Vitamin D in Health and Disease

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 April 2022) | Viewed by 26222

Special Issue Editors


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Guest Editor
Head of Allergology and Clinical Immunology Unit, Department of Internal Medicine, University of Genoa and San Bartolomeo Hospital, Sarzana, Italy
Interests: immunodeficiency; autoimmunity; neuro-endocrino-immunology; pharmacogenomics; soluble molecules; immune-mediated diseases; allergies; vaccines
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Guest Editor
Department of Clinical and Experimental Medicine, School and Operative Unit of Allergy and Clinical Immunology, University of Messina, 98125 Messina, Italy
Interests: inflammatory mediators; the citokine network (interleukins, chemokines, adhesion molecules, lipoxines); the oxidative stress in various areas of clinical immunology; allergy; oncology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vitamin D (VD) is a lipo-soluble hormone well known for its effects on calcium homeostasis and bone metabolism. Recently there has been growing interest in the extra-skeletal effects of VD. In particular, recent studies have highlighted how VD plays a fundamental role in immunomodulation processes in the context of both innate and adaptive immunity, with consequent anti-inflammatory and anti-oxidant effect in different immune-mediated pathologies, such as systemic sclerosis, psoriasis, atopic dermatitis and rheumatoid arthritis; as well as in various pro-inflammatory processes affecting the airways. Recent evidence has shown that VD is also closely related to other components such as the microbiome, with which it appears to be interconnected in the pathophysiology of many allergic diseases. In addition to the known immunomodulatory effects of VD, several studies have reported that it is also endowed with important anti-proliferative, anti-angiogenic and pro-differentiative effects in cancer thanks to its effects on the modulation of the expression of tumor miRNAs through its action at the VD receptor (VDR) level. In view of this, it is clear that VD supplementation represents a safe and valid therapeutic strategy capable of improving the clinical outcome of many diseases.

Prof. Dr. Giuseppe Murdaca
Dr. Sebastiano Gangemi
Guest Editors

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Keywords

  • vitamin D and the immune system
  • vitamin D and cytokines
  • vitamin D and microbiome
  • vitamin D and respiratory diseases
  • vitamin D and autoimmune diseases
  • vitamin D and allergies

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Published Papers (9 papers)

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Editorial

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4 pages, 190 KiB  
Editorial
Vitamin D in Health and Disease
by Giuseppe Murdaca and Sebastiano Gangemi
Biomedicines 2023, 11(1), 10; https://doi.org/10.3390/biomedicines11010010 - 21 Dec 2022
Cited by 8 | Viewed by 1525
Abstract
Vitamin D (VD) is a fat-soluble hormone that plays a fundamental role not only in calcium homeostasis and bone metabolism, but also has anti-inflammatory and antioxidant properties, acting on both innate and adaptive immunity [...] Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease)

