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Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0

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

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 67766

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Prof. Dr. Marijn Speeckaert

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Department of Internal Medicine, Nephrology Division, Ghent University Hospital, 9000 Ghent, Belgium
Interests: biochemistry; biomarkers; hypertension; cardiovascular disease; kidney disease
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Dear Colleagues,

Vitamin D functions in the human body through both an endocrine and an autocrine mechanism. Nearly all circulating vitamin D (~85–90%) circulates bound to vitamin D-binding protein (DBP), with a smaller proportion bound to albumin, leaving <5% circulating freely. DBP is a multifunctional protein that has attracted increasing interest in recent years. DBP may also play roles beyond vitamin D binding, with potential roles in the immune system and elsewhere. The consequences of low 25(OH)D status include increased risk of various chronic diseases, ranging from hypertension to diabetes to cancer and infections. Also, the DBP polymorphism with more than 120 variants has been linked to several diseases. Despite the enormous progress in the deciphering of the structure of DBP and its function, there remains an impressive list of major research questions. In this special issue, we welcome original papers and review articles, which focus on the role of vitamin and DBP in health and disease.

Prof. Dr. Marijn Speeckaert
Guest Editor

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Keywords

vitamin D
vitamin D binding protein (gc-globulin)
vitamin D receptor
vitamin D deficiency
immunomodulation
chronic inflammatory diseases
osteoporosis
vitamin D deficiency

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Published Papers (9 papers)

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Editorial

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4 pages, 177 KiB

Open AccessEditorial

Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0

by Charlotte Delrue and Marijn M. Speeckaert

Int. J. Mol. Sci. 2023, 24(12), 10316; https://doi.org/10.3390/ijms241210316 - 19 Jun 2023

Cited by 2 | Viewed by 1237

Abstract

Vitamin D, often referred to as the “sunshine nutrient”, has gained considerable attention in recent years due to its multifaceted impact on health and disease [...] Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0)

Research

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11 pages, 611 KiB

Open AccessArticle

A Simultaneous Extraction/Derivatization Strategy for Quantitation of Vitamin D in Dried Blood Spots Using LC–MS/MS: Application to Biomarker Study in Subjects Tested for SARS-CoV-2

by Yashpal S. Chhonker, Nusrat Ahmed, Christine M. Johnston, Ruanne V. Barnabas and Daryl J. Murry

Int. J. Mol. Sci. 2023, 24(6), 5489; https://doi.org/10.3390/ijms24065489 - 13 Mar 2023

Cited by 3 | Viewed by 2591

Abstract

Vitamin D plays a critical role in bone development and maintenance, and in other physiological functions. The quantitation of endogenous levels of individual vitamin D and its metabolites is crucial for assessing several disease state conditions. With cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leading to the coronavirus disease 2019 (COVID-19) pandemic, there are several studies that have associated lower levels of serum vitamin D with severity of infection in COVID-19 patients. In this context, we have developed and validated a robust LC–MS/MS method for simultaneous quantitation of vitamin D and its metabolites in human dried blood spot (DBS) obtained from participants tested for COVID-19. The chromatographic separation for vitamin D and metabolites was performed using an ACE Excel C18 PFP column protected with a C18 guard column (Phenomenex, Torrance, CA, USA). The mobile phase consisted of formic acid in water (0.1% v/v) as mobile phase A and formic acid in methanol (0.1% v/v) as mobile phase B, operated at a flow rate of 0.5 mL/min. Analysis was performed utilizing the LC–MS/MS technique. The method was sensitive with a limit of quantification of 0.78 ng/mL for all analytes, and had a large dynamic range (200 ng/mL) with a total run time of 11 min. The inter- and intraday accuracy and precision values met the acceptance criteria per the US Food and Drug Administration guidelines. Blood concentrations of 25(OH)D3, vitamin D3, 25(OH)D2, and vitamin D2 over a range of 2–195.6, 0.5–121.5, 0.6–54.9, and 0.5–23.9 ng/mL, respectively, were quantified in 909 DBS samples. In summary, our developed LC−MS/MS method may be used for quantification of vitamin D and its metabolites in DBS, and may be applied to investigations of the emerging role of these compounds in various physiological processes. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0)

