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Vitamin D deficiency (VDD) is widespread around the world and has been extensively documented to affect various health conditions, including the cognitive functioning of the brain. Serum 25-hydroxylated forms of vitamin D are traditionally used to determine vitamin D status. However, there is now evidence that cholecalciferol activation can occur and be controlled by locally expressed enzymes in the brain. This study aimed to investigate the effects of cholecalciferol supplementation on cognitive function in rats who underwent transient VDD in adulthood. Thirty-six adult Wistar rats were administered paricalcitol (seven doses of 32 ng injected every other day) along with a "vitamin D-free" diet to induce VDD, which was confirmed using a LC–MS/MS serum analysis of the cholecalciferol and 25-hydroxyvitamin D3 levels. Treatment was performed by including 1000 IU/kg and 10,000 IU/kg cholecalciferol in the diet. Cognitive performance was evaluated using the novel object recognition (NOR), Morris water maze (MWM), and radial arm maze (RAM) tests. An immunohistochemical analysis of the brain regions involved in learning and memory was performed by quantifying the neurons, astrocytes, and microglia labelled with anti-neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1) antibodies, respectively. The vitamin D deficient group showed the lowest performance in both the MWM and RAM tests. In contrast, the cholecalciferol-treated groups exhibited a faster learning curve. However, no difference was detected between the groups in the NOR test. On the other hand, differences in the cellular organization of the hippocampus and amygdala were observed between the groups. Cholecalciferol supplementation decreased the density of the Iba-1- and GFAP-labeled cells in the hilus and cornu Ammonis 3 (CA3) regions of the hippocampus and in the amygdala. These results support vitamin D's substantial role in learning and memory. They also highlight that subtle changes of cognitive function induced by transient VDD could be reversed by cholecalciferol supplementation. Further studies are needed to better understand VDD and cholecalciferol's effects on the brain structure and function. [ABSTRACT FROM AUTHOR]

Vitamin D3 plays a vital role in numerous physiological processes within the human body, including having a positive effect on eye health. It is renowned for its immunomodulatory, anti-inflammatory, antioxidant, and angiogenic properties. Its deficiency is evolving into a significant global challenge. In order to explain the connection between vitamin D3 and various ocular diseases, 84 relevant studies, mainly from the PubMed database, published in English between 1999 and 2024 were analyzed. Ocular tissues can activate and regulate vitamin D levels, which emphasizes the significance of this nutrient in maintaining eye homeostasis. While there is suggestive evidence for a probable association between vitamin D3 and ocular health, more robust research is needed to establish causation and inform clinical guidelines. [ABSTRACT FROM AUTHOR]

Hip fractures are a major health issue considerably impacting patients' quality of life and well-being. This is particularly evident in elderly subjects, in which the decline in bone and muscle mass coexists and predisposes individuals to fall and fracture. Among interventions to be implemented in hip fractured patients, the assessment and management of nutritional status is pivotal, particularly in subjects older than 65. Nutrition plays a central role in both primary and secondary preventions of fracture. An adequate protein intake improves muscle mass and strength and the intestinal absorption of calcium. Other nutrients with recognized beneficial effects on bone health are calcium, vitamins D, K, and C, potassium, magnesium, folate, and carotenoids. With reference to calcium, results from longitudinal studies showed that the consumption of dairy foods has a protective role against fractures. Moreover, the most recent systematic reviews and meta-analyses and one umbrella review demonstrated that the combination of calcium and vitamin D supplementation significantly reduces hip fracture risk, with presumed higher efficacy in older and institutionalized subjects. Owing to these reasons, the adequate intake of calcium, vitamin D, protein, and other macro and micronutrients has been successfully implemented in the Fracture Liaison Services (FLSs) that represent the most reliable model of management for hip fracture patients. In this narrative review, papers (randomized controlled trials, prospective and intervention studies, and systematic reviews) retrieved by records from three different databases (PubMed, Embase, and Medline) have been analyzed, and the available information on the screening, assessment, and management of nutritional and vitamin D status and calcium intake in patients with hip fractures is presented along with specific prevention and treatment measures. [ABSTRACT FROM AUTHOR]

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D3 formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D3 1000 IU (STD1000), (2) micellar Vitamin D3 1000 IU (LMD1000), (3) standard Vitamin D3 2500 IU (STD2500), and (4) micellar Vitamin D3 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5–60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D3 absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D3 concentrations than the STD1000 group (iAUC(30–60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)2D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D3 (LipoMicel®), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425. [ABSTRACT FROM AUTHOR]

The definition of "Vitamin D" encompasses a group of fat-soluble steroid compounds of different origins with similar chemical structures and the same biological effects. Vitamin D deficiency and/or a defect in the process of its synthesis or transport predispose individuals to several types of rickets. In addition to cholecalciferol, ergocalciferol, and vitamins D3 and D2, there are also active metabolites for the treatment of this condition which are commercially available. Calcitriol and aphacalcidiol are active metabolites that do not require the renal activation step, which is required with calcifediol, or hepatic activation. The purpose of this review is to summarize current approaches to the treatment of rickets for generalist physicians, focusing on the best vitamin D form to be used in each type, or, in the case of X-linked hypophosphatemic rickets (XLH), on both conventional and innovative monoclonal antibody treatments. [ABSTRACT FROM AUTHOR]

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

Background: Vitamin D testing (VDT) and supplement use (VDS) are on the rise, but most patients remain deficient (<30 ng/mL-VDD). We designed the present real-world study to assess this paradox. Methods: We reviewed data from all patients visiting our clinics between 2014 and 2022. We estimated the rate of patients with vitamin D adequacy (≥30 ng/mL) (VDA) by year and month of testing, the dose of VDS (low (≤1200 IU/day), medium (1201–3000 I/day) and high dose (>3000 IU/day)), intake duration (short-term (<12 months) and long-term use (≥12 months)), and timing of use (current use, former use, no use). Results: We enrolled n = 6912 subjects with vitamin D measurements: n = 5195 females (75.2%), age 44.0 ± 16.8 years, BMI 27.9 ± 6.5 kg/m2; never users: n = 5553 (80.3%), former users: n = 533 (7.7%), current users: n = 826 (12.0%). Current use of VDS was higher in females. VDT rose from 42.1% in 2014 to 92.7% in 2022, and VDA rose from 14.8% to 25.5% for the same time. VDA was found overall in n = 1511 (21.9%); Never users: n = 864 (15.6%), Former users: n = 123 (23.2%); and Current users: n = 370 (44.8%). The maximal VDA (67.9%) was found in subjects using high-dose VDS in the long term. Conclusions: Despite the significant rise in VDT and VDS use, VDA was found in a minority of patients. Prolonged use of high-dose supplements produces modest improvements in VDA. [ABSTRACT FROM AUTHOR]