Research

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16 pages, 1960 KiB  
Article
Vitamin D Counteracts Lipid Accumulation, Augments Free Fatty Acid-Induced ABCA1 and CPT-1A Expression While Reducing CD36 and C/EBPβ Protein Levels in Monocyte-Derived Macrophages
by Mirko Marino, Samuele Venturi, Cristian Del Bo’, Peter Møller, Patrizia Riso and Marisa Porrini
Biomedicines 2022, 10(4), 775; https://doi.org/10.3390/biomedicines10040775 - 26 Mar 2022
Cited by 10 | Viewed by 2545
Abstract
The biologically active form of vitamin D, calcitriol (VD3), has received great attention for its extraskeletal effects, such as a protective role on the cardiovascular system. The aim of the present work is to test the capacity of VD3 to affect lipid metabolism [...] Read more.
The biologically active form of vitamin D, calcitriol (VD3), has received great attention for its extraskeletal effects, such as a protective role on the cardiovascular system. The aim of the present work is to test the capacity of VD3 to affect lipid metabolism and fatty acid accumulation in an in vitro model of monocyte (THP-1)-derived macrophages. Cells were treated for 24 h with oleic/palmitic acid (500 μM, 2:1 ratio) and different VD3 concentrations (0.1, 1, 10, 50 and 100 nM). Lipid accumulation was quantified spectrophotometrically (excitation: 544 nm, emission: 590 nm). C/EBPβ, PPAR-γ1, CD36, CPT-1A, and ABCA1 protein levels were assessed by ELISA kits at different time-points (1, 2, 4, 8, and 24 h). VD3 at 50 and 100 nM significantly reduced fatty acids accumulation in macrophages by 27% and 32%, respectively. In addition, tested at 50 nM, VD3 decreased CD36, PPAR-γ1, and C/EBPβ, while it increased ABCA1 and CPT-1A protein levels in free fatty acid-exposed cells. In conclusion, VD3 reduced fatty acid accumulation in THP-1-derived macrophages exposed to lipid excess. The anti-atherogenic effect of VD3 could be ascribable to the regulation of proteins involved in lipid transport and clearance. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease)
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21 pages, 19411 KiB  
Article
Tipping the Balance: Vitamin D Inadequacy in Children Impacts the Major Gut Bacterial Phyla
by Parul Singh, Arun Rawat, Marwa Saadaoui, Duaa Elhag, Sara Tomei, Mohammed Elanbari, Anthony K. Akobeng, Amira Mustafa, Ibtihal Abdelgadir, Sharda Udassi, Mohammed A. Hendaus and Souhaila Al Khodor
Biomedicines 2022, 10(2), 278; https://doi.org/10.3390/biomedicines10020278 - 26 Jan 2022
Cited by 8 | Viewed by 3588
Abstract
Vitamin D inadequacy appears to be on the rise globally, and it has been linked to an increased risk of osteoporosis, as well as metabolic, cardiovascular, and autoimmune diseases. Vitamin D concentrations are partially determined by genetic factors. Specific single nucleotide polymorphisms (SNPs) [...] Read more.
Vitamin D inadequacy appears to be on the rise globally, and it has been linked to an increased risk of osteoporosis, as well as metabolic, cardiovascular, and autoimmune diseases. Vitamin D concentrations are partially determined by genetic factors. Specific single nucleotide polymorphisms (SNPs) in genes involved in vitamin D transport, metabolism, or binding have been found to be associated with its serum concentration, and these SNPs differ among ethnicities. Vitamin D has also been suggested to be a regulator of the gut microbiota and vitamin D deficiency as the possible cause of gut microbial dysbiosis and inflammation. This pilot study aims to fill the gap in our understanding of the prevalence, cause, and implications of vitamin D inadequacy in a pediatric population residing in Qatar. Blood and fecal samples were collected from healthy subjects aged 4–14 years. Blood was used to measure