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8 pages, 483 KiB

Open AccessCommunication

Vitamin D Status in Patients before Thyroidectomy

by Dominika Maciejewska-Markiewicz, Joanna Kochman, Karolina Jakubczyk, Piotr Bargiel, Zbigniew Szlosser, Ewa Stachowska, Marta Markowska, Anna Bucka, Norbert Czapla, Jan Petriczko, Anna Surówka, Sonia Hertman, Piotr Puchalski and Piotr Prowans

Int. J. Mol. Sci. 2023, 24(4), 3228; https://doi.org/10.3390/ijms24043228 - 6 Feb 2023

Cited by 4 | Viewed by 2136

Abstract

Thyroid neoplasms (tumors) are the most common pathology of the endocrine system that requires surgery, and in most cases changes are benign. The surgical treatment of thyroid neoplasms consists in total, subtotal, or one lobe excision. Our study aimed to assess the concentration of vitamin D and its metabolites in patients before thyroidectomy. The study included 167 patients with thyroid pathology. Before the thyroidectomy procedure calcidiol (25-OHD), calcitriol (1,25-(OH)₂D), and vitamin D binding protein (VDBP), as well as basic biochemical parameters, were measured using an enzyme-linked immunosorbent assay kit. Data analysis showed that the cohort of patients has a significant 25-OHD deficiency and proper concentration of 1,25-(OH)₂D. Before the surgery, more than 80% of patients have extreme vitamin D deficiency (<10 ng/mL), and only 4% of the study group has proper 25-OHD concentration. Patients undergoing thyroidectomy are exposed to many complications, including calcium reduction. Our research has shown that patients prior to surgery have a marked vitamin D deficiency, an indicator that may affect their subsequent convalescence and prognosis. The results suggest that determination of vitamin D levels prior to thyroidectomy may be useful for potential consideration of supplementation when vitamin D deficiency is marked and needs to be incorporated into the good clinical management of these patients. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0)

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10 pages, 1162 KiB

Open AccessArticle

Vitamin D and Weight Change: A Mendelian Randomization, Prospective Study

by Pollyanna Patriota, Serge Rezzi, Idris Guessous and Pedro Marques-Vidal

Int. J. Mol. Sci. 2022, 23(19), 11100; https://doi.org/10.3390/ijms231911100 - 21 Sep 2022

Cited by 2 | Viewed by 2274

Abstract

The association between 25-hydroxyvitamin D and 5-, 10-, or 15-year weight change were assessed in a population-based, prospective study conducted in Lausanne, Switzerland. Data from the first (2009–2012, N = 3527, 51.3% women), second (2014–2017, N = 3237, 53.8% women), and third (2018–2021, N = 2567, 54.2% women) follow-ups were used. A weighted genetic risk score (GRS) of 115 SNPs associated with vitamin D levels was constructed. At baseline, the GRS correlated positively with 25-hydroxyvitamin D levels based on a Spearman rank correlation and 95% confidence interval: 0.198 (0.166; 0.231), p < 0.001; and with body mass index: 0.036 (0.004; 0.068), p = 0.028. No association was found between quartiles of GRS and weight changes at 5, 10, or 15 years: multivariate-adjusted weight changes ± SEM at 5-years follow-up were 1.39 ± 0.17, 1.13 ± 0.17, 1.24 ± 0.17, and 1.00 ± 0.17 kg for the first to the fourth quartile of the GRS, respectively (p = 0.401). Two-step linear regression showed a significant but clinically meaningless association between GRS-derived vitamin D and weight change at 5- and 15-years: slope and 95% confidence interval for a 5 nmol/L increase in GRS-derived 25-hydroxyvitamin D levels: 0.082 (0.013; 0.150) and 0.130 (0.018; 0.243) kg, respectively. We conclude that there is little association between genetically determined 25-hydroxyvitamin D levels and weight gain. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0)