Background: 25-hydroxy vitamin D (Vit D)-deficiency is common among patients with chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD). African Americans (AAs) suffer disproportionately from CKD and CVD, and 80% of AAs are Vit D-deficient. The impact of Vit D repletion on cardio-renal biomarkers in AAs is unknown. We examined Vit D repletion on full-length osteopontin (flOPN), c-terminal fibroblast growth factor-23 (FGF-23), and plasminogen activator inhibitor-1 (PAI-1), which are implicated in vascular and kidney pathology. Methods: We performed a randomized, placebo-controlled study of high-risk AAs with Vit D deficiency, treated with 100,000 IU Vit D3 (cholecalciferol; n = 65) or placebo (n = 65) every 4 weeks for 12 weeks. We measured kidney function (CKD-EPI eGFR), protein-to-creatinine ratio, vascular function (pulse wave velocity; PWV), augmentation index, waist circumference, sitting, and 24-h-ambulatory blood pressure (BP), intact parathyroid hormone (iPTH) and serum calcium at baseline and study end, and compared Vit D levels with laboratory variables. We quantified plasma FGF-23, PAI-1, and flOPN by enzyme-linked immunosorbent assay. Multiple regression analyzed the relationship between log flOPN, FGF-23, and PAI-1 with vascular and renal risk factors. Results: Compared to placebo, Vit D3 repletion increased Vit D3 2-fold (p < 0.0001), decreased iPTH by 12% (p < 0.01) and was significantly correlated with PWV (p < 0.009). Log flOPN decreased (p = 0.03), log FGF-23 increased (p = 0.04), but log PAI-1 did not change. Multiple regression indicated association between log flOPN and PWV (p = 0.04) and diastolic BP (p = 0.02), while log FGF-23 was associated with diastolic BP (p = 0.05), and a trend with eGFR (p = 0.06). Conclusion: Vit D3 repletion may reduce flOPN and improve vascular function in high risk AAs with Vit D deficiency.

Vitamin D deficiency (VDD) is widespread around the world and has been extensively documented to affect various health conditions, including the cognitive functioning of the brain. Serum 25-hydroxylated forms of vitamin D are traditionally used to determine vitamin D status. However, there is now evidence that cholecalciferol activation can occur and be controlled by locally expressed enzymes in the brain. This study aimed to investigate the effects of cholecalciferol supplementation on cognitive function in rats who underwent transient VDD in adulthood. Thirty-six adult Wistar rats were administered paricalcitol (seven doses of 32 ng injected every other day) along with a “vitamin D-free” diet to induce VDD, which was confirmed using a LC–MS/MS serum analysis of the cholecalciferol and 25-hydroxyvitamin D3 levels. Treatment was performed by including 1000 IU/kg and 10,000 IU/kg cholecalciferol in the diet. Cognitive performance was evaluated using the novel object recognition (NOR), Morris water maze (MWM), and radial arm maze (RAM) tests. An immunohistochemical analysis of the brain regions involved in learning and memory was performed by quantifying the neurons, astrocytes, and microglia labelled with anti-neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1) antibodies, respectively. The vitamin D deficient group showed the lowest performance in both the MWM and RAM tests. In contrast, the cholecalciferol-treated groups exhibited a faster learning curve. However, no difference was detected between the groups in the NOR test. On the other hand, differences in the cellular organization of the hippocampus and amygdala were observed between the groups. Cholecalciferol supplementation decreased the density of the Iba-1- and GFAP-labeled cells in the hilus and cornu Ammonis 3 (CA3) regions of the hippocampus and in the amygdala. These results support vitamin D’s substantial role in learning and memory. They also highlight that subtle changes of cognitive function induced by transient VDD could be reversed by cholecalciferol supplementation. Further studies are needed to better understand VDD and cholecalciferol’s effects on the brain structure and function.

Vitamin D3 plays a vital role in numerous physiological processes within the human body, including having a positive effect on eye health. It is renowned for its immunomodulatory, anti-inflammatory, antioxidant, and angiogenic properties. Its deficiency is evolving into a significant global challenge. In order to explain the connection between vitamin D3 and various ocular diseases, 84 relevant studies, mainly from the PubMed database, published in English between 1999 and 2024 were analyzed. Ocular tissues can activate and regulate vitamin D levels, which emphasizes the significance of this nutrient in maintaining eye homeostasis. While there is suggestive evidence for a probable association between vitamin D3 and ocular health, more robust research is needed to establish causation and inform clinical guidelines.

Hip fractures are a major health issue considerably impacting patients’ quality of life and well-being. This is particularly evident in elderly subjects, in which the decline in bone and muscle mass coexists and predisposes individuals to fall and fracture. Among interventions to be implemented in hip fractured patients, the assessment and management of nutritional status is pivotal, particularly in subjects older than 65. Nutrition plays a central role in both primary and secondary preventions of fracture. An adequate protein intake improves muscle mass and strength and the intestinal absorption of calcium. Other nutrients with recognized beneficial effects on bone health are calcium, vitamins D, K, and C, potassium, magnesium, folate, and carotenoids. With reference to calcium, results from longitudinal studies showed that the consumption of dairy foods has a protective role against fractures. Moreover, the most recent systematic reviews and meta-analyses and one umbrella review demonstrated that the combination of calcium and vitamin D supplementation significantly reduces hip fracture risk, with presumed higher efficacy in older and institutionalized subjects. Owing to these reasons, the adequate intake of calcium, vitamin D, protein, and other macro and micronutrients has been successfully implemented in the Fracture Liaison Services (FLSs) that represent the most reliable model of management for hip fracture patients. In this narrative review, papers (randomized controlled trials, prospective and intervention studies, and systematic reviews) retrieved by records from three different databases (PubMed, Embase, and Medline) have been analyzed, and the available information on the screening, assessment, and management of nutritional and vitamin D status and calcium intake in patients with hip fractures is presented along with specific prevention and treatment measures.

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D3 formulations (softgels) in healthy adults, at single daily doses of 1000 and 2500 IU, over a 60-day period. A total of 69 participants were initially screened for eligibility in a double-blind randomized study with a four-arm parallel design; 35 participants were randomized to treatment groups: (1) standard Vitamin D3 1000 IU (STD1000), (2) micellar Vitamin D3 1000 IU (LMD1000), (3) standard Vitamin D3 2500 IU (STD2500), and (4) micellar Vitamin D3 2500 IU (LMD2500). Serum Vitamin D concentrations were determined through calcifediol [25(OH)D] at baseline (=before treatment), at day 5, 10, and 15 (=during treatment), at day 30 (=end of treatment), and at day 45 and 60 (=during follow-up/post treatment). Safety markers and minerals were evaluated at baseline and at day 30 and day 60. The pharmacokinetic parameters with respect to iAUC were found to be significantly different between LMD1000 vs. STD1000: iAUC(5–60): 992 ± 260 vs. 177 ± 140 nmol day/L; p < 0.05, suggesting up to 6 times higher Vitamin D3 absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D3 concentrations than the STD1000 group (iAUC(30–60): 680 ± 190 vs. 104 ± 91 nmol day/L; p < 0.05). However, no significant differences were found between the pharmacokinetics of the higher dosing groups STD2500 and LMD2500. No significant changes in serum 1,25(OH)2D concentrations or other biochemical safety markers were detected at day 60; no excess risks of hypercalcemia (i.e., total serum calcium > 2.63 mmol/L) or other adverse events were identified. LMD, a micellar delivery vehicle for microencapsulating Vitamin D3 (LipoMicel®), proved to be safe and only showed superior bioavailability when compared to standard Vitamin D at the lower dose of 1000 IU. This study has clinical trial registration: NCT05209425.

