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1
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Jørgensen HS, Vervloet M, Cavalier E, Bacchetta J, de Borst MH, Bover J, Cozzolino M, Ferreira AC, Hansen D, Herrmann M, de Jongh R, Mazzaferro S, Wan M, Shroff R, Evenepoel P. The role of nutritional vitamin D in chronic kidney disease-mineral and bone disorder in children and adults with chronic kidney disease, on dialysis, and after kidney transplantation-a European consensus statement. Nephrol Dial Transplant 2025; 40:797-822. [PMID: 39875204 PMCID: PMC11960744 DOI: 10.1093/ndt/gfae293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Indexed: 01/30/2025] Open
Abstract
Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and associates with poor outcomes. Current clinical practice guidelines recommend supplementation with nutritional vitamin D as for the general population. However, recent large-scale clinical trials in the general population failed to demonstrate a benefit of vitamin D supplementation on skeletal or non-skeletal outcomes, fueling a debate on the rationale for screening for and correcting vitamin D deficiency, both in non-CKD and CKD populations. In a collaboration between the European Renal Osteodystrophy initiative of the European Renal Association (ERA) and the European Society for Paediatric Nephrology (ESPN), an expert panel performed an extensive literature review and formulated clinical practice points on vitamin D supplementation in children and adults with CKD and after kidney transplantation. These were reviewed by a Delphi panel of members from relevant working groups of the ERA and ESPN. Key clinical practice points include recommendations to monitor for, and correct, vitamin D deficiency in children and adults with CKD and after kidney transplantation, targeting 25-hydroxyvitamin D levels >75 nmol/l (>30 ng/ml). Although vitamin D supplementation appears well-tolerated and safe, it is recommended to avoid mega-doses (≥100 000 IU) and very high levels of 25 hydroxyvitamin D (>150-200 nmol/l, or 60-80 ng/ml) to reduce the risk of toxicity. Future clinical trials should investigate the benefit of vitamin D supplementation on patient-relevant outcomes in the setting of vitamin D deficiency across different stages of CKD.
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Affiliation(s)
- Hanne Skou Jørgensen
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Nephrology, Aalborg University Hospital, Aalborg, Denmark
| | - Marc Vervloet
- Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Etienne Cavalier
- Department of Clinical Chemistry, CIRM, University of Liege, CHU de Liège, Liège, Belgium
| | - Justine Bacchetta
- Department of Pediatric Nephrology, Reference Center for Rare Diseases of Calcium and Phosphate, INSERM1033 Research Unit, Hospices Civils de Lyon, Université Lyon 1, Lyon, France
| | - Martin H de Borst
- Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
| | - Jordi Bover
- Department of Nephrology, University Hospital Germans Trias i Pujol, Badalona (Barcelona), Catalonià, Spain
| | - Mario Cozzolino
- Department of Health Sciences, Renal Division, University of Milan, Milan, Italy
| | - Ana Carina Ferreira
- Nephrology Department, Hospital Curry Cabral | ULS São José, Lisbon, Portugal and Nova Medical School, Lisbon, Portugal
| | - Ditte Hansen
- Department of Nephrology, Copenhagen University Hospital-Herlev, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Markus Herrmann
- Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
| | - Renate de Jongh
- Department of Endocrinology and Metabolism, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
| | - Sandro Mazzaferro
- Department of Translation and Precision Medicine, Sapienza University of Rome, Rome, Italy
| | - Mandy Wan
- Institute of Pharmaceutical Science, King's College London, London, UK and Department of Evelina Pharmacy, Guys' & St Thomas' NHS Foundation Trust, London, UK
| | - Rukshana Shroff
- Renal Unit, UCL Great Ormond Street Hospital for Children; University College London, London, UK
| | - Pieter Evenepoel
- Department of Microbiology, Immunology and Transplantation; Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium
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2
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Milan KL, Ramkumar KM. Regulatory mechanisms and pathological implications of CYP24A1 in Vitamin D metabolism. Pathol Res Pract 2024; 264:155684. [PMID: 39488987 DOI: 10.1016/j.prp.2024.155684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2024] [Revised: 09/23/2024] [Accepted: 10/25/2024] [Indexed: 11/05/2024]
Abstract
CYP24A1 is a crucial gene within the cytochrome P450 superfamily, responsible for encoding the enzyme 25-hydroxyvitamin D3-24-hydroxylase. This enzyme is involved in the catabolism of 1,25-dihydroxyvitamin D3, the biologically active form of vitamin D3, by hydroxylating its side chain. Through this process, CYP24A1 tightly regulates the bioavailability and physiological impact of vitamin D3 in the body. Dysregulation of CYP24A1, particularly its overexpression, has been increasingly associated with the progression of various diseases, including cancers, autoimmune disorders, and chronic inflammatory conditions. Elevated levels of CYP24A1 can lead to excessive degradation of vitamin D3, resulting in diminished levels of this critical hormone, which is essential for calcium homeostasis, immune function, and cellular proliferation. This review explores into the structural characteristics of CYP24A1, exploring how it influences its enzymatic activity. Furthermore, it examines the expression patterns of CYP24A1 across different diseases, emphasizing the enzyme's role in disease pathology. The review also discusses the regulatory mechanisms governing CYP24A1 expression, including genetic mutations, epigenetic modifications, and metabolite-mediated regulation. By understanding these mechanisms, the review provides insight into the potential therapeutic strategies that could target CYP24A1, aiming to alleviate its overexpression and restore vitamin D3 balance in disease states.
