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Applied Sciences
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Vitamin D in Human Health and Disease
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Vitamin D in Human Health and Disease

A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 21619

Special Issue Editor

Dr. Thomas S. Lisse

E-Mail Website
Guest Editor
Department of Biology, College of Arts and Sciences, Cox Science Center, University of Miami, Coral Gables, FL, USA
Interests: Vitamin D steroid receptor; genomics; mechanisms of action; endocrinology; metabolism; deficiency; supplementation trials; therapy; bone; microbiome; cancer; immunity; pregnancy

Special Issue Information

Dear Colleagues,

Vitamin D and its metabolites are well-studied steroid hormones that possess biological and physiology activities that extend far beyond the regulation of mineral homeostasis. Vitamin D deficiency or development of anomalies in metabolism and/or signaling can lead to an increased risk of developing debilitating conditions, not only towards one’s own skeletal system, but to the cardiovascular, cutaneous, nervous, immune, and energy metabolism systems, as well. This has become more evident based on the latest updates derived from large-scale vitamin D supplementation trials that take into consideration, in part, racial background and vitamin D status. These trials include the Vitamin D and Omege-3 trial (VITAL) that focused on acute and chronic conditions, such as cancer and cardiovascular disease. The VITAL study reported a decrease in invasive cancer-related death rates after 5 years of vitamin D daily supplementation adjusted for various parameters, including race and body composition. Recent advances in cancer research per se have also provided insights into how vitamin D and the nutritional environment dictate (stem) cells to contribute toward homeostasis and tumorigenesis. How vitamin D can differentially affect the progression of prostate cancer between African American and Caucasian men is starting to be explored in more detail as well. Collectively, these reports argue for an increase in the daily uptake of vitamin D to 2000 IU for adults, and the possibility of using low-calcemic vitamin D analogues to treat certain types of cancers.

In addition to cancer, new studies surrounding vitamin D metabolism and activity have investigated the relationship between the vitamin D binding protein and organ structures such as mammary glands, as well as the development of vitamin D metabolism-based biomarker systems that may better track chronic kidney disease progression. The impact of vitamin D on the microbiome and immunity has also been looked at of late. As an example, vitamin D plays a role in shaping the microbiome in patients with cystic fibrosis, and calcitriol has also been shown to suppress inflammation in an animal model for Epidermolysis bullosa acquisita, a severe skin-blistering disease. The impact of genetics and epigenetics on vitamin D has also taken center stage, as the genetic background of offspring and epigenetic dysregulation by maternal vitamin D deficiency can influence disease progression into the next generation, and perhaps beyond.

With the new genera of studies geared towards a better grasp of the basic and translational aspects of vitamin D, it is now a perfect time to put forth a Special Issue which focuses on vitamin D and human health and disease. Hence, the goal of this Special Issue is to provide a set of articles that bring to light the new opportunities, challenges, and prospects of vitamin D related to overall health.

Dr. Thomas S. Lisse
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Applied Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). 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 steroid receptor
  • Genomics
  • Mechanisms of action
  • Endocrinology
  • Metabolism
  • Deficiency
  • Nutrition
  • Supplementation trials
  • Therapy
  • Bone
  • Microbiome
  • Cancer
  • Immunity

Published Papers (6 papers)

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Research

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13 pages, 1468 KiB  
Article
Vitamin D Regulation of a SOD1-to-SOD2 Antioxidative Switch to Prevent Bone Cancer
by Thomas S. Lisse
Appl. Sci. 2020, 10(7), 2554; https://doi.org/10.3390/app10072554 - 8 Apr 2020
Cited by 9 | Viewed by 3574
Abstract
Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 [...] Read more.
Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study, real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)2D3. First, a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10 nM but not at 100 nM of 1,25(OH)2D3 treatment, suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation, gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1, SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1, no changes in gene expression were observed. However, a concomitant decrease in CAT and SOD1 mRNA, and increase in SOD2 mRNA after 24 h of 10 nM 1,25(OH)2D3 treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 ours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time. Full article
(This article belongs to the Special Issue Vitamin D in Human Health and Disease)
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Review

