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Current Understanding of Vitamin D in Chronic Diseases, Acute Respiratory Infections and All-Cause Mortality

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 53561

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Special Issue Editors

Prof. Dr. Sara Gandini

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Department of Experimental Oncology, European Institute of Oncology IRCCS, 20141 Milano, Italy
Interests: cancer risk factors; epidemiology; prevention; biomarkers; omics analysis; skin neoplasm; repurposing drugs; vitamin D
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Dr. Harriet Johansson

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Department of Experimental Oncology, European Institute of Oncology, Milano, Italy

Dr. Davide Serrano

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Department of Experimental Oncology, European Institute of Oncology, Milano, Italy
Interests: cancer preventive medicine; hereditary syndromes, particularly of breast and gastrointestinal tract; cascade screening and surveillance programs
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Prof. Dr. Sara Raimondi

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Department of Experimental Oncology, European Institute of Oncology, Milano, Italy

Dr.ssa Patrizia Gnagnarella

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Division of Epidemiology and Biostatistics, European Institute of Oncology, Milano, Italy
Interests: nutrient databanks;food;

Special Issue Information

Dear Colleagues,

Vitamin D, traditionally known as an essential nutrient, is a precursor of a potent steroid hormone that regulates a broad spectrum of physiological processes. In addition to its classical roles in bone metabolism, epidemiological, preclinical, and cellular research during the last several decades point to a key role in the prevention and treatment of many extra-skeletal diseases. Vitamin D deficiency has been associated with risks of morbidity and mortality from diabetes and cardiovascular disease, as well as with several cancers, including colorectal, breast, and melanoma cancer. Inadequate sun exposure, insufﬁcient intakes of vitamin D, obesity, gastrointestinal disorders, renal and liver diseases, and other various health conditions seem to contribute to its deﬁciency. Vitamin D has anti-inflammatory properties and has anti-proliferative effects on cancer cell lines, can inhibit tumor growth and tumor invasiveness, and promotes melanoma cell DNA repair.

However, investigations of dietary vitamin D intake or blood levels of vitamin D and cancer risk have yielded inconsistent results. This Issue aims to better define the role of vitamin D in chronic diseases, including cancer, acute respiratory infections, and all-cause mortality. We welcome different types of manuscript submissions, including original research articles and up-to-date reviews (systematic reviews and meta-analyses).

Prof. Dr. Sara Gandini
Dr. Harriet Johansson
Prof. Dr. Davide Serrano
Prof. Dr. Sara Raimondi
Dr.ssa Patrizia Gnagnarella
Guest Editors

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Keywords

Vitamin D Supplementation
Vitamin Binding Protein
Vitamin D Receptor
Microbiota
Diet
25(OH)D
Cancer
Prevention
Prognosis

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Published Papers (7 papers)

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Research

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11 pages, 585 KiB

Open AccessArticle

Vitamin D Level Trajectories of Adolescent Patients with Anorexia Nervosa at Inpatient Admission, during Treatment, and at One Year Follow Up: Association with Depressive Symptoms

by Manuel Föcker, Nina Timmesfeld, Judith Bühlmeier, Denise Zwanziger, Dagmar Führer, Corinna Grasemann, Stefan Ehrlich, Karin Egberts, Christian Fleischhaker, Christoph Wewetzer, Ida Wessing, Jochen Seitz, Beate Herpertz-Dahlmann, Johannes Hebebrand and Lars Libuda

Nutrients 2021, 13(7), 2356; https://doi.org/10.3390/nu13072356 - 9 Jul 2021

Cited by 5 | Viewed by 3023

Abstract

(1) Background: Evidence has accumulated that patients with anorexia nervosa (AN) are at higher risk for vitamin D deficiency than healthy controls. In epidemiologic studies, low 25(OH) vitamin D (25(OH)D) levels were associated with depression. This study analyzed the relationship between 25(OH)D serum levels in adolescent patients and AN and depressive symptoms over the course of treatment. (2) Methods: 25(OH)D levels and depressive symptoms were analyzed in 93 adolescent (in-)patients with AN from the Anorexia Nervosa Day patient versus Inpatient (ANDI) multicenter trial at clinic admission, discharge, and 1 year follow up. Mixed regression models were used to analyze the relationship between 25(OH)D levels and depressive symptoms assessed by the Beck Depression Inventory (BDI-II). (3) Results: Although mean 25(OH)D levels constantly remained in recommended ranges (≥50 nmol/L) during AN treatment, levels decreased from (in)patient admission to 1 year follow up. Levels of 25(OH)D were neither cross-sectionally, prospectively, nor longitudinally associated with the BDI-II score. (4) Conclusions: This study did not confirm that 25(OH)D levels are associated with depressive symptoms in patients with AN. However, increasing risks of vitamin D deficiency over the course of AN treatment indicate that clinicians should monitor 25(OH)D levels. Full article

