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

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

Vitamin D is a critical fat-soluble vitamin for the nervous system. Research suggests a potential link between vitamin D deficiency and attention-deficit hyperactivity disorder (ADHD), particularly in children and adolescents. The core symptoms of ADHD are associated with deficits in striatal functions, and maintaining sufficient levels of vitamin D may help prevent or alleviate ADHD symptoms. However, the molecular changes in the striatum caused by vitamin D supplementation that may contribute to the brain processes linked to ADHD symptoms remain unclear. In this study, we established a mouse model fed diets with three different dose gradients of vitamin D3 (0, 500, and 2000 IU/kg·day) from postnatal day 21 (P21) to 14 weeks of age. Striatal tissues from mice with gradient vitamin D3 intake were subjected to reduced representation bisulfite sequencing (RRBS), RNA-sequencing, and neurotransmitter profiling by liquid chromatography-mass spectrometry (LC-MS). Our findings indicate that vitamin D supplementation since childhood influenced the overall landscape of DNA methylations and the expression of many genes involved in critical neurological functions in a dose-dependent manner. Additionally, our data demonstrate how vitamin D modulated neuropeptide signaling pathways, as well as cholinergic and dopaminergic synapses in the striatum, through an orchestrated mechanism involving epigenetic and transcriptional regulations. Furthermore, we observed a synergistic effect of vitamin D on dopamine release following acute methylphenidate injection into our mouse model. In summary, this study provides mechanistic insights into how dietary vitamin D supplementation since childhood can modulate specific signal transductions among striatal cells, underscoring the importance of vitamin D supplementation for ADHD management., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

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

Background: Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation., Methods: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs., Results: The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR]: 0.99, 95% confidence interval [CI]: 0.97 to 1.01, I 2  = 49.6%). The subgroup dose-response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400-1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR: 0.92, 95% CI: 0.85 to 0.99, I 2  = 55.7%, number needed to treat [NNT]: 36), trials duration < 4 months (RR: 0.81, 95% CI: 0.67 to 0.97, I 2  = 48.8%, NNT: 16), summer-sparing seasons (RR: 0.85, 95% CI: 0.74 to 0.98, I 2  = 55.8%, NNT: 26), and winter-dominant seasons (RR: 0.79, 95% CI: 0.71 to 0.89, I 2  = 9.7%, NNT: 10)., Conclusion: Vitamin D supplementation may slightly prevent ARIs when taken daily at doses between 400 and 1200 IU/d during spring, autumn, or winter, which should be further examined in future clinical trials., (© 2024. The Author(s).)

Leg disorders have become increasingly common in broilers, leading to lower meat quality and major economic losses. This study evaluated the effects of dietary supplementation with Clostridium butyricum (C. butyricum) and 25-hydroxyvitamin D 3 (25-OH-D 3 ) on bone development by comparing growth performance, tibial parameters, Ca and P contents of tibial ash, bone development-related indicators' level, and cecal short-chain fatty acids in Cobb broilers. All birds were divided into four treatment groups, which birds fed either a basal diet (Con), basal diet + 75 mg chlortetracycline/kg (Anti), basal diet + C. butyricum at 10 9 CFU/kg (Cb), basal diet + C. butyricum at 10 9 CFU/kg and 25-OH-D 3 at 25 μg/kg (CbD), or basal diet + 25-OH-D 3 at 25 μg/kg (CD). Our results suggest that the dietary supplementation in Cb, CbD, and CD significantly increased the body weight (BW) and average daily gain (ADG), and reduced the feed-to-weight ratio (F/G) at different stages of growth (P < 0.05). Dietary supplementation in Cb, CbD, and CD prolonged (P < 0.05) the behavioral responses latency-to-lie (LTL) time, reduced (P < 0.05) the levels of osteocalcin (BGP) and peptide tyrosine (PYY), and increased (P < 0.05) serotonin (5-HT) and dopamine (DA). Treatment with Cb increased (P < 0.05) the levels of acetic acid, isobutyric acid, butyric acid, and isovaleric acid compared with those in Con group. The cecal metagenome showed that Alistipes spp. were significantly more abundant in Cb, CbD, and CD groups (P < 0.05). A total of 12 metabolic pathways were significantly affected by supplementation, including the signaling pathways of glucagon, insulin, and PI3K-AKT; primary and secondary bile acid biosynthesis; and P-type Ca 2+ transporters (P < 0.05). Hence, the CbD supplementation modulates bone metabolism by regulating the mediators of gut-brain axis, which may inform strategies to prevent leg diseases and improve meat quality in broilers., Competing Interests: DISCLOSURES The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Exercise-induced inflammation can influence iron metabolism. Conversely, the effects of vitamin D 3 , which possesses anti-inflammatory properties, on ultramarathon-induced heart damage and changes in iron metabolism have not been investigated. Thirty-five healthy long-distance semi-amateur runners were divided into two groups: one group received 150,000 IU of vitamin D 3 24 h prior to a race ( n = 16), while the other group received a placebo ( n = 19). Serum iron, hepcidin (HPC), ferritin (FER), erythroferrone (ERFE), erythropoietin (EPO), neopterin (NPT), and cardiac troponin T (cTnT) levels were assessed. A considerable effect of ultramarathon running on all examined biochemical markers was observed, with a significant rise in serum levels of ERFE, EPO, HPC, NPT, and cTnT detected immediately post-race, irrespective of the group factor. Vitamin D 3 supplementation showed a notable interaction with the UM, specifically in EPO and cTnT, with no other additional changes in the other analysed markers. In addition to the correlation between baseline FER and post-run ERFE, HPC was modified by vitamin D. The ultramarathon significantly influenced the EPO/ERFE/HPC axis; however, a single substantial dose of vitamin D 3 had an effect only on EPO, which was associated with the lower heart damage marker cTnT after the run.

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

Objective: The aim of this study was to explore the effects of vitamin D supplementation on metabolic parameters in women with polycystic ovary syndrome (PCOS)., Methods: A total of 60 PCOS women with vitamin D deficiency or insufficiency were enrolled in this randomized controlled trial. Participants were randomized to vitamin D group (2000 IU/day) or control group. The observational parameters were measured at baseline and after treatment, including body mass index (BMI), waist to hip ratio (WHR), oral glucose tolerance test (OGTT) and insulin release test, and lipid metabolism parameters., Results: The serum 25(OH)D concentrations at different time points after vitamin D supplementation were significantly higher than that in control group (P < 0.05). The BMI, WHR, insulin concentrations, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations in women of Vitamin D group after 12 weeks of treatment were significantly lower than that in women of control group (P < 0.05). The serum insulin concentrations and HOMA-IR at different time points of OGTT, serum TG, TC and LDL-C concentrations in women of vitamin D group (obesity) were significantly lower compared with control group (obesity) (P < 0.05). The BMI, WHR, TG, TC and LDL-C concentration in women of vitamin D group (IR) were significantly lower compared with control group (IR) (P < 0.05). No significant difference was observed in metabolic parameters between vitamin D group (non-obesity) and control group (non-obesity) (P > 0.05), and these differences of metabolic parameters were also not observed between vitamin D group (non-IR) and control group (non-IR) (P > 0.05)., Conclusion: Vitamin D supplementation had beneficial effects on metabolic parameters in PCOS women, especially in women with obesity or insulin resistance., (© 2024. The Author(s).)

