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11 pages, 1118 KiB

Open AccessArticle

Are Vitamin D₃ Tablets and Oil Drops Equally Effective in Raising S-25-Hydroxyvitamin D Concentrations? A Post-Hoc Analysis of an Observational Study on Immunodeficient Patients

by Maria Helde Frankling, Anna-Carin Norlin, Susanne Hansen, Emilie Wahren Borgström, Peter Bergman and Linda Björkhem-Bergman

Nutrients 2020, 12(5), 1230; https://doi.org/10.3390/nu12051230 - 26 Apr 2020

Cited by 3 | Viewed by 4803

Abstract

Background: Vitamin D₃ supplements are available as tablets or oil drops, but there is no consensus as to whether either of these preparations is more effective than the other. Methods: We compared the effectiveness of tablets versus oil in raising S-25-hydroxyvitamin D [...] Read more.

Background: Vitamin D₃ supplements are available as tablets or oil drops, but there is no consensus as to whether either of these preparations is more effective than the other. Methods: We compared the effectiveness of tablets versus oil in raising S-25-hydroxyvitamin D (S-25-OHD) in plasma by re-analyzing data from a previously performed observational study in which immunodeficient patients with S-25-OHD concentrations <75 nmol/L were randomly prescribed vitamin D₃ tablets (1600 IU/day) or vitamin D₃ oil-drops (1500 IU/day) for twelve months. Tablets and oil were compared for the effect on S-25-OHD concentrations after 3–5 months and antibiotic use. Results: Data on S-25-OHD after ≥ 3 months was available for 137 patients treated with tablets and 69 with oil drops. Both groups exhibited a significant increase in S-25-OHD—oil-drops from 55 to 86 nmol/L and tablets from 52 to 87 nmol/L—with no difference between groups (p = 0.77). In a subgroup of patients without immunoglobulin replacement, vitamin D₃ supplementation with oil drops (n = 34) but not with tablets (n = 60) resulted in significantly lower antibiotic administration (p < 0.001 and p = 0.58). Conclusion: Vitamin D₃ supplementation with tablets and oil drops were equally efficient in raising S-25-OHD concentrations. Only oil drops caused a reduction in antibiotic consumption in immuno-deficient patients who did not receive immunoglobulin replacement. Full article

(This article belongs to the Special Issue Vitamin D on Immune Function)

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18 pages, 3672 KiB

Open AccessArticle

Key Vitamin D Target Genes with Functions in the Immune System

by Oona Koivisto, Andrea Hanel and Carsten Carlberg

Nutrients 2020, 12(4), 1140; https://doi.org/10.3390/nu12041140 - 19 Apr 2020

Cited by 61 | Viewed by 12828

Abstract

The biologically active form of vitamin D₃, 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes [...] Read more.

The biologically active form of vitamin D₃, 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), modulates innate and adaptive immunity via genes regulated by the transcription factor vitamin D receptor (VDR). In order to identify the key vitamin D target genes involved in these processes, transcriptome-wide datasets were compared, which were obtained from a human monocytic cell line (THP-1) and peripheral blood mononuclear cells (PBMCs) treated in vitro by 1,25(OH)₂D₃, filtered using different approaches, as well as from PBMCs of individuals supplemented with a vitamin D₃ bolus. The led to the genes ACVRL1, CAMP, CD14, CD93, CEBPB, FN1, MAPK13, NINJ1, LILRB4, LRRC25, SEMA6B, SRGN, THBD, THEMIS2 and TREM1. Public epigenome- and transcriptome-wide data from THP-1 cells were used to characterize these genes based on the level of their VDR-driven enhancers as well as the level of the dynamics of their mRNA production. Both types of datasets allowed the categorization of the vitamin D target genes into three groups according to their role in (i) acute response to infection, (ii) infection in general and (iii) autoimmunity. In conclusion, 15 genes were identified as major mediators of the action of vitamin D in innate and adaptive immunity and their individual functions are explained based on different gene regulatory scenarios. Full article

(This article belongs to the Special Issue Vitamin D on Immune Function)