(This article belongs to the Special Issue Current Understanding of Vitamin D in Chronic Diseases, Acute Respiratory Infections and All-Cause Mortality)

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14 pages, 1173 KiB

Open AccessArticle

Vitamin D Supplementation and Disease-Free Survival in Stage II Melanoma: A Randomized Placebo Controlled Trial

by Harriet Johansson, Giuseppe Spadola, Giulio Tosti, Mario Mandalà, Alessandro M. Minisini, Paola Queirolo, Valentina Aristarco, Federica Baldini, Emilia Cocorocchio, Elena Albertazzi, Leonardo Zichichi, Saverio Cinieri, Costantino Jemos, Giovanni Mazzarol, Patrizia Gnagnarella, Debora Macis, Ines Tedeschi, Emanuela Omodeo Salè, Luigia Stefania Stucci, Bernardo Bonanni, Alessandro Testori, Elisabetta Pennacchioli, Pier Francesco Ferrucci, Sara Gandini and on behalf of the Italian Melanoma Intergroup (IMI) Show full author list Hide full author list

Nutrients 2021, 13(6), 1931; https://doi.org/10.3390/nu13061931 - 4 Jun 2021

Cited by 25 | Viewed by 6349

Abstract

Patients with newly resected stage II melanoma (n = 104) were randomized to receive adjuvant vitamin D3 (100,000 IU every 50 days) or placebo for 3 years to investigate vitamin D3 protective effects on developing a recurrent disease. Median age at diagnosis was 50 years, and 43% of the patients were female. Median serum 25-hydroxy vitamin D (25OHD) level at baseline was 18 ng/mL, interquartile range (IQ) was 13–24 ng/mL, and 80% of the patients had insufficient vitamin D levels. We observed pronounced increases in 25OHD levels after 4 months in the active arm (median 32.9 ng/mL; IQ range 25.9–38.4) against placebo (median 19.05 ng/mL; IQ range 13.0–25.9), constantly rising during treatment. Remarkably, patients with low Breslow score (<3 mm) had a double increase in 25OHD levels from baseline, whereas patients with Breslow score ≥3 mm had a significantly lower increase over time. After 12 months, subjects with low 25OHD levels and Breslow score ≥3 mm had shorter disease-free survival (p = 0.02) compared to those with Breslow score <3 mm and/or high levels of 25OHD. Adjusting for age and treatment arm, the hazard ratio for relapse was 4.81 (95% CI: 1.44–16.09, p = 0.011). Despite the evidence of a role of 25OHD in melanoma prognosis, larger trials with vitamin D supplementation involving subjects with melanoma are needed. Full article

(This article belongs to the Special Issue Current Understanding of Vitamin D in Chronic Diseases, Acute Respiratory Infections and All-Cause Mortality)

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9 pages, 786 KiB

Open AccessArticle

Association of Vitamin D Receptor and Vitamin D-Binding Protein Polymorphisms with Familial Breast Cancer Prognosis in a Mono-Institutional Cohort

by Valentina Aristarco, Harriet Johansson, Sara Gandini, Debora Macis, Cristina Zanzottera, Gianluca Tolva, Irene Feroce, Chiara Accornero, Bernardo Bonanni, Aliana Guerrieri-Gonzaga and Davide Serrano

