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The Role of Vitamin D in Human Health and Diseases 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 57306

Special Issue Editors

Dr. Francesca Silvagno

E-Mail Website
Guest Editor
Department of Oncology, University of Torino, Via Santena 5 bis, 10126 Torino, Italy
Interests: cancer metabolism; vitamin D; TGF beta; mitochondrial metabolism; biochemistry; electromagnetic field; cancer growth; dermal wound healing; nutraceuticals
Special Issues, Collections and Topics in MDPI journals
Dr. Loredana Bergandi

E-Mail Website
Guest Editor
Department of Oncology, University of Torino, Via Santena 5 bis, 10126 Torino, Italy
Interests: nitric oxide; oxidative/nitrosative stress; in vitro bioglass compatibility; asbestos; epithelial–mesenchymal transition; oocytes competence; metabolic shift; chemoresistance
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vitamin D has been described as a differentiative hormone, but this definition is reductive for a molecule targeting every tissue, produced in its active form by many kinds of cells and effective over the whole life of a cell by means of different mechanisms, which lead to nuclear, non-genomic, and mitochondrial effects. In fact, vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences cell metabolism to support specific nuclear programs. Given its broad spectrum of activity and molecular and cellular targets, it is not surprising that a deficiency in vitamin D is involved in many pathologies. In addition to its well-known impact on several functions, such as bone remodeling, skin differentiation, and the immune system, to cite just a few, many other tissues depend heavily on vitamin D for their health, and therefore, the correlation between low levels of vitamin D and the onset of many diseases has been reported. However, many other links could be revealed. For example, considering the current COVID-19 pandemic, a recent discovery showed that a deficiency in vitamin D is among the risk factors associated with the severity of COVID-19 symptoms and outcomes.

In vitro studies and those in animal models have demonstrated the efficacy of vitamin D treatment in many models of disease and have proposed the beneficial effects of vitamin D supplementation on health and prevention, as well as the regression of multiple diseases. As a result, several clinical trials are testing the efficacy of vitamin D supplementation in human disfunctions; although some results are encouraging, a few discrepancies can be due to differences in therapy protocols and resistance to the hormone, and in general, these discrepancies can be explained by an individual’s sensitivity to its action. More studies, both in vitro and in vivo, are needed to verify the mechanisms involved in successful or failed treatment with vitamin D, and further investigation is essential to set out an approach from bench to bedside, underlying personalized medicine.

This Special Issue gives insight into the evolving field of vitamin D regarding its mechanisms of action, causes of a deficit, proper supplementation, health benefits, and clinical applications.

Dr. Francesca Silvagno
Dr. Loredana Bergandi
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

 

Keywords

  • vitamin D
  • vitamin D receptor
  • health
  • disease
  • inflammation
  • gene transcription
  • cell metabolism
  • differentiation
  • vitamin D deficiency
  • vitamin D supplementation

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Published Papers (18 papers)

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Editorial

Jump to: Research, Review

3 pages, 191 KiB  
Editorial
Editorial of Special Issue “The Role of Vitamin D in Human Health and Diseases 2.0”
by Francesca Silvagno and Loredana Bergandi
Int. J. Mol. Sci. 2023, 24(5), 4337; https://doi.org/10.3390/ijms24054337 - 22 Feb 2023
Viewed by 1026
Abstract
Vitamin D performs a differentiating, metabolic and anti-inflammatory function, through genomic, non-genomic and mitochondrial mechanisms of action [...] Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)

