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Pleiotropic Actions of Vitamin D: Proceedings from the 6th International Conference “Vitamin D—Minimum, Maximum, Optimum”

A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 90162

Special Issue Editor


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Guest Editor
Department of Clinical Biochemistry, The Children's Memorial Health Institute, 04-730 Warsaw, Poland
Interests: vitamin D and its pleiotropic action; guidelines of vitamin D supplementation; disturbances of calcium-phosphate metabolism; disturbances of bone tissue metabolism; body composition and biological development; basics of statistics; GLP; research methodology
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Special Issue Information

Dear Colleagues,

It is a great pleasure to welcome you to this Special Issue of Nutrients related to the 6th International Conference “Vitamin D—Minimum, Maximum, Optimum”, under the auspices of the European Vitamin D Association (EVIDAS).

The conference and the forthcoming papers serve as an international forum for the presentation and discussion of current basic and clinical research in the field of vitamin D. Organizing this subsequent Special Issue has been truly challenging, given that the vitamin D has recently been shown by prestigious medical journals as an epiphenomenon that coincides with diseases, and that the correction of vitamin D deficits has limited clinical meaning. On the other hand, it is recognized that vitamin D deficiency is a global health problem with potential negative consequences on health, welfare, and morbidity during growth and adulthood, therefore influencing health care services worldwide. Thus, due to mutually exclusive conclusions, it is essential to discuss and share scientific reports and evidence demonstrating both the benefits and lack thereof in relation to human health.

Dr. Pawel Pludowski
Guest Editor

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Keywords

  • vitamin D
  • cholecalciferol
  • calcifediol
  • pleiotropic action of vitamin D

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Published Papers (11 papers)