Introduction: Vitamin D (VitD) has been shown to impact neurodevelopment. Studies have shown that higher 25-hydroxy-vitamin D (25(OH)D) concentrations (the indicator of vitD status) may be associated with better neurodevelopmental outcomes, although current data are conflicting. This study examined the relationship between total circulating 25(OH)D concentrations and neurodevelopmental outcomes in 3–5-year-old (3–5 yo) children. Methods: In this study, pregnant women were randomized to receive 400 (standard dose), 2000, or 4000 IU vitD3/day. Offspring then underwent the Brigance Screen at 3–5 yo. The 25(OH)D concentration was measured at birth and 3–5 yo. Relationships between Brigance scores and 25(OH)D and Brigance scores and vitamin D binding protein (VDBP) genotype were examined. Results: Higher 25(OH)D at the time of testing was associated with better overall performance on neurodevelopmental testing as measured by the Brigance quotient (B = 0.208, p = 0.049). Scores were then broken down into sub-scores. Children born to mothers in the 2000 IU/day group scored higher on the Brigance language component of the assessment versus the standard dose group (B = 4.667, p = 0.044). The group of children who had the Gc1f-1s or Gc1f-2 genotypes scored higher on the Brigance academic component (B = 9.993, p < 0.001) and lower on the Brigance language component versus the 1f1f genotype (B = −9.313, p < 0.001). Children with the Gc1s-1s, Gc1s-2, or Gc2-2 genotypes also scored lower than the Gc1f-1f genotype (B = −6.757, p = 0.003). Conclusion: These results suggest that higher 25(OH)D concentrations early in life and higher doses of maternal vitamin D supplementation during pregnancy may have a positive association with neurodevelopmental outcomes. This study also suggests that the VDBP genotype is associated with neurodevelopment and differentially affects various fields of neurodevelopment. [ABSTRACT FROM AUTHOR]

Introduction: Studies indicate a high prevalence of vitamin D deficiency in both the general population and at-risk groups. Given the association between vitamin D deficiency and various diseases, addressing this concern becomes crucial, especially in situations where routine monitoring is challenging. Materials and methods: A systematic literature review of the current knowledge on vitamin D dosing in diverse at-risk populations and the application of the findings to a broader clinical perspective. Results: The reviewed studies revealed a high prevalence of vitamin D deficiency among patients with musculoskeletal disorders, systemic connective tissue diseases, corticosteroid use, endocrine and metabolic conditions, malabsorption syndromes, obesity, chronic kidney disease, cancer, and central nervous system diseases. Vitamin D deficiency was often more severe compared to the general population. Higher dosages of vitamin D beyond the recommended levels for the general population were shown to be effective in improving vitamin D status in these at-risk individuals. Additionally, some studies suggested a potential link between intermittent vitamin D administration and improved adherence. Conclusion: Simplified dosing could empower clinicians to address vitamin D deficiency, particularly in high-risk populations, even without routine monitoring. Further research is needed to establish the optimal dosing regimens for specific at-risk populations. [ABSTRACT FROM AUTHOR]

Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS). However, its effect on disease symptoms remains unclear. The aim of this meta-analysis was to conduct a systematic review to assess the effect of vitamin D on fatigue in this population. The systematic review was conducted using the MEDLINE, Cochrane Library, Embase and Web of Science databases from inception to May 2023. Randomized controlled trials (RCTs) reporting pre–post changes in fatigue after vitamin D supplementation were included. Pooled effect sizes and 95% confidence intervals (95% CIs) were calculated by applying a random effects model with Stata/SE (Version 16.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of five studies with 345 individuals (271 females; age range: 25.4–41.1 years) were included. A significant reduction in fatigue was perceived when vitamin D supplementation was compared with a control group: −0.18 (95% CI: −0.36 to −0.01; I2 = 0%). Thus, our findings show that the therapeutic use of vitamin D on fatigue in people with MS could be considered. Nevertheless, due to the lack of agreement on the dose to be applied, it is recommended to use it under medical prescription. [ABSTRACT FROM AUTHOR]

Vitamin D (VD) deficiency (serum 25(OH)D < 50 nmol/L) affects 27.3% of preschool children in Mexico. The purpose of this study was to assess the effect of vitamin D supplementation at different doses on serum 25(OH)D concentrations in preschool children. In a randomized control trial, 222 children 12–30 months old were randomly assigned to one of four treatment groups: (1) Vitamin D2 (Ergocalciferol) 400 IU/day (n = 56); (2) Vitamin D2 (Ergocalciferol) 800 IU/day (n = 55); (3) Vitamin D3 (Cholecalciferol) 1000 IU/day (n = 56); or (4) multiple micronutrients (MM) non-VD (n = 55). Supplements were given five days/wk for three months. Serum 25(OH)D was measured at baseline and after three months. At baseline, mean serum 25(OH)D was 58.9 ± 12.6 nmol/L and 23.4% were VD-deficient. There was a statistically significant increase in serum concentrations of 25(OH)D (range across groups: +8.2 to +17.3 nmol/L). Additionally, the prevalence of vitamin D deficiency decreased after three months: for D2 400 IU, −9.0%; for D2 800 IU, −11.0%; for D3 1000 IU, −18.0%; and for MM non-VD, −2.8% (p < 0.05). No adverse effects were observed. VD supplementation for three months was effective for increasing serum 25(OH)D concentrations and for reducing VD deficiency in preschool children. The highest efficacy was observed by giving 1000 IU D3/d. [ABSTRACT FROM AUTHOR]

Background: This review aims to identify the current indications and gaps in the management of fat-soluble vitamins in pediatric patients with cholestasis. Methods: A comprehensive review of the literature using PubMed, Scopus, Web of Science and Embase was performed. Two authors independently identified the most relevant studies published over the past 20 years up to February 2022, including original papers, narrative reviews, observational studies, clinical trials, systematic reviews and meta-analyses. The literature was screened, and preclinical studies about pathogenetic mechanisms were also included. Keywords searched for each fat-soluble vitamin (A, D, E and K), alone or in combination, were "cholestasis", "chronic liver disease", "biliary atresia", "malnutrition" and "nutritional needs". Studies published prior to the selected time range were searched manually and, when considered relevant, included within the list of references. Results: Eight hundred twenty-six articles were initially screened. From these, 48 studies were selected. A comparison of the recommended methods of supplementation for fat-soluble vitamins was then carried out. The causes of malabsorption were explained and current methods for defining deficiency and monitoring complications were summarized. Conclusions: According to the literature, children with cholestasis are at a higher risk of fat-soluble vitamin deficiency. Although there are general recommendations, the treatment for vitamin deficiency is not uniformly validated. [ABSTRACT FROM AUTHOR]

