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The Role of Vitamin D in Human Health and Diseases 4.0

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 (31 October 2024) | Viewed by 8496

Special Issue Editors

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
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

Special Issue Information

Dear Colleagues,

Vitamin D has been described as a differentiative hormone, but this definition is reductive for molecule targeting of 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 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 underlined 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 dysfunctions; although some results are encouraging, a few discrepancies can be observed 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. Loredana Bergandi
Dr. Francesca Silvagno
Guest Editors

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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 (5 papers)

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Research

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17 pages, 2792 KiB  
Article
Population Pharmacokinetic Model of Vitamin D3 and Metabolites in Chronic Kidney Disease Patients with Vitamin D Insufficiency and Deficiency
by Stacey M. Tuey, Avisek Ghimire, Serge Guzy, Linda Prebehalla, Amandla-Atilano Roque, Gavriel Roda, Raymond E. West 3rd, Michel B. Chonchol, Nirav Shah, Thomas D. Nolin and Melanie S. Joy
Int. J. Mol. Sci. 2024, 25(22), 12279; https://doi.org/10.3390/ijms252212279 - 15 Nov 2024
Viewed by 332
Abstract
Vitamin D insufficiency and deficiency are highly prevalent in patients with chronic kidney disease (CKD), and their pharmacokinetics are not well described. The primary study objective was to develop a population pharmacokinetic model of oral cholecalciferol (VitD3) and its three major [...] Read more.
Vitamin D insufficiency and deficiency are highly prevalent in patients with chronic kidney disease (CKD), and their pharmacokinetics are not well described. The primary study objective was to develop a population pharmacokinetic model of oral cholecalciferol (VitD3) and its three major metabolites, 25-hydroxyvitamin D3 (25D3), 1,25-dihydroxyvitamin D3 (1,25D3), and 24,25-dihydroxyvitamin D3 (24,25D3), in CKD patients with vitamin D insufficiency and deficiency. CKD subjects (n = 29) were administered one dose of oral VitD3 (5000 I.U.), and nonlinear mixed effects modeling was used to describe the pharmacokinetics of VitD3 and its metabolites. The simultaneous fit of a two-compartment model for VitD3 and a one-compartment model for each metabolite represented the observed data. A proportional error model explained the residual variability for each compound. No assessed covariate significantly affected the pharmacokinetics of VitD3 and metabolites. Visual predictive plots demonstrated the adequate fit of the pharmacokinetic data of VitD3 and metabolites. This is the first reported population pharmacokinetic modeling of VitD3 and metabolites and has the potential to inform targeted dose individualization strategies for therapy in the CKD population. Based on the simulation, doses of 600 International Unit (I.U.)/day to 1000 I.U./day for 6 months are recommended to obtain the target 25D3 concentration of between 30 and 60 ng/mL. These simulation findings could potentially contribute to the development of personalized dosage regimens for vitamin D treatment in patients with CKD. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 4.0)
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15 pages, 2981 KiB  
Article
Anticancer Activity of Vitamin D, Lumisterol and Selected Derivatives against Human Malignant Melanoma Cell Lines
by Paweł Domżalski, Anna Piotrowska, Robert C. Tuckey and Michał A. Zmijewski
Int. J. Mol. Sci. 2024, 25(20), 10914; https://doi.org/10.3390/ijms252010914 - 10 Oct 2024
Viewed by 758
Abstract
Despite the recent development of improved methods of treating melanoma such as targeted therapy, immunotherapy or combined treatment, the number of new cases worldwide is increasing. It is well known that active metabolites of vitamin D3 and lumisterol (L3) exert [...] Read more.
Despite the recent development of improved methods of treating melanoma such as targeted therapy, immunotherapy or combined treatment, the number of new cases worldwide is increasing. It is well known that active metabolites of vitamin D3 and lumisterol (L3) exert photoprotective and antiproliferative effects on the skin, while UV radiation is a major environmental risk factor for melanoma. Thus, many natural metabolites and synthetic analogs of steroidal and secosteroidal molecules have been tested on various cancer cells and in animal models. In this study, we tested the anti-melanoma properties of several natural derivatives of vitamin D3 and L3 in comparison to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). A significant decrease in melanoma cell proliferation and cell mobility was observed for selected derivatives, with (25R)-27-hydroxyL3 showing the highest potency (lowest IC50) in A375 cells but lower potency in SK-MEL-28 cells, whereas the parent L3 failed to inhibit proliferation. The efficacy (% inhibition) by 1,24,25(OH)3D3 and 1,25(OH)2D3 were similar in both cell types. 1,25(OH)2D3 showed higher potency than 1,24,25(OH)3D3 in SK-MEL-28 cells, but lower potency in A375 cells for the inhibition of proliferation. As for 1,25(OH)2D3, but not the other derivatives tested, treatment of melanoma cells with 1,24,25(OH)3D3 markedly increased the expression of CYP24A1, enhanced translocation of the vitamin D receptor (VDR) from the cytoplasm to the nucleus and also decreased the expression of the proliferation marker Ki67. The effects of the other compounds tested were weaker and occurred only under certain conditions. Our data indicate that 1,24,25(OH)3D3, which has undergone the first step in 1,25(OH)2D3 inactivation by being hydroxylated at C24, still shows anti-melanoma properties, displaying higher potency than 1,25(OH)2D3 in SK-MEL-28 cells. Furthermore, hydroxylation increases the potency of some of the lumisterol hydroxy-derivatives, as in contrast to L3, (25R)-27(OH)L3 effectively inhibits proliferation and migration of the human malignant melanoma cell line A375. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 4.0)
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16 pages, 2656 KiB  
Article
Vitamin D and Sulforaphane Decrease Inflammatory Oxidative Stress and Restore the Markers of Epithelial Integrity in an In Vitro Model of Age-Related Macular Degeneration
by Loredana Bergandi, Giulia Palladino, Alessandro Meduri, Laura De Luca and Francesca Silvagno
Int. J. Mol. Sci. 2024, 25(12), 6404; https://doi.org/10.3390/ijms25126404 - 10 Jun 2024
Cited by 3 | Viewed by 1598
Abstract
Age-related macular degeneration (AMD) is strictly linked to chronic oxidative stress, inflammation, loss of epithelial barrier integrity, and often with abnormal new blood vessel development. In this study, the retinal epithelial cell line ARPE-19 was treated with pro-inflammatory transforming growth factor-beta (TGF-β) to [...] Read more.
Age-related macular degeneration (AMD) is strictly linked to chronic oxidative stress, inflammation, loss of epithelial barrier integrity, and often with abnormal new blood vessel development. In this study, the retinal epithelial cell line ARPE-19 was treated with pro-inflammatory transforming growth factor-beta (TGF-β) to investigate the activity of vitamin D (VD) and sulforaphane (SF) in abating the consequences of oxidative stress and inflammation. The administration of VD and SF lowered reactive oxygen species (ROS) levels, and abated the related expression of the pro-inflammatory cytokines interleukin-6 and interleukin-8 induced by TGF-β. We evaluated mitochondrial respiration as a source of ROS production, and we discovered that the increased transcription of respiratory elements triggered by TGF-β was prevented by VD and SF. In this model of inflamed epithelium, the treatment with VD and SF also reduced the secretion of VEGF, a key angiogenic factor, and restored the markers of epithelial integrity. Remarkably, all the observed biological effects were potentiated by the co-stimulation with the two compounds and were not mediated by VD receptor expression but rather by the ERK 1/2 pathway. Altogether, the results of this study reveal the powerful synergistic anti-inflammatory activity of SF and VD and lay the foundation for future clinical assessment of their efficacy in AMD. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 4.0)
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Review

