Trends in Vitamin D Prescription After Fragility Fracture-A Large Insurance Claims Database Study.

INTRODUCTION: Vitamin D plays a critical role in bone health, affecting bone mineral density and fracture healing. Insufficient serum vitamin D levels are associated with increased fracture rates. Despite guidelines advocating vitamin D supplementation, little is known about the prescription rates after fragility fractures. This study aims to characterize vitamin D prescription rates after three common fragility fractures in patients older than 50 years and explore potential factors influencing prescription rates. METHODS: The study used the PearlDiver Database, identifying patients older than 50 years with hip fractures, spinal compression fractures, or distal radius fractures between 2010 and 2020. Patient demographics, comorbidities, and vitamin D prescription rates were analyzed. Statistical methods included chi-square analysis and univariate and multivariable analyses. RESULTS: A total of 3,214,294 patients with fragility fractures were included. Vitamin D prescriptions increased from 2.50% to nearly 6% for all fracture types from 2010 to 2020. Regional variations existed, with the Midwest having the highest prescription rate (4.25%) and the West the lowest (3.31%). Patients with comorbidities such as diabetes, tobacco use, obesity, female sex, age older than 60 years, and osteoporosis were more likely to receive vitamin D prescriptions. DISCUSSION: Despite a notable increase in vitamin D prescriptions after fragility fractures, the absolute rates remain low. Patient comorbidities influenced prescription rates, perhaps indicating growing awareness of the link between vitamin D deficiency and these conditions. However, individuals older than 60 years, a high-risk group, were markedly less likely to receive prescriptions, possibly because of practice variations and concerns about polypharmacy. Educational initiatives and revised guidelines may have improved vitamin D prescription rates after fragility fractures. However, there is a need to raise awareness about the importance of vitamin D for bone health, particularly in older adults, and additional study variations in prescription practices. These findings emphasize the importance of enhancing post-fracture care to reduce morbidity and mortality associated with fragility fractures. LEVEL OF EVIDENCE: III.

Vitamin D levels in idiopathic inflammatory myopathy patients: a meta-analysis.

PURPOSE: This meta-analysis aimed to explore correlations between vitamin D and idiopathic inflammatory myopathy (IIM). METHODS: A comprehensive database search was conducted on 13 October 2020. Mean differences (MDs) and aggregated risk ratios (RR) with 95% confidence intervals (CIs) were used to determine the correlation between vitamin D deficiency (VDD) and IIM. Statistical analysis was performed with RevMan 5.4 and Stata15, statistical significance was set at p < 0.05. RESULTS: Search revealed five studies with 286 IIM patients and 480 healthy controls. Results with random-effects modeling indicated that serum vitamin D levels were significantly lower in IIM patients than in healthy controls (MD = -13.10 ng/mL; 95% CI: -16.51 to -9.68; p < 0.00001). No differences were found between patients with IIM and other autoimmune diseases on vitamin D levels (MD =-2.65 ng/mL; 95% CI: -11.31-6.01; p = 0.55). In two studies with 185 IIM patients, those with low vitamin D levels exhibited higher creatine kinase levels (MD = 85.20 IU/L; 95% CI: 72.67-97.73; p < 0.00001) than those with normal vitamin D levels. VDD was correlated with an increased risk of IIM (RR = 3.24, 95% CI: 1.81-5.79; p < 0.0001). CONCLUSION: This meta-analysis showed correlations between vitamin D level and IIM. The results indicated, VDD may be a risk factor for IIM, a determinant of immune dysregulation in IIM, or a consequence of IIM. Also, it implied further research to determine whether vitamin D supplementation is beneficial for patients with IIM.

Effect of vitamin D supplementation or fortification on bone turnover markers in women: a systematic review and meta-analysis.