Nutrients 2021, 13(4), 1208; https://doi.org/10.3390/nu13041208 - 6 Apr 2021

Cited by 8 | Viewed by 3261

Abstract

Low 25-hydroxyvitamin D (25OHD) has been associated with an increased cancer incidence and poorer prognosis. Single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) and vitamin D binding protein (GC gene) may interfere with vitamin D activity. This study assesses the role of VDR and GC SNPs on breast cancer (BC) recurrence and survival in a cohort of patients with a family history of breast cancer, without the pathogenic variant for BRCA1 and BRCA2. A consecutive series of patients who underwent genetic testing were genotyped for VDR and GC genes. Specifically, ApaI, FokI, TaqI, BsmI and rs2282679, rs4588, rs7041 SNPs were determined. A total of 368 wild type (WT) patients with BC were analyzed for VDR and GC SNPs. The GC rs2282679 minor allele was significantly associated with luminal subtype of the primary tumor compared to Her2+/TN breast cancer (p = 0.007). Multivariate Cox models showed that BmsI and TaqI are significantly associated with BC outcome. Patients with the major alleles showed more than 30% lower hazard of relapse (BsmI p = 0.02 and TaqI p = 0.03). Our study supports the evidence for a pivotal role of 25OHD metabolism in BC. GC SNPs may influence the hormone tumor responsiveness and VDR may affect tumor prognosis. Full article

(This article belongs to the Special Issue Current Understanding of Vitamin D in Chronic Diseases, Acute Respiratory Infections and All-Cause Mortality)

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19 pages, 4266 KiB

Open AccessArticle

Microbiome as Mediator of Diet on Colorectal Cancer Risk: The Role of Vitamin D, Markers of Inflammation and Adipokines

by Davide Serrano, Chiara Pozzi, Silvia Guglietta, Bruno Fosso, Mariano Suppa, Patrizia Gnagnarella, Federica Corso, Federica Bellerba, Debora Macis, Valentina Aristarco, Paolo Manghi, Nicola Segata, Cristina Trovato, Maria Giulia Zampino, Marinella Marzano, Bernardo Bonanni, Maria Rescigno and Sara Gandini

Nutrients 2021, 13(2), 363; https://doi.org/10.3390/nu13020363 - 25 Jan 2021

Cited by 16 | Viewed by 6961

Abstract

Obesity and diet are associated with colorectal cancer (CRC) risk, and microbiome could mediate this risk factor. To investigate this interaction, we performed a case–control study (34 CRC cases and 32 controls) and analyzed fecal microbiota composition using 16S rRNA metabarcoding and sub-sequential shotgun analyses of genomic bacterial DNA to evaluate the role of microbiome and diet in CRC etiology, taking into account vitamin D and other risk biomarkers. Dietary habits were evaluated using a short questionnaire. Multivariate methods for data integration and mediation analysis models were used to investigate causal relationships. CRC cases were significantly more often deficient in vitamin D than controls (p = 0.04); FokI and CYP24A1 polymorphism frequency were different between cases and controls (p = 0.03 and p = 0.02, respectively). A diet poor in fatty fish and rich in carbohydrates was found to be significantly associated with CRC risk (p = 0.011). The mediation analysis confirmed the significant role of the microbiome in mediating CRC risk—increasing levels of Bifidobacteria/Escherichia genera ratio, an indicator of “healthy” intestinal microbiome, can overcome the effect of diet on CRC risk (p = 0.03). This study suggests that microbiome mediates the diet effect on CRC risk, and that vitamin D, markers of inflammation, and adipokines are other factors to consider in order to achieve a better knowledge of the whole carcinogenic process. Full article

(This article belongs to the Special Issue Current Understanding of Vitamin D in Chronic Diseases, Acute Respiratory Infections and All-Cause Mortality)

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12 pages, 1234 KiB

Open AccessArticle

Vitamin D Receptor (VDR) Gene Polymorphism in Patients Diagnosed with Colorectal Cancer

by Maria Latacz, Dominika Rozmus, Ewa Fiedorowicz, Jadwiga Snarska, Beata Jarmołowska, Natalia Kordulewska, Huub Savelkoul and Anna Cieślińska

Nutrients 2021, 13(1), 200; https://doi.org/10.3390/nu13010200 - 11 Jan 2021

Cited by 16 | Viewed by 4383

Abstract

Colorectal cancer (CRC) is one of the most commonly occurring neoplasias in humans. The prevalence of CRC rates is still rising. Although the exact background of the disease still remains unknown, it is believed that CRC may not only be a result of environmental factors, but also genetic ones. One of the mechanisms underlying CRC might be the vitamin D pathway, as CRC is the most closely linked neoplasia to vitamin D deficiency. This study shows a possible association of the vitamin D receptor (VDR) polymorphisms FokI, BsmI, ApaI, and TaqI with CRC susceptibility. A total of 103 patients diagnosed with CRC (61 men and 42 women, aged 57–82 years) and 109 healthy people (50 men and 59 women, aged 47–68 years) were genotyped using PCR-RFLP for FokI, BsmI, ApaI, and TaqI. None of the single nucleotide polymorphisms (SNPs) individually increased or decreased the risk of CRC. The evaluation of haplotypes revealed two that might enhance the likelihood of CRC development: taB (OR = 30.22; 95% CI 2.81–325.31; p = 0.01) and tAb (OR = 3.84; 95% CI 1.29–11.38; p = 0.01). In conclusion, genotyping is an easy and robust procedure that needs to be performed only once in a lifetime. A creation of a relevant SNP’s panel might contribute to the identification of the groups that are at the greatest risk of CRC. Full article