serum metabolite of vitamin D, 25-hydroxycholecalciferol 25(OH)D. To evaluate the composition of the gut microbiota, fecal samples were subjected to 16S rRNA gene sequencing. High levels of vitamin D deficiency/insufficiency were observed in our cohort with 97% of the subjects falling into the inadequate category (with serum 25(OH)D < 75 nmol/L). The CT genotype in rs12512631, an SNP in the GC gene, was associated with low serum levels of vitamin D (ANOVA, p = 0.0356) and was abundant in deficient compared to non-deficient subjects. Overall gut microbial community structure was significantly different between the deficient (D) and non-deficient (ND) groups (Bray Curtis dissimilarity p = 0.049), with deficient subjects also displaying reduced gut microbial diversity. Significant differences were observed among the two major gut phyla, Firmicutes (F) and Bacteroidetes (B), where deficient subjects displayed a higher B/F ratio (p = 0.0097) compared to ND. Vitamin D deficient children also demonstrated gut enterotypes dominated by the genus Prevotella as opposed to Bacteroides. Our findings suggest that pediatric vitamin D inadequacy significantly impacts the gut microbiota. We also highlight the importance of considering host genetics and baseline gut microbiome composition in interpreting the clinical outcomes related to vitamin D deficiency as well as designing better personalized strategies for therapeutic interventions. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease)
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12 pages, 2182 KiB  
Article
Vitamin D Prevents High Glucose-Induced Lipid Droplets Accumulation in Cultured Endothelial Cells: The Role of Thioredoxin Interacting Protein
by Roberta Scrimieri, Alessandra Cazzaniga, Sara Castiglioni and Jeanette A. M. Maier
Biomedicines 2021, 9(12), 1874; https://doi.org/10.3390/biomedicines9121874 - 10 Dec 2021
Cited by 6 | Viewed by 2508
Abstract
Vitamin D (VitD) exerts protective effects on the endothelium, which is fundamental for vascular integrity, partly by inhibiting free radical formation. We found that VitD prevents high glucose-induced Thioredoxin Interacting Protein (TXNIP) upregulation. Increased amounts of TXNIP are responsible for the accumulation of [...] Read more.
Vitamin D (VitD) exerts protective effects on the endothelium, which is fundamental for vascular integrity, partly by inhibiting free radical formation. We found that VitD prevents high glucose-induced Thioredoxin Interacting Protein (TXNIP) upregulation. Increased amounts of TXNIP are responsible for the accumulation of reactive oxygen species and, as a consequence, of lipid droplets. This is associated with increased amounts of triglycerides as the result of increased lipogenesis and reduced fatty acid oxidation. Remarkably, VitD rebalances the redox equilibrium, restores normal lipid content, and prevents the accumulation of lipid droplets. Our results highlight TXNIP as one of the targets of VitD in high glucose-cultured endothelial cells and shed some light on the protective effect of VitD on the endothelium. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease)
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10 pages, 250 KiB  
Article
The Isoform GC1f of the Vitamin D Binding Protein Is Associated with Bronchiectasis Severity
by Martina Oriano, Stefano Aliberti, Franca Rosa Guerini, Cristina Agliardi, Carlotta Di Francesco, Alice Gelmini, Leonardo Terranova, Milena Zanzottera, Paola Marchisio, Mario Clerici and Francesco Blasi
Biomedicines 2021, 9(11), 1573; https://doi.org/10.3390/biomedicines9111573 - 29 Oct 2021
Cited by 3 | Viewed by 1417
Abstract
