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The National Institute of Standards and Technology (NIST), in collaboration with the National Institutes of Health, Office of Dietary Supplements (NIH ODS), introduced the first Standard Reference Material® (SRM) for determining vitamin D metabolites in 2009 motivated by significant concerns about the comparability and accuracy of different assays to assess vitamin D status. After 14 years, a suite of five serum matrix SRMs and three calibration solution SRMs are available. Values were also assigned for vitamin D metabolites in five additional SRMs intended primarily to support measurements of other clinical diagnostic markers. Both the SRMs and the certification approach have evolved from significant exogenous serum content to primarily endogenous content and from value assignment by combining the results of multiple analytical methods to the use of measurements exclusively from reference measurement procedures (RMPs). The impact of the availability of these SRMs can be assessed by both the distribution information (sales) and by reports in the scientific literature describing their use for method validation, quality control, and research. In this review, we describe the development of these SRMs, the evolution in design and value assignment, the expansion of information reported, and SRM use in validating analytical methods and providing quality assurance within the vitamin D measurement community., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Neonates with intrauterine growth retardation (IUGR) may present with fatal complications and permanent serious consequences. Vitamin status may influence fetal development. In this study we assessed vitamin A, E and D concentrations in umbilical cord blood in newborns with IUGR., Methods: Maternal data were obtained. Neonatal assessment included; age of gestation calculated from last menstrual period, Ultrasound (U/S), new Ballard, Apgar scores and anthropometric measurements including; Head circumference, length and weight. WHO growth percentile curves were used. Vitamin A, E and D in cord blood samples were measured by high performance liquid chromatography (HPLC) and ELISA consecutively., Results: A total of 86 full term newborns were enrolled in this study, 42 (48.8%) with IUGR with gestational age (33.59 ± 1.20) week by U/S and 44 (51.2%) appropriate for gestational age neonates with gestational age (38.70 ± 1.50). Ballard and Apgar scores (p < 0.05) and Z scores for weight, length and head circumference (p < 0.001) at birth were significantly lower in neonates with Intrauterine growth retardation (IUGR) than appropriate for gestational age (AGA) neonates. The levels of Vitamin A, E and D were significantly lower in the IUGR group than the AGA (p < 0.05) for all. Significant positive correlations of weight with vitamin A, and E cord blood levels were found (p < 0.05), while length was significantly positively correlated only with vitamin A (p < 0.05). Head circumference showed significant positive correlations with the three vitamins (p < 0.05) for all., Conclusion: Neonates with IUGR had significantly lower levels of Vitamin A, E and D than AGA neonates. Significant positive correlations of weight with vitamin A, and E cord blood levels was detected, while neonatal length was associated only with vitamin A level. The present study highlights the significance of nutritional policies for inhibiting deficiency of these vitamins during pregnancy and childhood., (© 2024. The Author(s).)

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.

Introduction: Preventing falls is a priority for aged care providers. Research to date has focused on fall prevention strategies in single settings (e.g., residential aged care (RAC) or community settings). However, some aged care providers deliver care, including fall prevention interventions, across RAC and community settings. We conducted an umbrella review to identify what type of fall prevention interventions had the greatest impact on falls outcomes in RAC and community settings., Methods: Five databases were searched for systematic reviews of falls prevention randomised control trials in older adults living in the community or RAC. Data extracted included systematic review methods, population characteristics, intervention characteristics, setting details (RAC or community), and fall-related outcomes (falls, people who have had a fall, fall-related hospitalisations, and fall-related fractures). Review quality was appraised using the Assessment of Multiple Systematic Reviews-2 tool., Results: One-hundred and six systematic reviews were included; 63 and 19 of these stratified results by community and RAC settings respectively, the remainder looked at both settings. The most common intervention types discussed in reviews included 'exercise' (61%, n = 65), 'multifactorial' (two or more intervention types delivered together) (26%, n = 28), and 'vitamin D' (18%, n = 19). In RAC and community settings, 'exercise' interventions demonstrated the most consistent reduction in falls and people who have had a fall compared to other intervention types. 'Multifactorial' interventions were also beneficial in both settings however demonstrated more consistent reduction in falls and people who fall in RAC settings compared to community settings. 'Vitamin D' interventions may be beneficial in community-dwelling populations but not in RAC settings. It was not possible to stratify fall-related hospitalisation and fall-related fracture outcomes by setting due to limited number of RAC-specific reviews (n = 3 and 0 respectively)., Conclusion: 'Exercise' interventions may be the most appropriate falls prevention intervention for older adults in RAC and community settings as it is beneficial for multiple fall-related outcomes (falls, fall-related fractures, and people who have had a fall). Augmenting 'exercise' interventions to become 'multifactorial' interventions may also improve the incidence of falls in both settings., (© 2024. The Author(s).)

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/m 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.

This systematic review aims to assess whether edible vegetable oils and fats fortified with vitamin A and/or D are effective and safe in improving vitamin intake and ameliorating deficiency states in the general population. In November 2022, we systematically searched MEDLINE, Cochrane CENTRAL, Scopus, Global Index Medicus, ClinicalTrials.gov, and WHO ICTRP (International Clinical Trials Registry Platform) for randomized controlled trials (RCT) and non-randomized studies of interventions (NRSI) investigating the fortification of edible vegetable oils and fats with either vitamin A or vitamin D or both as compared to the same vegetable oils and/or fats without vitamin A and D fortification or no interventions, in the general population, without age restriction. We assessed the methodological quality of included RCTs using Cochrane's risk of bias tool 2.0 and of NRSIs using ROBINS-I tool. We performed random-effects meta-analysis and assessed certainty of evidence using GRADE. We included eight studies. Available evidence showed no significant effect of fortification with vitamin A on serum retinol levels (RCTs: MD 0.35 µmol/L, 95% CI -0.43 to 1.12; two trials; 514 participants; low-certainty evidence; CCTs: MD 0.31 µmol/L, 95% CI -0.18 to 0.80; two trials; 205 participants; very low-certainty evidence) and on subclinical vitamin A deficiency. Low-certainty evidence showed no effect of vitamin D fortification on serum 25-hydroxy vitamin D concentration (MD 6.59 nmol/L, 95% CI -6.89 to 20.07; one trial; 62 participants). In conclusion, vitamin A-fortified vegetable oils and fats may result in little to no difference in serum retinol levels in general populations. The dose of vitamin A used in the trials may be safe but may not be sufficient to reduce subclinical vitamin A deficiency. Further, the evidence suggests that vitamin D fortification results in little to no difference in serum 25-hydroxy vitamin D concentration. Several aspects of providing fortified oils and fats to the general population as a public health intervention should be further investigated, including optimal fortification dose, effects on vitamin D deficiency and its clinical symptoms and potential adverse effects.