Research

Jump to: Editorial, Review

9 pages, 554 KiB  
Article
Influence of Single-Nucleotide Polymorphisms on Vitamin D Receptor Expression in Periodontal Ligament Fibroblasts as a Response to Orthodontic Compression
by Erika Calvano Küchler, Agnes Schröder, Gerrit Spanier, Geraldo Thedei, Jr., Maria Beatriz Carvalho Ribeiro de Oliveira, Maria Angélica Hueb de Menezes-Oliveira, Peter Proff and Christian Kirschneck
Int. J. Mol. Sci. 2022, 23(24), 15948; https://doi.org/10.3390/ijms232415948 - 15 Dec 2022
Cited by 4 | Viewed by 1452
Abstract
This study aimed to evaluate if single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene are associated with gene expression in human periodontal ligament (hPDL) fibroblasts under simulated orthodontic compressive force. hPDL samples from 57 patients were used. A physiological compressive strain [...] Read more.
This study aimed to evaluate if single-nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene are associated with gene expression in human periodontal ligament (hPDL) fibroblasts under simulated orthodontic compressive force. hPDL samples from 57 patients were used. A physiological compressive strain was performed to simulate orthodontic tooth movement in pressure areas under cell culture conditions. The RNA from hPDL fibroblasts was isolated to determine the relative gene expression (mRNA) of the VDR. The DNA was also isolated for the genotyping analysis of five SNPs in the VDR gene: BglI (rs739837, G/T), BsmI (rs1544410, T/C), ApaI (rs7975232, A/C), FokI (rs2228570, A/G), and TaqI (rs731236, A/G). Real-time polymerase chain reaction was used for both analyses. Kruskal–Wallis tests were used to compare VDR expression among genotypes of each SNP. A linear regression analysis was performed to evaluate SNP–SNP interaction. An established alpha of 5% was used. The relative mRNA VDR expression according to the genotypes in the SNPs BglI, BsmI, ApaI, FokI, and TaqI was not statistically significantly different (p > 0.05). The SNP–SNP interaction evaluated by regression analysis did not demonstrate any statistically significant association. No association was observed (p > 0.05). In conclusion, the SNPs BglI (rs739837), BsmI (rs1544410), ApaI (rs7975232), FokI (rs2228570), and TaqI (rs731236) did not show an impact on VDR gene expression in hPDL fibroblasts under simulated orthodontic compressive force. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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11 pages, 564 KiB  
Communication
Association between 25-OH Vitamin D Deficiency and COVID-19 Severity in Pregnant Women
by Johana Vásquez-Procopio, Johnatan Torres-Torres, Hector Borboa-Olivares, Salvador Espino Y Sosa, Raigam Jafet Martínez-Portilla, Mario Solis-Paredes, Mari-Cruz Tolentino-Dolores, Addy Cecilia Helguera-Repetto, Karla Cecilia Marrufo-Gallegos, Fanis Missirlis, Otilia Perichart-Perera and Guadalupe Estrada-Gutierrez
Int. J. Mol. Sci. 2022, 23(23), 15188; https://doi.org/10.3390/ijms232315188 - 2 Dec 2022
Cited by 5 | Viewed by 5415
Abstract
Evidence from studies in the general population suggests an association between vitamin D insufficiency/deficiency and COVID-19 susceptibility and disease severity. The present study was performed on 165 third-trimester pregnant women at the time of delivery. Seventy-nine women tested negative for SARS-CoV-2. From 86 [...] Read more.
Evidence from studies in the general population suggests an association between vitamin D insufficiency/deficiency and COVID-19 susceptibility and disease severity. The present study was performed on 165 third-trimester pregnant women at the time of delivery. Seventy-nine women tested negative for SARS-CoV-2. From 86 women testing positive, 32 were asymptomatic, 44 presented a mild form of the disease, and 10 experienced severe symptoms. Serum 25-OH vitamin D levels were measured on blood samples collected on admission. Low vitamin D levels were detected in symptomatic but not asymptomatic COVID-19 patients compared to healthy women (p = 0.0227). In addition, 20 (45.4%) pregnant women in the mild COVID-19 group and 6 (60%) in the severe group were vitamin D deficient (p = 0.030). On the other hand, lasso regression analysis showed that 25-OH vitamin D deficiency is an independent predictor of severe COVID-19 with an odds ratio (OR) of 5.81 (95% CI: 1.108–30.541; p = 0.037). These results show the relationship between vitamin D deficiency in pregnant women and the severity of COVID-19 infection and support the recommendation to supplement with vitamin D to avoid worse COVID-19 outcomes during pregnancy. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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20 pages, 2940 KiB  