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Affiliation(s)
- K L Milan
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603 203, India
| | - K M Ramkumar
- Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur, Tamil Nadu 603 203, India.
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Pang J, Yang C, Liu J, Wang Z, Tao X, Cao Z. Correlation between vitamin D metabolic pathway-related gene polymorphisms and cardiovascular disease. Food Funct 2024; 15:11342-11364. [PMID: 39494806 DOI: 10.1039/d4fo03234a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2024]
Abstract
Vitamin D plays important roles in various physiological processes such as cardiovascular health, calcium balance regulation, bone health, immune system support, neurological function regulation, muscle function maintenance, and anti-inflammatory effects. Therefore, maintaining its adequate levels is essential for overall health. Genetic polymorphisms in vitamin D metabolic pathways have become a key factor affecting the susceptibility and progression of cardiovascular disease (CVD). This article reviews the relationship between gene polymorphisms in vitamin D metabolic pathways and vitamin D levels or CVD. It is emphasized that the polymorphisms of key genes such as GC, VDR, CYP2R1, CYP24A1 and CYP27B1 are related to the pathogenesis of CVD. These polymorphisms can regulate serum levels of vitamin D, thereby affecting the susceptibility, comorbidities and clinical manifestations of CVD. Despite the progress made, there are still inconsistencies and gaps in the literature. Thus, it is necessary to conduct large-scale, multicenter studies to verify these findings and deepen our understanding of the intricate interactions between gene polymorphisms in vitamin D metabolic pathways and CVD.
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Affiliation(s)
- Jiao Pang
- Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, 110122, China.
- College of Life Science, Northwest University, Xi'an City, 710069, China
| | - Chunshuo Yang
- Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, 110122, China.
- Department of Pain Medicine, The First Hospital of China Medical University, Shenyang, 110001, China.
| | - Jiaqi Liu
- State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing 211103, China
| | - Zhilin Wang
- Department of Pain Medicine, The First Hospital of China Medical University, Shenyang, 110001, China.
| | - Xueshu Tao
- Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, 110122, China.
- Department of Pain Medicine, The First Hospital of China Medical University, Shenyang, 110001, China.
| | - Zhipeng Cao
- Department of Forensic Pathology, School of Forensic Medicine, China Medical University, Shenyang, 110122, China.
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4
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Callejo M, Morales-Cano D, Olivencia MA, Mondejar-Parreño G, Barreira B, Tura-Ceide O, Martínez VG, Serrano-Navarro A, Moreno L, Morrell N, Perros F, Vicente A, Cogolludo A, Perez-Vizcaino F. Vitamin D receptor and its antiproliferative effect in human pulmonary arterial hypertension. Sci Rep 2024; 14:27445. [PMID: 39523384 PMCID: PMC11551162 DOI: 10.1038/s41598-024-78380-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 10/30/2024] [Indexed: 11/16/2024] Open
Abstract
Vitamin D (vitD) deficiency is frequently observed in patients with pulmonary arterial hypertension (PAH) and, in these patients, low levels of vitD correlate with worse prognosis. The aim of this study was to examine the expression and the antiproliferative role of vitD receptor (VDR) and its signalling pathway in the human pulmonary vasculature. VDR presence and expression was analyzed in lungs, pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) from controls and PAH-patients. VDR expression and VDR-target genes were examined in PASMC treated with calcitriol. The antiproliferative effect of 48 h-calcitriol was studied in PASMC by MTT and BrdU assays. VDR is expressed in PASMC. It is downregulated in lungs and in PASMC, but not in PAEC, from PAH-patients compared to non-hypertensive controls. Calcitriol strongly upregulated VDR expression in PASMC and the VDR target genes KCNK3 (encoding TASK1), BIRC5 (encoding survivin) and BMP4. Calcitriol produced an antiproliferative effect which was diminished by silencing or by pharmacological inhibition of survivin or BMPR2, but not of TASK1. In conclusion, the expression of VDR is low in PAH-patients and can be rescued by calcitriol. VDR exerts an antiproliferative effect in PASMC by modulating survivin and the BMP signalling pathway.