Background: Vitamin D deficiency is associated with several obstetric complications in singleton pregnancy. The aim of this study was to assess whether vitamin D levels affect the outcomes of twin pregnancy and if targeted supplementation can improve perinatal outcomes., Methods: The serum vitamin D levels of 143 women with twin pregnancies were measured during their first trimester. Those with insufficient (10-30 ng/mL; IL group) or severely deficient (<10 ng/mL, DL group) vitamin D levels were supplemented. In the third trimester, vitamin D levels were reassessed. Perinatal outcomes of the IL and DL groups were compared with those of patients with sufficient levels (>30 ng/mL, SL group) since the beginning of pregnancy., Results: Women in the IL and DL groups had a higher incidence of hypertensive disorders of pregnancy (HDP) compared to the SL group (24.8% and 27.8% vs. 12.5%, p = 0.045): OR = 1.58 for the IL group and 1.94 for the DL group compared to the SL group. In patients whose vitamin D levels were restored after supplementation, HDP incidence was lower than in patients who remained in the IL or DL groups (23.4% vs. 27.3%) but higher than those who were always in the SL group (12.5%)., Conclusions: Insufficient or severely deficient levels of vitamin D in the first trimester are associated with an increased risk of HDP in twin pregnancy. The beneficial effect of targeted vitamin D supplementation in reducing HDP seems limited.

There is increasing evidence that vitamin D (VitD) supplementation may reduce inflammation in individuals with multiple sclerosis (MS). The aim of this study was to evaluate the effect of different doses of VitD on selected markers of inflammation in patients with relapsing-remitting MS (RRMS). Participants were divided depending on the supplemented dose of VitD into a high-dose (2000 IU/d; HD) group and a low-dose (15,960 IU/month; LD) group ( n = 23 and n = 29, respectively). The concentration of 25(OH)D and the levels of CXCL16, PTX3, ALCAM, IL-1RA, and OPG were measured initially and after six months of VitD supplementation in blood serum. A significant increase in the concentrations of CXCL16, PTX3, and OPG was observed during the study ( p = 0.02, p = 0.01, and p < 0.01, respectively). Furthermore, a higher increase in PTX3 and OPG in the LD group was observed ( p = 0.04 and p = 0.03, respectively). A significant positive correlation was observed between the 25(OH)D serum concentration and PTX3 (R = 0.28, p < 0.05) and OPG (R = 0.28, p < 0.05) only at the beginning of the study. In patients with RRMS, such doses of VitD might be too low to induce obvious beneficial effects on the pro-inflammatory and inflammatory balance.

The activation of the vitamin D receptor (VDR) in the ileum has been shown to regulate Paneth cell-specific defensins, a large family of antimicrobial peptides; hence, this may serve as a potential mechanism to maintain intestinal homeostasis. Previously, we have demonstrated that a combination of vitamin D 3 (VD) and fructooligosaccharides (FOSs) upregulates colonic Vdr in mice. Here, we aim to examine the effect of VD, alone or in combination with FOSs, on intestinal barrier integrity and the secretion of antimicrobial peptides, as well as the gut microbial community. Male and female C57BL/6J mice at 6 weeks old were randomized into three groups to receive the following dietary regimens (n = 10/sex/group) for 8 weeks: (1) standard AIN-93G control diet (CTR), (2) CTR + 5000 IU vitamin D 3 (VD), and (3) VD + 5% fructooligosaccharides (VF). VD and VF differentially regulated the mRNA expressions of tight junction proteins in the colon and ileum. VF suppressed the upregulation of colonic ZO-1 and occludin , which was induced by VD supplementation alone. In the ileum, occludin but not ZO-1 was upregulated 20-fold in the VF-treated mice. While VD did not alter the mRNA expressions of Vdr and defensins in the ileum, these targets were downregulated by VF. Microbial analysis further reveals a shift of microbial beta diversity and a reduction in Romboutsia ilealis , a pathobiont, in VF-treated mice. Though the implications of these phenotypical and microbial changes remain to be determined, the administration of FOSs in the presence of VD may serve as an effective dietary intervention for maintaining intestinal homeostasis.

Objective: This study aimed to investigate the association of maternal first-trimester vitamin D levels and vitamin D supplementation during pregnancy with infant atopic dermatitis (AD) and to determine the effect of variables such as mode of conception on the association., Methods: This study was based on the Shanghai sub-cohort of the International Birth Cohort of China. A total of 4051 woman-infant pairs with singleton pregnancies were recruited. Vitamin D deficiency and insufficiency were defined as serum 25-hydroxyvitamin D concentrations of 25 and 50 nmol/L, respectively. AD in infants was assessed during the first six months using a standardized questionnaire based on the British Working Party criteria. Modified Poisson regression estimated the association between maternal vitamin D status and infant AD., Results: The risk of AD in infants was higher in women with deficient 25-hydroxyvitamin D levels in the first trimester (RR: 1.77, 95% CI: 1.41-2.23). This increased risk was seen in naturally conceived pregnancies, but not in those conceived using assisted reproductive technology (ART). The incidence of AD decreased in infants of mothers who took multi-vitamin (RR: 0.79, 95% CI: 0.67-1.98) and vitamin D supplements (RR: 0.51, 95% CI: 0.37-0.71) compared to those whose mothers did not take any supplements. Maternal vitamin D deficiency had varying effects on AD risk based on passive smoking exposure and breastfeeding patterns., Conclusions: Our findings highlight the importance of monitoring and supplementing vitamin D during pregnancy, especially in specific maternal populations, to reduce the risk of AD in offspring.

Vitamin D (vitD) deficiency (25-hydroxy-vitamin D < 50 nmol/L) is common in pregnancy and associated with an increased risk of adverse pregnancy outcomes. High-dose vitD supplementation is suggested to improve pregnancy health, but there is limited knowledge about the effects on placental vitD transport and metabolism and the vitD status of newborns. Comparing the current standard maternal supplementation, 10 µg/day to a 90 µg vitD supplement, we investigated placental gene expression, maternal vitD transport and neonatal vitD status. Biological material was obtained from pregnant women randomized to 10 µg or 90 µg vitD supplements from week 11-16 onwards. Possible associations between maternal exposure, neonatal vitD status and placental expression of the vitD receptor ( VDR ), the transporters (Cubilin, CUBN and Megalin, LRP2 ) and the vitD-activating and -degrading enzymes ( CYP24A1 , CYP27B1 ) were investigated. Maternal vitD-binding protein (VDBP) was determined before and after supplementation. Overall, 51% of neonates in the 10 µg vitD group were vitD-deficient in contrast to 11% in the 90 µg group. High-dose vitD supplementation did not significantly affect VDBP or placental gene expression. However, the descriptive analyses indicate that maternal obesity may lead to the differential expression of CUBN , CYP24A1 and CYP27B1 and a changed VDBP response. High-dose vitD improves neonatal vitD status without affecting placental vitD regulation.

Objetives: To evaluate the impact of cholecalciferol (D₃) supplementation using clinical and paraclinical variables in patients with RA and vitamin D insufficiency and deficiency., Methods: A randomized, double-blind, placebo-controlled study included patients from 5 to 40 years with a diagnosis of RA and vitamin D insufficiency and deficiency. They were supplemented for 8 weeks with 4000 or 5000 IU, depending on age. Total nasal symptoms score (TNSS) was measured monthly and 25(OH)D₃ levels at baseline and at the end of the study., Results: A total of 31 patients were included, with a mean age of 18.19 years. In the active group, there was a significant improvement in symptomatology with respect to the TNSS score and an increase in serum vitamin D levels (p < 0.01). There were no adverse reactions with cholecalciferol or placebo., Conclusions: Supplementing patients with vitamin D₃, at the evaluated dose, together with conventional treatent for allergic rhinitis results in symptoms and quality of life improvement in patients with this disease., Competing Interests: Los autores declaran no tener conflicto de intereses.