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Review

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17 pages, 2242 KiB

Open AccessReview

Vitamin D and Periodontitis: A Systematic Review and Meta-Analysis

by Vanessa Machado, Sofia Lobo, Luís Proença, José João Mendes and João Botelho

Nutrients 2020, 12(8), 2177; https://doi.org/10.3390/nu12082177 - 22 Jul 2020

Cited by 56 | Viewed by 6726

Abstract

To explore the vitamin D levels of periodontitis patients in comparison with periodontally healthy ones, and to assess the influence of vitamin D supplementation as an adjunctive during nonsurgical periodontal treatment (NSPT). Five databases (Pubmed, Embase, Scholar, Web of Sciences, and Cochrane Library) [...] Read more.

To explore the vitamin D levels of periodontitis patients in comparison with periodontally healthy ones, and to assess the influence of vitamin D supplementation as an adjunctive during nonsurgical periodontal treatment (NSPT). Five databases (Pubmed, Embase, Scholar, Web of Sciences, and Cochrane Library) were searched until May 2020. Mean difference (MD) meta-analysis with corresponding 95% confidence interval (95% CI) and sensitivity tests via meta-regression were used. We followed Strength of Recommendation Taxonomy (SORT) to appraise the strength and quality of the evidence. Sixteen articles were included, fourteen case-control and two intervention studies, all reporting 25-hydroxyvitamin D (25(OH)D) levels. Compared with the healthy controls, the circulating 25(OH)D levels were significantly lower in chronic periodontitis patients (pooled MD = −6.80, 95% CI: −10.59 to −3.02). Subgroup analysis revealed differences among 25(OH)D measurements, with liquid chromatography-mass spectrometry being the most homogeneous method (pooled MD = −2.05, 95% CI: −3.40 to −0.71). Salivary levels of 25(OH)D showed no differences between groups. Due to the low number of studies, conclusions on aggressive periodontitis and in the effect of vitamin D supplementation after NSPT were not possible to ascribe. Compared with healthy controls, 25(OH)D serum levels are significantly lower in chronic periodontitis patients, with an overall SORT A recommendation. Future studies are needed to clarify the effect of vitamin D supplementation and the biological mechanisms linking vitamin D to the periodontium. Full article

(This article belongs to the Special Issue Vitamin D on Immune Function)

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28 pages, 5704 KiB

Open AccessReview

Immunologic Effects of Vitamin D on Human Health and Disease

by Nipith Charoenngam and Michael F. Holick

Nutrients 2020, 12(7), 2097; https://doi.org/10.3390/nu12072097 - 15 Jul 2020

Cited by 522 | Viewed by 114073

Abstract

Vitamin D is responsible for regulation of calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. It is also known as an immunomodulatory hormone. Experimental studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts immunologic activities on multiple [...] Read more.

Vitamin D is responsible for regulation of calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. It is also known as an immunomodulatory hormone. Experimental studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts immunologic activities on multiple components of the innate and adaptive immune system as well as endothelial membrane stability. Association between low levels of serum 25-hydroxyvitamin D and increased risk of developing several immune-related diseases and disorders, including psoriasis, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, tuberculosis, sepsis, respiratory infection, and COVID-19, has been observed. Accordingly, a number of clinical trials aiming to determine the efficacy of administration of vitamin D and its metabolites for treatment of these diseases have been conducted with variable outcomes. Interestingly, recent evidence suggests that some individuals might benefit from vitamin D more or less than others as high inter-individual difference in broad gene expression in human peripheral blood mononuclear cells in response to vitamin D supplementation has been observed. Although it is still debatable what level of serum 25-hydroxyvitamin D is optimal, it is advisable to increase vitamin D intake and have sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at least 30 ng/mL (75 nmol/L), and preferably at 40–60 ng/mL (100–150 nmol/L) to achieve the optimal overall health benefits of vitamin D. Full article

(This article belongs to the Special Issue Vitamin D on Immune Function)