According to published meta-analyses, vitamin D exerts different beneficial effects in preventing and controlling risk factors associated with noncommunicable chronic diseases; however, the results are still conflicting. The purpose of this umbrella meta-analysis was to investigate the effect of vitamin D supplementation on low-density lipoprotein cholesterol, high-density lipoprotein (HDL) cholesterol, total cholesterol (TC), and triglyceride (TG) as components of the lipid profile. PubMed, Scopus, Web of Science, and Cochrane Database of Systematic Reviews were systematically searched for meta-analyses of randomized controlled trials. The umbrella meta-analysis followed the PRISMA guidelines. The random-effects model was employed to estimate the overall effect size (ES). Overall, 25 meta-analyses were included. In the standardized mean difference analysis, vitamin D significantly decreased TG (ES: -0.15; 95% CI: -0.23, -0.08; P ≤ 0.001) and TC levels (ES: -0.17; 95% CI: -0.23, -0.11; P ≤ 0.001) and increased HDL levels (ES: 0.08; 95% CI: 0.01, 0.15; P = 0.025). In the weighted mean difference analysis, vitamin D significantly decreased only TG levels (ES: -4.63 mg/dL; 95% CI: -7.70, -1.57; P = 0.003). The present study supports that vitamin D supplementation could be considered a beneficial adjuvant therapy in managing lipid profile levels, especially in individuals with vitamin D deficiency. This systematic review was registered in PROSPERO as CRD42022306334., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective:  It is well known that female infertility is multifactorial. Therefore, we aimed to compare the effects of thyroid dysfunction, vitamin deficiency, and microelement deficiency in fertile and infertile patients., Materials and Methods:  Between May 1st, 2017, and April 1st, 2019, we conducted a retrospective case-control study with of 380 infertile and 346 pregnant patients (who normally fertile and able to conceive spontaneously). The fertile patients were selected among those who got pregnant spontaneously without treatment, had a term birth, and did not have systemic or obstetric diseases. The levels of thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), anti-thyroid peroxidase (anti-TPO), vitamin D, vitamin B12, folic acid, ferritin, and zinc of both groups were compared., Results:  There was no difference between patients in the infertile and pregnant groups in terms of low normal and high serum T3 and T4 levels ( p  = 0.938; p  > 0.05) respectively, nor in terms of normal and high anti-TPO levels ( p  = 0.182; p  > 0.05) respectively. There was no significant difference regarding patients with low, insufficient, and sufficient vitamin D levels in the infertile and pregnant groups ( p  = 0.160; p >0.05) respectively. The levels of folic acid, ferritin, and zinc of the infertile group were significantly lower than those of the pregnant group., Conclusion:  The serum levels of folic acid, ferritin, and zinc in infertile patients presenting to our outpatient clinic were lower than those o the fertile patients., Competing Interests: The authors have no conflict of interests to declare., (Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Introduction: there is growing interest in the link between maternal and infant vitamin D (VD) levels. Breast milk transmission and the fact that the mother and her child may share risk factors for VD, such as exposure to sunlight, diet, and sociocultural influences may impact VD status, the magnitude of which is largely unknown in our topical low-middle income setting. We assessed the connection between maternal and infant VD status including their correlates., Methods: this cross-sectional study investigated 95 maternal-infant pairs in Jos. Mothers were interviewed using a questionnaire. Blood sampling and analysis of serum total 25 hydroxy VD were performed using the chemiluminescent immunoassay method. Maternal and infant VD levels were classified as VD deficient (VDD), VD insufficient (VDI), and VD sufficient (VDS). The mean maternal and infant VD were compared, and the Spearman correlation between them was assessed, a stepwise linear regression was also performed with infant vitamin D as a dependent variable. For all statistical analysis, p<0.05 was considered significant., Results: the median maternal and infant VD was 29.68 ng/ml and 29.41 ng/ml, respectively. The mean infant VD (32.19 ± 10.61 ng/ml) was comparable to maternal VD (31.12 ± 12.94 ng/ml) (p=0.483), with a Spearman correlation coefficient of 0.3 (p=0.037). Maternal vitamin D (beta=0.539, duration of exclusive breastfeeding (beta=-3.490), and infant age (beta=1.655) were found to be significant independent predictors of infant vitamin., Conclusion: beyond neonatal age, a significant positive relationship between maternal and infants´ VD levels exists and suggests that family-focused vitamin D intervention might be an effective public health approach in the tropical city of Jos., Competing Interests: The authors declare no competing interests., (Copyright: Ishaya Ibrahim Abok et al.)

Introduction: The worldwide obesity epidemic continues unabated. Obesity and its associated health risks are considered as the major causes of morbidity and mortality. Currently, bariatric surgery is the most effective treatment for people with severe obesity resulting in sustainable weight loss and a reduced risk for co-morbidities. Sleeve gastrectomy is the most common bariatric procedure undertaken in Tunisia., Aim: we aim to evaluate the vitamin status of the obese patients before and after sleeve gastrectomy., Methods: Thirty obese patients undergoing sleeve gastrectomy, were recruited from Obesity unit. In this study. A biological assessment was performed pre-operatively and controlled 6 months following the sleeve gastrectomy including: calcemia, parathyroid hormone (PTH), albuminemia and dosage of vitamin D, vitamin B9 and vitamin B12., Results: Six months post sleeve gastrectomy, vitamin deficiencies were more prevalent: the mean level of vitamin B9, vitamin B12 and vitamin D respectively, has decreased from 5.03±3.28 ng / ml to 2.71±1.52 ng / ml, from 348.06±158.92 pg/ml to 264.62±119.77 pg/ml and from 17.18±11.45 ng/ml to 11.69±8.22 ng/ml, with a statistically significant difference (p=0.008, p=0.01 and p=0.012). Sleeve gastrectomy has proven to be an effective weight loss treatment. However, nutritional deficiencies have worsened during postoperative period., Conclusion: This study highlights the importance of early identification, appropriate treatment and prophylactic micronutrient supplementation.