Article
Vitamin D Deficiency and COVID-19: A Biological Database Study on Pathways and Gene-Disease Associations
by Ángela Alcalá-Santiago, Miguel Rodríguez-Barranco, Marta Rava, María Ángeles Jiménez-Sousa, Ángel Gil, María José Sánchez and Esther Molina-Montes
Int. J. Mol. Sci. 2022, 23(22), 14256; https://doi.org/10.3390/ijms232214256 - 17 Nov 2022
Cited by 3 | Viewed by 2602
Abstract
Vitamin D (VD) is a fat-soluble vitamin, and pivotal for maintaining health. Several genetic markers have been related to a deficient VD status; these markers could confer an increased risk to develop osteoporosis and other chronic diseases. A VD deficiency could also be [...] Read more.
Vitamin D (VD) is a fat-soluble vitamin, and pivotal for maintaining health. Several genetic markers have been related to a deficient VD status; these markers could confer an increased risk to develop osteoporosis and other chronic diseases. A VD deficiency could also be a determinant of a severe COVID-19 disease. This study aimed to interrogate genetic/biological databases on the biological implications of a VD deficiency and its association with diseases, to further explore its link with COVID-19. The genetic variants of both a VD deficiency and COVID-19 were identified in the genome-wide association studies (GWAS) catalog and other sources. We conducted enrichment analyses (considering corrected p-values < 0.05 as statistically significant) of the pathways, and gene-disease associations using tools, such as FUMA, REVIGO, DAVID and DisGeNET, and databases, such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). There were 26 and 46 genes associated with a VD deficiency and COVID-19, respectively. However, there were no genes shared between the two. Genes related to a VD deficiency were involved in the metabolism of carbohydrates, retinol, drugs and xenobiotics, and were associated with the metabolic syndrome and related factors (obesity, hypertension and diabetes mellitus), as well as with neoplasms. There were few enriched pathways and disease connections for the COVID-19-related genes, among which some of the aforementioned comorbidities were also present. In conclusion, genetic factors that influence the VD levels in the body are most prominently associated with nutritional and metabolic diseases. A VD deficiency in high-risk populations could be therefore relevant in a severe COVID-19, underlining the need to examine whether a VD supplementation could reduce the severity of this disease. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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13 pages, 1667 KiB  
Article
A Single Oral Vitamin D3 Bolus Reduces Inflammatory Markers in Healthy Saudi Males
by Shareefa A. AlGhamdi, Nusaibah N. Enaibsi, Hadeil M. Alsufiani, Huda F. Alshaibi, Sawsan O. Khoja and Carsten Carlberg
Int. J. Mol. Sci. 2022, 23(19), 11992; https://doi.org/10.3390/ijms231911992 - 9 Oct 2022
Cited by 4 | Viewed by 1589
Abstract
Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of [...] Read more.
Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of vitamin D3 is 4000 IU (100 µg) per day. In this study, we investigated whether a single vitamin D3 bolus can reduce the levels of the inflammatory markers interleukin (IL) 6, IL8 and tumor necrosis factor (TNF) within one month. Fifty healthy Saudi males were recruited from the local community in Jeddah city and were orally supplemented with a single dose of 80,000 IU vitamin D3. Serum samples were collected at time points 0, 1 and 30 days, and serum levels of IL6, IL8 and TNF, parathyroid hormone (PTH), 25-hydroxyvitamin D3 (25(OH)D3), triglycerides, cholesterol, calcium (Ca2+) and phosphate (PO4−) were determined. On average, the vitamin D3 bolus resulted in a significant increase in vitamin D status as well as in a significant decrease in the levels of inflammatory cytokines even one month after supplementation without changing serum Ca2+, PO4− or lipid levels. In conclusion, single high-dose vitamin D3 supplementation is safe for reducing inflammation markers and may lead to an update of current recommendations for vitamin D intake, in order to prevent critical health problems. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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15 pages, 2549 KiB  
Article
Effects of Vitamin D Supplementation on Adipose Tissue Inflammation and NF-κB/AMPK Activation in Obese Mice Fed a High-Fat Diet
by Eugene Chang
Int. J. Mol. Sci. 2022, 23(18), 10915; https://doi.org/10.3390/ijms231810915 - 18 Sep 2022