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Research

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12 pages, 696 KiB  
Article
Classification of Vitamin D Status Based on Vitamin D Metabolism: A Randomized Controlled Trial in Hypertensive Patients
by Sieglinde Zelzer, Andreas Meinitzer, Dietmar Enko, Martin H. Keppel, Markus Herrmann, Verena Theiler-Schwetz, Christian Trummer, Lisa Schmitt, Andreas Tomaschitz, Patrick Sadoghi, Jutta Dierkes, Pawel Pludowski, Armin Zittermann, Winfried März and Stefan Pilz
Nutrients 2024, 16(6), 839; https://doi.org/10.3390/nu16060839 - 14 Mar 2024
Cited by 2 | Viewed by 2344
Abstract
Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite [...] Read more.
Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of “functional vitamin D deficiency”, i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs. Full article
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14 pages, 4698 KiB  
Article
Protein Disulfide Isomerase Family A Member 3 Knockout Abrogate Effects of Vitamin D on Cellular Respiration and Glycolysis in Squamous Cell Carcinoma
by Joanna I. Nowak, Anna M. Olszewska, Oliwia Król and Michał A. Żmijewski
Nutrients 2023, 15(21), 4529; https://doi.org/10.3390/nu15214529 - 25 Oct 2023
Cited by 1 | Viewed by 1058
Abstract
PDIA3 is an endoplasmic reticulum disulfide isomerase, which is involved in the folding and trafficking of newly synthesized proteins. PDIA3 was also described as an alternative receptor for the active form of vitamin D (1,25(OH)2D3). Here, we investigated an [...] Read more.
PDIA3 is an endoplasmic reticulum disulfide isomerase, which is involved in the folding and trafficking of newly synthesized proteins. PDIA3 was also described as an alternative receptor for the active form of vitamin D (1,25(OH)2D3). Here, we investigated an impact of PDIA3 in mitochondrial morphology and bioenergetics in squamous cell carcinoma line A431 treated with 1,25(OH)2D3. It was observed that PDIA3 deletion resulted in changes in the morphology of mitochondria including a decrease in the percentage of mitochondrial section area, maximal diameter, and perimeter. The 1,25(OH)2D3 treatment of A431∆PDIA3 cells partially reversed the effect of PDIA3 deletion increasing aforementioned parameters; meanwhile, in A431WT cells, only an increase in mitochondrial section area was observed. Moreover, PDIA3 knockout affected mitochondrial bioenergetics and modulated STAT3 signaling. Oxygen consumption rate (OCR) was significantly increased, with no visible effect of 1,25(OH)2D3 treatment in A431∆PDIA3 cells. In the case of Extracellular Acidification Rate (ECAR), an increase was observed for glycolysis and glycolytic capacity parameters in the case of non-treated A431WT cells versus A431∆PDIA3 cells. The 1,25(OH)2D3 treatment had no significant effect on glycolytic parameters. Taken together, the presented results suggest that PDIA3 is strongly involved in the regulation of mitochondrial bioenergetics in cancerous cells and modulation of its response to 1,25(OH)2D3, possibly through STAT3. Full article
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14 pages, 721 KiB  
Article
Correlation between Serum 25-Hydroxyvitamin D Concentration, Monocyte-to-HDL Ratio and Acute Coronary Syndrome in Men with Chronic Coronary Syndrome—An Observational Study
by Ewelina A. Dziedzic, Jakub S. Gąsior, Agnieszka Tuzimek, Marek Dąbrowski and Wacław Kochman
Nutrients 2023, 15(20), 4487; https://doi.org/10.3390/nu15204487 - 23 Oct 2023
Cited by 2 | Viewed by 1435
Abstract
Cardiovascular disease (CVD) continues to be the leading cause of death in European men. Atherosclerosis and its clinical consequence, chronic coronary syndrome (CCS), comprise two main elements: dysfunction of lipoprotein metabolism and an important inflammatory component that contributes to the development of complications, [...] Read more.
Cardiovascular disease (CVD) continues to be the leading cause of death in European men. Atherosclerosis and its clinical consequence, chronic coronary syndrome (CCS), comprise two main elements: dysfunction of lipoprotein metabolism and an important inflammatory component that contributes to the development of complications, including acute coronary syndrome (ACS). Measures of both components are combined in a composite marker called monocyte-to-HDL ratio (MHR). Vitamin D was previously described to influence inflammation processes, and its deficiency influences CVD risk factors. This research describes the differences in MHR and total serum 25-hydroxyvitamin D (25(OH)D) concentration between male patients with different diagnoses of CCS and the correlation between 25(OH)D and MHR in this group. Significant differences were observed between ACS and CCS patients in 25(OH)D and MHR—the highest HDL and serum 25(OH)D concentrations were observed in patients with CCS, whereas the highest value of MHR was observed in patients with STEMI. A significant correlation was observed between 25(OH)D, HDL, and MHR. Due to the significant but small nominal difference in MHR values between groups of patients diagnosed with ACS and CCS, and the possible influence of age and hyperlipidemia status on the differences in vitamin D levels in these groups, this subject requires further well-designed research. The suggested bidirectional relationship between MHR and 25(OH)D and the role of MHR as a predictor of vitamin D status in the body also needs to be verified. Full article