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists' voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20–30 ng/mL (50–75 nmol/L)], and optimal concentration [30–50 ng/mL (75–125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland. [ABSTRACT FROM AUTHOR]

Background: The aim of the present review was to summarize the current evidence about the impact of vitamin D deficiency on pathology and clinical manifestations of Sjögren's disease (SD). Methods: Databases PubMed, Web of Science, Scopus, and Cochrane library were searched for studies assessing the levels of vitamin D in SD patients using the following keywords: (vitamin D OR calciferol OR cholecalciferol OR 25-hydroxyvitamin D OR 25-hydroxycholecalciferol OR calcidiol OR calcitriol OR 1,25-dihydroxycholecalciferol) AND (Sjögren's Syndrome OR Sjögren's disease) accessed on 20 September 2022. Out of 248 retrieved studies, following the systematic review methodology and defined inclusion and exclusion criteria, 9 clinical studies were eligible to be included in the present review: 4 of them case-control, 4 cross-sectional, and 1 cohort study. Results: Nine studies totaling 670 SD patients and 857 healthy controls were eligible for meta-analysis with moderate to high methodological quality as determined by the Newcastle–Ottawa Quality Scale (NOS). According to the obtained results, a high prevalence of hypovitaminosis D was observed in SD patients when compared to healthy controls (95% CI −10.43, −2.39; p < 0.01). Conclusion: Available evidence points to lower levels of vitamin D in patients with SD in comparison to healthy controls. However, further studies are necessary to understand the underlying mechanisms associated with the role of vitamin D in the development and disease severity of SD. [ABSTRACT FROM AUTHOR]

The definition of “Vitamin D” encompasses a group of fat-soluble steroid compounds of different origins with similar chemical structures and the same biological effects. Vitamin D deficiency and/or a defect in the process of its synthesis or transport predispose individuals to several types of rickets. In addition to cholecalciferol, ergocalciferol, and vitamins D3 and D2, there are also active metabolites for the treatment of this condition which are commercially available. Calcitriol and aphacalcidiol are active metabolites that do not require the renal activation step, which is required with calcifediol, or hepatic activation. The purpose of this review is to summarize current approaches to the treatment of rickets for generalist physicians, focusing on the best vitamin D form to be used in each type, or, in the case of X-linked hypophosphatemic rickets (XLH), on both conventional and innovative monoclonal antibody treatments.

Background: Vitamin D testing (VDT) and supplement use (VDS) are on the rise, but most patients remain deficient (3000 IU/day)), intake duration (short-term (2; never users: n = 5553 (80.3%), former users: n = 533 (7.7%), current users: n = 826 (12.0%). Current use of VDS was higher in females. VDT rose from 42.1% in 2014 to 92.7% in 2022, and VDA rose from 14.8% to 25.5% for the same time. VDA was found overall in n = 1511 (21.9%); Never users: n = 864 (15.6%), Former users: n = 123 (23.2%); and Current users: n = 370 (44.8%). The maximal VDA (67.9%) was found in subjects using high-dose VDS in the long term. Conclusions: Despite the significant rise in VDT and VDS use, VDA was found in a minority of patients. Prolonged use of high-dose supplements produces modest improvements in VDA.

Deficiency in vitamin D (VitD), a lipid-soluble vitamin and steroid hormone, affects approximately 24% to 40% of the population of the Western world. In addition to its well-documented effects on the musculoskeletal system, VitD also contributes importantly to the promotion and preservation of cardiovascular health via modulating the immune and inflammatory functions and regulating cell proliferation and migration, endothelial function, renin expression, and extracellular matrix homeostasis. This brief overview focuses on the cardiovascular and cerebrovascular effects of VitD and the cellular, molecular, and functional changes that occur in the circulatory system in VitD deficiency (VDD). It explores the links among VDD and adverse vascular remodeling, endothelial dysfunction, vascular inflammation, and increased risk for cardiovascular and cerebrovascular diseases. Improved understanding of the complex role of VDD in the pathogenesis of atherosclerotic cardiovascular diseases, stroke, and vascular cognitive impairment is crucial for all cardiologists, dietitians, and geriatricians, as VDD presents an easy target for intervention. [ABSTRACT FROM AUTHOR]

The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The objective of our study was to evaluate vitamin D status and its predictors in Slovenian premenopausal and postmenopausal women. A cross-sectional study was carried out between 1 March 2021 and 31 May 2021. A total of 319 healthy women from the Central Slovenian region aged between 44 and 65 were recruited; 176 were included in the final analysis. The vitamin D status was determined by measuring the total 25-Hydroxycholecalciferol (25(OH)D) concentration, vitamin D binding protein (DBP), and albumin and calculating the bioavailable 25(OH)D and free 25(OH)D. For the calculation of bioavailable and free 25(OH)D, we developed a new online calculator. The Endocrine Society's thresholds for vitamin D deficiency and insufficiency were used; 29.0% of premenopausal and 24.4% of postmenopausal subjects were found to be vitamin D deficient (total 25(OH)D < 50 nmol/L); 76.8% of the premenopausal and 61.7% of postmenopausal subjects were found to have insufficient levels (total 25(OH)D < 75 nmol/L). Premenopausal women had 11.8% lower total 25(OH)D, 32.2% lower bioavailable 25(OH)D, and 25.2% higher DBP than postmenopausal women. The most important predictors of vitamin D status were vitamin D supplementation and time spent in the sun. Contrary to similar studies, the vitamin D status in Slovenian postmenopausal women was significantly better than in premenopausal women. In postmenopausal women, the measurement of free or bioavailable 25(OH)D instead of the total 25(OH)D could be advantageous. [ABSTRACT FROM AUTHOR]

Vitamin D is among the increasingly consumed dietary supplements during the COVID-19 pandemic. It plays a regulatory role in the immune system and moderates the renin–angiotensin system, which is implicated in infection pathogenesis. However, the investigation of serum levels of vitamin D3 forms and their relative ratios in COVID-19 patients is worth investigation to understand the impacts of disease severity. Hence, we investigated the serum levels of vitamin D3 (cholecalciferol) and its metabolites (calcifediol and calcitriol), in addition to their relative ratios and correlations with angiotensin-converting enzyme 2 (ACE2), interleukin-6 (Il-6), and neutrophil–lymphocyte ratio (NLR) in COVID-19 patients compared with healthy controls. Oropharyngeal specimens were collected from the study subjects for polymerase chain reaction testing for COVID-19. Whole blood samples were obtained for blood count and NLR testing, and sera were used for the analysis of the levels of the vitamin and its metabolites, ACE2, and IL-6. We enrolled 103 patients and 50 controls. ACE2, Il-6, and NLR were significantly higher in the patients group (72.37 ± 18.67 vs. 32.36 ± 11.27 U/L, 95.84 ± 25.23 vs. 2.76 ± 0.62 pg/mL, and 1.61 ± 0.30 vs. 1.07 ± 0.16, respectively). Cholecalciferol, calcifediol, and calcitriol were significantly lower in patients (18.50 ± 5.36 vs. 29.13 ± 4.94 ng/mL, 14.60 ± 3.30 vs. 23.10 ± 3.02 ng/mL, and 42.90 ± 8.44 vs. 65.15 ± 7.11 pg/mL, respectively). However, their relative ratios were normal in both groups. Levels of the vitamin and metabolites were strongly positively, strongly negatively, and moderately negatively correlated with ACE2, Il-6, and NLR, respectively. COVID-19 infection severity is associated with a significant decrease in vitamin D3 and its metabolites in a parallel pattern, and with a significant increase in ACE2, Il-6, and NLR. Higher levels of vitamin D and its metabolites are potentially protective against severe infection. [ABSTRACT FROM AUTHOR]