Chemotherapy represents the main pharmacological cancer treatment. Recently, positive effects emerged with the combination of anticancer therapy and nutraceutical products. The aim of this systematic review is to collect and synthesize the available scientific evidence regarding the potential effects of nutraceuticals on cancer cells. A systematic literature search of randomized clinical trials of nutraceutical products in patients with cancer published up to 15 December 2022 was conducted using three data sources: Embase, PubMed, and Web of Science. The effect of high-dose isoflavone supplements on prostate cancer resulted in stabilization or reduction of PSA concentrations in 50% of isoflavone group patients six months after treatment. High doses of vitamin D supplementation plus chemotherapy in patients with advanced or metastatic colorectal cancer showed a median PFS of 13.0 months (95% CI, 10.1-14.7 months) for 49 patients. The effect of vitamin D supplementation on markers of inflammatory level and antioxidant capacity in women with breast cancer showed a significant increase in serum vitamin D concentration (28 ± 2.6 to 39 ± 3.5; p = 0.004) after 8 weeks of treatment. In conclusion, nutraceutical supplements represent a potentially growing sector and can be utilized in medical treatment or nutrition to provide integrated medical care.

Background: As one of the few modifiable risk factors, the importance of dietary patterns for both disease prevention and treatment outcome in pediatric oncology has gained increasing popularity. Malnutrition is associated with lower survival rates, tolerance to treatment, and quality of life. Yet, especially in children with malignancies, nutritional deterioration is common, and pediatric cancer patients often present with inadequate intake of micro- and macronutrients alike. Despite the reported widespread use of dietary supplements, few empirical data provide a basis for clinical recommendations, and evidence for their efficacy is inconsistent. Current literature lacks a systematic approach as to how and which supplements should be recommended for specific patients, types of cancer, or during specific treatments. The aim of this review is to highlight the role of the most frequently used nutrients in pediatric malignant diseases and to give a practical guide based on current scientific evidence., Methods: A comprehensive literature search was conducted on PubMed through April 2023 to select meta-analyses, systematic reviews, observational studies, and individual randomized controlled trials (RCTs) of macro- and micronutrient supplementation in pediatric oncology. The search strategy included the following medical subject headings (MeSH) and keywords: "childhood cancer", "pediatric oncology", "nutritional status", "dietary supplements", "vitamins", "micronutrients", "calcium", "magnesium", "vitamin D", "zinc" "glutamine", "selen", and "omega-3 fatty acids". The reference lists of all relevant articles were screened to include potentially pertinent studies., Results: The present review provides a comprehensive and updated overview of the latest evidence about the role of nutrition and diet in pediatric oncology, also focusing on different nutritional interventions available for the management of the disease. We summarize evidence about the importance of adequate nutrition in childhood cancer and the role of several micronutrients and critically interpret the findings. Possible effects and benefits of supplementation during chemotherapy are discussed, as are strategies for primary and secondary prevention., Conclusions: We here describe the obvious benefits of dietary supplementation for childhood cancer. Further large-scale clinical trials are required to verify the impacts of deficiencies and the possible benefits of supplementation and optimal dosages. (337 words).

The objective was to explore the patterns of contribution from vitamin D metabolites (D 2 and D 3 ) to total vitamin D concentrations in Indian families. This cross-sectional study was carried out in slum-dwelling families residing in Pune city. Data on demography, socio-economic status, sunlight exposure, anthropometry, and biochemical parameters (serum 25OHD 2 , 25OHD 3 ) via the liquid chromatography-tandem mass spectrometry method were collected. The results are presented for 437 participants (5 to 80 years). One-third were vitamin-D-deficient. Intake of foods containing vitamin D 2 or D 3 was rarely reported. Irrespective of gender, age, and vitamin D status, the contribution of D 3 to total 25OHD concentrations far exceeded that of D 2 ( p < 0.05). The contribution of D 2 ranged from 8% to 33% while that of D 3 to 25OHD concentrations ranged from 67% to 92%. 25OHD 3 is a major contributor to overall vitamin D concentrations, and the contribution of 25OHD 2 was found to be negligible. This implies that sunlight and not diet is currently the major source of vitamin D. Considering that lifestyle and cultural practices may lead to insufficient sunlight exposure for large sections of the society, especially women, dietary contribution to vitamin D concentrations through fortification may play an important role in improving the vitamin D status of Indians.

The link between vitamin D and multiple sclerosis (MS) has been suggested in epidemiological, genetic, immunological, and clinical studies. The aim of the present systematic review of the literature was to assess the effects of vitamin D supplementation on clinical and imaging outcomes in patients with MS. The outcomes we assessed included relapse events, disability progression, and magnetic resonance imaging (MRI) lesions. The search was conducted using PubMed, ClinicalTrials.gov, and EudraCT databases, and it included records published up until 28 February 2023. The systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Nineteen independent clinical studies (corresponding to 24 records) were included in the systematic review. The risk of bias in randomized controlled trials (RCTs) was analyzed using the Cochrane risk-of-bias tool. Fifteen trials investigated relapse events, and most of them reported no significant effect of vitamin D supplementation. Eight of 13 RCTs found that vitamin D supplementation had no effect on disability [assessed by Expanded Disability Status Scale (EDSS) scores] compared to controls. Interestingly, recent RCTs reported a significant reduction in new MRI lesions in the central nervous system of MS patients during supplementation with vitamin D3.

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.

In this study, the liquid chromatographic (LC) parameters were optimized using response surface methodology (RSM) as a novel approach to achieve optimal separation of six vitamers of vitamin D and K during simultaneous estimation. Analytes were separated using an Accucore C18 column (50 x 4.6 mm, 2.6 µm), 0.1% aqueous formic acid (pH = 3.5), and methanol as mobile phase components. The Box-Behnken design (BBD) predicted the best combination of the selected critical quality attributes such as organic solvent composition in the mobile phase (90%), mobile phase flow rate (0.42 mL/min), and column oven temperature (40oC). Multiple regression analysis was used to fit the experimental data from 17 sample runs to a second-order polynomial equation. The adjusted coefficient of determination (R2) for three desired responses were 0.983 (retention time of K3 = R1), 0.988 (resolution between D2 and D3 = R2), and 0.992 (retention time of K2-7 = R3), all with significant probability values (p<0.0001), indicating a high significance for the regression model. Q-ToF/MS detection was interfaced with an electrospray combined ionization source. The optimized detection parameters delivered specific, sensitive, linear, accurate, precise, and robust quantification of all six analytes in the tablet dosage form.