Background: Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear., Methods: Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability., Discussion: Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results., Trial Registration: ClinicalTrials.gov NCT05459298. Registered on July 14, 2022., (© 2024. The Author(s).)

We previously reported that a combined myo -inositol, probiotics, and enriched micronutrient supplement (intervention) taken preconception and in pregnancy reduced postpartum blood loss (PBL) and major postpartum hemorrhage compared with a standard micronutrient supplement (control), as secondary outcomes of the NiPPeR trial. This study aimed to identify the intervention components that may contribute to this effect. Associations of plasma concentrations of myo -inositol and vitamins B2, B6, B12, and D at preconception (before and after supplementation), early (~7-weeks), and late pregnancy (~28-weeks) with PBL were assessed by multiple linear regression, adjusting for site, ethnicity, preconception BMI, parity, and previous cesarean section. Amongst 583 women, a higher concentration of myo -inositol in early pregnancy was associated with a PBL reduction [β adj -1.26 (95%CI -2.23, -0.29) mL per µmol/L myo -inositol increase, p = 0.011]. Applying this co-efficient to the increase in mean 7-week- myo -inositol concentration of 23.4 µmol/L with the intervention equated to a PBL reduction of 29.5 mL (~8.4% of mean PBL of 350 mL among controls), accounting for 84.3% of the previously reported intervention effect of 35 mL. None of the examined vitamins were associated with PBL. Therefore, myo -inositol may be a key intervention component mediating the PBL reduction. Further work is required to determine the mechanisms involved., Competing Interests: S.-Y.C., W.S.C., and K.M.G. are part of an academic consortium that report grants from Soci&eacute;t&eacute; Des Produits Nestl&eacute; S.A. during the conduct of the study and are co-inventors on patent filings by Nestl&eacute; S.A. relating to the NiPPeR intervention or its components. S.-Y.C. has received reimbursement and honoraria into her research funds from Nestl&eacute; Nutrition Institute and EGOI (Experts Group on Inositols) for speaking at conferences. K.M.G. has received reimbursement for speaking at conferences sponsored by companies selling nutritional products. L.L., J.M.R.-N., J.-P.G., and I.S.-Z. are employees of Soci&eacute;t&eacute; Des Produits Nestl&eacute; S.A. All other authors declare no competing interests.

Vitamin D receptors are expressed in many organs and tissues, which suggests that vitamin D (VD) affects physiological functions beyond its role in maintaining bone health. Deficiency or inadequacy of 25(OH)VD is widespread globally. Population studies demonstrate that a positive association exists between a high incidence of VD deficiency and a high incidence of chronic diseases, including dementia, diabetes, and heart disease. However, many subjects have difficulty achieving the required circulating levels of 25(OH)VD even after high-dose VD supplementation, and randomized controlled clinical trials have reported limited therapeutic success post-VD supplementation. Thus, there is a discordance between the benefits of VD supplementation and the prevention of chronic diseases in those with VD deficiency. Why this dissociation exists is currently under debate and is of significant public interest. This review discusses the downregulation of VD-metabolizing genes needed to convert consumed VD into 25(OH)VD to enable its metabolic action exhibited by subjects with metabolic syndrome, obesity, and other chronic diseases. Research findings indicate a positive correlation between the levels of 25(OH)VD and glutathione (GSH) in both healthy and diabetic individuals. Cell culture and animal experiments reveal a novel mechanism through which the status of GSH can positively impact the expression of VD metabolism genes. This review highlights that for better success, VD deficiency needs to be corrected at multiple levels: (i) VD supplements and/or VD-rich foods need to be consumed to provide adequate VD, and (ii) the body needs to be able to upregulate VD-metabolizing genes to convert VD into 25(OH)VD and then to 1,25(OH)2VD to enhance its metabolic action. This review outlines the association between 25(OH)VD deficiency/inadequacy and decreased GSH levels, highlighting the positive impact of combined VD+LC supplementation on upregulating GSH, VD-metabolizing genes, and VDR. These effects have the potential to enhance 25(OH)VD levels and its therapeutic efficacy.

Background: The current study sought to investigate the correlation between vitamin D supplementation in pregnant women with vitamin D deficiency in early pregnancy and the incidence of prenatal depression prior to delivery., Methods: This is a retrospective, single-center study that was conducted at a tertiary hospital in Chengdu, China. We conducted an analysis on pregnant women who were initially diagnosed with vitamin D deficiency at 12-14 weeks of gestation. After starting vitamin D supplementation at a dose of 800 IU daily from 14 weeks onwards, we measured both their vitamin D concentration and depression scores again during median gestational week 39 prior to delivery., Results: The study cohort comprised 1365 women who had been diagnosed with vitamin D deficiency at 12-14 weeks of gestation between November 1st, 2021 to November 1st, 2022. 537 pairs were matched based on a propensity score to control for other confounding factors. After propensity score matching, the baseline vitamin D levels were made consistent between the groups (P = 0.512). The incidence of depression in patients in vitamin D deficiency group following vitamin D supplementation was significantly higher than insufficiency group and reached statistical significance (P < 0.001). Additionally, we observed that serum 25-(OH) D concentration achieving insufficiency status after supplementation was 59.12%., Conclusion: Our study indicates that daily supplementation of 800IU of vitamin D can improve the depressive symptoms of individuals who are vitamin D deficiency during early pregnancy but achieve vitamin D insufficiency after supplementation during prenatal period., (© 2024. The Author(s).)

Background: Recently, Serum vitamin D (Vit. D) levels evaluation and the use of Vit. D supplements have increased substantially. There is no specific guideline for the duration of Vit. D supplementation, so yet Vit. D supplementation duration has remained a critical and controversial issue. This study aimed to determine the vit. D supplementation duration to reach an adequate or optimal Vit. D status and its effect on lipid profile., Methods: In this longitudinal study, 345 women with different status of Vit. D levels were enrolled and followed up for one year. Eligible participants received 50,000 IU Vit. D 3 (cholecalciferol) once a month for 12 consecutive months. The serum Vit. D levels and lipid profiles were measured at baseline, 3rd, 6th, and 12th months after the intervention. Participants were categorized based on Vit. D level at baseline into deficiency (< 20 ng/mL), inadequate (20-30 ng/mL), and adequate (> 30 ng/mL) groups, and the data were compared at different times between the three groups., Results: Three deficiency (n = 73), inadequate (n = 138) and adequate (n = 134) groups of participants were followed. In all participants the average amount of Vit. D level changes were 8 ng/mL after one year of supplementation. The mean changes of serum Vit. D level in 6th and 12th months vs. 3th month was as below: In deficiency group: 4.08 ± 0.85 and 10.01 ± 1.02 ng/mL; (p < 0.001), in inadequate group: 3.07 ± 0.59 and 7.26 ± 0.78 ng/mL; (p = 0.001) and in adequate group: 2.02 ± 0.88 and 6.44 ± 1.005 ng/ml; (p = 0.001). Lipid profiles were improved in three groups. So, the mean changes of lipid profiles at the end of the study comparing with the baseline were: -5.86 ± 2.09, -7.22 ± 1.43 and - 6.17 ± 1.72 (mg/dl) for LDL (p < 0.05); -12.24 ± 3.08, -13.64 ± 3.21 and - 17.81 ± 2.94 (mg/dl) for cholesterol (p < 0.05) in deficiency, inadequate and adequate groups, respectively. For triglyceride, the mean changes were - 13.24 ± 5.78 and - 15.85 ± 7.49 (mg/dl) in deficiency and adequate groups, respectively (p < 0.05). Although the triglyceride decreased in the inadequate group at the end of the study but this difference was not significant (p = 0.67)., Conclusion: Taking of 50,000 IU Vit. D 3 monthly for 12 months resulted in reaching its level to adequate level in both deficiency and insufficient groups; however, in the adequate group its level did not reach above than 50 ng/mL. Therefore, 50,000 IU Vit. D 3 supplementation monthly for one year can have beneficial effects on lipid profiles and there is no risk of toxicity in healthy women., (© 2024. The Author(s).)