The effects of different cholecalciferol supplementation regimens on serum inflammatory cytokines in healthy subjects with vitamin D deficiency are still lacking. This is a single-center, open-label, randomized, parallel group study involving healthy subjects deficient in vitamin D (baseline 25OHD < 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. IL-17A, IL-6, IL-8, IL-10, IL-23 and TNFα were measured at baseline and at week 4, 8, 12, and 16. 75 healthy subjects were enrolled (58.7% female), with an average age of 34.1 ± 10.2 years. No statistical differences were observed among groups at baseline for either IL-6, IL-17A, IL-23, IL-8 or IL-10 at any time point; TNFα was indetectable. Concerning the whole sample, the time trend analysis showed a statistically significant linear trend for decreasing values over the treatment period for IL-6 (p = 0.016) and IL-17A (p = 0.006), while no significant time trends were observed for the other teste cytokines. No significant differences were found in the serum concentrations of the tested cytokines between week 12 and week 16. In young healthy individuals deficient in vitamin D, cholecalciferol administration showed a decrease in the serum IL-6 and IL-17A concentrations, without marked differences using the three regimens. [ABSTRACT FROM AUTHOR]

Introduction: Vitamin D (VitD) has been shown to impact neurodevelopment. Studies have shown that higher 25-hydroxy-vitamin D (25(OH)D) concentrations (the indicator of vitD status) may be associated with better neurodevelopmental outcomes, although current data are conflicting. This study examined the relationship between total circulating 25(OH)D concentrations and neurodevelopmental outcomes in 3–5-year-old (3–5 yo) children. Methods: In this study, pregnant women were randomized to receive 400 (standard dose), 2000, or 4000 IU vitD3/day. Offspring then underwent the Brigance Screen at 3–5 yo. The 25(OH)D concentration was measured at birth and 3–5 yo. Relationships between Brigance scores and 25(OH)D and Brigance scores and vitamin D binding protein (VDBP) genotype were examined. Results: Higher 25(OH)D at the time of testing was associated with better overall performance on neurodevelopmental testing as measured by the Brigance quotient (B = 0.208, p = 0.049). Scores were then broken down into sub-scores. Children born to mothers in the 2000 IU/day group scored higher on the Brigance language component of the assessment versus the standard dose group (B = 4.667, p = 0.044). The group of children who had the Gc1f-1s or Gc1f-2 genotypes scored higher on the Brigance academic component (B = 9.993, p < 0.001) and lower on the Brigance language component versus the 1f1f genotype (B = −9.313, p < 0.001). Children with the Gc1s-1s, Gc1s-2, or Gc2-2 genotypes also scored lower than the Gc1f-1f genotype (B = −6.757, p = 0.003). Conclusion: These results suggest that higher 25(OH)D concentrations early in life and higher doses of maternal vitamin D supplementation during pregnancy may have a positive association with neurodevelopmental outcomes. This study also suggests that the VDBP genotype is associated with neurodevelopment and differentially affects various fields of neurodevelopment.

Introduction: Studies indicate a high prevalence of vitamin D deficiency in both the general population and at-risk groups. Given the association between vitamin D deficiency and various diseases, addressing this concern becomes crucial, especially in situations where routine monitoring is challenging. Materials and methods: A systematic literature review of the current knowledge on vitamin D dosing in diverse at-risk populations and the application of the findings to a broader clinical perspective. Results: The reviewed studies revealed a high prevalence of vitamin D deficiency among patients with musculoskeletal disorders, systemic connective tissue diseases, corticosteroid use, endocrine and metabolic conditions, malabsorption syndromes, obesity, chronic kidney disease, cancer, and central nervous system diseases. Vitamin D deficiency was often more severe compared to the general population. Higher dosages of vitamin D beyond the recommended levels for the general population were shown to be effective in improving vitamin D status in these at-risk individuals. Additionally, some studies suggested a potential link between intermittent vitamin D administration and improved adherence. Conclusion: Simplified dosing could empower clinicians to address vitamin D deficiency, particularly in high-risk populations, even without routine monitoring. Further research is needed to establish the optimal dosing regimens for specific at-risk populations.

(1) Background: In the present paper we aimed to review the evidence about the potential implication of vitamin D in the pathogenesis and management of systemic sclerosis (SSc); (2) Methods: we performed a review of the literature looking for studies evaluating the potential role of vitamin D and its analogs in SSc. We searched the PubMed, Medline, Embase, and Cochrane libraries using the following strings: (vitamin D OR cholecalciferol) AND (systemic sclerosis OR scleroderma). We included cohort studies, case-control studies, randomized controlled trials, and observational studies. (3) Results: we identified nine pre-clinical and 21 clinical studies. Pre-clinical data suggest that vitamin D and its analogs may suppress fibrogenesis. Clinical data are concordant in reporting a high prevalence of hypovitaminosis D and osteoporosis in SSc patients; data about the association with clinical manifestations and phenotypes of SSc are, conversely, far less consistent; (4) Conclusions: in vitro data suggest that vitamin D may play an antifibrotic role in SSc, but clinical data confirming this finding are currently lacking. Hypovitaminosis D is common among SSc patients and should be treated to reduce the risk of osteoporosis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Hypovitaminosis D is prevalent in epidemic proportions in many developed countries. The aim of this study is to investigate the prevalence of adequate 25-hydroxyvitamin D [25(OH)D] levels in two Mediterranean countries, Greece and Cyprus. METHODS: Data such as 25(OH)D, the month of blood sample collection, and demographic information were blindly collected from 8780 Greek and 2594 Cypriot individuals over 5 years. Comorbidities were also recorded for 839 Greek subjects. Univariate and multivariate analyses were used to examine the relationship between these variables and 25(OH)D levels. RESULTS: In the samples studied, 72.7% of the Greek and 69.3% of the Cypriot population sample had inadequate levels of 25(OH)D. The mean level for the Greek subjects was 25.1 ng/mL and for Cypriots 25.8 ng/mL. For both samples, only month and gender were significantly associated with 25(OH)D levels, and the highest mean levels were recorded in September. For the recorded diseases, the lowest levels were recorded in sickle cell anaemia 13.6 ± 10.2 ng/mL, autoimmune diseases 13.0 ± 8.4 ng/mL, and cancer 22.6 ± 9.5 ng/mL. CONCLUSIONS: The prevalence of vitamin D deficiency is paradoxically high in both Mediterranean countries. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) has already killed more than 6 million people around the world. A growing body of epidemiological evidence suggests that low 25-hydroxy vitamin D (25-OH-vitamin D) plasma levels are associated with an increased risk of developing COVID-19 and —most importantly—with a higher risk of developing more severe COVID-19 and dying. On the other hand, vitamin D supplementation during the early phases of COVID-19 has been related to a decreased length of hospital stay, less frequent need for oxygen, and a reduced mortality rate in inpatients. This seems to be particularly true when high dosages are used. In light of this evidence, further studies are needed to define the best timing for vitamin D supplementation and the most effective dosage schedule. [ABSTRACT FROM AUTHOR]