Cited by 11 | Viewed by 2441
Abstract
Adipose tissue expansion is strongly associated with increased adipose macrophage infiltration and adipocyte-derived pro-inflammatory cytokines, contributing to obesity-associated low-grade inflammation. Individuals with vitamin D deficiency have an increased prevalence of obesity and increased circulating inflammatory cytokines. However, the effect of vitamin D supplementation [...] Read more.
Adipose tissue expansion is strongly associated with increased adipose macrophage infiltration and adipocyte-derived pro-inflammatory cytokines, contributing to obesity-associated low-grade inflammation. Individuals with vitamin D deficiency have an increased prevalence of obesity and increased circulating inflammatory cytokines. However, the effect of vitamin D supplementation on obesity-induced inflammation remains controversial. Male C57BL/6J mice received a low-fat (10% fat) or high-fat (HF, 60% fat diet) containing 1000 IU vitamin D/kg diet, or HF supplemented with 10,000 IU vitamin D/kg diet for 16 weeks (n = 9/group). Vitamin D supplementation did not decrease HF-increased body weight but attenuated obesity-induced adipose hypertrophy and macrophage recruitment as demonstrated by the number of crown-like structures. Vitamin D supplementation significantly reduced the mRNA expression of CD11c, CD68, and iNOS, specific for inflammatory M1-like macrophages, and decreased serum levels of NO. In addition, significant reductions in pro-inflammatory gene expression of IL-6, MCP-1, and TNFα and mRNA levels of ASC-1, CASP1, and IL-1β involved in NLRP3 inflammasome were found in obese mice supplemented with vitamin D. Vitamin D supplementation significantly increased obesity-decreased AMPK activity and suppressed HF-increased NF-κB phosphorylation in adipose tissue from obese mice. These observed beneficial effects of vitamin D supplementation on adipose tissue expansion, macrophage recruitment, and inflammation might be related to AMPK/NF-κB signaling. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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13 pages, 2167 KiB  
Article
The Diurnal Blood Metabolome and Effects of Vitamin D Supplementation: A Randomised Crossover Trial in Postmenopausal Women
by Rasmus Espersen, Banny Silva Barbosa Correia, Lars Rejnmark and Hanne Christine Bertram
Int. J. Mol. Sci. 2022, 23(17), 9748; https://doi.org/10.3390/ijms23179748 - 28 Aug 2022
Cited by 1 | Viewed by 1573
Abstract
A way to maintain an adequate vitamin D status is through supplementation. Demonstration of blood-metabolome rhythmicity of vitamin D3 post-dosing effects is lacking in the pharmaco-metabonomics area. Thus, the overall aim of this study was to investigate the diurnal changes in the [...] Read more.
A way to maintain an adequate vitamin D status is through supplementation. Demonstration of blood-metabolome rhythmicity of vitamin D3 post-dosing effects is lacking in the pharmaco-metabonomics area. Thus, the overall aim of this study was to investigate the diurnal changes in the blood metabolome and how these are affected by vitamin D3 supplementation. The study was conducted as a crossover study, and the treatment included 200 µg (8000 IU) of vitamin D3 as compared with placebo with a washout period of at least 10 days. The participants were postmenopausal women aged 60–80 years (N = 29) with vitamin D insufficiency (serum 25-hydroxyvitamin D < 50 nmol/L) but otherwise healthy. During the intervention day, blood samples were taken at 0 h, 2 h, 4 h, 6 h, 8 h, 10 h, 12 h, and 24 h, and plasma was analysed by proton nuclear magnetic resonance (NMR) spectroscopy as a metabolomics approach. In general, diurnal effects were identified for the majority of the 20 quantified metabolites, and hierarchical cluster analysis revealed a change in the overall plasma metabolome around 12 AM (6 h after intervention), suggesting that the diurnal rhythm is reflected in two diurnal plasma metabolomes; a morning metabolome (8–12 AM) and an afternoon/evening metabolome (2–8 PM). Overall, the effect of vitamin D supplementation on the blood metabolome was minor, with no effect on the diurnal rhythm. However, a significant effect of the vitamin D supplementation on plasma acetone levels was identified. Collectively, our findings reveal an influence of diurnal rhythm on the plasma metabolome, while vitamin D supplementation appears to have minor influence on fluctuations in the plasma metabolome. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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Graphical abstract