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20 pages, 1426 KiB

Open AccessReview

Immunomodulatory Effects of Vitamin D in Thyroid Diseases

by Chiara Mele, Marina Caputo, Alessandro Bisceglia, Maria Teresa Samà, Marco Zavattaro, Gianluca Aimaretti, Loredana Pagano, Flavia Prodam and Paolo Marzullo

Nutrients 2020, 12(5), 1444; https://doi.org/10.3390/nu12051444 - 16 May 2020

Cited by 31 | Viewed by 9199

Abstract

Vitamin D is a secosteroid with a pleiotropic role in multiple physiological processes. Besides the well-known activity on bone homeostasis, recent studies suggested a peculiar role of vitamin D in different non-skeletal pathways, including a key role in the modulation of immune responses. [...] Read more.

Vitamin D is a secosteroid with a pleiotropic role in multiple physiological processes. Besides the well-known activity on bone homeostasis, recent studies suggested a peculiar role of vitamin D in different non-skeletal pathways, including a key role in the modulation of immune responses. Recent evidences demonstrated that vitamin D acts on innate and adaptative immunity and seems to exert an immunomodulating action on autoimmune diseases and cancers. Several studies demonstrated a relationship between vitamin D deficiency, autoimmune thyroid disorders, and thyroid cancer. This review aims to summarize the evidences on the immunomodulatory effect of vitamin D on thyroid diseases. Full article

(This article belongs to the Special Issue Vitamin D on Immune Function)

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20 pages, 1292 KiB

Open AccessReview

Vitamin D Effects on the Immune System from Periconception through Pregnancy

by Bianca Schröder-Heurich, Clara Juliane Pacifica Springer and Frauke von Versen-Höynck

Nutrients 2020, 12(5), 1432; https://doi.org/10.3390/nu12051432 - 15 May 2020

Cited by 41 | Viewed by 8631

Abstract

Vitamin D is a well-known secosteroid and guardian of bone health and calcium homeostasis. Studies on its role in immunomodulatory functions have expanded its field in recent years. In addition to its impact on human physiology, vitamin D influences the differentiation and proliferation [...] Read more.

Vitamin D is a well-known secosteroid and guardian of bone health and calcium homeostasis. Studies on its role in immunomodulatory functions have expanded its field in recent years. In addition to its impact on human physiology, vitamin D influences the differentiation and proliferation of immune system modulators, interleukin expression and antimicrobial responses. Furthermore, it has been shown that vitamin D is synthesized in female reproductive tissues and, by modulating the immune system, affects the periconception period and reproductive outcomes. B cells, T cells, macrophages and dendritic cells can all synthesize active vitamin D and are involved in processes which occur from fertilization, implantation and maintenance of pregnancy. Components of vitamin D synthesis are expressed in the ovary, decidua, endometrium and placenta. An inadequate vitamin D level has been associated with recurrent implantation failure and pregnancy loss and is associated with pregnancy-related disorders like preeclampsia. This paper reviews the most important data on immunomodulatory vitamin D effects in relation to the immune system from periconception to pregnancy and provides an insight into the possible consequences of vitamin D deficiency before and during pregnancy. Full article

(This article belongs to the Special Issue Vitamin D on Immune Function)

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18 pages, 2019 KiB

Open AccessReview

Impact of Epigenetics on Complications of Fanconi Anemia: The Role of Vitamin D-Modulated Immunity

by Eunike Velleuer and Carsten Carlberg

Nutrients 2020, 12(5), 1355; https://doi.org/10.3390/nu12051355 - 09 May 2020

Cited by 5 | Viewed by 6338

Abstract

Fanconi anemia (FA) is a rare disorder with the clinical characteristics of (i) specific malformations at birth, (ii) progressive bone marrow failure already during early childhood and (iii) dramatically increased risk of developing cancer in early age, such as acute myeloid leukemia and [...] Read more.