Objectives: Observational studies have suggested that a higher 25-hydroxyvitamin D concentration may be associated with longer telomere length; however, this has not been investigated in randomised controlled trials. We conducted an ancillary study within a randomised, double-blind, placebo-controlled trial of monthly vitamin D (the D-Health Trial) for the prevention of all-cause mortality, conducted from 2014 to 2020, to assess the effect of vitamin D supplementation on telomere length (measured as the telomere to single copy gene (T/S) ratio)., Design, Setting, Participants, and Intervention: Participants were Australians aged 60-84 years and we randomly selected 1,519 D-Health participants (vitamin D: n=744; placebo: n=775) for this analysis. We used quantitative polymerase chain reaction to measure the relative telomere length (T/S ratio) at 4 or 5 years after randomisation. We compared the mean T/S ratio between the vitamin D and placebo groups to assess the effect of vitamin D supplementation on relative telomere length, using a linear regression model with adjustment for age, sex, and state which were used to stratify the randomisation., Results: The mean T/S ratio was 0.70 for both groups (standard deviation 0.18 and 0.16 for the vitamin D and placebo groups respectively). The adjusted mean difference (vitamin D minus placebo) was -0.001 (95% CI -0.02 to 0.02). There was no effect modification by age, sex, body mass index, or predicted baseline 25-hydroxyvitamin D concentration., Conclusion: In conclusion, routinely supplementing older adults, who are largely vitamin D replete, with monthly doses of vitamin D is unlikely to influence telomere length., Competing Interests: PM Webb has funding from Astra Zeneca for an unrelated study of ovarian cancer. PR Ebeling reports grants and other from Amgen, other from Sanofi, grants and other from Novartis, grants from Eli-Lilly, and grants from Alexion. RE Neale has funding from Viatris for an unrelated study of pancreatic cancer. All other authors declare no competing interests.

Background and Objectives: One of the pathogenetic hypotheses of delirium is the "neuroinflammatory theory" with consequent neurotoxicity of brain connectivity networks. Micronutrients may play a significant role in the prevention of neuroinflammation. This systematic review addresses the role of micronutrients in the development of delirium in older populations., Methods: The EBSCO, Cochrane, PubMed, and Web of Science databases were searched for articles on delirium and micronutrients. The methodological quality of the studies included in the review was evaluated with the Newcastle-Ottawa Scales for observational studies and for case-control studies., Results: 1326 papers were identified from the searches, 7 of which met the inclusion criteria (see section 2.3). All the papers included were written in English. Delirium was predominantly secondary to post-operative dysfunction or acute medical conditions. By altering the production of neurotransmitters resulting in an imbalance, and by reducing their immunomodulatory role with a consequent increase in inflammatory oxidative stress, micronutrient deficiency seems to be associated with an increased incidence of delirium., Conclusions: This review supports the existence of an association between micronutrient deficiency (i.e. cobalamin, thiamine, and vitamin D) and an increased incidence of delirium, with a greater prevalence in hospitalized patients., Competing Interests: All authors declare they have no competing interests.

Little is known about the impact of high-normal range of 25-hydroxyvitamin D [25(OH)D] on reproductive function. The aim of this study was to investigate the effect of different dose vitamin D supplementation in female mice on the pregnancy outcomes. Three groups of female mice were fed with fodder containing different dose of vitamin D at both pre-gestational and gestational stages. Serum 25(OH)D and calcium concentrations were monitored. The expression levels of vitamin D receptor (VDR) mRNA and protein in placenta were determined by real-time RT-PCR and western blot. Pregnancy outcomes were evaluated and compared among the three groups. Compared with the medium and low dose groups, serum 25(OH)D concentration was significantly increased and approximated to high-normal range in the high dose group (pre-gestational: 81.3±5.75 vs 52.8±6.24 and 25.0±3.99 ng/mL; gestational: 86.8±5.99 vs 52.6±9.29 and 27.9±4.96 ng/mL, respectively; all p<0.001). Interestingly, the average number of live fetuses per litter was much larger in the high dose group than in other two groups (19.8±5.31 vs 13.8±1.30 and 12.8±3.55 respectively, both p<0.05). However, no significant differences of the expression levels of VDR mRNA and protein in placenta were identified among the three groups. Supplementation of high dose vitamin D can enhance the female mice reproductive function. Further study is warranted to explore the mechanism by which high level of 25(OH)D in female mice increases the number of fetuses.

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease associated with severe systemic inflammation. The optimal status of vitamins and microelements is considered crucial for the proper functioning of the immune system and necessary for successful recovery. Most patients with respiratory distress in COVID-19 are vitamin and microelement deficient, with vitamin D and Se deficiency being the most common. Anyway, various micronutrient supplements are widely and arbitrarily used for prevention or in the treatment of COVID-19. We aimed to summarise current knowledge about molecular and physiological mechanisms of vitamins (D, A, C, B 6 , B 9 and B 12 ) and microelements (Se, Zn, Cu and Fe) involved in the immune system regulation in consideration with COVID-19 pathogenesis, as well as recent findings related to their usage and effects in the prevention and treatment of COVID-19. In the early course of the pandemic, several, mainly observational, studies reported an association of some micronutrients, such as vitamin C, D and Zn, with severity reduction and survival improvement. Still, emerging randomised controlled trials showed no effect of vitamin D on hospitalisation length and no effect of vitamin C and Zn on symptom reduction. Up to date, there is evidence neither for nor against the use of micronutrients in the treatment of COVID-19. The doses that exceed the recommended for the general population and age group should not be used, except in clinical trials. Benefits of supplementation are primarily expected in populations prone to micronutrient deficiencies, who are, as well, at a higher risk of worse outcomes in COVID-19.