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11 pages, 624 KiB  
Article
25(OH)D Concentration in Neonates, Infants, Toddlers, Older Children and Teenagers from Poland—Evaluation of Trends during Years 2014–2019
by Marek Wójcik, Maciej Jaworski and Paweł Płudowski
Nutrients 2023, 15(15), 3477; https://doi.org/10.3390/nu15153477 - 6 Aug 2023
Cited by 3 | Viewed by 1310
Abstract
Introduction: Local and international guidelines have provided schedules for the vitamin D supplementation of general populations of different ages, including children. Our study aimed to assess 25(OH)D concentration and its potential change during a growth and maturation period, adding parameters that reflect the [...] Read more.
Introduction: Local and international guidelines have provided schedules for the vitamin D supplementation of general populations of different ages, including children. Our study aimed to assess 25(OH)D concentration and its potential change during a growth and maturation period, adding parameters that reflect the risk of hypercalcemia. Materials and methods: The available 25(OH)D concentration values (n = 17,636; 7.8 ± 6.0 years), calcium (n = 2673; 16.3 ± 6.1 years) and phosphate (n = 2830; 3.8 ± 5.2 years) metabolism markers were analyzed in a studied group of patients (0–18 years). Results: In the studied group the mean 25(OH)D concentration was 29.4 ± 11.7 ng/mL. Concentrations of 25(OH)D < 10 ng/mL were observed in 1.7% of patients (n = 292), 10–20 ng/mL in 17.2% (n = 3039), 20–30 ng/mL in 39.5% (n = 6960) and 30–50 ng/mL in 37.2% (n = 6567). In patients with a 25(OH)D concentration <10 ng/mL, normal calcemia (2.25–2.65 mmol/L) was observed in 29.5% of cases (n = 86). Three patients had 25(OH)D concentrations above 100 ng/mL with co-existing hypercalcemia; the mean was Ca = 3.40 mmol/L. Hypocalcemia (Ca < 2.25 mmol/L) was observed in 10,4% of patients (n = 2797). Furthermore, 5.0% of patients showed an increased calcium concentration >2.65 mmol/L (n = 1327). The highest mean 25(OH)D concentration of 32.1 ng/mL ± 12.9 was noted in the years 2018–2019 (n = 3931) and the lowest in the year 2015 (27.2 ng/mL ± 11.0; n = 2822). Conclusions: Vitamin D deficiency (<20 ng/mL) was noted in 18,9% of subjects in the years 2014–2019. An effective prevention of vitamin D deficiency was observed in children aged 3 years and younger. A relationship between the concentrations of calcium and 25(OH)D was not observed. Full article
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14 pages, 1409 KiB  
Article
Vitamin D Deficiency Prevalence in Hospitalized Patients with COVID-19 Significantly Decreased during the Pandemic in Slovakia from 2020 to 2022 Which Was Associated with Decreasing Mortality
by Juraj Smaha, Peter Jackuliak, Martin Kužma, Filip Max, Neil Binkley and Juraj Payer
Nutrients 2023, 15(5), 1132; https://doi.org/10.3390/nu15051132 - 23 Feb 2023
Cited by 3 | Viewed by 2441
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has led to changes in lifestyle, which could influence vitamin D status on a population level. The purpose of our study was to compare 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized because of severe COVID-19 during two [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has led to changes in lifestyle, which could influence vitamin D status on a population level. The purpose of our study was to compare 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized because of severe COVID-19 during two waves of the pandemic (2020/21 vs. 2021/22). A total of 101 patients from the 2021/22 wave were compared with 101 sex- and age-matched subjects from the 2020/21 wave. Patients from both groups were hospitalized during the winter season from 1 December to 28 February. Men and women were analyzed together and separately. The mean 25(OH)D concentration increased from 17.8 ± 9.7 ng/mL to 25.2 ± 12.6 ng/mL between waves. The prevalence of vitamin D deficiency (<20 ng/mL) decreased from 82% to 54%. The prevalence of adequate serum 25(OH)D concentration (>30 ng/mL) increased from 10% to 34% (p < 0.0001). The proportion of patients with a history of vitamin D supplementation increased from 18% to 44% (p < 0.0001). Low serum 25(OH)D concentration was independently associated with mortality after adjusting for age and sex for the whole cohort of patients (p < 0.0001). The prevalence of inadequate vitamin D status in hospitalized patients with COVID-19 in Slovakia decreased significantly, probably due to a higher rate of vitamin D supplementation during the COVID-19 pandemic. Full article
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Review