Diets omitting whole food groups pose a risk for micronutrient insufficiencies, but there are no data as to whether those are suitably attenuated with dietary supplements (DS). Micronutrient intakes with food and DSs were analyzed in 130 healthy adults: 32 vegans, 37 vegetarians, 24 following low-carbohydrate high-fat diet (LCHF), and 37 omnivores. A total of 63% used DS (84% of vegans, 75% of LCHF, 54% of vegetarians, and 46% of omnivores); however, a DS did not always tackle dietary insufficiencies. Vitamin B 12 was often supplemented in vegans in doses substantially higher than recommended, but it was supplemented less often in vegetarians, despite the low prevalence of sufficient intake. Only 43% of participants supplemented vitamin D in wintertime, 23% of them with an insufficient dose. Supplementation of potassium, calcium, and iodine was rare, despite low intake adequacy with food alone in all groups. Some micronutrients were supplemented unnecessarily, such as vitamin K, riboflavin, biotin, and iron. Multimicronutrient DSs were used often; they increased intake adequacy of group B vitamins but failed to sufficiently supplement vitamin D, potassium, calcium, and iodine. Although DS use increased micronutrient intake sufficiency when used properly, the knowledge on micronutrient inadequacy in all dietary patterns should be increased and the public should be educated on the proper use of DSs. Multimicronutrient DSs should be reformulated to tackle the insufficiencies., Competing Interests: The authors declare no conflict of interest.

Recent studies hypothesized that vitamin D supplementation and subsequent higher 25(OH)D serum levels could protect against respiratory infections in children. This cross-sectional study, conducted from May 2022 to December 2023 in Timisoara, Romania, aimed to evaluate the potential influence of vitamin D supplementation on the incidence of respiratory infections among preschool-age children. This study examined 215 children over 18 months who were split into a group of patients with recurrent respiratory infections ( n = 141) and another group of patients with only one respiratory tract infection in the past 12 months ( n = 74). Patients were evaluated based on their serum vitamin D levels 25(OH)D, demographic characteristics, and health outcomes. The study identified that preschool-age children with recurrent infections had significantly lower mean vitamin D concentrations (24.5 ng/mL) compared to the control group (29.7 ng/mL, p < 0.001). Additionally, a higher proportion of vitamin D deficiency was observed among children with recurrent infections in the past 12 months. Notably, vitamin D supplementation above 600 IU/week significantly reduced the likelihood of respiratory infections, evidenced by an odds ratio of 0.523 ( p < 0.001), indicating that preschool-age children receiving a dose of vitamin D higher than 600 IU/week were about half as likely to experience respiratory infections compared to those who did not. Furthermore, no significant associations were found between sun exposure, daily sunscreen use, and the incidence of respiratory infections. Conclusively, this study underscores the potential role of vitamin D in helping the immune system against respiratory infections in preschool-age children. The observed protective effect of vitamin D supplementation suggests a potential public health strategy to mitigate the incidence of respiratory infections in preschool children on top of the already known benefits.

The aim of this pilot study was to evaluate and compare bioavailability and safety of two Vitamin D 3 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 D 3 1000 IU (STD1000), (2) micellar Vitamin D 3 1000 IU (LMD1000), (3) standard Vitamin D 3 2500 IU (STD2500), and (4) micellar Vitamin D 3 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 D 3 absorption of LMD when measured incrementally. During follow-up, participants in the LMD1000 treatment group showed approx. 7 times higher Vitamin D 3 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) 2 D 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 D 3 (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.

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.

Objectives: Sleeve gastrectomy (SG) is one of the most commonly performed weight loss (WL) bariatric procedures. The main goal of WL is reducing total body weight (TBW) and fat mass (FM). However, TBW loss is systematically accompanied by a decline in fat-free mass (FFM), predominantly in the first post-surgical month, despite protein supplementation. Branched-chain amino acids (BCAAs) and vitamin D seem to attenuate loss of FFM and, thus, reduce the decline in muscle strength (MS). However, data on the role of an integrated supplementation with whey protein plus BCAAs plus vitamin D (P+BCAAs+Vit.D) vs. protein alone on total weight loss (TWL), fat mass (FM), fat-free mass (FFM), and (MS) in the first month after SG are lacking. Therefore, the present study aims to evaluate the impact of P+BCAAs+Vit.D vs. protein alone supplementation on TWL, FM, FFM, and MS in the first month after SG., Materials and Methods: Before SG and at 1 month afterward, we prospectively measured and compared TBW, FM, FFM, and MS in 57 patients who received either a supplementation with P+BCAAs+Vit.D (n = 31) or protein alone (n = 26). The impact of P+BCAAs+Vit.D and protein alone supplementation on clinical status was also evaluated., Results: Despite non-significant variation in TBW, FM decreased more significantly (18.5% vs. 13.2%, p = 0.023) with the P+BCAA+Vit.D supplementation compared to protein alone. Furthermore, the P+BCAA+Vit.D group showed a significantly lower decrease in FFM (4.1% vs. 11.4%, p < 0.001) and MS (3.8% vs. 18.5%, p < 0.001) compared to the protein alone group. No significant alterations in clinical status were seen in either group., Conclusion: P+BCAA+Vit.D supplementation is more effective than protein alone in determining FM loss and is associated with a lower decrease in FFM and MS, without interfering with clinical status in patients 1 month after SG.

Adequate vitamin D (VD) intake during pregnancy is needed for fetal development and maternal health maintenance. However, while there is no doubt regarding its importance, there is not a unified recommendation regarding adequate intake. The main aim of our study was to measure the VD serum level of studied women, together with its potential influencing factors: demographic (i.e., age, level of education, relationship status and type of residence), conception and pregnancy related factors. Results are based on secondary data analyses of a retrospective case-control study of 100 preterm and 200 term pregnancies, where case and control groups were analyzed together. Data collection was based on a self-administered questionnaire, health documentation, and maternal serum VD laboratory tests. VD intake was evaluated by diet and dietary supplement consumption. According to our results, 68.1% of women took some kind of prenatal vitamin, and only 25.9% of them knew about its VD content. Only 12.1% of included women reached the optimal, 75 nmol/L serum VD level. Higher maternal serum levels were associated with early pregnancy care visits ( p = 0.001), assisted reproductive therapy ( p = 0.028) and advice from gynecologists ( p = 0.049). A correlation was found between VD intake and serum levels ( p < 0.001). Despite the compulsory pregnancy counselling in Hungary, health consciousness, VD intake and serum levels remain below the recommendations. The role of healthcare professionals is crucial during pregnancy regarding micronutrients intake and the appropriate supplementation dose.