Fat-soluble vitamins are important efficacy indicators in health foods because they are essential for human physiological functions. The existing method for the simultaneous determination of fat-soluble vitamins has various problems, such as limited determination components, complex sample, pretreatment process, and high requirements for personnel operating ability. Therefore, establishing a fast, simple, and accurate method that can detect various common fat-soluble vitamins at the same time is necessary. In this study, a method for the simultaneous determination of 10 commonly used fat-soluble vitamins such as vitamin A acetate (VA acetate), vitamin A palmitate (VA palmitate), vitamin E acetate (VE acetate), vitamin K 1 (VK 1 ), α -tocopherol, β -tocopherol, γ -tocopherol, δ -tocopherol, vitamin D 2 (VD 2 ) and vitamin D 3 (VD 3 ) in health foods was established by ultra performance convergence chromatography (UPC 2 ). First, the contents of about 1.0 g of capsule samples were accurately weighed. A grinder was used to grind tablet samples into powder. The powder mixture was then precisely weighed at 2.0 g. Both substances were placed in 50 mL brown stopper tubes. The test tube was then filled with 20 mL 75% dimethylsulfoxide (DMSO) aqueous solution for demulsification. The tubes were then sonicated before being extracted with n -hexane. The centrifuged supernatant was added to vials for detection. Viridis HSS C18 SB column (100 mm×3.0 mm, 1.8 μm) was applied and CO 2 was used as the mobile phase A. After comparing the influence of acetonitrile, methanol, and their mixture on chromatographic peak separation, acetonitrile-methanol (85∶15, v/v) was used as the mobile phase B. The injection volume was 1 μL. Using simulator software, the optimal chromatographic conditions were obtained after a set of three-factor orthogonal experiments of flow rate, gradient slope, and column temperature. The flow rate and column temperature were both set at 1.9 mL/min and 30 ℃. Furthermore, the maximum absorption wavelength of these 10 fat-soluble vitamins was selected for detection. Ten vitamins were baseline separated after 7 min of gradient elution. The limits of detection (LODs) and quantification (LOQs) of capsule samples were 0.4-60 μg/g and 2-150 μg/g, respectively, whereas the results for tablet samples were 0.2-30 μg/g and 0.8-75 μg/g. The linear ranges of the 10 fat-soluble vitamins were 0.1-100 μg/mL. The recoveries of spiked samples ranged from 96.5% to 113.9%, with RSD values less than 4%. Precision, stability, and repeatability RSD values were all less than 2%. By comparison, the determination results of this method were basically consistent with the existing national food safety standards. This method is simple, rapid, sensitive, and accurate, and it can meet the detection requirements of the 10 fat-soluble vitamins in health foods. Simultaneously, this method lays the foundation for the rapid and simultaneous detection of fat-soluble vitamins in existing health foods.

Vitamin D plays an important role in immune function and inflammation and the physical activity demonstrate relationship near to syntheses of vitamin D, considering to necessary to factors immunologics, environmental and physical. We searched five databases through February 20, 2021. Two reviewers screened the studies, collected data, assessed the risk of bias, and ranked the evidence for each outcome across the studies, independently and in duplicate. The prespecified endpoints of interest were Cardiorespiratory Fitness; Sunlight Exposure; Body Mass Index (BMI). We only included data from peer-reviewed articles in our primary analyses. In our primary analysis, there was a positive trend between serum 25(OH)D <20 ng/ml and body mass index, this result should be interpreted with caution, considering confidence intervals (RR 1.10 95% CI 0.37 to 1.83. We identified 4 high quality evidence that vitamin D levels and high physical activity required a direct relationship considering (four trials with 2,253) ; RR 0. (RR 0.0; 95% CI -0.15 to 0.15) (RR 0.59; 95% CI 0.43 to 0.75. Although the evidence available so far, from observational studies of medium quality, can be seen as showing a trend towards an association between sufficient serum levels of 25(OH)D and physical activity, this relationship has been shown. have a stimulating effect on vitamin D synthesis, the relationship of low body mass index with sufficient vitamin D levels is not based on solid evidence. We await results from ongoing studies to determine this effectiveness.

Objective: Numerous physiological changes occur during pregnancy, which affect both the mother and the fetus. The objective of this study was to evaluate the magnesium, calcium, phosphate, parathormone (PTH), and vitamin D levels in each trimester of pregnancy., Methods: In this study, 30 pregnant women in the first trimester, 30 pregnant women in the second trimester, 30 pregnant women in the third trimester, and 30 healthy, non-pregnant women (control) in the same age group were included. The serum magnesium, calcium, phosphate, PTH, and vitamin D levels were measured in all the participants., Results: No statistically significant difference was found in the PTH and phosphate levels within the groups. In contrast, a significant difference was found in the vitamin D, calcium, and magnesium levels (p<0.001 for all). By analyzing the differences between the groups, the vitamin D, calcium, and magnesium levels were found to decrease with increase in the gestational weeks., Conclusion: For maintaining a healthy pregnancy and fetus, we recommend vitamin D, calcium, and magnesium levels to be included in routine follow-ups for each trimester and supplemented in case of deficiency.

The aim of the study was to assess the need and safety of vitamin supplementation in adults with obesity post bariatric surgery (SG), based on intake assessment. Patients with obesity class III, and with obesity class II with comorbidities were followed up at 3, 6 and 9 months post bariatric surgery. Based on a 4-day food record questionnaire, the intake of vitamins and calories was assessed and an interview regarding the consumption of supplements was conducted. The study showed a deficiency in the dietary intake of vitamin D, folate (B 9 ) and vitamin B 1 (in 93-100% of respondents), vitamins E and C (in 53-67% of respondents), vitamins A, PP and vitamins B 2 and B 6 (in 10 to 23% of respondents) and vitamin B 12 (only 1 woman). The intake of multivitamin supplements was implemented by 72% of respondents, independently, all patients were taking a vitamin D supplement. Vitamin deficiencies were only reported in a small percentage of patients (3-17%), who did not take supplements throughout the observation period. Supplementation with vitamins D, E, C, B 1 and folic acid (B 9 ), used regularly, supplemented the nutritional deficiencies of patients. The intake of vitamin A, B 2 , PP, and B 6 with supplements did not significantly affect the overall intake. Supplementation with vitamin B 12 turned out to be unjustified to the nutritional recommendations. The dietary and/or supplemental intake of vitamins did not exceed the tolerable upper intake level (UL). The results of the study confirm the need to implement vitamin supplementation for bariatric patients and its safety., (© 2022. The Author(s).)