Vitamin D is a vital indicator of musculoskeletal health, as it plays an important role through the regulation of bone and mineral metabolism. This meta-analysis was performed to investigate the effects of vitamin D supplementation/fortification on bone turnover markers in women. All human randomised clinical trials reported changes in bone resorption markers (serum C-terminal telopeptide of type-I collagen (sCTX) and urinary type I collagen cross-linked N-telopeptide (uNTX)) or bone formation factors (osteocalcin (OC), bone alkaline phosphatase (BALP) and procollagen type-1 intact N-terminal propeptide (P1NP)) following vitamin D administration in women (aged ≥ 18 years) were considered. Mean differences (MD) and their respective 95 % CI were calculated based on fixed or random effects models according to the heterogeneity status. Subgroup analyses, meta-regression models, sensitivity analysis, risk of bias, publication bias and the quality of the included studies were also evaluated. We found that vitamin D supplementation had considerable effect on sCTX (MD: -0·038, n 22) and OC (MD: -0·610, n 24) with high heterogeneity and uNTX (MD: -8·188, n 6) without heterogeneity. Our results showed that age, sample size, dose, duration, baseline vitamin D level, study region and quality of studies might be sources of heterogeneity in this meta-analysis. Subgroup analysis also revealed significant reductions in P1NP level in dose less than 600 µg/d and larger study sample size (>100 participants). Moreover, no significant change was found in BALP level. Vitamin D supplementation/fortification significantly reduced bone resorption markers in women. However, results were inconsistent for bone formation markers.

Comparison of the Effect of Daily Vitamin D2 and Vitamin D3 Supplementation on Serum 25-Hydroxyvitamin D Concentration (Total 25(OH)D, 25(OH)D2, and 25(OH)D3) and Importance of Body Mass Index: A Systematic Review and Meta-Analysis.

BACKGROUND: Two previous meta-analyses showed smaller differences between vitamin D3 and vitamin D2 in raising serum 25-hydroxyvitamin D [25(OH)D] and a consistently high heterogeneity when only including daily dosing studies. OBJECTIVE: This study aimed to compare more frequently dosed vitamin D2 and vitamin D3 in improving total 25(OH)D and determine the concomitant effect of response modifiers on heterogeneity, and secondly, to compare the vitamin D2-associated change in 25(OH)D2 with the vitamin D3-associated change in 25(OH)D3. METHODS: PubMed, EMBASE, Cochrane, and the Web of Science Core collection were searched for randomized controlled trials of vitamin D2 compared with vitamin D3, daily or once/twice weekly dosed. After screening for eligibility, relevant data were extracted for meta-analyses to determine the standardized mean difference when different methods of 25(OH)D analyses were used. Otherwise, the weighted mean difference (WMD) was determined. RESULTS: Overall, the results based on 20 comparative studies showed vitamin D3 to be superior to vitamin D2 in raising total 25(OH)D concentrations, but vitamin D2 and vitamin D3 had a similar positive impact on their corresponding 25(OH)D hydroxylated forms. The WMD in change in total 25(OH)D based on 12 daily dosed vitamin D2-vitamin D3 comparisons, analyzed using liquid chromatography-tandem mass spectrometry, was 10.39 nmol/L (40%) lower for the vitamin D2 group compared with the vitamin D3 group (95% confidence interval: -14.62, -6.16; I2 = 64%; P < 00001). Body mass index (BMI) appeared to be the strongest response modifier, reducing heterogeneity to 0% in both subgroups. The vitamin D2- and vitamin D3-induced change in total 25(OH)D lost significance predominantly in subjects with a BMI >25 kg/m2 (P = 0.99). However, information on BMI was only available in 13/17 daily dosed comparisons. CONCLUSIONS: Vitamin D3 leads to a greater increase of 25(OH)D than vitamin D2, even if limited to daily dose studies, but vitamin D2 and vitamin D3 had similar positive impacts on their corresponding 25(OH)D hydroxylated forms. Next to baseline 25(OH)D concentration, BMI should be considered when comparing the effect of daily vitamin D2 and vitamin D3 supplementation on total 25(OH)D concentration. This study was registered in PROSPERO as CRD42021272674.

Effect of Daily Vitamin D Supplementation on Risk of Upper Respiratory Infection in Older Adults: A Randomized Controlled Trial.

BACKGROUND: Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up. RESULTS: Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI}, .86-1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI, .28-1.30]). Statistical power to assess effect modification in other subgroups was limited. CONCLUSIONS: In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259.

Vitamin D Deficiency Is Associated With Increased Length of Stay After Acute Burn Injury: A Multicenter Analysis.