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MESH Headings
- Humans
- Receptors, Calcitriol/metabolism
- Receptors, Calcitriol/genetics
- Cell Proliferation/drug effects
- Calcitriol/pharmacology
- Pulmonary Artery/metabolism
- Pulmonary Artery/pathology
- Pulmonary Artery/drug effects
- Survivin/metabolism
- Survivin/genetics
- Myocytes, Smooth Muscle/metabolism
- Myocytes, Smooth Muscle/drug effects
- Female
- Male
- Pulmonary Arterial Hypertension/metabolism
- Pulmonary Arterial Hypertension/drug therapy
- Pulmonary Arterial Hypertension/pathology
- Pulmonary Arterial Hypertension/genetics
- Potassium Channels, Tandem Pore Domain/metabolism
- Potassium Channels, Tandem Pore Domain/genetics
- Signal Transduction/drug effects
- Bone Morphogenetic Protein 4/metabolism
- Bone Morphogenetic Protein 4/genetics
- Middle Aged
- Bone Morphogenetic Protein Receptors, Type II/metabolism
- Bone Morphogenetic Protein Receptors, Type II/genetics
- Endothelial Cells/metabolism
- Endothelial Cells/drug effects
- Lung/metabolism
- Lung/pathology
- Adult
- Cells, Cultured
- Hypertension, Pulmonary/metabolism
- Hypertension, Pulmonary/drug therapy
- Hypertension, Pulmonary/pathology
- Nerve Tissue Proteins
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Affiliation(s)
- Maria Callejo
- Department of Pharmacology and Toxicology, Facultad de Medicina, School of Medicine, Universidad Complutense de Madrid, Pza Ramón y Cajal s/n., 28040, Madrid, Spain
- CIBER Enfermedades Respiratorias (CibeRes), Madrid, Spain
| | - Daniel Morales-Cano
- Department of Pharmacology and Toxicology, Facultad de Medicina, School of Medicine, Universidad Complutense de Madrid, Pza Ramón y Cajal s/n., 28040, Madrid, Spain
- CIBER Enfermedades Respiratorias (CibeRes), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain
| | - Miguel A Olivencia
- Department of Pharmacology and Toxicology, Facultad de Medicina, School of Medicine, Universidad Complutense de Madrid, Pza Ramón y Cajal s/n., 28040, Madrid, Spain
- CIBER Enfermedades Respiratorias (CibeRes), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain
| | - Gema Mondejar-Parreño
- Department of Medicine, Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Stanford, USA
| | - Bianca Barreira
- Department of Pharmacology and Toxicology, Facultad de Medicina, School of Medicine, Universidad Complutense de Madrid, Pza Ramón y Cajal s/n., 28040, Madrid, Spain
- CIBER Enfermedades Respiratorias (CibeRes), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain
| | - Olga Tura-Ceide
- CIBER Enfermedades Respiratorias (CibeRes), Madrid, Spain
- Department of Pulmonary Medicine, Servei de Pneumologia, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Villarroel, 170, 08036, Barcelona, Spain
- Translational Research Group on Cardiovascular Respiratory Diseases (CAREs), Institut d'Investigació Biomèdica de Girona (IDIBGI-CERCA), Parc Hospitalari Martí i Julià, Edifici M2, 17190, Salt, Spain
| | - Victor G Martínez
- Biomedical Research Institute I + 12, University Hospital, 12 de Octubre, Madrid, Spain
- Molecular Oncology Unit, CIEMAT (Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas), Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
| | | | - Laura Moreno
- Department of Pharmacology and Toxicology, Facultad de Medicina, School of Medicine, Universidad Complutense de Madrid, Pza Ramón y Cajal s/n., 28040, Madrid, Spain
- CIBER Enfermedades Respiratorias (CibeRes), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain
| | - Nick Morrell
- Department of Medicine, School of Clinical Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK
| | - Frédéric Perros
- Laboratoire CarMeN, INSERM U.1060, INRAe U.1397, Université Claude Bernard Lyon1, Pierre Bénite, France
| | - Angeles Vicente
- Department of Cell Biology, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - Angel Cogolludo
- Department of Pharmacology and Toxicology, Facultad de Medicina, School of Medicine, Universidad Complutense de Madrid, Pza Ramón y Cajal s/n., 28040, Madrid, Spain
- CIBER Enfermedades Respiratorias (CibeRes), Madrid, Spain
- Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain
| | - Francisco Perez-Vizcaino
- Department of Pharmacology and Toxicology, Facultad de Medicina, School of Medicine, Universidad Complutense de Madrid, Pza Ramón y Cajal s/n., 28040, Madrid, Spain.