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15 pages, 640 KiB  
Review
Vitamin D Supplementation: A Review of the Evidence Arguing for a Daily Dose of 2000 International Units (50 µg) of Vitamin D for Adults in the General Population
by Pawel Pludowski, William B. Grant, Spyridon N. Karras, Armin Zittermann and Stefan Pilz
Nutrients 2024, 16(3), 391; https://doi.org/10.3390/nu16030391 - 29 Jan 2024
Cited by 10 | Viewed by 24739
Abstract
Vitamin D deficiency is considered a public health problem due to its worldwide high prevalence and adverse clinical consequences regarding musculoskeletal health. In addition, vitamin D may also be crucial for the prevention of certain extraskeletal diseases. Despite decades of intensive scientific research, [...] Read more.
Vitamin D deficiency is considered a public health problem due to its worldwide high prevalence and adverse clinical consequences regarding musculoskeletal health. In addition, vitamin D may also be crucial for the prevention of certain extraskeletal diseases. Despite decades of intensive scientific research, several knowledge gaps remain regarding the precise definition of vitamin D deficiency and sufficiency, the health benefits of improving vitamin D status, and the required vitamin D intakes. Consequently, various societies and expert groups have released heterogeneous recommendations on the dosages for vitamin D supplementation. In this brief narrative review, we outline and discuss recent advances regarding the scientific evidence arguing for a daily vitamin D supplementation with 2000 international units (IU) (50 µg) of vitamin D3 to prevent and treat vitamin D deficiency. According to data from randomized controlled trials (RCTs), such a dose may improve some health outcomes and is sufficient to raise and maintain serum 25(OH)D concentrations above 50 nmol/L (20 ng/mL) and above 75 nmol/L (30 ng/mL) in >99% and >90% of the general adult population, respectively. According to large vitamin D RCTs, there are no significant safety concerns in supplementing such a dose for several years, even in individuals with an already sufficient vitamin D status at baseline. A daily vitamin D supplementation with 2000 IU (50 µg) may be considered a simple, effective, and safe dosage to prevent and treat vitamin D deficiency in the adult general population. Full article
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14 pages, 334 KiB  
Review
Ukrainian Consensus on Diagnosis and Management of Vitamin D Deficiency in Adults
by Nataliia Grygorieva, Mykola Tronko, Volodymir Kovalenko, Serhiy Komisarenko, Tetiana Tatarchuk, Ninel Dedukh, Mykola Veliky, Serhiy Strafun, Yulia Komisarenko, Andrii Kalashnikov, Valeria Orlenko, Volodymyr Pankiv, Oleg Shvets, Inna Gogunska and Svitlana Regeda
Nutrients 2024, 16(2), 270; https://doi.org/10.3390/nu16020270 - 16 Jan 2024
Cited by 5 | Viewed by 2391
Abstract
Vitamin D deficiency (VDD) is a global problem, however, there were no Ukrainian guidelines devoted to its screening, prevention, and treatment, which became the reason for the Consensus creation. This article aimed to present the Consensus of Ukrainian experts devoted to VDD management. [...] Read more.
Vitamin D deficiency (VDD) is a global problem, however, there were no Ukrainian guidelines devoted to its screening, prevention, and treatment, which became the reason for the Consensus creation. This article aimed to present the Consensus of Ukrainian experts devoted to VDD management. Following the creation of the multidisciplinary Consensus group, consent on the formation process, drafting and fine-tuning of key recommendations, and two rounds of voting, 14 final recommendations were successfully voted upon. Despite a recent decrease in VDD prevalence in Ukraine, we recommend raising awareness regarding VDD’s importance and improving the strategies for its decline. We recommend screening the serum 25-hydroxyvitamin D (25(OH)D) level in risk groups while maintaining a target concentration of 75–125 nmol/L (30–50 ng/mL). We recommend prophylactic cholecalciferol supplementation (800–2000 IU/d for youthful healthy subjects, and 3000–5000 IU/d for subjects from the risk groups). For a VDD treatment, we recommend a short-term administration of increased doses of cholecalciferol (4000–10,000 IU/d) with 25(OH)D levels monitored after 4–12 weeks of treatment, followed by the use of maintenance doses. Additionally, we recommend assessing serum 25(OH)D levels before antiosteoporotic treatment and providing vitamin D and calcium supplementation throughout the full course of the antiosteoporotic therapy. Full article
13 pages, 303 KiB  
Review
Supplementing Vitamin D in Different Patient Groups to Reduce Deficiency
by Pawel Pludowski
Nutrients 2023, 15(17), 3725; https://doi.org/10.3390/nu15173725 - 25 Aug 2023
Cited by 6 | Viewed by 3035
Abstract
Introduction: Studies indicate a high prevalence of vitamin D deficiency in both the general population and at-risk groups. Given the association between vitamin D deficiency and various diseases, addressing this concern becomes crucial, especially in situations where routine monitoring is challenging. Materials and [...] Read more.
Introduction: Studies indicate a high prevalence of vitamin D deficiency in both the general population and at-risk groups. Given the association between vitamin D deficiency and various diseases, addressing this concern becomes crucial, especially in situations where routine monitoring is challenging. Materials and methods: A systematic literature review of the current knowledge on vitamin D dosing in diverse at-risk populations and the application of the findings to a broader clinical perspective. Results: The reviewed studies revealed a high prevalence of vitamin D deficiency among patients with musculoskeletal disorders, systemic connective tissue diseases, corticosteroid use, endocrine and metabolic conditions, malabsorption syndromes, obesity, chronic kidney disease, cancer, and central nervous system diseases. Vitamin D deficiency was often more severe compared to the general population. Higher dosages of vitamin D beyond the recommended levels for the general population were shown to be effective in improving vitamin D status in these at-risk individuals. Additionally, some studies suggested a potential link between intermittent vitamin D administration and improved adherence. Conclusion: Simplified dosing could empower clinicians to address vitamin D deficiency, particularly in high-risk populations, even without routine monitoring. Further research is needed to establish the optimal dosing regimens for specific at-risk populations. Full article