8 pages, 1354 KiB  
Communication
Anti-Inflammatory Effects of 1,25(OH)2D/Calcitriol in T Cell Immunity: Does Sex Make a Difference?
by Daniela Peruzzu, Maria Luisa Dupuis, Marina Pierdominici, Katia Fecchi, Maria Cristina Gagliardi, Elena Ortona and Maria Teresa Pagano
Int. J. Mol. Sci. 2022, 23(16), 9164; https://doi.org/10.3390/ijms23169164 - 15 Aug 2022
Cited by 5 | Viewed by 1474
Abstract
Hypovitaminosis D is involved in various inflammatory, infectious and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Moreover, the active form of vitamin D, calcitriol, has been shown to modulate the immune response, playing an anti-inflammatory effect. However little is known about [...] Read more.
Hypovitaminosis D is involved in various inflammatory, infectious and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Moreover, the active form of vitamin D, calcitriol, has been shown to modulate the immune response, playing an anti-inflammatory effect. However little is known about the mechanisms underlying this anti-inflammatory effect and the potential sex differences of calcitriol immune regulation. Hence, the aim of this study was to investigate whether calcitriol could act differently in modulating T cell immunity of age-matched male and female healthy donors. We analyzed the effects of calcitriol in T lymphocytes from healthy women and men on the expression levels of the vitamin D receptor (VDR) and pro- and anti-inflammatory cytokine production. We showed that a treatment with calcitriol induced a significant increase in the VDR expression levels of activated T lymphocytes from male and female healthy subjects. Moreover, we found that calcitriol significantly reduced the expression level of pro-inflammatory cytokines IL-17, INF-γ and TNF-α in the T lymphocytes of both sexes. Notably, we observed that calcitriol induced a significant increase in the expression level of anti-inflammatory cytokine IL-10 only in the T lymphocytes from female healthy donors. In conclusion, our study provides new insights regarding the sex-specific anti-inflammatory role of calcitriol in T cell immunity. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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16 pages, 1099 KiB  
Article
Uptake of Phosphate, Calcium, and Vitamin D by the Pregnant Uterus of Sheep in Late Gestation: Regulation by Chorionic Somatomammotropin Hormone
by Claire Stenhouse, Katherine M. Halloran, Amelia R. Tanner, Larry J. Suva, Paul J. Rozance, Russell V. Anthony and Fuller W. Bazer
Int. J. Mol. Sci. 2022, 23(14), 7795; https://doi.org/10.3390/ijms23147795 - 14 Jul 2022
Cited by 3 | Viewed by 2140
Abstract
Minerals are required for the establishment and maintenance of pregnancy and regulation of fetal growth in mammals. Lentiviral-mediated RNA interference (RNAi) of chorionic somatomammotropin hormone (CSH) results in both an intrauterine growth restriction (IUGR) and a non-IUGR phenotype in sheep. This study determined [...] Read more.
Minerals are required for the establishment and maintenance of pregnancy and regulation of fetal growth in mammals. Lentiviral-mediated RNA interference (RNAi) of chorionic somatomammotropin hormone (CSH) results in both an intrauterine growth restriction (IUGR) and a non-IUGR phenotype in sheep. This study determined the effects of CSH RNAi on the concentration and uptake of calcium, phosphate, and vitamin D, and the expression of candidate mRNAs known to mediate mineral signaling in caruncles (maternal component of placentome) and cotyledons (fetal component of placentome) on gestational day 132. CSH RNAi Non-IUGR pregnancies had a lower umbilical vein–umbilical artery calcium gradient (p < 0.05) and less cotyledonary calcium (p < 0.05) and phosphate (p < 0.05) compared to Control RNAi pregnancies. CSH RNAi IUGR pregnancies had less umbilical calcium uptake (p < 0.05), lower uterine arterial and venous concentrations of 25(OH)D (p < 0.05), and trends for lower umbilical 25(OH)D uptake (p = 0.059) compared to Control RNAi pregnancies. Furthermore, CSH RNAi IUGR pregnancies had decreased umbilical uptake of calcium (p < 0.05), less uterine venous 25(OH)D (vitamin D metabolite; p = 0.055), lower caruncular expression of SLC20A2 (sodium-dependent phosphate transporter; p < 0.05) mRNA, and lower cotyledonary expression of KL (klotho; p < 0.01), FGFR1 (fibroblast growth factor receptor 1; p < 0.05), FGFR2 (p < 0.05), and TRPV6 (transient receptor potential vanilloid member 6; p < 0.05) mRNAs compared to CSH RNAi Non-IUGR pregnancies. This study has provided novel insights into the regulatory role of CSH for calcium, phosphate, and vitamin D utilization in late gestation. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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Review