- CIBER Enfermedades Respiratorias (CibeRes), Madrid, Spain.
- Instituto de Investigación Sanitaria Gregorio Marañón (IISGM), Madrid, Spain.
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5
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de Macêdo LP, de Castro Tavares R, Torres Braga M, Dos Santos LM, Donato G, Lima Júnior FASD, de Macêdo RP, Ugulino Netto A, Franke K, Vansant Oliveira Eugênio P, Batista Cezar-Junior A, Vilela Faquini I, Júnior Silva JL, de Carvalho Júnior EV, Almeida NS, Bandeira E Farias FA, Moraes Valença M, Rocha Cirne Azevedo-Filho H. The relationship between the level of vitamin D and ruptured intracranial aneurysms among patients with high sun exposure. Sci Rep 2024; 14:3555. [PMID: 38347057 PMCID: PMC10861505 DOI: 10.1038/s41598-024-53676-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2023] [Accepted: 02/03/2024] [Indexed: 02/15/2024] Open
Abstract
Non-traumatic subarachnoid hemorrhage (SAH) accounts for 3-5% of acute strokes. Intracranial aneurysm is the most common cause of non-traumatic SAH. Vitamin D influences the cardiovascular system, including the formation and rupture of cerebral aneurysms. To evaluate the serum vitamin D level in patients living in the tropical zone who suffered aneurysmal subarachnoid hemorrhage and its correlation with demographic and neurological characteristics. This is an analytical cross-sectional study to assess the serum level of vitamin D in a study population of 99 patients treated and diagnosed with aSAH in a public hospital in Recife-PE over a period of 12 months. In the study sample, composed of individuals with high sun exposure due to the lifestyle they lead in a tropical region, we observed hypovitaminosis D (85.9%), with a median of 19.9 ng/ml, although the majority of individuals are skin with high concentration of melanin (Fitzpatrick skin type IV and V). In addition, rates of sun exposure are high to all patients (Solar Index 9.03 P50). Most individuals were female (79.8%); there was no statistical difference in solar exposure/solar index between genders. As for the neurological repercussions, there was no statistical relevance in the clinical prognostic scales evaluated. As the sample was composed mainly of individuals whose economic activity is agriculture, the values of solar index found are vastly higher than those of other studies conducted in high latitude regions. In line with the literature review, some aspects were raised with the objective of justifying such findings that go from the base of the poor diet of these individuals, the increase of melanin in the skin and genetic alterations that directs us to possible mechanisms of natural photoprotection to high sun exposure. Thus, we had a vast majority (85%) of hypovitaminosis D, which in fact makes us wonder if there is any influence of calcitriol on vitamin D receptors in vascular walls and in the cardiovascular system as a whole, which influence bleeding events of this nature. As for the neurological repercussions, measured using assessment scales (Glasgow coma scale, WFNS scale, Hunt-Hess and Fisher's tomographic scale) there was no significant difference in the results. As it is only a descriptive study, the causal relationship of the facts cannot be established. However, in a population exposed to high sun exposure and affected by aneurysmal SAH, there is a significant rate of hypovitaminosis D, which supports the hypothesis that vitamin D plays a role in vascular pathologies, such as cerebral aneurysms and SAH.