In burn patients, vitamin D deficiency has been associated with increased incidence of sepsis and infectious complications. The objective of this study was to assess the impact of vitamin D deficiency in adult burn patients on hospital length of stay (LOS). This was a multicenter retrospective study of adult patients at 7 burn centers admitted over a 3.5-year period, who had a 25-hydroxyvitamin D concentration drawn within the first 7 days of injury. Of 1147 patients screened, 412 were included. Fifty-seven percent were vitamin D deficient. Patients with vitamin D deficiency had longer LOS (18.0 vs 12.0 days, P < .001), acute kidney injury (AKI) requiring renal replacement therapy (7.3 vs 1.7%, P = .009), more days requiring vasopressors (mean 1.24 vs 0.58 days, P = .008), and fewer ventilator-free days of the first 28 days (mean 22.9 vs 25.1, P < .001). Univariable analysis identified burn center, AKI, TBSA, inhalation injury, admission concentration, days until concentration drawn, days until initiating supplementation, and dose as significantly associated with LOS. After controlling for center, TBSA, age, and inhalation injury, vitamin D deficiency was associated with longer LOS. In conclusion, patients with thermal injuries and vitamin D deficiency on admission have increased LOS and worsened clinical outcomes when compared with patients with nondeficient vitamin D concentrations.

Correlation of CYP2R1 gene promoter methylation with circulating vitamin D levels among healthy adults.

Background & objectives: Despite being a tropical country, vitamin D deficiency is highly prevalent in India with studies indicating 40-99 per cent prevalence. Apart from calcium and phosphate metabolism, vitamin D is involved in cell cycle regulation, cardiovascular, hepatoprotection. The metabolism of vitamin D is regulated by vitamin D tool genes (CYP2R1/CYP27B1/CYP24A1/VDR). The promoter regions of some of these genes have CpG islands, making them prone to methylation induced gene silencing, which may cause a reduction in circulating vitamin D levels. Epigenetic basis of vitamin D deficiency is yet to be studied in India, and hence, this pilot study was aimed to analyze whether methylation levels of CYP2R1 gene were correlated with the levels of 25(OH)D in healthy, adult individuals in Indian population. Methods: In this cross-sectional study, healthy adults of 18-45 yr of age with no history of malabsorption, thyroidectomy, chronic illness or therapeutic vitamin D supplementation were recruited. DNA methylation analysis was carried out by methylation specific quantitative PCR. Serum calcium, phosphate and vitamin D levels were also quantified. Statistical analysis was done by R 4.0.5 software. Results: A total of 61 apparently healthy adults were analyzed. The serum vitamin D levels did not correlate with CYP2R1 methylation levels in our study population. Significant positive correlation was observed between age and serum vitamin D levels. Significant association of gender was found with CYP2R1 methylation levels. Interpretation & conclusions: This study found no significant correlation between levels of CYP2R1 methylation and circulating 25(OH)D deficiency. Further studies on the Indian population having a larger sample size including entire vitamin D tool genes, among different ethnic groups may be conducted to elucidate molecular etiology of circulating 25(OH)D deficiency. The high prevalence of normal serum calcium and phosphate levels among vitamin D deficient subjects in this study coupled with the strikingly high prevalence of the deficiency at the national level, may suggest the need to revise the cut-off criteria for vitamin D deficiency in the Indian population.

The effect of 1-hydroxy-vitamin D treatment in hospitalized patients with COVID-19: A retrospective study.

BACKGROUND & AIMS: The efficacy of vitamin D supplementation in coronavirus disease 2019 (COVID-19) remains unclear. This study aimed to evaluate the effect of 1-hydroxy-vitamin D on the prevention of severe disease and mortality in patients hospitalized for COVID-19. METHODS: This retrospective study included 312 patients with COVID-19 who were admitted to our hospital between April 2021 and October 2021 (primarily the Delta variant) and between July 2022 and September 2022 (primarily Omicron variant). Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at the time of admission and 1-hydroxy-vitamin D was prescribed by the treating physicians. The patients were divided into two groups: those administered 1-hydroxy-vitamin D (Vit D group) and those who were not (control group). The composite primary endpoint was the need for additional respiratory support, including high-flow oxygen therapy or invasive mechanical ventilation, and in-hospital mortality rate. RESULTS: Of 312 patients, 122 (39%) received 1-hydroxy-vitamin D treatment. Although the median age was not significantly higher in the Vit D group than in the control group (66 vs. 58 years old, P = 0.06) and there was no significant difference in the proportion of vitamin D deficiency (defined as serum 25(OH)D level less than 20 ng/mL, 77% vs. 65%, P = 0.07), patients in the control group had a more severe baseline profile compared to the Vit D group according to the Japanese disease severity definition for COVID-19 (P = 0.01). The proportion of those requiring more respiratory support and in-hospital mortality was significantly lower in the Vit D group than in the control group (6% vs. 14%, P = 0.01 log-rank test). After propensity score matching, a statistically significant difference in the primary endpoint was observed (P = 0.03 log-rank test). CONCLUSIONS: 1-hydroxy-vitamin treatment may improve outcomes in hospitalized patients with COVID-19, reducing composite outcomes including the need for additional respiratory support and in-hospital mortality.