Vitamin D modulates immune responses and its deficiency has been observed in more than 60% of bronchiectasis patients. Vitamin D binding protein (DBP) is coded by the GC gene, is involved in the transport of vitamin D, and includes a number of isoforms [...] Read more.
Vitamin D modulates immune responses and its deficiency has been observed in more than 60% of bronchiectasis patients. Vitamin D binding protein (DBP) is coded by the GC gene, is involved in the transport of vitamin D, and includes a number of isoforms based on single nucleotide polymorphisms (SNPs) in the coding region at rs7041 and rs4855. We evaluated the possible clinical impact of DBP polymorphisms and isoforms in an observational, cross-sectional study conducted in 116 bronchiectasis patients, who were genetically characterized for rs4588 and rs7041 SNPs. Results showed that the GC1f isoform (rs7041/rs4588 A/G) correlated with a more severe disease (18.9% vs. 6.3%, p = 0.038), a higher incidence of chronic infections (63.6% vs. 42%, p = 0.041), and a lower BACI score (0.0 (0.0, 2.5) vs. 3.0 (0.0, 3.0), p = 0.035). Moreover, blood concentration of vitamin D was higher in patients carrying GC1s (median (IQR): 20.5 (14.3, 29.7 vs. 15.8 (7.6, 22.4), p = 0.037)). Patients carrying GC1f isoform have a more severe disease, more chronic infections and lower asthmatic comorbidity in comparison to those without the GC1f isoform. Presence of the GC1s isoform (rs7041/rs4588 C/G) seems to be associated to a milder clinical phenotype with increased vitamin D levels and lower comorbidities score. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease)
14 pages, 2878 KiB  
Article
Impact of Vitamin D Supplementation on Bone Mineral Density and All-Cause Mortality in Heart Transplant Patients
by Mahmoud M. A. Abulmeaty, Deema A. Almutawa, Nedim Selimovic, May Almuammar, Abdulaziz A. Al-Khureif, Mohamed I. Hashem, Heba M. Hassan and Doaa A. Abdel Moety
Biomedicines 2021, 9(10), 1450; https://doi.org/10.3390/biomedicines9101450 - 12 Oct 2021
Cited by 2 | Viewed by 1857
Abstract
Vitamin D (VD) deficiency is frequently reported in heart transplant (HT) recipients and routinely supplemented. However, the efficacy of VD supplementation on bone mineral density (BMD) and its association with all-cause mortality is underinvestigated. The VD levels and BMD were studied for two [...] Read more.
Vitamin D (VD) deficiency is frequently reported in heart transplant (HT) recipients and routinely supplemented. However, the efficacy of VD supplementation on bone mineral density (BMD) and its association with all-cause mortality is underinvestigated. The VD levels and BMD were studied for two years, and the association of VD and BMD with all-cause mortality risk was investigated. Ninety-six HT patients (38.18 ± 12.10 years old; 74% men) were followed up during VD, Ca, and Mg supplementation. Anthropometric measurements, BMD by Dual-energy X-ray absorptiometry (DEXA) scan, VD concentrations, and related biochemical parameters were analyzed before, 1 year, and 2 years after HT. Despite significant improvement of VD3 and 25-hydroxy VD (25OHVD) levels especially in the men, BMD parameters were insignificantly changed. After 2 years, the all-cause mortality rate was 15.6%. High pretransplant levels of 25OHVD failed to improve the survival probability. Cox’s regression showed a 32.7% increased hazard ratio for each unit increase in body mass index (95% CI: 1.015–1.733, p = 0.038), in the VD-deficient group rather than in the VD-sufficient one. In conclusion, VD supplementation improves the biochemical status, especially in VD-deficient HT. However, its impact on the BMD and mortality was not as usually expected. Further investigation of the disturbed VD metabolism in HT is warranted. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease)
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Review