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12 pages, 1873 KiB  
Review
Vitamin D and Primary Ciliary Dyskinesia: A Topic to Be Further Explored
by Consolato M. Sergi
Appl. Sci. 2021, 11(9), 3818; https://doi.org/10.3390/app11093818 - 23 Apr 2021
Cited by 3 | Viewed by 2358
Abstract
Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. The diagnosis of PCD relies on a combination of clinical evaluation and ultrastructural (electron microscopic) analysis of the ciliary architecture. This diagnosis may be challenging due to clinical and [...] Read more.
Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormalities in ciliary structure/function. The diagnosis of PCD relies on a combination of clinical evaluation and ultrastructural (electron microscopic) analysis of the ciliary architecture. This diagnosis may be challenging due to clinical and genetic heterogeneity and artifacts during the ciliary ultrastructure preparation and assessment. Recently, vitamin D supplementation has been proposed for several groups probably suffering from D-hypovitaminosis. Some patients with inflammatory bowel disease may have significant malabsorption, and vitamin D supplementation in these patients is recommended. Two recent reports suggest that a low plasmatic level of this vitamin is present in the PCD population. The utility of vitamin D supplementation may be essential in this group of individuals, and further investigations are warranted. Still, in examining the literature papers, it seems relevant that the authors concentrate solely on lung function in both studies. Future studies should probably target the intestinal function in patients with PCD independently from the vitamin D supplementation to fully evaluate its role. Full article
(This article belongs to the Special Issue Vitamin D in Human Health and Disease)
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15 pages, 748 KiB  
Review
Vitamin D and the NLRP3 Inflammasome
by Matthew Tunbridge and Pedro Henrique França Gois
Appl. Sci. 2020, 10(23), 8462; https://doi.org/10.3390/app10238462 - 27 Nov 2020
Cited by 6 | Viewed by 3033
Abstract
Vitamin D (VD) is a steroid hormone classically known for its key role in maintaining calcium homeostasis in the body. VD also has important immunomodulatory functions. This review explores evidence for a role of VD in attenuating the activation of the nucleotide-binding domain-like [...] Read more.
Vitamin D (VD) is a steroid hormone classically known for its key role in maintaining calcium homeostasis in the body. VD also has important immunomodulatory functions. This review explores evidence for a role of VD in attenuating the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Dysregulated and inappropriate NLRP3 inflammasome activation occurs in a range of human diseases, including autoinflammatory disorders, metabolic disorders, and infections. VD appears to mediate its effects by binding of the VD receptor (VDR) to the sensor protein NLRP3, inhibiting deubiquitination and downstream inflammasome assembly. Some early clinical evidence suggests improved outcomes in inflammasome-mediated disorders when VD-deficient patients are treated with supplementation therapy. Full article
(This article belongs to the Special Issue Vitamin D in Human Health and Disease)
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19 pages, 357 KiB  
Review
Prevention and Management of Gestational Diabetes Using Vitamin D Supplementation: An Overview and Appraisal of Clinical Trials
by Aya Mousa
Appl. Sci. 2020, 10(22), 8141; https://doi.org/10.3390/app10228141 - 17 Nov 2020
Cited by 2 | Viewed by 2400
Abstract
A number of studies have examined the role of vitamin D in reproductive processes and disorders of pregnancy such as gestational diabetes mellitus (GDM). Although observational studies have linked maternal vitamin D deficiency with a plethora of adverse pregnancy outcomes including GDM, intervention [...] Read more.
A number of studies have examined the role of vitamin D in reproductive processes and disorders of pregnancy such as gestational diabetes mellitus (GDM). Although observational studies have linked maternal vitamin D deficiency with a plethora of adverse pregnancy outcomes including GDM, intervention trials generally do not support the use of vitamin D supplementation for GDM prevention or management. This narrative review provides an up-to-date overview and critical appraisal of randomised controlled trials (RCTs) to describe the current state of knowledge regarding the efficacy of vitamin D supplementation for preventing and/or managing GDM. Overall, although RCT data indicates a potential benefit of vitamin D in maternal glycaemic control, results are highly disparate and the data published to date have not conclusively established the efficacy of vitamin D in GDM prevention. There are, however, several limitations within the existing literature, including some considerable challenges that are unique to vitamin D trials, which should be carefully considered in the interpretation of the evidence and design of future studies. For now, many unanswered questions remain, and there is still a need for adequately powered and well-designed trials before routine supplementation can be recommended in the context of GDM. Full article