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Affiliation(s)
- Lívio Pereira de Macêdo
- Department of Neurosurgery, Hospital da Restauração, Recife, Pernambuco, Brazil.
- Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil.
- , Recife, Brasil.
| | | | | | | | - Glaudir Donato
- Medical Student, Centro de Ciências Médicas, Universidade Federal da Paraíba, João Pessoa, Paraíba, Brazil
| | | | | | | | - Kauê Franke
- Department of Neurosurgery, Hospital da Restauração, Recife, Pernambuco, Brazil
| | | | | | - Igor Vilela Faquini
- Department of Neurosurgery, Hospital da Restauração, Recife, Pernambuco, Brazil
| | | | | | - Nivaldo S Almeida
- Department of Neurosurgery, Hospital da Restauração, Recife, Pernambuco, Brazil
| | | | | | - Hildo Rocha Cirne Azevedo-Filho
- Department of Neurosurgery, Hospital da Restauração, Recife, Pernambuco, Brazil
- Universidade Federal de Pernambuco, Recife, Pernambuco, Brazil
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6
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Janubová M, Žitňanová I. The effects of vitamin D on different types of cells. Steroids 2024; 202:109350. [PMID: 38096964 DOI: 10.1016/j.steroids.2023.109350] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 11/24/2023] [Accepted: 12/07/2023] [Indexed: 12/25/2023]
Abstract
Vitamin D is neccessary for regulation of calcium and phosphorus metabolism in bones, affects imunity, the cardiovascular system, muscles, skin, epithelium, extracellular matrix, the central nervous system, and plays arole in prevention of aging-associated diseases. Vitamin D receptor is expressed in almost all types of cells and its activation leads to modulation of different signaling pathways. In this review, we have analysed the current knowledge of 1,25-dihydroxyvitamin D3 or 25-hydroxyvitamin D3 effects on metabolism of cells important for the function of the cardiovascular system (endothelial cells, vascular smooth muscle cells, cardiac cells and pericytes), tissue healing (fibroblasts), epithelium (various types of epithelial cells) and the central nervous system (neurons, astrocytes and microglia). The goal of this review was to compare the effects of vitamin D on the above mentioned cells in in vitro conditions and to summarize what is known in this field of research.
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Affiliation(s)
- Mária Janubová
- Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University, 813 72 Bratislava, Slovakia.
| | - Ingrid Žitňanová
- Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University, 813 72 Bratislava, Slovakia
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7
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Yao M, Oduro PK, Akintibu AM, Yan H. Modulation of the vitamin D receptor by traditional Chinese medicines and bioactive compounds: potential therapeutic applications in VDR-dependent diseases. Front Pharmacol 2024; 15:1298181. [PMID: 38318147 PMCID: PMC10839104 DOI: 10.3389/fphar.2024.1298181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Accepted: 01/08/2024] [Indexed: 02/07/2024] Open
Abstract
The Vitamin D receptor (VDR) is a crucial nuclear receptor that plays a vital role in various physiological functions. To a larger extent, the genomic effects of VDR maintain general wellbeing, and its modulation holds implications for multiple diseases. Current evidence regarding using vitamin D or its synthetic analogs to treat non-communicable diseases is insufficient, though observational studies suggest potential benefits. Traditional Chinese medicines (TCMs) and bioactive compounds derived from natural sources have garnered increasing attention. Interestingly, TCM formulae and TCM-derived bioactive compounds have shown promise in modulating VDR activities. This review explores the intriguing potential of TCM and bioactive compounds in modulating VDR activity. We first emphasize the latest information on the genetic expression, function, and structure of VDR, providing a comprehensive understanding of this crucial receptor. Following this, we review several TCM formulae and herbs known to influence VDR alongside the mechanisms underpinning their action. Similarly, we also discuss TCM-based bioactive compounds that target VDR, offering insights into their roles and modes of action.