(This article belongs to the Special Issue Current Understanding of Vitamin D in Chronic Diseases, Acute Respiratory Infections and All-Cause Mortality)

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Review

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14 pages, 683 KiB

Open AccessReview

Vitamin D and Cardiovascular Disease: Current Evidence and Future Perspectives

by Nicola Cosentino, Jeness Campodonico, Valentina Milazzo, Monica De Metrio, Marta Brambilla, Marina Camera and Giancarlo Marenzi

Nutrients 2021, 13(10), 3603; https://doi.org/10.3390/nu13103603 - 14 Oct 2021

Cited by 92 | Viewed by 17345

Abstract

Vitamin D deficiency is a prevalent condition, occurring in about 30–50% of the population, observed across all ethnicities and among all age groups. Besides the established role of vitamin D in calcium homeostasis, its deficiency is emerging as a new risk factor for cardiovascular disease (CVD). In particular, several epidemiological and clinical studies have reported a close association between low vitamin D levels and major CVDs, such as coronary artery disease, heart failure, and atrial fibrillation. Moreover, in all these clinical settings, vitamin deficiency seems to predispose to increased morbidity, mortality, and recurrent cardiovascular events. Despite this growing evidence, interventional trials with supplementation of vitamin D in patients at risk of or with established CVD are still controversial. In this review, we aimed to summarize the currently available evidence supporting the link between vitamin D deficiency and major CVDs in terms of its prevalence, clinical relevance, prognostic impact, and potential therapeutic implications. Full article

(This article belongs to the Special Issue Current Understanding of Vitamin D in Chronic Diseases, Acute Respiratory Infections and All-Cause Mortality)

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17 pages, 1020 KiB

Open AccessReview

The Association between Vitamin D and Gut Microbiota: A Systematic Review of Human Studies

by Federica Bellerba, Valeria Muzio, Patrizia Gnagnarella, Federica Facciotti, Susanna Chiocca, Paolo Bossi, Diego Cortinovis, Ferdinando Chiaradonna, Davide Serrano, Sara Raimondi, Barbara Zerbato, Roberta Palorini, Stefania Canova, Aurora Gaeta and Sara Gandini

Nutrients 2021, 13(10), 3378; https://doi.org/10.3390/nu13103378 - 26 Sep 2021

Cited by 57 | Viewed by 10114

Abstract

Recent evidence has shown a number of extra-skeletal functions of Vitamin D (VD), primarily involving the immune system. One of these functions is mediated by the modulation of gut microbiota, whose alterations are linked to many diseases. Our purpose is to contribute to the understanding of existing evidence on the association between VD and gastrointestinal microbiota alterations. A systematic review of studies with human subjects has been conducted up to January 2021. We included publications reporting the association between gut microbiota and VD, including VD supplementation, dietary VD intake and/or level of 25(OH)D. We identified 25 studies: 14 were interventional and 11, observational. VD supplementation was found to be associated with a significant change in microbiome composition, in particular of Firmicutes, Actinobacteria and Bacteroidetes phyla. Furthermore, Firmicutes were found to be correlated with serum VD. Concerning alpha and beta diversity, a high nutritional intake of VD seems to induce a shift in bacterial composition and/or affects the species’ richness. Veillonellaceae and Oscillospiraceae families, in the Firmicutes phylum, more frequently decreased with both increasing levels of 25(OH)D and vitamin D supplementation. We found evidence of an association, even though the studies are substantially heterogeneous and have some limitations, resulting sometimes in conflicting results. To further understand the role of VD on the modulation of the gastrointestinal microbiota, future research should be geared toward well-designed animal-based studies or larger randomized controlled trials (RCTs). Full article

(This article belongs to the Special Issue Current Understanding of Vitamin D in Chronic Diseases, Acute Respiratory Infections and All-Cause Mortality)

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