13 pages, 1339 KiB  
Review
Intervention Approaches in Studying the Response to Vitamin D3 Supplementation
by Emilia Gospodarska, Ranjini Ghosh Dastidar and Carsten Carlberg
Nutrients 2023, 15(15), 3382; https://doi.org/10.3390/nu15153382 - 29 Jul 2023
Cited by 10 | Viewed by 2408
Abstract
Vitamin D intervention studies are designed to evaluate the impact of the micronutrient vitamin D3 on health and disease. The appropriate design of studies is essential for their quality, successful execution, and interpretation. Randomized controlled trials (RCTs) are considered the “gold standard” [...] Read more.
Vitamin D intervention studies are designed to evaluate the impact of the micronutrient vitamin D3 on health and disease. The appropriate design of studies is essential for their quality, successful execution, and interpretation. Randomized controlled trials (RCTs) are considered the “gold standard” for intervention studies. However, the most recent large-scale (up to 25,000 participants), long-term RCTs involving vitamin D3 did not provide any statistically significant primary results. This may be because they are designed similarly to RCTs of a therapeutic drug but not of a nutritional compound and that only a limited set of parameters per individual were determined. We propose an alternative concept using the segregation of study participants into different groups of responsiveness to vitamin D3 supplementation and in parallel measuring a larger set of genome-wide parameters over multiple time points. This is in accordance with recently developed mechanistic modeling approaches that do not require a large number of study participants, as in the case of statistical modeling of the results of a RCT. Our experience is based on the vitamin D intervention trials VitDmet, VitDbol, and VitDHiD, which allowed us to distinguish the study participants into high, mid, and low vitamin D responders. In particular, investigating the vulnerable group of low vitamin D responders will provide future studies with more conclusive results both on the clinical and molecular benefits of vitamin D3 supplementation. In conclusion, our approach suggests a paradigm shift towards detailed investigations of transcriptome and epigenome-wide parameters of a limited set of individuals, who, due to a longitudinal design, can act as their own controls. Full article
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22 pages, 374 KiB  
Review
Guidelines for Preventing and Treating Vitamin D Deficiency: A 2023 Update in Poland
by Paweł Płudowski, Beata Kos-Kudła, Mieczysław Walczak, Andrzej Fal, Dorota Zozulińska-Ziółkiewicz, Piotr Sieroszewski, Jarosław Peregud-Pogorzelski, Ryszard Lauterbach, Tomasz Targowski, Andrzej Lewiński, Robert Spaczyński, Mirosław Wielgoś, Jarosław Pinkas, Teresa Jackowska, Ewa Helwich, Artur Mazur, Marek Ruchała, Arkadiusz Zygmunt, Mieczysław Szalecki, Artur Bossowski, Justyna Czech-Kowalska, Marek Wójcik, Beata Pyrżak, Michał A. Żmijewski, Paweł Abramowicz, Jerzy Konstantynowicz, Ewa Marcinowska-Suchowierska, Andrius Bleizgys, Spirydon N. Karras, William B. Grant, Carsten Carlberg, Stefan Pilz, Michael F. Holick and Waldemar Misiorowskiadd Show full author list remove Hide full author list
Nutrients 2023, 15(3), 695; https://doi.org/10.3390/nu15030695 - 30 Jan 2023
Cited by 89 | Viewed by 35992
Abstract
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 [...] Read more.
Introduction: All epidemiological studies suggest that vitamin D deficiency is prevalent among the Polish general population. Since vitamin D deficiency was shown to be among the risk factors for many diseases and for all-cause mortality, concern about this problem led us to update the previous Polish recommendations. Methods: After reviewing the epidemiological evidence, case-control studies and randomized control trials (RCTs), a Polish multidisciplinary group formulated questions on the recommendations for prophylaxis and treatment of vitamin D deficiency both for the general population and for the risk groups of patients. The scientific evidence of pleiotropic effects of vitamin D as well as the results of panelists’ voting were reviewed and discussed. Thirty-four authors representing different areas of expertise prepared position statements. The consensus group, representing eight Polish/international medical societies and eight national specialist consultants, prepared the final Polish recommendations. Results: Based on networking discussions, the ranges of total serum 25-hydroxyvitamin D concentration indicating vitamin D deficiency [<20 ng/mL (<50 nmol/L)], suboptimal status [20–30 ng/mL (50–75 nmol/L)], and optimal concentration [30–50 ng/mL (75–125 nmol/L)] were confirmed. Practical guidelines for cholecalciferol (vitamin D3) as the first choice for prophylaxis and treatment of vitamin D deficiency were developed. Calcifediol dosing as the second choice for preventing and treating vitamin D deficiency was introduced. Conclusions: Improving the vitamin D status of the general population and treatment of risk groups of patients must be again announced as healthcare policy to reduce a risk of spectrum of diseases. This paper offers consensus statements on prophylaxis and treatment strategies for vitamin D deficiency in Poland. Full article