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Affiliation(s)
- Minghe Yao
- Henan University of Chinese Medicine, Zhengzhou, China
- Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, China
| | - Patrick Kwabena Oduro
- Jacobs School of Medicine and Biomedical Sciences, The State University of New York, University at Buffalo, Buffalo, NY, United States
| | - Ayomide M. Akintibu
- School of Community Health and Policy, Morgan State University, Baltimore, MD, United States
| | - Haifeng Yan
- The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
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Zakerihamidi M, Rakhshanizadeh F, Moradi A, Boskabadi H. Comparison of maternal 25 (OH) vitamin D levels between premature infants with/without asphyxia. J Neonatal Perinatal Med 2024; 17:583-588. [PMID: 38905059 DOI: 10.3233/npm-230229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/23/2024]
Abstract
OBJECTIVES Perinatal asphyxia is the main risk factor for mortality and morbidity in neonates and neurological disorders in survived infants. We compared the neonatal and maternal 25 (OH) vitamin D levels in neonates with/without asphyxia. MATERIALS AND METHODS This cross-sectional research was done on 229 neonates (including 158 neonates [69%] without asphyxia [control group] and 71 neonates [31%] with asphyxia [case group]) from 2020 to 2023 using the available sampling method. 25 (OH) Vit D levels in mothers and neonates were assessed and compared in the 2 groups. The data collection instrument was a researcher-made checklist, containing the maternal and neonatal characteristics and laboratory evaluations. Data were analyzed by SPSS 23 using the t-test. RESULTS The mean maternal 25 (OH) Vit D levels in the case and control groups were 16.34±11.87 and 22.80±12.67 ng/mL, respectively. The mean neonatal 25 (OH) Vit D levels in the case and control groups were respectively 12.13±8.62 and 19.55±11.62 ng/mL (P = 0.002). The case group showed severer maternal and neonatal 25 (OH) Vit D deficiency (P = 0.000) compared to the control group. CONCLUSIONS Neonatal and maternal 25 (OH) Vit D deficiency can increase the risk of perinatal asphyxia. Therefore, administration of 25 (OH) Vit D supplements to pregnant mothers may reduce the incidence of asphyxia.
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Affiliation(s)
- M Zakerihamidi
- Department of Midwifery, School of Medical Sciences, Tonekabon Branch, Islamic Azad University, Tonekabon, Iran
| | - F Rakhshanizadeh
- Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - A Moradi
- Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Clinical Research Development Unit, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
| | - H Boskabadi
- Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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9
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Dziedzic EA, Gąsior JS, Tuzimek A, Dąbrowski M, Kochman W. Correlation between Serum 25-Hydroxyvitamin D Concentration, Monocyte-to-HDL Ratio and Acute Coronary Syndrome in Men with Chronic Coronary Syndrome-An Observational Study. Nutrients 2023; 15:4487. [PMID: 37892562 PMCID: PMC10609971 DOI: 10.3390/nu15204487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2023] [Revised: 10/19/2023] [Accepted: 10/21/2023] [Indexed: 10/29/2023] Open
Abstract
Cardiovascular disease (CVD) continues to be the leading cause of death in European men. Atherosclerosis and its clinical consequence, chronic coronary syndrome (CCS), comprise two main elements: dysfunction of lipoprotein metabolism and an important inflammatory component that contributes to the development of complications, including acute coronary syndrome (ACS). Measures of both components are combined in a composite marker called monocyte-to-HDL ratio (MHR). Vitamin D was previously described to influence inflammation processes, and its deficiency influences CVD risk factors. This research describes the differences in MHR and total serum 25-hydroxyvitamin D (25(OH)D) concentration between male patients with different diagnoses of CCS and the correlation between 25(OH)D and MHR in this group. Significant differences were observed between ACS and CCS patients in 25(OH)D and MHR-the highest HDL and serum 25(OH)D concentrations were observed in patients with CCS, whereas the highest value of MHR was observed in patients with STEMI. A significant correlation was observed between 25(OH)D, HDL, and MHR. Due to the significant but small nominal difference in MHR values between groups of patients diagnosed with ACS and CCS, and the possible influence of age and hyperlipidemia status on the differences in vitamin D levels in these groups, this subject requires further well-designed research. The suggested bidirectional relationship between MHR and 25(OH)D and the role of MHR as a predictor of vitamin D status in the body also needs to be verified.