(This article belongs to the Special Issue Vitamin D in Human Health and Disease)
15 pages, 575 KiB  
Review
Vitamin D Merging into Immune System-Skeletal Muscle Network: Effects on Human Health
by Clara Crescioli
Appl. Sci. 2020, 10(16), 5592; https://doi.org/10.3390/app10165592 - 12 Aug 2020
Cited by 5 | Viewed by 2407
Abstract
The concept that extra-skeletal functions of vitamin D impact on human health have taken place since quite ago. Among all, the beneficial effects of vitamin D on immune regulation, skeletal muscle function, and metabolism are undeniable. Adequate vitamin D levels maintain the immune [...] Read more.
The concept that extra-skeletal functions of vitamin D impact on human health have taken place since quite ago. Among all, the beneficial effects of vitamin D on immune regulation, skeletal muscle function, and metabolism are undeniable. Adequate vitamin D levels maintain the immune system and skeletal muscle metabolism integrity, promoting whole-body homeostasis; hypovitaminosis D associates with the important decline of both tissues and promotes chronic inflammation, which is recognized to underlie several disease developments. Growing evidence shows that the immune system and skeletal muscle reciprocally dialogue, modulating each other’s function. Within this crosstalk, vitamin D seems able to integrate and converge some biomolecular signaling towards anti-inflammatory protective effects. Thus, vitamin D regulation appears even more critical at the immune system-muscle signaling intersection, rather than at the single tissue level, opening to wider/newer opportunities in clinical applications to improve health. This paper aims to focus on the immune system-skeletal muscle interplay as a multifaceted target for vitamin D in health and disease after recalling the main regulatory functions of vitamin D on those systems, separately. Some myokines, particularly relevant within the immune system/skeletal muscle/vitamin D networking, are discussed. Since vitamin D supplementation potentially offers the opportunity to maintain health, comments on this issue, still under debate, are included. Full article
(This article belongs to the Special Issue Vitamin D in Human Health and Disease)
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20 pages, 746 KiB  
Review
Natural Epigenetic Modulators of Vitamin D Receptor
by Giulia Apprato, Camilla Fiz, Isabella Fusano, Loredana Bergandi and Francesca Silvagno
Appl. Sci. 2020, 10(12), 4096; https://doi.org/10.3390/app10124096 - 14 Jun 2020
Cited by 6 | Viewed by 7276
Abstract
Vitamin D plays an important role in every tissue due to its differentiating properties and the control of calcium homeostasis. The reversion of the epigenetic repression of the vitamin D receptor (VDR) could lead to an increased sensitivity of the cells to the [...] Read more.
Vitamin D plays an important role in every tissue due to its differentiating properties and the control of calcium homeostasis. The reversion of the epigenetic repression of the vitamin D receptor (VDR) could lead to an increased sensitivity of the cells to the beneficial activity of the hormone and could be exploited in many vitamin D-resistant diseases. In this study we analyzed the effects of three natural epigenetic modulators: sulforaphane, curcumin, and the products of the fermentative activity of probiotics. Sulforaphane and curcumin are inhibitors of the DNA methyltransferases (DNMT) and of the histone deacetylases (HDAC); it has been demonstrated that sulforaphane and curcumin increase VDR expression in intestinal epithelial cells and in a human liver cancer cell line, respectively. The anti-inflammatory properties associated with the probiotic administration in vivo can be linked to the increased activity of intestinal VDR. Butyrate, an inhibitor of HDAC and a known modulator of VDR expression, is the candidate byproduct of fermentation by gut microbiome that could mediate the enhanced expression of VDR triggered by probiotics in vivo. Many other natural compounds wait to be investigated and recognized as epigenetic modulators of VDR, thus opening promising therapeutic avenues for many diseases by natural means. Full article
(This article belongs to the Special Issue Vitamin D in Human Health and Disease)
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