Certain micronutrients exhibit immunomodulatory effects. However, no intervention has yet investigated the effect of individualized supplementation on the severity of upper respiratory tract infections (URIs). Therefore, we investigated whether a personalized supplementation moderates the incidence and severity of URI. Selenium, zinc, and vitamin D were measured in dried blood spots from 59 healthy participants. Accordingly, a personalized supplement was provided with or without the respective micronutrients. We used WURSS-21 questionnaires to assess the disease status. The blood values converged during the intervention and micronutrients no longer differed between treated and untreated volunteers at the end of the intervention period. The incidence and severity of the illness did not significantly differ between the groups. However, when analyzing the WURSS-21 scores by the intention to treat, the initially randomized treatment arm revealed a significantly higher score than the placebo arm. Upon acute administration, individualized combinations of selenium, zinc and vitamin D do not reduce the number, or contribute to a milder course of URIs. Therefore, supplementation in acute infectious situations seems questionable. Further studies must address the habitual diet in more detail, to better understand the impact of individual micronutrient status on the prevention of URI.

Background: The association between vitamin D supplementation and the risk of falls in older adults has been controversial. This systematic review and network meta-analysis aims to assess the efficacy of vitamin D, calcium, and combined supplementation in the prevention of falls., Methods: Randomized controlled trials (RCTs) on the efficacy of vitamin D in fall prevention were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science from inception to May 9, 2023. The network meta-analysis was performed using a random effects model in R4.1.3 and Stata15.0. Heterogeneity was evaluated by the I 2 statistic, and publication bias was assessed using funnel plots, Begg's test, and Egger's tests. Data were pooled and expressed as relative risk (RR) and 95% confidence interval (CI)., Results: A total of 35 RCTs involving 58,937 participants were included in this study, among which 11 RCTs (31.4%) applied calcium combined with vitamin D. There was low heterogeneity (I 2  = 11%) among the included studies. Vitamin D supplementation at 800-1000 International Unit (IU)/d resulted in a lower risk of falls than placebo or no treatment (RR = 0.85, 95%CI: 0.74-0.95). In addition, 800-1000 IU/d of vitamin D with or without calcium were more effective in preventing falls than calcium alone. High-dose vitamin D (> 1000 IU/day) increased the risk of falls compared with 800-1000 IU/d of vitamin D. According to the subgroup analysis, daily administration of 800-1000 IU/d vitamin D was associated with a 22% reduction in the risk of falls (RR = 0.78, 95%CI:0.64-0.92), whereas intermittent vitamin D administration had no preventive effect. Furthermore, 800-1000 IU/d of vitamin D also significantly decreased the risk of falls in old adults with ≤ 50 nmol/L 25-hydroxyvitamin D [25(OH)D] (RR = 0.69, 95%CI:0.52-0.86) but not in individuals with > 50 nmol/L 25(OH)D., Conclusion: Vitamin D supplementation at 800-1000 IU/d is associated with a lower risk of falls among older adults. 800-1000IU/d of vitamin D has a benefit on prevention of falls in population received daily dose regimens and in population with vitamin D deficiency., (© 2024. The Author(s).)

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; I 2 = 20·4 %, P = 0·285) and observational studies (ES = 1·99; 95 % CI: 1·37, 2·62, P < 0·001; I = 0·944). Also, vitamin D deficiency increased the risk of infection and disease severity among patients.2 = 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.

In the last few decades, vitamin D has undeniably been one of the most studied nutrients. Despite our ability to produce vitamin D through sunlight exposure, its presence in several natural food sources and fortified foods, and its widespread availability as a dietary supplement, vitamin D deficiency is a serious public health problem, affecting nearly 50% of the global population. Low serum levels of vitamin D are being associated with increased susceptibility to numerous health conditions, including respiratory infections, mental health, autoimmune diseases, and different cancer types. Although the association between vitamin D status and health is well-established, the exact beneficial effects of vitamin D are still inconclusive and indefinite, especially when considering the prevention and treatment of different health conditions and the determination of an appropriate dosage to exert those beneficial effects in various population groups. Therefore, further research is needed. With constant improvements in our understanding of individual variations in vitamin D metabolism and requirements, in the future, precision nutrition and personalized supplementation plans could prove beneficial., Competing Interests: Author Ena Bagari&#263; is employed by the company Almagea Ltd., which did not have any role in the design, investigation, interpretation, or the writing of this manuscript, nor did it fund the present research in any way. The remaining authors declare no conflicts of interest.

Menopause is the transition period in female life cycle. Resultant hormonal changes lead to adverse health effects. Women may seek treatment due to significant impairment in quality of life. Vitamin D deficiency is a globally prevalent problem. Vitamin D deficiency in menopausal women may aggravate the adverse health risks associated with menopause. In this article, the authors discuss endocrinology and clinical features of menopause, Vitamin D and its links with menopause, and the potential role of Vitamin D supplementation to combat detrimental multi-organ system effects of menopause.

Background: Iron and Vitamin D3 deficiency is one of the major global health problems in teenagers and adolescent population. This study was aimed to monitor the utilization and predictive factors of Iron and Vitamin D Supplementations Program (IVDSP) in high schools' girls., Methods: In a cross sectional study, the pattern of Iron and D3 consumption based on IVDSP on 400 high schools' girl in Qom, Iran assesses. Data collection was used by a reliable and standard researcher based questionnaire and daily, weekly, monthly and seasonally consumption of complementary minerals in schools were gathered. Data analysis conducted using SPSS version 20 (SPSS Inc., Chicago, IL, USA) by chi square, independent t-test and multivariate logistic regression., Results: The mean age of subjects was 15.14 ± 1.52 years and ranged from 12 to 18 years old. The total weekly prevalence of D3 and Iron consumption in high schools' girls was calculated 36.73% and the weekly prevalence of Iron and monthly prevalence of Vitamin D3 consumption was 33.75% and 40.5%, respectively. The most common causes of non-consumption were bad taste 49.31%, Iranian made drug 20.27%, drug sensitivity 19.82% and drug interaction 10.60%, respectively., Conclusions: The inadequate and incomplete rate of IVDSP in Qom was high and more than 60% of distributed supplementations have been wasted. Results showed that students who were participated in educational orientation classes were more successful and eager in Iron and Vitamin D3 consumption. Therefore, more educational explanatory interventions for both students and her parents recommended to increase the efficiency of the program., Competing Interests: None declared., (©2024 Pacini Editore SRL, Pisa, Italy.)

Over the past few decades, vitamin D has been found to play a crucial role in bone homeostasis, muscle function, oncogenesis, immune response and metabolism. In the context of the COVID-19 pandemic, numerous researchers have tried to determine the role vitamin D might play in the immune response to the virus. The aim of this systematic review and meta-analysis is to demonstrate that preventive vitamin D supplementation can play a protective role in the incidence of COVID-19, mortality and admission to intensive care units (ICUs). A comprehensive search on the PubMed/MEDLINE, Scopus, Cochrane and Google Scholar databases was performed on 15 May 2023, and two of the authors independently screened the literature. As effect measures, we calculated the Odds Ratios with their corresponding 95% confidence intervals (ICs). The assessment of potential bias and the evaluation of study quality will be conducted independently by two researchers. Sixteen publications were selected for inclusion in the meta-analysis. Our findings indicate that vitamin D supplementation has a protective effect against the incidence of COVID-19 in RCT studies (OR 0.403, 95% IC 0.218, 0.747), in the incidence of COVID-19 in analytical studies (OR = 0.592, 95% IC 0.476-0.736) and in ICU admission (OR 0.317, 95% IC 0.147-0.680). Subsequent analyses were conducted by type of subject treated (patient/healthcare workers) and type of supplementation (vitamin D vs. placebo/no treatment or high dose vs. low dose). Our meta-analysis suggests a definitive and significant association between the protective role of vitamin D and COVID-19 incidence and ICU admission.