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Affiliation(s)
- Ewelina A. Dziedzic
- Cardiovascular Clinic, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Jakub S. Gąsior
- Department of Pediatric Cardiology and General Pediatrics, Medical University of Warsaw, 02-091 Warsaw, Poland
| | - Agnieszka Tuzimek
- Cardiovascular Clinic, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
| | - Marek Dąbrowski
- Department of Cardiology, Bielanski Hospital, 01-809 Warsaw, Poland
| | - Wacław Kochman
- Cardiovascular Clinic, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland
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10
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Kamal K, Tewari J, Bharti V, Sharma D, Atam I, Atam V, Rana A, Roy S. Serum Vitamin D Level as a Risk Factor and Prognostic Marker for Acute Ischemic Stroke: A Case-Control Study at a Tertiary Care Centre in Northern India. Cureus 2023; 15:e46117. [PMID: 37900424 PMCID: PMC10612136 DOI: 10.7759/cureus.46117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/28/2023] [Indexed: 10/31/2023] Open
Abstract
Introduction Stroke is a predominant cause of death worldwide. Major risk factors for stroke in any age group are diabetes, hypertension, heart disease, smoking, and long-term alcohol abuse. It is of utmost importance to identify the risk factors for stroke to prevent recurrence. Vitamin D deficiency is identified as a risk factor for stroke. Therefore, we attempted to look for a correlation between vitamin D levels and acute ischemic stroke. Methods This observational case-control study was conducted with 150 patients (75 cases and 75 controls). On the day of admission, the National Institutes of Health Stroke Scale (NIHSS) score was calculated, and vitamin D levels were measured for each patient. The functional outcome was determined by the modified Rankin scale (mRS). Results The most common risk factors identified in this study were hypertension (61.3%), diabetes mellitus (41.3%), and smoking (37.3%). Out of 75 patients enrolled in the study, 49.4% had significant vitamin D deficiency, and 30.6% had insufficient vitamin D levels. Our study showed a significant correlation between vitamin D sufficiency in the body and the incidence of stroke (x2=3.888 and p=0.048). A significant correlation (p=0.03) was found between the NIHSS score and vitamin D levels in patients with acute ischemic stroke. Conclusion In this observational case-control study, we concluded that the increasing severity of vitamin D deficiency was associated with more deaths and poor outcomes.
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Affiliation(s)
- Kislaya Kamal
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Jay Tewari
- Medicine, King George's Medical University, Lucknow, IND
| | - Vipin Bharti
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Deepak Sharma
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Isha Atam
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Virendra Atam
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Anadika Rana
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Shubhajeet Roy
- Medicine, King George's Medical University, Lucknow, IND
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11
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Khalaji A, Behnoush AH, Tajdini M. Association between vitamin D deficiency and vasovagal syncope: A systematic review and meta-analysis. Clin Cardiol 2023; 46:721-728. [PMID: 37226313 PMCID: PMC10352974 DOI: 10.1002/clc.24035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Revised: 04/18/2023] [Accepted: 05/08/2023] [Indexed: 05/26/2023] Open
Abstract
Vasovagal syncope (VVS) is the most prevalent type of syncope and its management includes pharmacologic and non-pharmacologic interventions. Recently, studies have investigated vitamin D levels in VVS patients. In this systematic review and meta-analysis, we aim to review these studies to find possible associations between vitamin D deficiency and vitamin D levels with VVS. International databases including Scopus, Web of Science, PubMed, and Embase were searched with keywords related to "vasovagal syncope" and "vitamin D." Studies were screened and the data were extracted from them. Random-effect meta-analysis was conducted to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) for vitamin D levels in comparison to VVS patients and controls. Also, VVS occurrence was measured and the odds ratio (OR) and 95% CI were calculated for comparison of vitamin D deficient cases and nondeficient individuals. Six studies were included with 954 cases investigated. Meta-analysis showed that patients with VVS had significantly lower vitamin D serum levels in comparison to non-VVS cases (SMD -1.05, 95% CI -1.54 to -0.57, p-value < .01). Moreover, VVS occurrence was higher in vitamin D-deficient individuals (OR 5.43, 95% CI 2.40 to 12.27, p-value < .01). Our findings which show lower vitamin D levels in VVS patients can have clinical implications in order for clinicians to pay attention to this when approaching VVS. Further randomized controlled trials are certainly warranted to assess the role of vitamin D supplementation in individuals with VVS.