The role of anti-Mullerian hormone and other correlates in patients with polycystic ovary syndrome.

BACKGROUND: Anti-Müllerian hormone (AMH) has recently emerged as a promising biomarker for the detection of polycystic ovarian morphology. In polycystic ovary syndrome (PCOS), an elevated level of AMH has been suggested to add value to the Rotterdam criteria in cases of diagnostic uncertainty. In this study, we evaluated the correlation between AMH and PCOS, and the potential role of AMH in PCOS diagnosis. METHODS: A case-control study was performed on a total of 200 females, 100 of which were diagnosed with PCOS as per Rotterdam revised criteria (2003) and 100 as the control (non-PCOS group). Patient medical records were therefore retrieved for clinical, biochemical and ultrasound markers for PCOS diagnosis. Sensitivity, specificity, area under receiver operating characteristic (AUROC) curve, and multivariate linear regression models were applied to analyze our data. RESULTS: Mean serum levels of LH and AMH, and LH/FSH ratio were significantly different between compared groups. In the PCOS group, the mean serum AMH level was 6.78 ng/mL and LH/FSH ratio was 1.53 while those of controls were 2.73 ng/mL and 0.53, respectively (p < .001). The most suitable compromise between 81% specificity and 79% sensitivity was obtained with a cutoff value of 3.75 ng/mL (26.78 pmol/L) serum AMH concentration for PCOS prediction, with an AUROC curve of 0.9691. CONCLUSION: Serum AMH cutoff level of 3.75 ng/mL was identified as a convenient gauge for the prediction of PCOS and an adjuvant to the Rotterdam criteria.

Prevalence of Vitamin-D deficiency and insufficiency among prisoners across the globe: A systematic review and meta-analysis.

BACKGROUND AND AIM: Inadequate nutrition is linked to a wide range of detrimental chronic and infectious illness outcomes among the prison populations. However, there is a paucity of thorough analysis of the prevalence of vitamin D deficiency among jail inmates. Consequently, in order to bridge this gap, we conducted a thorough research to ascertain the incidence of vitamin D deficiency among prisoners worldwide. METHOD: Six computer-based literature indexes were thoroughly searched for topic focused publications. The I2 test was used to determine heterogeneity among the studies. The overall effect was assessed using a random-effects model with a 95% confidence interval. We used metafor package in R version 4.2.1 for the analysis of data. RESULT: Out of 612 studies, 4 studies were included for analysis. The estimated pooled prevalence of vitamin D deficiency was 55% among prisoners. On the other hand, 29.41% were found to have insufficient vitamin D levels. CONCLUSION: Despite the scant available research, vitamin D deficiency is prevalent among prisoners. Regular vitamin D status evaluations using reliable health tests, dietary inspection and supplementation are crucial. PROSPERO REGISTRATION ID: CRD42023396203.

Micronutrients, genetics and COVID-19.

PURPOSE OF REVIEW: Marked inter-individual differences in the clinical manifestation of coronavirus disease 2019 (COVID-19) has initiated studies in the field of genetics. This review evaluates recent genetic evidence (predominantly in the last 18 months) related to micronutrients (vitamins and trace elements) and COVID-19. RECENT FINDINGS: In patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), altered circulating levels of micronutrients may serve as prognostic markers of disease severity. Mendelian randomization (MR) studies did not find significant effect of variable genetically predicted levels of micronutrients on COVID-19 phenotypes, however, recent clinical studies on COVID-19 point out to vitamin D and zinc supplementation as a nutritional strategy to reduce disease severity and mortality. Recent evidence also points to variants in vitamin D receptor ( VDR ) gene, most notably rs2228570 (FokI) "f" allele and rs7975232 (ApaI) "aa" genotype as poor prognostic markers. SUMMARY: Since several micronutrients were included in the COVID-19 therapy protocols, research in the field of nutrigenetics of micronutrients is in progress. Recent findings from MR studies prioritize genes involved in biological effect, such as the VDR gene, rather than micronutrient status in future research. Emerging evidence on nutrigenetic markers may improve patient stratification and inform nutritional strategies against severe COVID-19.