We aimed to study supplement use in relation to dietary intake among pregnant women in Sweden, and adherence to the Nordic Nutrition Recommendations among supplement and non-supplement users. Pregnant women were recruited at registration to antenatal care in 2013–2014. In third trimester, supplement use was collected using a questionnaire, and dietary intake was collected using a FFQ. The majority (64 %) of the 1044 women reported use of one or more supplements. Among all, 0–23 % reported dietary intakes above recommended intake (RI) of vitamin D, folate, Fe and Se. Median dietary intakes of thiamine (1·4 v . 1·3 mg P = 0·013), phosphorus (1482 v . 1440 mg P = 0·007), folate (327 v . 316 µg P = 0·02), Fe (12 v . 11·5 mg P = 0·009), Mg (361 v . 346 mg P < 0·001) and Zn (10·7 v . 10·4 mg P = 0·01) were higher among supplement users compared with non-users. Larger proportions of supplement users than non-users adhered to RI of dietary intakes of thiamine (42 % v . 35 % P = 0·04) and Mg (75 % v . 69 % P = 0·05). Among non-users, a minority had dietary intakes above RI for vitamin D (6 %), folate (10 %) and Fe (21 %). The majority (75–100 %) of supplement users had total intakes above RI for most nutrients. In conclusion, supplement use contributed substantially to reaching RI for vitamin D, folate and Fe. Supplement users had a higher dietary intake of several nutrients than non-users. This highlights that non-supplement users are at risk of inadequate nutrient intakes during pregnancy, suggesting a need for heightened awareness of nutritional adequacy for pregnant women.

Background: According to the findings from observational studies and clinical trials assessing the effect of vitamin D supplements on cardiovascular diseases (CVDs), there are still contradictory results. This systematic review aimed to assess the effect of vitamin D supplements on CVDs considering cohort studies and clinical trials. Study Design: A systematic review., Methods: MEDLINE/PubMed, Science Direct, Embase, and Cochrane Library databases were reviewed by two reviewers independently until 2022. The study effect is risk ratio (RR) and 95% confidence interval (CI) according to Mantel Haenszel's random-effects model. Then, Stata version 14 was used for statistical analysis., Results: In clinical trial studies, the incidence of CVDs among the vitamin D-consuming group was not significantly different from that in the placebo group (RR: 0.99, 95% CI: 0.95-1.03; P =0.77; I 2 =0%). CVD mortality was also not significantly different between the two groups (RR: 0.97, 95% CI: 0.90-1.05; P =0.72; I 2 =0%). In cohort studies, circulating 25 (OH) D increased the risk of CVD incidence by 31% (RR: 1.31, 95% CI: 1.19-1.45) and CVD mortality by 37% (RR: 1.37, 95% CI: 1.17-1.61)., Conclusion: According to current evidence from clinical trials, vitamin D supplementation should not be recommended for CVD prevention. However, there is a direct association between vitamin D deficiency and the incidence of CVDs as well as its mortality. According to the results of clinical trial studies carrying higher levels of scientific evidence, it can be concluded that vitamin D supplementation does not exert a significant effect on the incidence, mortality, and reduction of CVDs., (© 2023 The Author(s); Published by Hamadan University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Vitamin D insufficiency has been linked to multiple conditions including bone disease, respiratory disease, cardiovascular disease, diabetes, and cancer. Observational studies indicate lower healthcare costs and healthcare utilization with sufficient vitamin D levels. The secondary aims of our previously published pragmatic clinical trial of vitamin D3 supplementation were comparisons of healthcare costs and healthcare utilization. Comparisons were made between the vitamin D3 at 5000 IU supplementation group and a non-supplemented control group. Costs of care between the groups differed but were not statistically significant. Vitamin D3 supplementation reduced healthcare utilization in four major categories: hospitalizations for any reason (rate difference: -0.19 per 1000 person-days, 95%-CI: -0.21 to -0.17 per 1000 person-days, p < 0.0001); ICU admissions for any reason (rate difference: -0.06 per 1000 person-days, 95%-CI: -0.08 to -0.04 per 1000 person-days, p < 0.0001); emergency room visits for any reason (rate difference: -0.26 per 1000 person-days, 95%-CI: -0.46 to -0.05 per 1000 person-days, p = 0.0131; and hospitalizations due to COVID-19 (rate difference: -8.47 × 10 -3 per 1000 person-days, 95%-CI: -0.02 to -1.05 × 10 -3 per 1000 person-days, p = 0.0253). Appropriately powered studies of longer duration are recommended for replication of these utilization findings and analysis of cost differences.

Background: Since the connection between muscle atrophy and vitamin D and estradiol status ambiguous, this study was thus conducted to determine whether low skeletal muscle mass (SMM) in middle-aged and elderly women was affected by estradiol and vitamin D levels together., Methods: Baseline data from a sub-cohort of the China Northwest Natural Population Cohort: Ningxia Project (CNC-NX) were analyzed. Serum 25-hydroxyvitamin D (25(OH) D) and estradiol were measured by chemiluminescence immunoassay analyzer. Bivariate logistic regression and multiplicative interaction analyses were used to assess the impact of estradiol level and vitamin D status on low SMM, as well as the combined impact of estradiol and low vitamin D status on low SMM., Results: A total of 287 (9.49%) participants had low SMM, which had lower levels of estradiol and vitamin D concentration than normal SMM group. While, after adjusting the confounding variables, these correlations were maintained in estradiol Q1, Q2, Q3 and vitamin D Q1. Furthermore, the significant combined effect of the highest quartile of estradiol concentrations and non-vitamin D deficiency, and interactions between vitamin D Q1 and estradiol Q2, vitamin D Q1 and estradiol Q3, vitamin D Q2 and estradiol Q1, vitamin D Q3 and estradiol Q3 on low SMM were stably reflected (P for interaction < 0.05)., Conclusions: Estradiol and vitamin D were interrelated with low SMM in middle-aged and elderly women. Combination of estradiol and vitamin D supplements should be encouraged for middle-aged and elderly women who are at risk of muscle atrophy or experiencing muscle atrophy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

To obtain reliable data that allow health authorities to re-evaluate recommendations for oral vitamin D uptake, we conducted a meta-analysis to investigate the impact of supplementation on serum 25-hydroxyvitamin D (25(OH)D) levels in healthy adults in Europe. Of the publications identified (n = 4005) in our literature search (PUBMED, through 2 January 2022), 49 primary studies (7320 subjects, 73 study arms) were eligible for inclusion in our meta-analysis. The risk of bias was assessed using the Cochrane RoB tool based on seven categories, according to which each study is rated using three grades, and overall was rated as rather low. The median duration of intervention was 136.78 days (range, 1088 days); the mean weighted baseline 25(OH)D concentration and mean age were 33.01 vs. 33.84 nmol/L and 46.8 vs. 44.8 years in the vitamin D and placebo groups, respectively. Using random-effects models, 25(OH)D levels were increased by 36.28 nmol/L (95% CI 31.97-40.59) in the vitamin D group compared to the placebo, with a relative serum increment of 1.77 nmol/L per 2.5 μg of vitamin D daily. Notably, the relative serum 25(OH)D increment was affected by various factors, including the dosage and baseline serum 25(OH)D concentration, decreasing with increasing vitamin D doses and with increasing baseline serum levels. We estimate that supplementation in all healthy adults in Europe with appr. 25 μg of vitamin D (1000 IU) daily would raise serum 25(OH)D levels in 95% of the population to ≥50 nmol/L. Our work provides health authorities with reliable data that can help to re-evaluate recommendations for oral vitamin D supplementation.