This study compared the efficacies of enteral cholecalciferol and/or intravenous (IV) calcitriol administration on mesenteric lymph node (MLN) cluster-of-differentiation-4-positive (CD4+) T cell distribution and intestinal barrier damage in obese mice complicated with sepsis. Mice were fed a high-fat diet for 16 weeks and then sepsis was induced by cecal ligation and puncture (CLP). Mice were divided into the following sepsis groups: without vitamin D (VD) (S); with oral cholecalciferol 1 day before CLP (G); with IV calcitriol 1 h after CLP (V); and with both cholecalciferol before and IV calcitriol after CLP (GV). All mice were sacrificed at 12 or 24 h after CLP. The findings show that the S group had a higher T helper (Th)17 percentage than the VD-treated groups at 12 h after CLP. The V group exhibited a higher Th1 percentage and Th1/Th2 ratio than the other groups at 24 h, whereas the V and GV groups had a lower Th17/regulatory T (Treg) ratio 12 h post-CLP in MLNs. In ileum tissues, the VD-treated groups had higher tight junction protein and cathelicidin levels, and higher mucin gene expression than the S group at 24 h post-CLP. Also, aryl hydrocarbon receptor (AhR) and its associated cytochrome P450 1A1 and interleukin 22 gene expressions were upregulated. In contrast, levels of lipid peroxides and inflammatory mediators in ileum tissues were lower in the groups with VD treatment after CLP. These results suggest that IV calcitriol seemed to have a more-pronounced effect on modulating the homeostasis of Th/Treg subsets in MLNs. Both oral cholecalciferol before and IV calcitriol after CLP promoted cathelicidin secretion, alleviated intestinal inflammation, and ameliorated the epithelial integrity in obese mice complicated with sepsis possibly via VD receptor and AhR signaling pathways. [ABSTRACT FROM AUTHOR]

Retrospective studies showed a relationship between vitamin D status and COVID-19 severity and mortality, with an inverse relation between SARS-CoV-2 positivity and circulating calcifediol levels. The objective of this pilot study was to investigate the effect of vitamin D supplementation on the length of hospital stay and clinical improvement in patients with vitamin D deficiency hospitalized with COVID-19. The study was randomized, double blind and placebo controlled. A total of 50 subjects were enrolled and received, in addition to the best available COVID therapy, either vitamin D (25,000 IU per day over 4 consecutive days, followed by 25,000 IU per week up to 6 weeks) or placebo. The length of hospital stay decreased significantly in the vitamin D group compared to the placebo group (4 days vs. 8 days; p = 0.003). At Day 7, a significantly lower percentage of patients were still hospitalized in the vitamin D group compared to the placebo group (19% vs. 54%; p = 0.0161), and none of the patients treated with vitamin D were hospitalized after 21 days compared to 14% of the patients treated with placebo. Vitamin D significantly reduced the duration of supplemental oxygen among the patients who needed it (4 days vs. 7 days in the placebo group; p = 0.012) and significantly improved the clinical recovery of the patients, as assessed by the WHO scale (p = 0.0048). In conclusion, this study demonstrated that the clinical outcome of COVID-19 patients requiring hospitalization was improved by administration of vitamin D. [ABSTRACT FROM AUTHOR]

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

Vitamin D supplementation has been considered a possible treatment to reduce the risk of disease activity and progression in people with multiple sclerosis (MS). However, its effect on disease symptoms remains unclear. The aim of this meta-analysis was to conduct a systematic review to assess the effect of vitamin D on fatigue in this population. The systematic review was conducted using the MEDLINE, Cochrane Library, Embase and Web of Science databases from inception to May 2023. Randomized controlled trials (RCTs) reporting pre–post changes in fatigue after vitamin D supplementation were included. Pooled effect sizes and 95% confidence intervals (95% CIs) were calculated by applying a random effects model with Stata/SE (Version 16.0; StataCorp., College Station, TX, USA). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A total of five studies with 345 individuals (271 females; age range: 25.4–41.1 years) were included. A significant reduction in fatigue was perceived when vitamin D supplementation was compared with a control group: −0.18 (95% CI: −0.36 to −0.01; I2 = 0%). Thus, our findings show that the therapeutic use of vitamin D on fatigue in people with MS could be considered. Nevertheless, due to the lack of agreement on the dose to be applied, it is recommended to use it under medical prescription.

Vitamin D (VD) deficiency (serum 25(OH)D < 50 nmol/L) affects 27.3% of preschool children in Mexico. The purpose of this study was to assess the effect of vitamin D supplementation at different doses on serum 25(OH)D concentrations in preschool children. In a randomized control trial, 222 children 12–30 months old were randomly assigned to one of four treatment groups: (1) Vitamin D2 (Ergocalciferol) 400 IU/day (n = 56); (2) Vitamin D2 (Ergocalciferol) 800 IU/day (n = 55); (3) Vitamin D3 (Cholecalciferol) 1000 IU/day (n = 56); or (4) multiple micronutrients (MM) non-VD (n = 55). Supplements were given five days/wk for three months. Serum 25(OH)D was measured at baseline and after three months. At baseline, mean serum 25(OH)D was 58.9 ± 12.6 nmol/L and 23.4% were VD-deficient. There was a statistically significant increase in serum concentrations of 25(OH)D (range across groups: +8.2 to +17.3 nmol/L). Additionally, the prevalence of vitamin D deficiency decreased after three months: for D2 400 IU, −9.0%; for D2 800 IU, −11.0%; for D3 1000 IU, −18.0%; and for MM non-VD, −2.8% (p < 0.05). No adverse effects were observed. VD supplementation for three months was effective for increasing serum 25(OH)D concentrations and for reducing VD deficiency in preschool children. The highest efficacy was observed by giving 1000 IU D3/d.

Background: This review aims to identify the current indications and gaps in the management of fat-soluble vitamins in pediatric patients with cholestasis. Methods: A comprehensive review of the literature using PubMed, Scopus, Web of Science and Embase was performed. Two authors independently identified the most relevant studies published over the past 20 years up to February 2022, including original papers, narrative reviews, observational studies, clinical trials, systematic reviews and meta-analyses. The literature was screened, and preclinical studies about pathogenetic mechanisms were also included. Keywords searched for each fat-soluble vitamin (A, D, E and K), alone or in combination, were “cholestasis”, “chronic liver disease”, “biliary atresia”, “malnutrition” and “nutritional needs”. Studies published prior to the selected time range were searched manually and, when considered relevant, included within the list of references. Results: Eight hundred twenty-six articles were initially screened. From these, 48 studies were selected. A comparison of the recommended methods of supplementation for fat-soluble vitamins was then carried out. The causes of malabsorption were explained and current methods for defining deficiency and monitoring complications were summarized. Conclusions: According to the literature, children with cholestasis are at a higher risk of fat-soluble vitamin deficiency. Although there are general recommendations, the treatment for vitamin deficiency is not uniformly validated.