Background and Objectives : Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis and related clinical consequences are still unclear. Early diagnosis and dynamic monitoring of prognostic factors are essential to improve the ability to manage COVID-19 infection. This study aimed to provide an account of the role played by vitamins C and D on the onset, progression and severity of COVID-19. Clinical features and infection-related risk factors are also briefly discussed. Material and Methods : In March 2022, the main online databases were accessed. All the articles that investigate the possible role of vitamins C and D on COVID-19 susceptibility, severity and progression were considered. Results : The current evidence on vitamin C and D supplementation in patients with COVID-19 infection is inconsistent and controversial. In some studies, vitamins were used as coadjuvant of a formal experimental therapy, while in others as main treatment. Ethnicity and hospital setting (inpatient/outpatient) were also variable. Moreover, there was no consensus between studies in administration protocol: high heterogeneity in dosage, administration, and duration of the treatment were evident. Finally, some studies administered vitamins pre- and/or during COVID infection, in patients with different risk factors and infection severity. Conclusions : While waiting to develop a targeted, safe and effective therapy, it is important to investigate individual predisposition and proper disease management. Concluding, available data on the use of nutraceuticals in COVID-19 are inconsistent. However, there is a lack of evidence-based guidelines which recommend vitamin C and D supplementation in patients with COVID-19, and results from high quality randomised controlled trials (RCTs) are inconsistent. Current investigations so far are mostly observational, and include a relatively small sample size which can lead to biased results. Large-scale multicentre studies are therefore needed.

A novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) that was initially reported from Wuhan, China in December 2019, was declared a pandemic by the WHO in March 2020. Considering the current COVID-19 pandemic, where there are no specific effective preventive or therapeutic drugs available, a healthy immune system is one of the most important tools that should be considered. Vitamins and minerals supplements have been well known to help the immune system in battling viral infections in general. Physicians worldwide are largely interested in vitamin and mineral supplements to help them battle COVID-19 whether through protection or treatment. Dietary supplementations especially vitamin D, vitamin C, and Zinc offer good prophylactic and therapeutic support to the currently available treatment regimens. They are relatively safe and were proven to aid recovery in other respiratory infections. Further studies should be encouraged especially those examining their role in prophylaxis from COVID-19 while maintaining current recommendations for social distancing and proper protective gear., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2022 Eman El Sabbagh, Mohammad El-Sayed, Tamer Elbaz.)

New and more efficient routes of chemical synthesis of vitamin D 3 (D 3 ) hydroxy (OH) metabolites, including 20S(OH)D 3 , 20S,23S(OH) 2 D 3 and 20S,25(OH) 2 D 3 , that are endogenously produced in the human body by CYP11A1, and of 20S,23R(OH) 2 D 3 were established. The biological evaluation showed that these compounds exhibited similar properties to each other regarding inhibition of cell proliferation and induction of cell differentiation but with subtle and quantitative differences. They showed both overlapping and differential effects on T-cell immune activity. They also showed similar interactions with nuclear receptors with all secosteroids activating vitamin D, liver X, retinoic acid orphan and aryl hydrocarbon receptors in functional assays and also as indicated by molecular modeling. They functioned as substrates for CYP27B1 with enzymatic activity being the highest towards 20S,25(OH) 2 D 3 and the lowest towards 20S(OH)D 3 . In conclusion, defining new routes for large scale synthesis of endogenously produced D 3 -hydroxy derivatives by pathways initiated by CYP11A1 opens an exciting era to analyze their common and differential activities in vivo, particularly on the immune system and inflammatory diseases., (Copyright © 2022. Published by Elsevier Inc.)

Background: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown., Objectives: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19., Methods: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in São Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1β, IL-6, IL-10, TNF-α, and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1β (MIP-1β), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes., Results: The study included 200 patients with a mean ± SD age of 55.5 ± 14.3 y and BMI of 32.2 ± 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes., Conclusions: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.This trial was registered at clinicaltrials.gov as NCT04449718., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Vitamin D (VD) is a calcium- and phosphate-controlling hormone used to treat bone disorders; yet, several other effects are progressively emerging. VD deficiency is highly prevalent worldwide, with suboptimal exposure to sunlight listed among the leading causes: oral supplementation with either cholecalciferol or calcitriol is used. However, there is a scarcity of clinical studies investigating how quickly VD concentrations can increase after supplementation. In this pilot study, the commercial supplement ImmuD3 (by Erboristeria Magentina ® ) was chosen as the source of VD and 2000 IU/day was administered for one month to 21 healthy volunteers that had not taken any other VD supplements in the previous 30 days. Plasma VD levels were measured through liquid chromatography coupled to tandem mass spectrometry after 7, 14, and 28 days of supplementation. We found that 95% of the participants had insufficient VD levels at baseline (<30 ng/mL; median 23.72 ng/mL; IQR 18.10-26.15), but after 28 days of supplementation, this percentage dropped to 62% (median 28.35 ng/mL; IQR 25.78-35.20). The median increase in VD level was 3.09 ng/mL (IQR 1.60-5.68) after 7 days and 8.85 ng/mL (IQR 2.85-13.97F) after 28 days. This study suggests the need for continuing VD supplementation and for measuring target level attainment.

As a consequence of epidemiological studies showing significant associations of vitamin D deficiency with a variety of adverse extra-skeletal clinical outcomes including cardiovascular diseases, cancer, and mortality, large vitamin D randomized controlled trials (RCTs) have been designed and conducted over the last few years. The vast majority of these trials did not restrict their study populations to individuals with vitamin D deficiency, and some even allowed moderate vitamin D supplementation in the placebo groups. In these RCTs, there were no significant effects on the primary outcomes, including cancer, cardiovascular events, and mortality, but explorative outcome analyses and meta-analyses revealed indications for potential benefits such as reductions in cancer mortality or acute respiratory infections. Importantly, data from RCTs with relatively high doses of vitamin D supplementation did, by the vast majority, not show significant safety issues, except for trials in critically or severely ill patients or in those using very high intermittent vitamin D doses. The recent large vitamin D RCTs did not challenge the beneficial effects of vitamin D regarding rickets and osteomalacia, that therefore continue to provide the scientific basis for nutritional vitamin D guidelines and recommendations. There remains a great need to evaluate the effects of vitamin D treatment in populations with vitamin D deficiency or certain characteristics suggesting a high sensitivity to treatment. Outcomes and limitations of recently published large vitamin D RCTs must inform the design of future vitamin D or nutrition trials that should use more personalized approaches.