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13 pages, 325 KiB  
Review
The Pathogenesis of Cardiac Arrhythmias in Vitamin D Deficiency
by Maria Barsan, Anca Monica Brata, Abdulrahman Ismaiel, Dinu Iuliu Dumitrascu, Andrei-Vlad Badulescu, Traian Adrian Duse, Stefana Dascalescu, Stefan Lucian Popa, Simona Grad, Lucian Muresan, Carmen Maria Maerescu, Gabriel Cismaru and Vlad Dumitru Brata
Biomedicines 2022, 10(6), 1239; https://doi.org/10.3390/biomedicines10061239 - 26 May 2022
Cited by 5 | Viewed by 2968
Abstract
The global prevalence of vitamin D deficiency is more than 20%, and the main causes include insufficient intake, reduced absorption, abnormal metabolism, or resistance to its effects. The levels of serum vitamin D appear to influence cardiovascular risk, and the mechanism involved is [...] Read more.
The global prevalence of vitamin D deficiency is more than 20%, and the main causes include insufficient intake, reduced absorption, abnormal metabolism, or resistance to its effects. The levels of serum vitamin D appear to influence cardiovascular risk, and the mechanism involved is linked to the transient outward current and the ultrarapid delayed rectifier K+ current densities, activated through the nuclear vitamin D receptor and Akt pathway. A significant number of studies have correlated vitamin D deficiency with an increased risk of developing cardiac arrhythmias and sudden cardiac death. For this reason, the purpose of this review is to analyze the relation between vitamin D deficiency and the pathogenesis of cardiac arrhythmias. Atrial fibrillation, increased QT interval, and QT dispersion were the most common findings associated with vitamin D deficiency. Due to the heterogeneity among existing studies, further research is necessary to confirm the existing data and to analyze its relationship with other types of arrhythmias. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease)
20 pages, 1416 KiB  
Review
Current Overview on Therapeutic Potential of Vitamin D in Inflammatory Lung Diseases
by Muhammad Afzal, Imran Kazmi, Fahad A. Al-Abbasi, Sultan Alshehri, Mohammed M. Ghoneim, Syed Sarim Imam, Muhammad Shahid Nadeem, Maryam Hassan Al-Zahrani, Sami I. Alzarea and Ali Alquraini
Biomedicines 2021, 9(12), 1843; https://doi.org/10.3390/biomedicines9121843 - 6 Dec 2021
Cited by 5 | Viewed by 3861
Abstract
Inflammatory lung disorders (ILDs) are one of the world’s major reasons for fatalities and sickness, impacting millions of individuals of all ages and constituting a severe and pervasive health hazard. Asthma, lung cancer, bronchiectasis, pulmonary fibrosis acute respiratory distress syndrome, and COPD all [...] Read more.
Inflammatory lung disorders (ILDs) are one of the world’s major reasons for fatalities and sickness, impacting millions of individuals of all ages and constituting a severe and pervasive health hazard. Asthma, lung cancer, bronchiectasis, pulmonary fibrosis acute respiratory distress syndrome, and COPD all include inflammation as a significant component. Microbe invasions, as well as the damage and even death of host cells, can cause and sustain inflammation. To counteract the negative consequences of irritants, the airways are equipped with cellular and host defense immunological systems that block the cellular entrance of these irritants or eliminate them from airway regions by triggering the immune system. Failure to activate the host defense system will trigger chronic inflammatory cataracts, leading to permanent lung damage. This damage makes the lungs more susceptible to various respiratory diseases. There are certain restrictions of the available therapy for lung illnesses. Vitamins are nutritional molecules that are required for optimal health but are not produced by the human body. Cholecalciferol (Vitamin D) is classified as a vitamin, although it is a hormone. Vitamin D is thought to perform a function in bone and calcium homeostasis. Recent research has found that vitamin D can perform a variety of cellular processes, including cellular proliferation; differentiation; wound repair; healing; and regulatory systems, such as the immune response, immunological, and inflammation. The actions of vitamin D on inflammatory cells are dissected in this review, as well as their clinical significance in respiratory illnesses. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease)
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13 pages, 473 KiB  
Review
Role of Vitamin D in the Clinical Course of Nasal Polyposis
by Giuseppe Murdaca, Francesca Paladin and Sebastiano Gangemi
Biomedicines 2021, 9(8), 855; https://doi.org/10.3390/biomedicines9080855 - 21 Jul 2021
Cited by 6 | Viewed by 4473
Abstract
Vitamin D is a lipo-soluble hormone well known for its effects on calcium homeostasis and bone metabolism. Recently, there has been growing interest in the extraskeletal effects of vitamin D. In particular, recent studies have highlighted how vitamin D plays a fundamental role [...] Read more.
Vitamin D is a lipo-soluble hormone well known for its effects on calcium homeostasis and bone metabolism. Recently, there has been growing interest in the extraskeletal effects of vitamin D. In particular, recent studies have highlighted how vitamin D plays a fundamental role in immunomodulation processes in the context of both innate and adaptive immunity, with consequent anti-inflammatory and anti-oxidant effect in different immune-mediated pathologies, such as systemic sclerosis, psoriasis, atopic dermatitis and rheumatoid arthritis; as well as in various pro-inflammatory processes affecting the airways, including chronic rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyposis. We analyze the role of vitamin D in the genesis and progression of CRSwNP/sNP and its supplementation as a safe and valid therapeutic strategy capable of improving the clinical outcome of standard therapies. Full article
(This article belongs to the Special Issue Vitamin D in Health and Disease)
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