Background: Low 25-hydroxyvitamin D (25[OH]D) concentrations (<30 ng/mL [<50 nmol/L]) have been associated with muscle weakness and impaired physical performance in observational studies. However, the effect of vitamin D supplementation on changes in muscle strength and physical performance in randomized controlled trials has been mixed., Objectives: To determine the effect of daily vitamin D supplementation on leg power, strength, and physical performance in low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL., Methods: In this double-blind, randomized controlled trial, 136 low-functioning [Short Physical Performance Battery (SPPB) scores ≤10] adults aged 65-89 y with 25(OH)D concentrations of 18 to <30 ng/mL were randomly assigned to 2000 IU/d vitamin D 3 or placebo for 12 mo. Lower-extremity leg power (primary outcome), leg and grip strength, SPPB, timed up and go (TUG), postural sway, and gait velocity and spatiotemporal parameters (secondary outcomes) were assessed at baseline, 4 and 12 mo. A subset (n = 37) also underwent a muscle biopsy at baseline and 4 mo and muscle fiber composition and contractile properties were assessed., Results: Participants' mean ± SD age and SPPB scores at baseline were 73.4 ± 6.3 y and 7.8 ± 1.8, respectively. Mean ± SD 25(OH)D concentrations at baseline and 12 mo were 19.4 ± 4.2 ng/mL and 28.6 ± 6.7 ng/mL in the vitamin D group and 19.9 ± 4.9 ng/mL and 20.2 ± 5.0 ng/mL in the placebo group for a mean ± SE difference of 9.1 ± 1.1 ng/mL (P < 0.0001). However, there were no differences in change in leg power, leg or grip strength, SPPB score, TUG, postural sway, or gait velocity and spatiotemporal parameters by intervention group over 12 mo or muscle fiber composition and contractile properties over 4 mo., Conclusions: In low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL, randomization to 2000 IU/d vitamin D 3 did not result in improvements in leg power, strength, or physical performance or muscle fiber composition and contractile properties. This trial was registered at clinicaltrials.gov as NCT02015611., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Nowadays, the most important aspect related to the use of dietary supplements seems to be their quality. There are many reports indicating their insufficient quality primarily related to a much lower content of ingredients or even their absence. Currently, there is an increasing interest in supplementing the diet with various kinds of supplements, including those containing combinations of vitamins and minerals, among which preparations with vitamin D are very popular. This is probably due to the reduced production of this vitamin, depending on the amount of time spent in the sun and the use of UV-filters. Very often, preparations with cholecalciferol also contain vitamin K 2 , which is associated with their synergistic effect. Therefore, the question arises about the effectiveness of supplementation, which may be correlated with the quality of commonly available dietary supplements. In the presented work, it was undertaken to develop optimal conditions for the qualitative and quantitative determination of vitamins D 2 , D 3 and K 2 in dietary supplements available in various forms, using thin-layer chromatography with densitometric detection. As a result, the methodology for analyzing the content of three vitamins from various matrices was developed, optimized and validated in accordance with ICH requirements. The obtained results allow us to conclude that it is reliable and meets the requirements for analytical procedures used in the analysis of medicinal products. Based on the results obtained for examined dietary supplements, it can be stated that the amount of vitamin D 3 in analyzed products is basically similar to that declared by the manufacturer, in contrast to vitamin K 2 , the content of which is diverse. The developed methodology seems to be a good, low-cost and quick way to control the quality of dietary supplements so that they can supplement the human diet and be a wholesome product.

The objective of the present study was to evaluate the efficacy of oral administration of vitamin D supplementation in reducing BMI and lipid profile in adolescents and young adults from a cohort in Bucaramanga, Colombia. One hundred and one young adults were randomly assigned to one of two doses of vitamin D [1000 international units (IU) or 200 IU] administered daily for 15 weeks. The primary outcomes were serum 25(OH)D levels, BMI and lipid profile. The secondary outcomes were waist-hip ratio, skinfolds and fasting blood glucose. We found a mean ± sd plasma concentration of 25-hydroxyvitamin D [25(OH)D] was 25⋅0 ± 7⋅0 ng/ml at baseline, and after 15 weeks, it increased to 31⋅0 ± 10⋅0 ng/ml in the participants who received a daily dose of 1000 IU, ( P < 0⋅0001). For the participants in the control group (200 IU), it went from 26⋅0 ± 8⋅0 ng/ml to 29⋅0 ± 8⋅0 ng/ml ( P = 0⋅002). There were no differences between groups in body mass index. There was a statistically significant decrease in LDL-cholesterol between the intervention group v. the control group (mean difference -11⋅50 mg/dl (95 % CI -21⋅86 to -1⋅15; P = 0⋅030). The conclusions of the present study were two different doses of vitamin D supplementation (200 IU v . 1000 IU) produced changes in serum 25(OH)D levels over 15 weeks of administration in healthy young adults. No significant changes were found in the body mass index when the effect of the treatments was compared. A significant reduction in LDL-cholesterol was found when comparing the two intervention groups. Trial registration: NCT04377386., (© The Author(s) 2023.)

Vitamin D is a nutrient potentially beneficial in the treatment of depression. The study aimed to carry out a systematic review of the studies assessing the influence of vitamin D supplementation on depression within Randomized Controlled Trials (RCTs). The systematic review was prepared on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42020155779). The peer-reviewed studies available within PubMed or Web of Science databases until September 2021 were taken into account. The number of screened records was 8514, and 8 records were included. Two independent researchers conducted screening, including, reporting, and risk of bias assessment using the revised Cochrane risk-of-bias tool for randomized trials. The included studies presented a population of patients with major depressive disorders or general depression, as well as bipolar depression or postpartum depression. The majority of included studies were conducted for 8 weeks or 12 weeks, while one study was conducted for 6 months. Within the large number of included studies, a daily dose of 1500 IU, 1600 IU, or 2800 IU was applied, while within some studies, a vitamin D dose of 50,000 IU was applied weekly or biweekly. Among applied psychological measures of depression, there were various tools. In spite of the fact that the majority of included studies (five studies) supported the positive effect of vitamin D supplementation for the psychological measure of depression, for three studies the positive influence was not supported. A medium risk of bias was indicated for six studies, while a high risk of bias was defined for only two studies, due to deviations from the intended interventions and in measurement of the outcome, as well as for one study, also arising from the randomization process and due to missing outcome data. Based on conducted assessment, it should be emphasized that there are only four studies supporting the positive influence of vitamin D supplementation for the psychological measure of depression of the medium risk of bias, while two studies of a medium risk of bias did not support it. Taking this into account, the conducted systematic review is not a strong confirmation of the effectiveness of vitamin D supplementation in the treatment of depression.