Jump to: Editorial, Research

12 pages, 734 KiB  
Review
Vitamin D, Gut Microbiota, and Cardiometabolic Diseases—A Possible Three-Way Axis
by Ayah Sukik, Joud Alalwani and Vijay Ganji
Int. J. Mol. Sci. 2023, 24(2), 940; https://doi.org/10.3390/ijms24020940 - 4 Jan 2023
Cited by 11 | Viewed by 3969
Abstract
Metabolic syndrome (MetSyn) is a precursor for several cardiometabolic diseases such as obesity, type-2 diabetes mellitus (T2DM), and cardiovascular diseases. Emerging evidence suggests that vitamin D deficiency links to cardiometabolic diseases through microbiota. A combination of poor vitamin D status and dysbiosis may [...] Read more.
Metabolic syndrome (MetSyn) is a precursor for several cardiometabolic diseases such as obesity, type-2 diabetes mellitus (T2DM), and cardiovascular diseases. Emerging evidence suggests that vitamin D deficiency links to cardiometabolic diseases through microbiota. A combination of poor vitamin D status and dysbiosis may contribute to the progression of cardiometabolic diseases. Therefore, in this review, we present the relationship among vitamin D, microbiota, and cardiometabolic diseases with a focus on MetSyn. We searched major databases for reports on vitamin D, microbiota, and MetSyn until June 2022. We reviewed 13 reports on the relation between vitamin D and MetSyn (6 randomized controlled and 7 cross-sectional studies) and 6 reports on the effect of vitamin D on the gut microbiome. Adequate vitamin D status has a beneficial effect on gut microbiota, therefore preventing the progression of MetSyn. Further, well-controlled studies are needed for a better understanding of the mechanisms of action involving vitamin D and microbiota in the pathogenesis of cardiometabolic diseases. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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21 pages, 2068 KiB  
Review
Maternal Vitamin D Levels during Pregnancy and Offspring Psychiatric Outcomes: A Systematic Review
by Subina Upadhyaya, Tiia Ståhlberg, Sanju Silwal, Bianca Arrhenius and Andre Sourander
Int. J. Mol. Sci. 2023, 24(1), 63; https://doi.org/10.3390/ijms24010063 - 21 Dec 2022
Cited by 10 | Viewed by 2176
Abstract
Prenatal exposure to vitamin D may play a significant role in human brain development and function. Previous epidemiological studies investigating the associations between maternal vitamin D status and offspring developmental and psychiatric outcomes in humans have been inconclusive. We aimed to systematically assess [...] Read more.
Prenatal exposure to vitamin D may play a significant role in human brain development and function. Previous epidemiological studies investigating the associations between maternal vitamin D status and offspring developmental and psychiatric outcomes in humans have been inconclusive. We aimed to systematically assess the results of previously published studies that examined the associations between maternal vitamin D levels, measured as circulating 25(OH)D levels in pregnancy or at birth, and offspring neuropsychiatric and psychiatric outcomes. Systematic searches were conducted using MEDLINE, Embase, PsychINFO and Web of Science for studies published by 10 August 2022. We included human observational studies that examined associations between prenatal or perinatal vitamin D levels and offspring neuropsychiatric and psychiatric outcomes and were published in English in peer-reviewed journals. Of the 3729 studies identified, 66 studies were screened for full texts and 29 studies published between 2003 and 2022 were included in the final review. There was a small amount of evidence for the association between prenatal vitamin D deficiency and autism spectrum disorder. When studies with larger sample sizes and stricter definitions of vitamin D deficiency were considered, positive associations were also found for attention-deficit/hyperactivity disorder and schizophrenia. Future studies with larger sample sizes, longer follow-up periods and prenatal vitamin D assessed at multiple time points are needed. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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14 pages, 511 KiB  
Review
Vitamin D and Beta Cells in Type 1 Diabetes: A Systematic Review
by Josephine Yu, Preeti Sharma, Christian M. Girgis and Jenny E. Gunton
Int. J. Mol. Sci. 2022, 23(22), 14434; https://doi.org/10.3390/ijms232214434 - 20 Nov 2022
Cited by 14 | Viewed by 3715
Abstract
The prevalence of type 1 diabetes (T1D) is rising steadily. A potential contributor to the rise is vitamin D. In this systematic review, we examined the literature around vitamin D and T1D. We identified 22 papers examining the role of vitamin D in [...] Read more.
The prevalence of type 1 diabetes (T1D) is rising steadily. A potential contributor to the rise is vitamin D. In this systematic review, we examined the literature around vitamin D and T1D. We identified 22 papers examining the role of vitamin D in cultured β-cell lines, islets, or perfused pancreas, and 28 papers examining vitamin D in humans or human islets. The literature reports strong associations between T1D and low circulating vitamin D. There is also high-level (systematic reviews, meta-analyses) evidence that adequate vitamin D status in early life reduces T1D risk. Several animal studies, particularly in NOD mice, show harm from D-deficiency and benefit in most studies from vitamin D treatment/supplementation. Short-term streptozotocin studies show a β-cell survival effect with supplementation. Human studies report associations between VDR polymorphisms and T1D risk and β-cell function, as assessed by C-peptide. In view of those outcomes, the variable results in human trials are generally disappointing. Most studies using 1,25D, the active form of vitamin D were ineffective. Similarly, studies using other forms of vitamin D were predominantly ineffective. However, it is interesting to note that all but one of the studies testing 25D reported benefit. Together, this suggests that maintenance of optimal circulating 25D levels may reduce the risk of T1D and that it may have potential for benefits in delaying the development of absolute or near-absolute C-peptide deficiency. Given the near-complete loss of β-cells by the time of clinical diagnosis, vitamin D is much less likely to be useful after disease-onset. However, given the very low toxicity of 25D, and the known benefits of preservation of C-peptide positivity for long-term complications risk, we recommend considering daily cholecalciferol supplementation in people with T1D and people at high risk of T1D, especially if they have vitamin D insufficiency. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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15 pages, 1168 KiB  