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14 pages, 826 KiB  
Review
Autoimmune Thyroiditis and Vitamin D
by Teodoro Durá-Travé and Fidel Gallinas-Victoriano
Int. J. Mol. Sci. 2024, 25(6), 3154; https://doi.org/10.3390/ijms25063154 - 9 Mar 2024
Cited by 3 | Viewed by 2928
Abstract
Hashimoto’s thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this [...] Read more.
Hashimoto’s thyroiditis (HT) is marked by self-tissue destruction as a consequence of an alteration in the adaptive immune response that entails the evasion of immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review of the relationship between vitamin D status and HT and the role of vitamin D supplementation in reducing HT risk by modulating the immune system. There is extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titers decreased significantly. Further knowledge of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases requires the execution of additional randomized, double-blind, placebo-controlled trials and longer follow-up periods. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 4.0)
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16 pages, 2018 KiB  
Review
Vitamin D/Bone Mineral Density and Triglyceride Paradoxes Seen in African Americans: A Cross-Sectional Study and Review of the Literature
by Christopher M. Stevens and Sushil K. Jain
Int. J. Mol. Sci. 2024, 25(2), 1305; https://doi.org/10.3390/ijms25021305 - 21 Jan 2024
Cited by 4 | Viewed by 2036
Abstract
Vitamin D is known to have a positive effect on bone health. Despite the greater frequency of vitamin D deficiency in African Americans (AA), they have a higher bone mineral density (BMD) compared to whites, demonstrating a disconnect between BMD and vitamin D [...] Read more.
Vitamin D is known to have a positive effect on bone health. Despite the greater frequency of vitamin D deficiency in African Americans (AA), they have a higher bone mineral density (BMD) compared to whites, demonstrating a disconnect between BMD and vitamin D levels in AA. Another intriguing relationship seen in AA is the triglyceride (TG) paradox, an unusual phenomenon in which a normal TG status is observed even when patients house conditions known to be characterized by high TG levels, such as Type II diabetes. To the best of our knowledge, no study has examined whether these two paradoxical relationships exist simultaneously in AA subjects with Type II diabetes. In this study, we compared levels of blood markers, including HbA1c, TG, and vitamin D, measured as serum 25-hydroxyvitamin D [25(OH)VD] µM/mL, [25(OH)VD]/TG, calcium, and BMD in AA (n = 56) and white (n = 26) subjects with Type II diabetes to see whether these relationships exist concurrently. We found that AA subjects had significantly lower TG and [25(OH)VD] levels and a significantly higher BMD status compared to white subjects, even when the ages, BMI, duration of diabetes, HbA1c, and calcium levels were similar between the two groups. This demonstrates that these two paradoxical relationships exist simultaneously in Type II diabetic AA subjects. In addition to these findings, we discuss the current hypotheses in the literature that attempt to explain why these two intriguing relationships exist. This review also discusses four novel hypotheses, such as altered circulating levels and the potential role of estrogen and hydrogen sulfide on BMD and HMG-CoA reductase as a possible contributor to the TG paradox in AA subjects. This manuscript demonstrates that there are still many unanswered questions regarding these two paradoxical relationships and further research is needed to determine why they exist and how they can be implemented to improve healthcare. Full article
(This article belongs to the Special Issue The Role of Vitamin D in Human Health and Diseases 4.0)
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