The objectives of this experiment were to determine the effects of supplementing 25-hydroxyvitamin D 3 (calcidiol, CAL) compared with vitamin D 3 (cholecalciferol, CHOL) at 1 or 3 mg/d in late gestation on production outcomes of dairy cows. One hundred thirty-three parous and 44 nulliparous pregnant Holstein cows were enrolled in the experiment. Cows were blocked by parity and previous lactation milk yield (parous) or genetic merit (nulliparous) and assigned randomly to receive 1 or 3 mg/d of CAL or CHOL in a 2 × 2 factorial arrangement of treatments (CAL1, CAL3, CHOL1, and CHOL3). Treatments were provided to individual cows as a top-dress to the prepartum diet from 250 d in gestation until parturition. The prepartum diet had a dietary cation-anion difference of -128 mEq/kg of dry matter. Production and disease were evaluated for the first 42 d in milk, and reproduction was evaluated to 300 d in milk. Incidence of postpartum diseases did not differ among treatments. Feeding CAL compared with CHOL increased yields of colostrum and colostrum fat, protein, and total solids, resulting in an increased amount of net energy for lactation secreted as colostrum (CHOL = 7.0 vs. CAL = 9.0 ± 0.7 Mcal). An interaction between source and amount was observed for milk yield: CAL3 increased milk yield compared with CHOL3 (CHOL3 = 34.1 vs. CAL3 = 38.7 ± 1.4 kg/d) but milk yield did not differ between CAL1 and CHOL1 (CHOL1 = 36.9 vs. CAL1 = 36.4 ± 1.4 kg/d). Concentrations of serum calcidiol on day of calving and average serum Ca from d 2 to 11 postpartum were positively associated with milk yield in the first 42 d in milk. Interactions between source and amount of vitamin D were also observed for pregnancy after first AI: the percentage of cows receiving CHOL1 and CAL3 that became pregnant was smaller than that of cows receiving CHOL3 and CAL1. However, pregnancy per AI and pregnancy by 300 d in milk did not differ among treatments. Overall, CAL3 increased milk yield compared with CHOL3, whereas in cows fed 1 mg/d (CAL1 and CHOL1), the source of vitamin D generally had no effect. The effect of CAL3 may be explained in part by serum CAL concentrations and postpartum serum Ca, which were associated with milk yield., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

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 D 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.

Observational studies suggest a link between vitamin D and the composition of the gut microbiome, but there is little evidence from randomized controlled trials of vitamin D supplementation. We analyzed data from the D-Health Trial, a randomized, double-blind, placebo-controlled trial. We recruited 21,315 Australians aged 60-84 y and randomized them to 60,000 IU of vitamin D 3 or placebo monthly for 5 y. Stool samples were collected from a sample of 835 participants (417 in the placebo and 418 in the vitamin D group) approximately 5 y after randomization. We characterized the gut microbiome using 16S rRNA gene sequencing. We used linear regression to compare alpha diversity indices (i.e. Shannon index (primary outcome), richness, inverse Simpson index), and the ratio of Firmicutes to Bacteroidetes between the two groups. We analyzed between-sample (beta) diversity (i.e. Bray Curtis distance and UniFrac index) using principal coordinate analysis and used PERMANOVA to test for significant clustering according to randomization group. We also assessed the difference in the abundance of the 20 most abundant genera between the two groups using negative binomial regression model with adjustment for multiple testing. Approximately half the participants included in this analysis were women (mean age 69.4 y). Vitamin D supplementation did not alter the Shannon diversity index (mean 3.51 versus 3.52 in the placebo and vitamin D groups, respectively, p  = 0.50). Similarly, there was little difference between the groups for other alpha diversity indices, the abundance of different genera, and the Firmicutes-to-Bacteroidetes ratio. We did not observe clustering of bacterial communities according to randomization group. In conlusion, monthly doses of 60,000 IU of vitamin D supplementation for 5 y did not alter the composition of the gut microbiome in older Australians.

Background: Vitamin D deficiency, a common problem among pregnant women, is linked with maternal inflammation, oxidative stress and consequent adverse pregnancy outcomes. The aim of this systematic review was to evaluate the effect of vitamin D supplementation on oxidative stress and inflammatory biomarkers in pregnant women according to the PRISMA guidance., Methods: Four databases including PubMed/MEDLINE, Scopus, Web of Science and Cochrane were used for searching papers published until 25 th July 2022. Clinical trials that assessed 25-Hydroxyvitamin D (25(OH)D), inflammatory markers (including high sensitivity C-reactive protein (hs-CRP) and certain cytokines) and oxidative stress markers (including malondialdehyde (MDA), total antioxidant capacity (TAC) and glutathione (GSH)) in pregnant women, were included in this review. The primary search of three databases displayed 21571 records. After removing duplicates and irrelevant articles, 17 eligible RCTs included for more evaluation. Random effect model and Der Simonian-Laird method were used to pool the data of studies. Risk of bias assessed according to version 2 of the Cochrane risk-of-bias tool for randomized trials., Results: According to the meta-analysis result, vitamin D supplementation caused a significant increase in the maternal circulating concentrations of 25(OH)D (SMD 2.07; 95%, CI 1.51, 2.63; p < 0.001), TAC (SMD 2.13, 95% CI 1.04 to 3.23, p < 0.001) and GSH (SMD 4.37, 95% CI 2.9 to 5.74, p < 0.001) as well as a significant decrease in the levels of MDA (SMD -0.46, 95% CI -0.87 to -0.05, p = 0.02). However, it had no significant impact on hs-CRP concentrations (SMD 0.24; 95% CI, -0.55, 1.03; p = 0.50)., Conclusion: In the present study, vitamin D supplementation led to increased levels of 25(OH)D, TAC and GSH and also decreased concentration of MDA. Nevertheless, because of low certainty of evidence, these findings have to be declared conservatively., Trial Registration: Registration code in PROSPERO website: CRD42020202600., (© 2022. The Author(s).)

Background: Attention deficit/hyperactivity disorder (ADHD) is the most common chronic mental and behavioral disorder among children. Some studies showed the lower levels of vitamin D in patients with ADHD compared with the healthy people. Few clinical trials were conducted in this field. The present study will be performed to examine the effect of vitamin D supplementation in children with ADHD., Methods: We will conduct a double-blind, randomized controlled clinical trial to investigate the effect of vitamin D supplementation on brain waves, behavioral performance, serum nitric oxide, malondialdehyde, and high-sensitivity C-reactive protein in 50 patients with ADHD. The intervention group will receive one capsule 50,000 IU vitamin D every week, for 8 weeks. The control group will receive one placebo capsule containing 1000 mg olive oil every week. Electroencephalography will be performed for 10 min using Brain Master Discovery from 19 scalp sites both before the first intervention and the 10 sessions of the therapy. The artifact-free periods of 1-min electroencephalography data will be analyzed for quantitative electroencephalography measures., Discussion: For the first time, this clinical trial will evaluate the effect of vitamin D supplementation on brain waves, serum nitric oxide, malondialdehyde, and high-sensitivity C-reactive protein in patients with ADHD. The results of the present clinical trial will provide a better vision about the vitamin D efficacy in patients with ADHD., Trial Registration: Registered on 5 November 2020 at Iranian Registry of Clinical Trials with code number IRCT20200922048802N1 ( https://www.irct.ir/trial/51410 )., (© 2022. The Author(s).)

Vitamin D exerts important extra-skeletal effects, exhibiting an exquisite immune regulatory ability, affecting both innate and adaptive immune responses through the modulation of immunocyte function and signaling. Remarkably, the immune function of working skeletal muscle, which is fully recognized to behave as a secretory organ with immune capacity, is under the tight control of vitamin D as well. Vitamin D status, meaning hormone sufficiency or insufficiency, can push toward strengthening/stabilization or decline of immune surveillance, with important consequences for health. This aspect is particularly relevant when considering the athletic population: while exercising is, nowadays, the recommended approach to maintain health and counteract inflammatory processes, "too much" exercise, often experienced by athletes, can increase inflammation, decrease immune surveillance, and expose them to a higher risk of diseases. When overexercise intersects with hypovitaminosis D, the overall effects on the immune system might converge into immune depression and higher vulnerability to diseases. This paper aims to provide an overview of how vitamin D shapes human immune responses, acting on the immune system and skeletal muscle cells; some aspects of exercise-related immune modifications are addressed, focusing on athletes. The crossroad where vitamin D and exercise meet can profile whole-body immune response and health., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Crescioli.)