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Review

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22 pages, 2005 KiB

Open AccessReview

Latest Knowledge on the Role of Vitamin D in Hypertension

by Niklas S. Jensen, Markus Wehland, Petra M. Wise and Daniela Grimm

Int. J. Mol. Sci. 2023, 24(5), 4679; https://doi.org/10.3390/ijms24054679 - 28 Feb 2023

Cited by 24 | Viewed by 9561

Abstract

Hypertension is the third leading cause of the global disease burden, and while populations live longer, adopt more sedentary lifestyles, and become less economically concerned, the prevalence of hypertension is expected to increase. Pathologically elevated blood pressure (BP) is the strongest risk factor for cardiovascular disease (CVD) and related disability, thus making it imperative to treat this disease. Effective standard pharmacological treatments, i.e., diuretics, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocker (ARBs), beta-adrenergic receptor blockers (BARBs), and calcium channel blockers (CCBs), are available. Vitamin D (vitD) is known best for its role in bone and mineral homeostasis. Studies with vitamin D receptor (VDR) knockout mice show an increased renin–angiotensin–aldosterone system (RAAS) activity and increased hypertension, suggesting a key role for vitD as a potential antihypertensive agent. Similar studies in humans displayed ambiguous and mixed results. No direct antihypertensive effect was shown, nor a significant impact on the human RAAS. Interestingly, human studies supplementing vitD with other antihypertensive agents reported more promising results. VitD is considered a safe supplement, proposing its great potential as antihypertensive supplement. The aim of this review is to examine the current knowledge about vitD and its role in the treatment of hypertension. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0)

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17 pages, 936 KiB

Open AccessReview

Vitamin D and the Thyroid: A Critical Review of the Current Evidence

by Mirjana Babić Leko, Iva Jureško, Iva Rozić, Nikolina Pleić, Ivana Gunjača and Tatijana Zemunik

Int. J. Mol. Sci. 2023, 24(4), 3586; https://doi.org/10.3390/ijms24043586 - 10 Feb 2023

Cited by 18 | Viewed by 12488

Abstract

Vitamin D is necessary for the normal functioning of many organs, including the thyroid gland. It is, therefore, not surprising that vitamin D deficiency is considered a risk factor for the development of many thyroid disorders, including autoimmune thyroid diseases and thyroid cancer. However, the interaction between vitamin D and thyroid function is still not fully understood. This review discusses studies involving human subjects that (1) compared vitamin D status (primarily determined by serum calcidiol (25-hydroxyvitamin D [25(OH)D]) levels) with thyroid function assessed by thyroid stimulating hormone (TSH), thyroid hormones, and anti-thyroid antibody levels; and (2) evaluated the effect of vitamin D supplementation on thyroid function. Due to the many inconsistencies in the results between the studies, it is still difficult to draw a definite conclusion on how vitamin D status affects thyroid function. Studies in healthy participants observed either a negative correlation or no association between TSH and 25(OH)D levels, while the results for thyroid hormones showed high variability. Many studies have observed a negative association between anti-thyroid antibodies and 25(OH)D levels, but equally many studies have failed to observe such an association. Regarding the studies that examined the effect of vitamin D supplementation on thyroid function, almost all observed a decrease in anti-thyroid antibody levels after vitamin D supplementation. Factors that could contribute to the high variability between the studies are the use of different assays for the measurement of serum 25(OH)D levels and the confounding effects of sex, age, body-mass index, dietary habits, smoking, and the time of year when the samples were collected. In conclusion, additional studies with larger numbers of participants are needed to fully understand the effect of vitamin D on thyroid function. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0)

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21 pages, 1216 KiB

Open AccessReview

Vitamin D Deficiency: An Underestimated Factor in Sepsis?

by Charlotte Delrue, Reinhart Speeckaert, Joris R. Delanghe and Marijn M. Speeckaert

Int. J. Mol. Sci. 2023, 24(3), 2924; https://doi.org/10.3390/ijms24032924 - 2 Feb 2023