Review
The Effects of Vitamin D Supplementation in COVID-19 Patients: A Systematic Review
by Ángela Feiner Solís, Ana Avedillo Salas, María José Luesma Bartolomé and Sonia Santander Ballestín
Int. J. Mol. Sci. 2022, 23(20), 12424; https://doi.org/10.3390/ijms232012424 - 17 Oct 2022
Cited by 11 | Viewed by 2139
Abstract
Vitamin D has an immune-modulating effect on respiratory tract infections. For this reason, it has been proposed as part of the treatment in COVID-19. Furthermore, vitamin D deficiency has been associated with worse clinical outcomes of this disease. The aim of this systematic [...] Read more.
Vitamin D has an immune-modulating effect on respiratory tract infections. For this reason, it has been proposed as part of the treatment in COVID-19. Furthermore, vitamin D deficiency has been associated with worse clinical outcomes of this disease. The aim of this systematic review was to determine whether vitamin D supplementation modifies the disease course. Therefore, eleven studies involving randomised clinical trials are analysed, in which groups of COVID-19 patients with or without vitamin D supplementation as part of the treatment are compared. A control group was treated with best available therapy, and in some of the clinical trials, also with a placebo. According to the outcomes, it seems that patients benefit from receiving a daily or maintained in time vitamin D dose regardless of vitamin D serum levels at the beginning of the trial. The administration of a single vitamin D dose does not seem to have any effect on the health status of these patients. However, the outcomes are heterogeneous and larger clinical trials are necessary. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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22 pages, 2560 KiB  
Review
The Perspective of Vitamin D on suPAR-Related AKI in COVID-19
by Tzu-Hsien Liao, Hsien-Chang Wu, Min-Tser Liao, Wan-Chung Hu, Kuo-Wang Tsai, Ching-Chieh Lin and Kuo-Cheng Lu
Int. J. Mol. Sci. 2022, 23(18), 10725; https://doi.org/10.3390/ijms231810725 - 14 Sep 2022
Cited by 4 | Viewed by 2588
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of millions of people around the world. Severe vitamin D deficiency can increase the risk of death in people with COVID-19. There is growing evidence that acute kidney injury (AKI) is common in [...] Read more.
The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of millions of people around the world. Severe vitamin D deficiency can increase the risk of death in people with COVID-19. There is growing evidence that acute kidney injury (AKI) is common in COVID-19 patients and is associated with poorer clinical outcomes. The kidney effects of SARS-CoV-2 are directly mediated by angiotensin 2-converting enzyme (ACE2) receptors. AKI is also caused by indirect causes such as the hypercoagulable state and microvascular thrombosis. The increased release of soluble urokinase-type plasminogen activator receptor (suPAR) from immature myeloid cells reduces plasminogen activation by the competitive inhibition of urokinase-type plasminogen activator, which results in low plasmin levels and a fibrinolytic state in COVID-19. Frequent hypercoagulability in critically ill patients with COVID-19 may exacerbate the severity of thrombosis. Versican expression in proximal tubular cells leads to the proliferation of interstitial fibroblasts through the C3a and suPAR pathways. Vitamin D attenuates the local expression of podocyte uPAR and decreases elevated circulating suPAR levels caused by systemic inflammation. This decrease preserves the function and structure of the glomerular barrier, thereby maintaining renal function. The attenuated hyperinflammatory state reduces complement activation, resulting in lower serum C3a levels. Vitamin D can also protect against COVID-19 by modulating innate and adaptive immunity, increasing ACE2 expression, and inhibiting the renin–angiotensin–aldosterone system. We hypothesized that by reducing suPAR levels, appropriate vitamin D supplementation could prevent the progression and reduce the severity of AKI in COVID-19 patients, although the data available require further elucidation. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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13 pages, 1575 KiB  
Review
Vitamin D and the Kidney: Two Players, One Console
by Fulvia Zappulo, Maria Cappuccilli, Alessandra Cingolani, Anna Scrivo, Anna Laura Croci Chiocchini, Miriam Di Nunzio, Chiara Donadei, Marianna Napoli, Francesco Tondolo, Giuseppe Cianciolo and Gaetano La Manna
Int. J. Mol. Sci. 2022, 23(16), 9135; https://doi.org/10.3390/ijms23169135 - 15 Aug 2022
Cited by 12 | Viewed by 8024
Abstract
Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose [...] Read more.
Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D’s role in different settings, with a special focus on chronic kidney disease and kidney transplant. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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12 pages, 633 KiB  
Review
Vitamin D-Related Genetic Variations and Nonalcoholic Fatty Liver Disease: A Systematic Review