The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine/chemokine storm, regulating the renin–angiotensin–bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents. [ABSTRACT FROM AUTHOR]

The vitamin D and microRNA (miR) systems may play a role in the pathogenesis of cardiometabolic disorders, including hypertension. The HYPODD study was a double-blind placebo-controlled trial aiming to assess the effects of cholecalciferol treatment in patients with well-controlled hypertension and hypovitaminosis D (25OHD levels < 50 nmol/L). In addition to this clinical trial, we also evaluated the effects of cholecalciferol and calcitriol treatment on miR-21 expression in vivo and in vitro, respectively. Changes in the cardiovascular risk profiles were evaluated in HYPODD patients treated with cholecalciferol (C-cohort) or with placebo (P-cohort). The miR-21circulating levels were measured in four C-cohort patients and five P-cohort patients. In vitro, the miR-21 levels were measured in HEK-293 cells treated with calcitriol or with ethanol vehicle control. Cholecalciferol treatment increased 25OHD levels and reduced parathormone, total cholesterol, and low-density lipoprotein cholesterol levels in C-cohort patients, whereas no significant changes in these parameters were observed in P-cohort patients. The miR-21 circulating levels did not change in the C- or the P-cohort patients upon treatment. Calcitriol treatment did not affect miR-21 levels in HEK-293 cells. In conclusion, hypovitaminosis D correction ameliorated the cardiovascular risk profiles in hypertensive patients treated with cholecalciferol but did not influence the miR-21 expression. [ABSTRACT FROM AUTHOR]

Calcifediol is the prohormone of the vitamin D endocrine system (VDES). It requires hydroxylation to move to 1,25(OH)2D3 or calcitriol, the active form that exerts its functions by activating the vitamin D receptor (VDR) that is expressed in many organs, including the lungs. Due to its rapid oral absorption and because it does not require first hepatic hydroxylation, it is a good option to replace the prevalent deficiency of vitamin D (25 hydroxyvitamin D; 25OHD), to which patients with respiratory pathologies are no strangers. Correcting 25OHD deficiency can decrease the risk of upper respiratory infections and thus improve asthma and COPD control. The same happens with other respiratory pathologies and, in particular, COVID-19. Calcifediol may be a good option for raising 25OHD serum levels quickly because the profile of inflammatory cytokines exhibited by patients with inflammatory respiratory diseases, such as asthma, COPD or COVID-19, can increase the degradation of the active metabolites of the VDES. The aim of this narrative revision is to report the current evidence on the role of calcifediol in main respiratory diseases. In conclusion, good 25OHD status may have beneficial effects on the clinical course of respiratory diseases, including COVID-19. This hypothesis should be confirmed in large, randomized trials. Otherwise, a rapid correction of 25(OH)D deficiency can be useful for patients with respiratory disease. [ABSTRACT FROM AUTHOR]

Calcifediol (25-OH-vitamin D3) is the prohormone of the vitamin D endocrine system. It is used to prevent and treat vitamin D deficiency. Calcifediol, as well as cholecalciferol (vitamin D3), is efficient and safe in the general population, although calcifediol has certain advantages over cholecalciferol, such as its rapid onset of action and greater potency. This review analyzed studies comparing the efficacy and safety of both calcifediol and cholecalciferol drugs in the short and long term (>6 months). Calcifediol was found to be more efficacious, with no increase in toxicity. We also assessed the predictability of both molecules. A 25OHD increase depends on the dose and frequency of calcifediol administration. In contrast, after cholecalciferol administration, 25OHD increase depends on more factors than dose and frequency of administration, also phenotypic aspects (such as obesity and malabsorption), and genotypic factors impacts in this increase. [ABSTRACT FROM AUTHOR]

The intent of this study was an evaluation of our effort to reduce the incidence of hypercalcemia in critically ill vitamin D-deficient patients with multiple traumatic injuries given cholecalciferol. Vitamin D deficiency was defined as a serum 25-hydroxy vitamin D concentration (25-OH vit D) of <20 ng/mL. Adult patients (>17 years of age) were given 10,000 IU of cholecalciferol daily with an intended target 25-OH vit D of >19.9 ng/mL. These patients were compared to a historical control group that underwent therapy with a higher target of >29.9 ng/mL. Patients received cholecalciferol via the feeding tube along with enteral nutrition (EN) until the target 25-OH vit D was achieved, EN discontinued, the nutrition support service signed off the patient, or the patient was discharged from the TICU. Patients were included if two consecutive weekly 25-OH vit D were measured. One hundred and three critically ill trauma patients were retrospectively studied. Fifty were given cholecalciferol therapy with the new lower target 25-OH vit D, and 53 were from a historical cohort aiming for the higher target. Hypercalcemia (serum ionized calcium concentration > 1.32 mmol/L) was reduced from 40% (21 out of 53 patients) to 4% (2 out of 50 patients; p < 0.001). None of the hypercalcemic patients were symptomatic. Readjustment of target 25-OH vit D concentration resulted in a ten-fold decrease in the rate of hypercalcemia and improved the safety of cholecalciferol therapy for critically ill patients with traumatic injuries. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency has a high worldwide prevalence, but actions to improve this public health problem are challenged by the heterogeneity of nutritional and clinical vitamin D guidelines, with respect to the diagnosis and treatment of vitamin D deficiency. We aimed to address this issue by providing respective recommendations for adults, developed by a European expert panel, using the Delphi method to reach consensus. Increasing the awareness of vitamin D deficiency and efforts to harmonize vitamin D guidelines should be pursued. We argue against a general screening for vitamin D deficiency but suggest 25-hydroxyvitamin D (25(OH)D) testing in certain risk groups. We recommend a vitamin D supplementation dose of 800 to 2000 international units (IU) per day for adults who want to ensure a sufficient vitamin D status. These doses are also recommended for the treatment of vitamin D deficiency, but higher vitamin D doses (e.g., 6000 IU per day) may be used for the first 4 to 12 weeks of treatment if a rapid correction of vitamin D deficiency is clinically indicated before continuing, with a maintenance dose of 800 to 2000 IU per day. Treatment success may be evaluated after at least 6 to 12 weeks in certain risk groups (e.g., patients with malabsorption syndromes) by measurement of serum 25(OH)D, with the aim to target concentrations of 30 to 50 ng/mL (75 to 125 nmol/L). [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011–2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, p values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all p-values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (−0.196 per ng/mL 25(OH)D, 95% CI (−0.325 to −0.067); p = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency. [ABSTRACT FROM AUTHOR]