Cited by 17 | Viewed by 5415

Abstract

Vitamin D is an important immune modulator that is linked to infection susceptibility. It has been suggested that vitamin D deficiency plays a role in sepsis and septic shock because vitamin-D-related pathways are associated with various immunological, endocrine, and endothelial functions. Previous research has yielded inconclusive results regarding the link between mortality and vitamin D deficiency in sepsis patients. In patients with sepsis and severe vitamin D deficiency, an adequate vitamin D concentration may reduce mortality. Randomized controlled trials to assess the influence of vitamin D supplementation on clinical outcomes in sepsis patients with vitamin D deficiency are uncommon. We will provide an overview of the current knowledge about the relationship between vitamin D and sepsis in this review, as well as consider the potential value of vitamin D supplementation in this situation. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0)

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18 pages, 1792 KiB

Open AccessReview

The Role of Vitamin D and Vitamin D Binding Protein in Chronic Liver Diseases

by Tudor Lucian Pop, Claudia Sîrbe, Gabriel Benţa, Alexandra Mititelu and Alina Grama

Int. J. Mol. Sci. 2022, 23(18), 10705; https://doi.org/10.3390/ijms231810705 - 14 Sep 2022

Cited by 38 | Viewed by 6631

Abstract

Vitamin D (calciferol) is a fat-soluble vitamin that has a significant role in phospho-calcium metabolism, maintaining normal calcium levels and bone health development. The most important compounds of vitamin D are cholecalciferol (vitamin D3, or VD3) and ergocalciferol (vitamin D2, or VD2). Besides its major role in maintaining an adequate level of calcium and phosphate concentrations, vitamin D is involved in cell growth and differentiation and immune function. Recently, the association between vitamin D deficiency and the progression of fibrosis in chronic liver disease (CLD) was confirmed, given the hepatic activation process and high prevalence of vitamin D deficiency in these diseases. There are reports of vitamin D deficiency in CLD regardless of the etiology (chronic viral hepatitis, alcoholic cirrhosis, non-alcoholic fatty liver disease, primary biliary cirrhosis, or autoimmune hepatitis). Vitamin D binding protein (VDBP) is synthesized by the liver and has the role of binding and transporting vitamin D and its metabolites to the target organs. VDBP also plays an important role in inflammatory response secondary to tissue damage, being involved in the degradation of actin. As intense research during the last decades revealed the possible role of vitamin D in liver diseases, a deeper understanding of the vitamin D, vitamin D receptors (VDRs), and VDBP involvement in liver inflammation and fibrogenesis could represent the basis for the development of new strategies for diagnosis, prognosis, and treatment of liver diseases. This narrative review presents an overview of the evidence of the role of vitamin D and VDBP in CLD, both at the experimental and clinical levels. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0)

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29 pages, 1588 KiB

Open AccessReview

An Update on the Effects of Vitamin D on the Immune System and Autoimmune Diseases

by Claudia Sîrbe, Simona Rednic, Alina Grama and Tudor Lucian Pop

Int. J. Mol. Sci. 2022, 23(17), 9784; https://doi.org/10.3390/ijms23179784 - 29 Aug 2022

Cited by 91 | Viewed by 23900

Abstract

Vitamin D intervenes in calcium and phosphate metabolism and bone homeostasis. Experimental studies have shown that 1,25-dihydroxyvitamin D (calcitriol) generates immunologic activities on the innate and adaptive immune system and endothelial membrane stability. Low levels of serum 25-hydroxyvitamin D (25(OH)D) are associated with an increased risk of developing immune-related diseases such as psoriasis, type 1 diabetes, multiple sclerosis, and autoimmune diseases. Various clinical trials describe the efficacy of supplementation of vitamin D and its metabolites for treating these diseases that result in variable outcomes. Different disease outcomes are observed in treatment with vitamin D as high inter-individual difference is present with complex gene expression in human peripheral blood mononuclear cells. However, it is still not fully known what level of serum 25(OH)D is needed. The current recommendation is to increase vitamin D intake and have enough sunlight exposure to have serum 25(OH)D at a level of 30 ng/mL (75 nmol/L) and better at 40–60 ng/mL (100–150 nmol/L) to obtain the optimal health benefits of vitamin D. Full article

(This article belongs to the Special Issue Vitamin D and Vitamin D Binding Protein in Health and Disease 2.0)

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