by Aunchalee Jaroenlapnopparat, Pichatorn Suppakitjanusant, Ben Ponvilawan and Nipith Charoenngam
Int. J. Mol. Sci. 2022, 23(16), 9122; https://doi.org/10.3390/ijms23169122 - 14 Aug 2022
Cited by 8 | Viewed by 2005
Abstract
Background: Studies have demonstrated the link between vitamin-D-related genetic variations and nonskeletal outcomes. We aimed to identify all available data on the association of vitamin-D-related genetic variations with nonalcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline [...] Read more.
Background: Studies have demonstrated the link between vitamin-D-related genetic variations and nonskeletal outcomes. We aimed to identify all available data on the association of vitamin-D-related genetic variations with nonalcoholic fatty liver disease (NAFLD). Methods: Potentially eligible studies were identified from Embase and Medline databases from inception to June 2022 using a search strategy that comprised terms for “Vitamin D” and “NAFLD”. Eligible studies must report the association between vitamin D-related genetic variations and presence, severity or response to treatment of NAFLD. Data were extracted from each eligible study. Results: A total of 3495 articles were identified. After a systematic review, twelve studies were included. A total of 26 genetic variations were identified. Presence of NAFLD was associated with variations of GC (rs222054, rs222020, rs10011000, rs7041), VDR (rs2228570, rs11168287, rs10783219, rs4752), CYP24A1 (rs3787557, rs6068816, rs2296241, rs2248359) and CYP27B1 (rs4646536). Severity of NAFLD was associated with variations of GC (rs4588), VDR (rs2228570, rs4334089), CYP2R1 (rs10741657), DHCR7 (rs1544410, rs3829251, rs12785878) and CYP24A1 (rs3787557, rs6068816, rs6097809, rs6127119, rs2248359, rs3787554, rs4809960, rs6022999). Response to calcitriol treatment was associated with variation of VDR (rs10735810). Conclusions: Multiple vitamin D-related genetic variations were associated with NAFLD, indicating the role of vitamin D in the pathogenesis of NAFLD. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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21 pages, 2006 KiB  
Review
Role of Vitamin D in Liver Disease and Complications of Advanced Chronic Liver Disease
by Federico Ravaioli, Alessandra Pivetti, Lorenza Di Marco, Christou Chrysanthi, Gabriella Frassanito, Martina Pambianco, Chiara Sicuro, Noemi Gualandi, Tomas Guasconi, Maddalena Pecchini and Antonio Colecchia
Int. J. Mol. Sci. 2022, 23(16), 9016; https://doi.org/10.3390/ijms23169016 - 12 Aug 2022
Cited by 11 | Viewed by 8621
Abstract
Vitamin D is a crucial nutrient with many pleiotropic effects on health and various chronic diseases. The purpose of this review is to provide a detailed report on the pathophysiological mechanisms underlying vitamin D deficiency in patients with chronic liver disease, addressing the [...] Read more.
Vitamin D is a crucial nutrient with many pleiotropic effects on health and various chronic diseases. The purpose of this review is to provide a detailed report on the pathophysiological mechanisms underlying vitamin D deficiency in patients with chronic liver disease, addressing the different liver etiologies and the condition of advanced chronic liver disease (cirrhosis) with related complications. To date, patients with liver disease, regardless of underlying etiology, have been shown to have reduced levels of vitamin D. There is also evidence of the predictive role of vitamin D values in complications and progression of advanced disease. However, specific indications of vitamin D supplementation are not conclusive concerning what is already recommended in the general population. Future studies should make an effort to unify and validate the role of vitamin D supplementation in chronic liver disease. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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18 pages, 1992 KiB  
Review
The Role of Vitamin D in SARS-CoV-2 Infection and Acute Kidney Injury
by Ming-Chun Hsieh, Po-Jen Hsiao, Min-Tser Liao, Yi-Chou Hou, Ya-Chieh Chang, Wen-Fang Chiang, Kun-Lin Wu, Jenq-Shyong Chan and Kuo-Cheng Lu
Int. J. Mol. Sci. 2022, 23(13), 7368; https://doi.org/10.3390/ijms23137368 - 1 Jul 2022
Cited by 10 | Viewed by 2887
Abstract
Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences [...] Read more.
Vitamin D has been described as an essential nutrient and hormone, which can cause nuclear, non-genomic, and mitochondrial effects. Vitamin D not only controls the transcription of thousands of genes, directly or indirectly through the modulation of calcium fluxes, but it also influences the cell metabolism and maintenance specific nuclear programs. Given its broad spectrum of activity and multiple molecular targets, a deficiency of vitamin D can be involved in many pathologies. Vitamin D deficiency also influences mortality and multiple outcomes in chronic kidney disease (CKD). Active and native vitamin D serum levels are also decreased in critically ill patients and are associated with acute kidney injury (AKI) and in-hospital mortality. In addition to regulating calcium and phosphate homeostasis, vitamin D-related mechanisms regulate adaptive and innate immunity. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have a role in excessive proinflammatory cell recruitment and cytokine release, which contribute to alveolar and full-body endothelial damage. AKI is one of the most common extrapulmonary manifestations of severe coronavirus disease 2019 (COVID-19). There are also some correlations between the vitamin D level and COVID-19 severity via several pathways. Proper vitamin D supplementation may be an attractive therapeutic strategy for AKI and has the benefits of low cost and low risk of toxicity and side effects. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 2.0)
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