Fanconi anemia (FA) is a rare disorder with the clinical characteristics of (i) specific malformations at birth, (ii) progressive bone marrow failure already during early childhood and (iii) dramatically increased risk of developing cancer in early age, such as acute myeloid leukemia and squamous cell carcinoma. Patients with FA show DNA fragility due to a defect in the DNA repair machinery based on predominately recessive mutations in 23 genes. Interestingly, patients originating from the same family and sharing an identical mutation, frequently show significant differences in their clinical presentation. This implies that epigenetics plays an important role in the manifestation of the disease. The biologically active form of vitamin D, 1α,25-dihydroxyvitamin D₃ controls cellular growth, differentiation and apoptosis via the modulation of the immune system. The nuclear hormone activates the transcription factor vitamin D receptor that affects, via fine-tuning of the epigenome, the transcription of >1000 human genes. In this review, we discuss that changes in the epigenome, in particular in immune cells, may be central for the clinical manifestation of FA. These epigenetic changes can be modulated by vitamin D suggesting that the individual FA patient’s vitamin D status and responsiveness are of critical importance for disease progression. Full article

(This article belongs to the Special Issue Vitamin D on Immune Function)

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22 pages, 610 KiB

Open AccessReview

Vitamin D’s Effect on Immune Function

by Pieter-Jan Martens, Conny Gysemans, Annemieke Verstuyf and Chantal Mathieu

Nutrients 2020, 12(5), 1248; https://doi.org/10.3390/nu12051248 - 28 Apr 2020

Cited by 217 | Viewed by 29773

Abstract

Ever since its discovery by Windhaus, the importance of the active metabolite of vitamin D (1,25-dihydroxyvitamin D₃; 1,25-(OH)2D₃) has been ever expanding. In this review, the attention is shifted towards the importance of the extra-skeletal effects of vitamin D, [...] Read more.

Ever since its discovery by Windhaus, the importance of the active metabolite of vitamin D (1,25-dihydroxyvitamin D₃; 1,25-(OH)2D₃) has been ever expanding. In this review, the attention is shifted towards the importance of the extra-skeletal effects of vitamin D, with special emphasis on the immune system. The first hint of the significant role of vitamin D on the immune system was made by the discovery of the presence of the vitamin D receptor on almost all cells of the immune system. In vitro, the overwhelming effect of supra-physiological doses of vitamin D on the individual components of the immune system is very clear. Despite these promising pre-clinical results, the translation of the in vitro observations to solid clinical effects has mostly failed. Nevertheless, the evidence of a link between vitamin D deficiency and adverse outcomes is overwhelming and clearly points towards avoidance of vitamin D deficiency especially in early life. Full article

(This article belongs to the Special Issue Vitamin D on Immune Function)

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29 pages, 719 KiB

Open AccessReview

Vitamin D and Immunity in Infants and Children

by Geneviève Mailhot and John H. White

Nutrients 2020, 12(5), 1233; https://doi.org/10.3390/nu12051233 - 27 Apr 2020

Cited by 87 | Viewed by 16774

Abstract

The last couple of decades have seen an explosion in our interest and understanding of the role of vitamin D in the regulation of immunity. At the molecular level, the hormonal form of vitamin D signals through the nuclear vitamin D receptor (VDR), [...] Read more.

The last couple of decades have seen an explosion in our interest and understanding of the role of vitamin D in the regulation of immunity. At the molecular level, the hormonal form of vitamin D signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. The VDR and vitamin D metabolic enzymes are expressed throughout the innate and adaptive arms of the immune system. The advent of genome-wide approaches to gene expression profiling have led to the identification of numerous VDR-regulated genes implicated in the regulation of innate and adaptive immunity. The molecular data infer that vitamin D signaling should boost innate immunity against pathogens of bacterial or viral origin. Vitamin D signaling also suppresses inflammatory immune responses that underlie autoimmunity and regulate allergic responses. These findings have been bolstered by clinical studies linking vitamin D deficiency to increased rates of infections, autoimmunity, and allergies. Our goals here are to provide an overview of the molecular basis for immune system regulation and to survey the clinical data from pediatric populations, using randomized placebo-controlled trials and meta-analyses where possible, linking vitamin D deficiency to increased rates of infections, autoimmune conditions, and allergies, and addressing the impact of supplementation on these conditions. Full article

(This article belongs to the Special Issue Vitamin D on Immune Function)

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