Background: The aim of the present review was to summarize the current evidence about the impact of vitamin D deficiency on pathology and clinical manifestations of Sjögren’s disease (SD). Methods: Databases PubMed, Web of Science, Scopus, and Cochrane library were searched for studies assessing the levels of vitamin D in SD patients using the following keywords: (vitamin D OR calciferol OR cholecalciferol OR 25-hydroxyvitamin D OR 25-hydroxycholecalciferol OR calcidiol OR calcitriol OR 1,25-dihydroxycholecalciferol) AND (Sjögren’s Syndrome OR Sjögren’s disease) accessed on 20 September 2022. Out of 248 retrieved studies, following the systematic review methodology and defined inclusion and exclusion criteria, 9 clinical studies were eligible to be included in the present review: 4 of them case-control, 4 cross-sectional, and 1 cohort study. Results: Nine studies totaling 670 SD patients and 857 healthy controls were eligible for meta-analysis with moderate to high methodological quality as determined by the Newcastle–Ottawa Quality Scale (NOS). According to the obtained results, a high prevalence of hypovitaminosis D was observed in SD patients when compared to healthy controls (95% CI −10.43, −2.39; p < 0.01). Conclusion: Available evidence points to lower levels of vitamin D in patients with SD in comparison to healthy controls. However, further studies are necessary to understand the underlying mechanisms associated with the role of vitamin D in the development and disease severity of SD.

Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists’ voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland.

Deficiency in vitamin D (VitD), a lipid-soluble vitamin and steroid hormone, affects approximately 24% to 40% of the population of the Western world. In addition to its well-documented effects on the musculoskeletal system, VitD also contributes importantly to the promotion and preservation of cardiovascular health via modulating the immune and inflammatory functions and regulating cell proliferation and migration, endothelial function, renin expression, and extracellular matrix homeostasis. This brief overview focuses on the cardiovascular and cerebrovascular effects of VitD and the cellular, molecular, and functional changes that occur in the circulatory system in VitD deficiency (VDD). It explores the links among VDD and adverse vascular remodeling, endothelial dysfunction, vascular inflammation, and increased risk for cardiovascular and cerebrovascular diseases. Improved understanding of the complex role of VDD in the pathogenesis of atherosclerotic cardiovascular diseases, stroke, and vascular cognitive impairment is crucial for all cardiologists, dietitians, and geriatricians, as VDD presents an easy target for intervention.

Vitamin D is among the increasingly consumed dietary supplements during the COVID-19 pandemic. It plays a regulatory role in the immune system and moderates the renin–angiotensin system, which is implicated in infection pathogenesis. However, the investigation of serum levels of vitamin D3 forms and their relative ratios in COVID-19 patients is worth investigation to understand the impacts of disease severity. Hence, we investigated the serum levels of vitamin D3 (cholecalciferol) and its metabolites (calcifediol and calcitriol), in addition to their relative ratios and correlations with angiotensin-converting enzyme 2 (ACE2), interleukin-6 (Il-6), and neutrophil–lymphocyte ratio (NLR) in COVID-19 patients compared with healthy controls. Oropharyngeal specimens were collected from the study subjects for polymerase chain reaction testing for COVID-19. Whole blood samples were obtained for blood count and NLR testing, and sera were used for the analysis of the levels of the vitamin and its metabolites, ACE2, and IL-6. We enrolled 103 patients and 50 controls. ACE2, Il-6, and NLR were significantly higher in the patients group (72.37 ± 18.67 vs. 32.36 ± 11.27 U/L, 95.84 ± 25.23 vs. 2.76 ± 0.62 pg/mL, and 1.61 ± 0.30 vs. 1.07 ± 0.16, respectively). Cholecalciferol, calcifediol, and calcitriol were significantly lower in patients (18.50 ± 5.36 vs. 29.13 ± 4.94 ng/mL, 14.60 ± 3.30 vs. 23.10 ± 3.02 ng/mL, and 42.90 ± 8.44 vs. 65.15 ± 7.11 pg/mL, respectively). However, their relative ratios were normal in both groups. Levels of the vitamin and metabolites were strongly positively, strongly negatively, and moderately negatively correlated with ACE2, Il-6, and NLR, respectively. COVID-19 infection severity is associated with a significant decrease in vitamin D3 and its metabolites in a parallel pattern, and with a significant increase in ACE2, Il-6, and NLR. Higher levels of vitamin D and its metabolites are potentially protective against severe infection.

The coronavirus disease (COVID-19) pandemic represents a global health challenge, particularly considering concomitant diseases. Patients with inflammatory bowel diseases (IBD) can be considered a population at risk. On the other hand, the risk of developing IBD and COVID-19 have both been described as modulated by vitamin D (VD) levels. In this work, a cohort of 106 adult patients affected by IBD was prospectively enrolled, during the second wave of the pandemic in Italy. In these patients, VD plasma levels, demographic, and clinical characteristics were tested for a correlation/an association with the risk of infection with SARS-CoV-2 in the study period (anti-spike IgG positivity) and the severity of COVID-19 symptoms. By multivariate logistic regression analysis, VD supplementation (Odds Ratio; OR 0.116, p = 0.002), therapy with monoclonal antibodies (OR 0.227, p = 0.007), and the use of mesalazine (OR 2.968, p = 0.046) were found to be independent predictors of SARS-CoV-2 positivity. Moreover, hypertension was associated with severe disease (p = 0.019), while a VD level higher than 30 ng/mL (p = 0.031, OR 0.078) was associated with asymptomatic infection. No interplay between IBD activity and COVID-19 risk of infection or symptoms was observed. These results confirm the importance of VD levels in defining the risk of COVID-19 and give encouraging data about the safety of maintaining immunomodulatory treatments for IBD during the COVID-19 pandemic.

The effects of different cholecalciferol supplementation regimens on serum inflammatory cytokines in healthy subjects with vitamin D deficiency are still lacking. This is a single-center, open-label, randomized, parallel group study involving healthy subjects deficient in vitamin D (baseline 25OHD < 20 ng/mL) receiving oral cholecalciferol with three different dosing regimens: Group A: 10,000 IU/day for 8 weeks followed by 1000 IU/day for 4 weeks; Group B: 50,000 IU/week for 12 weeks and Group C: 100,000 IU every other week for 12 weeks. IL-17A, IL-6, IL-8, IL-10, IL-23 and TNFα were measured at baseline and at week 4, 8, 12, and 16. 75 healthy subjects were enrolled (58.7% female), with an average age of 34.1 ± 10.2 years. No statistical differences were observed among groups at baseline for either IL-6, IL-17A, IL-23, IL-8 or IL-10 at any time point; TNFα was indetectable. Concerning the whole sample, the time trend analysis showed a statistically significant linear trend for decreasing values over the treatment period for IL-6 (p = 0.016) and IL-17A (p = 0.006), while no significant time trends were observed for the other teste cytokines. No significant differences were found in the serum concentrations of the tested cytokines between week 12 and week 16. In young healthy individuals deficient in vitamin D, cholecalciferol administration showed a decrease in the serum IL-6 and IL-17A concentrations, without marked differences using the three regimens.