India is coming to grips with a stage of nutrition transition. According to the Food Safety and Standards Authority of India (FSSAI), preventable micronutrient deficiency is arising public health precedence in India. However, the foremost public health concern is the lack of national prevalence data. The present study was carried out to estimate the pooled age-wise prevalence of six preventable micronutrient deficiencies (vitamin A, vitamin B 12 , vitamin D, iron, iodine and folic acid) in India. A systematic review was carried out on PubMed and Global Index Medicus databases using the Boolean search strategy. Statistical analyses were done using R software, version 3.6. 2. PRISMA guidelines were strictly adhered to during the review. A preliminary literature search yielded 4302 articles; however, 270 original research articles were found eligible to be included in quantitative synthesis. The estimated overall prevalence was 17 % [95 % confidence interval (CI) 0⋅07, 0⋅26] for iodine deficiency, 37 % (95 % CI 0⋅27, 0⋅46) for folic acid deficiency, 54 % (95 % CI 0⋅49, 0⋅59) for iron deficiency, 53 % (95 % CI 0⋅41, 0⋅64) for vitamin B 12 deficiency, 19 % (95 % CI 0⋅09, 0⋅29) for vitamin A deficiency and 61 % (95 % CI 0⋅07, 0⋅26) for vitamin D with high heterogeneity. We classified the population into infants (0-5 years), adolescents (<18 years), adults (>18 years) and pregnant women. Iron deficiency was most prevalent (61 %) in pregnant women. The results of the present study reinforce the data on micronutrient deficiency in India and warrant the immediate need for further active public health interventions to address these deficiencies. The study is registered with PROSPERO (CRD42020205043)., (© The Author(s) 2021.)

Fat-soluble vitamin deficiency remains a challenge in cystic fibrosis (CF), chronic pancreatitis, and biliary atresia. Liposomes and cyclodextrins can enhance their bioavailability, thus this multi-center randomized placebo-controlled trial compared three-month supplementation of fat-soluble vitamins in the form of liposomes or cyclodextrins to medium-chain triglycerides (MCT) in pancreatic-insufficient CF patients. The daily doses were as follows: 2000 IU of retinyl palmitate, 4000 IU of vitamin D3, 200 IU of RRR-α-tocopherol, and 200 µg of vitamin K2 as menaquinone-7, with vitamin E given in soybean oil instead of liposomes. All participants received 4 mg of β-carotene and 1.07 mg of vitamin K1 to ensure compliance with the guidelines. The primary outcome was the change from the baseline of all-trans-retinol and 25-hydroxyvitamin D3 concentrations and the percentage of undercarboxylated osteocalcin. Out of 75 randomized patients ( n = 28 liposomes, n = 22 cyclodextrins, and n = 25 MCT), 67 completed the trial (89%; n = 26 liposomes, n = 18 cyclodextrins, and n = 23 MCT) and had a median age of 22 years (IQR 19-28), body mass index of 20.6 kg/m 2 [18.4-22.0], and forced expiratory volume in 1 s of 65% (44-84%). The liposomal formulation of vitamin A was associated with the improved evolution of serum all-trans-retinol compared to the control (median +1.7 ng/mL (IQR -44.3-86.1) vs. -38.8 ng/mL (-71.2-6.8), p = 0.028). Cyclodextrins enhanced the bioavailability of vitamin D3 (+9.0 ng/mL (1.0-17.0) vs. +3.0 ng/mL (-4.0-7.0), p = 0.012) and vitamin E (+4.34 µg/mL (0.33-6.52) vs. -0.34 µg/mL (-1.71-2.15), p = 0.010). Liposomes may augment the bioavailability of vitamin A and cyclodextrins may strengthen the supplementation of vitamins D3 and E relative to MCT in pancreatic-insufficient CF but further studies are required to assess liposomal vitamin E (German Clinical Trial Register number DRKS00014295, funded from EU and Norsa Pharma).

Background: Inadequate vitamin D levels may increase the risk of caries during childhood. The purpose of this study was to investigate the association between 25-hydroxyvitamin D (25(OH)D) status and severe early childhood caries (S-ECC) in preschool children., Methods: Data were obtained from children <72 months of age in two case-control studies in Winnipeg, Manitoba and Richmond, Virginia. Serum analysis assessed 25(OH)D, calcium and parathyroid concentrations. Data on demographics, dental history and oral hygiene were obtained via questionnaires. Bivariate and multiple logistic regression analyses were performed to assess the relationships between demographic and biological variables and S-ECC. A p -value of ≤0.05 was significant., Results: Data were available for 200 children with S-ECC and 144 caries-free controls. Children with S-ECC had significantly lower 25(OH)D levels than those who were caries-free ( p < 0.001), and children with deficient 25(OH)D levels were 10 times more likely to have S-ECC ( p < 0.001). Multiple logistic regression revealed that having higher 25(OH)D and calcium concentrations ( p = 0.019 and p < 0.0001, respectively), as well as being breastfed in infancy ( p < 0.001), were significantly and independently associated with lower odds of S-ECC, while dental insurance ( p = 0.006) was associated with higher odds of S-ECC., Conclusions: This study provides additional evidence of an association between nutritional status, specifically vitamin D and calcium levels, and S-ECC.

Optimising nutrition intake is a key component for supporting athletic performance and supporting adaption to training. Athletes often use micronutrient supplements in order to correct vitamin and mineral deficiencies, improve immune function, enhance recovery and or to optimise their performance. The aim of this review was to investigate the recent literature regarding micronutrients (specifically iron, vitamin C, vitamin E, vitamin D, calcium) and their effects on physical performance. Over the past ten years, several studies have investigated the impacts of these micronutrients on aspects of athletic performance, and several reviews have aimed to provide an overview of current use and effectiveness. Currently the balance of the literature suggests that micronutrient supplementation in well-nourished athletes does not enhance physical performance. Excessive intake of dietary supplements may impair the body's physiological responses to exercise that supports adaptation to training stress. In some cases, micronutrient supplementation is warranted, for example, with a diagnosed deficiency, when energy intake is compromised, or when training and competing at altitude, however these micronutrients should be prescribed by a medical professional. Athletes are encouraged to obtain adequate micronutrients from a wellbalanced and varied dietary intake., (Copyright © 2021. Published by Elsevier Ltd.)