Other

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15 pages, 771 KiB  
Conference Report
Rickets Types and Treatment with Vitamin D and Analogues
by Giacomo Biasucci, Valentina Donini and Giuseppe Cannalire
Nutrients 2024, 16(3), 416; https://doi.org/10.3390/nu16030416 - 31 Jan 2024
Cited by 1 | Viewed by 5377
Abstract
The definition of “Vitamin D” encompasses a group of fat-soluble steroid compounds of different origins with similar chemical structures and the same biological effects. Vitamin D deficiency and/or a defect in the process of its synthesis or transport predispose individuals to several types [...] Read more.
The definition of “Vitamin D” encompasses a group of fat-soluble steroid compounds of different origins with similar chemical structures and the same biological effects. Vitamin D deficiency and/or a defect in the process of its synthesis or transport predispose individuals to several types of rickets. In addition to cholecalciferol, ergocalciferol, and vitamins D3 and D2, there are also active metabolites for the treatment of this condition which are commercially available. Calcitriol and aphacalcidiol are active metabolites that do not require the renal activation step, which is required with calcifediol, or hepatic activation. The purpose of this review is to summarize current approaches to the treatment of rickets for generalist physicians, focusing on the best vitamin D form to be used in each type, or, in the case of X-linked hypophosphatemic rickets (XLH), on both conventional and innovative monoclonal antibody treatments. Full article
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