In this study we aimed to assess vitamin D metabolism in patients with Cushing's disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D 3 , 25(OH)D 2 , 1,25(OH) 2 D 3 , 3-epi-25(OH)D 3 and 24,25(OH) 2 D 3 ), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D 3 levels ( p > 0.05) and higher 25(OH)D 3 /24,25(OH) 2 D 3 ratios ( p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels ( p < 0.05) despite similar DBP levels ( p > 0.05) and lower albumin levels ( p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D 3 /24,25(OH) 2 D 3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D 3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI ( p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently higher 25(OH)D 3 /24,25(OH) 2 D 3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

Background: Hyperuricemia induces nephropathy through the mediation of oxidative stress, tubular injury, inflammation, and fibrosis. The high uric acid level is associated with the reduction of vitamin D levels. However, the reno-protective effects of this vitamin in hyperuricemia condition remain unknown. This study aimed to elucidate calcitriol treatment in a uric acid-induced hyperuricemia mice model., Methods: : Uric acid (125 mg/kg body weight [BW]) was administered intraperitoneally for 7 (UA7) and 14 (UA14) days. Calcitriol (0.5 g/kg BW) was intraperitoneally injected for the following seven days, after 14 days of uric acid induction (UA14VD7 group). The control group received NaCl 0.9%, by the same route. Serum creatinine was measured using calorimetric method, and uric acid levels were assessed using enzymatic calorimetric assay. Tubular injury and fibrosis were assessed using PAS and Sirius red staining. RT-PCR and real-time reverse transcription PCR were carried out for the analyses of SOD-1, Collagen-1, and TGF-1 mRNA expression in the kidney. Immunostaining of super oxide dismutase type 1 (SOD-1) was performed to detect its expression in the kidney., Results: Uric acid and creatinine levels markedly increased in UA14 groups, followed by an exacerbation of tubular injury. RT-PCR revealed the upregulation of Collagen-1 and TGF-1, along with the downregulation of SOD-1. Calcitriol treatment attenuated the injury with reducing uric acid and creatinine levels, as well as tubular injury. This was associated with lower Collagen-1 and TGF-1 mRNA expression compared to the UA7 and UA14 groups. SOD-1 was upregulated in epithelial cells in the UA14VD7 group., Conclusion: Calcitriol treatment after uric acid induction may attenuate kidney injury through upregulation of SOD-1 and downregulation of Collagen-1 and TGF-1 gene expression.

The Western-style diet, which is common in developed countries and spreading into developing countries, is unbalanced in many respects. For instance, micronutrients (vitamins A, B complex, C, D, E, and K plus iron, zinc, selenium, and iodine) are generally depleted in Western food (causing what is known as 'hidden hunger'), whereas some others (such as phosphorus) are added beyond the daily allowance. This imbalance in micronutrients can induce cellular damage that can increase the risk of cancer. Interestingly, there is a large body of evidence suggesting a strong correlation between vitamin intake as well as vitamin blood concentrations with the occurrence of certain types of cancer. The direction of association between the concentration of a given vitamin and cancer risk is tumor specific. The present review summarized the literature regarding vitamins and cancer risk to assess whether these could be used as diagnostic or prognostic markers, thus confirming their potential as biomarkers. Despite many studies that highlight the importance of monitoring vitamin blood or tissue concentrations in cancer patients and demonstrate the link between vitamin intake and cancer risk, there is still an urgent need for more data to assess the effectiveness of vitamins as biomarkers in the context of cancer. Therefore, this review aims to provide a solid basis to support further studies on this promising topic.

Prevention of preeclampsia (PE) remains one of the most significant problems in perinatal medicine. Due to the possible unpredictable course of hypertension in pregnancy, primarily PE and the high complication rate for the mother and fetus/newborn, it is urgent to offer pregnant women in high-risk groups effective methods of preventing the PE development or delaying its appearance. In addition, due to the association of PE with an increased risk of developing cardiovascular diseases (CVD) in later life, effective preeclampsia prevention could also be important in reducing their incidence. Ideal PE prophylaxis should target the pathogenetic changes leading to the development of PE and be safe for the mother and fetus, inexpensive and freely available. Currently, the only recognized method of PE prevention recommended by many institutions around the world is the use of a small dose of acetylsalicylic acid in pregnant women with risk factors. Unfortunately, some cases of PE are diagnosed in women without recognized risk factors and in those in whom prophylaxis with acetylsalicylic acid is not adequate. Hence, new drugs which would target pathogenetic elements in the development of preeclampsia are studied. Vitamin D (Vit D) seems to be a promising agent due to its beneficial effect on placental implantation, the immune system, and angiogenic factors. Studies published so far emphasize the relationship of its deficiency with the development of PE, but the data on the benefits of its supplementation to reduce the risk of PE are inconclusive. In the light of current research, the key issue is determining the protective concentration of Vit D in a pregnant woman. The study aims to present the possibility of using Vit D to prevent PE, emphasizing its impact on the pathogenetic elements of preeclampsia development.

To date, vitamin D seems to have a significant role in affecting the prevention and immunomodulation in COVID-19 disease. Nevertheless, it is important to highlight that this pro-hormone has other several activities, such as affecting drug concentrations, since it regulates the expression of cytochrome P450 (CYP) genes. Efavirenz (EFV) pharmacokinetics is influenced by CYPs, but no data are available in the literature concerning the association among vitamin D levels, seasonality (which affects vitamin D concentrations) and EFV plasma levels. For this reason, the aim of this study was to evaluate the effect of 25-hydroxy vitamin D (25(OH)D3) levels on EFV plasma concentrations in different seasons. We quantified 25(OH)D3 by using chemiluminescence immunoassay, whereas EFV plasma concentrations were quantified with the HPLC-PDA method. A total of 316 patients were enrolled in Turin and Rome. Overall, 25(OH)D3levels resulted in being inversely correlated with EFV concentrations. Some patients with EFV levels higher than 4000 ng/mL showed a deficient 25(OH)D3 concentration in Turin and Rome cohorts and together. EFV concentrations were different in patients without vitamin D supplementation, whereas, for vitamin D-administered individuals, no difference in EFV exposure was present. Concerning seasonality, EFV concentrations were associated with 25(OH)D3 deficiency only in winter and in spring, whereas a significant influence was highlighted for 25(OH)D3 stratification for deficient, insufficient and sufficient values in winter, spring and summer. A strong and inverse association between 25(OH)D3and EFV plasma concentrations was suggested. These data suggest that vitamin D is able to affect drug exposure in different seasons; thus, the achievement of the clinical outcome could be improved by also considering this pro-hormone.