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Affiliation(s)
- Amirmohammad Khalaji
- Tehran Heart Center, Cardiovascular Diseases Research InstituteTehran University of Medical SciencesTehranIran
- Non–Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
- School of MedicineTehran University of Medical SciencesTehranIran
| | - Amir Hossein Behnoush
- Tehran Heart Center, Cardiovascular Diseases Research InstituteTehran University of Medical SciencesTehranIran
- Non–Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences InstituteTehran University of Medical SciencesTehranIran
- School of MedicineTehran University of Medical SciencesTehranIran
| | - Masih Tajdini
- Tehran Heart Center, Cardiovascular Diseases Research InstituteTehran University of Medical SciencesTehranIran
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12
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Orsatti CL, Orsatti FL, de Souza JPEA, Nahas EAP. Impact of vitamin D supplementation on modulating heat-shock proteins in postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2023; 30:758-765. [PMID: 37220771 DOI: 10.1097/gme.0000000000002197] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
OBJECTIVE The aim of this study was to examine the effect of vitamin D (VitD) supplementation on serum heat-shock proteins (HSP) in postmenopausal women (PW). METHODS In this double-blind, placebo-controlled trial, 160 PW aged 45 to 65 years with amenorrhea 12 months or more were randomized into two groups: 80 PW in VitD group (oral supplementation with 1,000 IU VitD 3 /d) or 80 PW in placebo group. The PW were assessed at baseline and after 10 months of intervention. Plasma concentrations of 25-hydroxyVitD (25[OH]D) were measured by high-performance liquid chromatography. HSP27/pS78/pS82, HSP27/total, HSP60, HSP70/72, and HSP90α levels were assessed in serum using a multiplexed bead immunoassay. RESULTS HSP27 (pS78/pS82 [ P < 0.035] and total [ P < 0.001]) levels increased in the supplemented group when compared with the control group. There was no effect of VitD supplementation on HSP60, HSP70/72, and HSP90α levels. CONCLUSIONS Vitamin D supplementation increases serum HSP27 level in PW.
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Affiliation(s)
| | - Fábio Lera Orsatti
- Applied Physiology, Nutrition and Exercise Research Group (PhyNEr), Institute of Health Sciences, Federal University of Triangulo Mineiro (UFTM), Uberaba, Brazil
| | | | - Eliana Aguiar Petri Nahas
- Department of Gynecology and Obstetrics, Botucatu Medical School, Sao Paulo State University-UNESP, São Paulo, Brazil
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13
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Dey SK, Kumar S, Rani D, Maurya SK, Banerjee P, Verma M, Senapati S. Implications of vitamin D deficiency in systemic inflammation and cardiovascular health. Crit Rev Food Sci Nutr 2023; 64:10438-10455. [PMID: 37350746 DOI: 10.1080/10408398.2023.2224880] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/24/2023]
Abstract
Clinical, epidemiological, and molecular studies have sufficiently highlighted the vitality of vitamin D [25(OH)D and 1,25(OH)2D] in human health and wellbeing. Globally, vitamin D deficiency (VDD) has become a public health concern among all age groups. There is a very high prevalence of VDD per the estimates from several epidemiological studies on different ethnic populations. But, population-specific scales do not support these estimates to define VDD clinically and consistent genetic associations. However, clinical studies have shown the relevance of serum vitamin D screening and oral supplementation in improving health conditions, pointing toward a more prominent role of vitamin D in health and wellness. Routinely, the serum concentration of vitamin D is measured to determine the deficiency and is correlated with physiological conditions and clinical symptoms. Recent research points toward a more inclusive role of vitamin D in different disease pathologies and is not just limited to otherwise bone health and overall growth. VDD contributes to the natural history of systemic ailments, including cardiovascular and systemic immune diseases. Considering its significant impact on premature morbidity and mortality, there is a compelling need to comprehensively review and document the direct and indirect implications of VDD in immune system deregulation, systemic inflammatory conditions, and cardio-metabolism. The recommendations from this review call for furthering our research concerning vitamin D and its direct and indirect implications.
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Affiliation(s)
- Sanjay Kumar Dey
- Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India
| | - Shashank Kumar
- Department of Biochemistry, Central University of Punjab, Bathinda, Punjab, India
| | - Diksha Rani
- Dr. B.R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India
| | | | - Pratibha Banerjee
- Immunogenomics Laboratory, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, Punjab, India
| | - Madhur Verma
- Department of Community and Family Medicine, All India Institute of Medical Sciences, Bathinda, Punjab, India
| | - Sabyasachi Senapati
- Immunogenomics Laboratory, Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda, Punjab, India
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14
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Ginsberg C, Hoofnagle AN, Katz R, Cheng JH, Hsu S, Budoff MJ, Kado DM, Kestenbaum B, Siscovick DS, Michos ED, Ix JH, de Boer IH. Vitamin D Metabolite Ratio and Coronary Artery Calcification in the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc Imaging 2023; 16:e015055. [PMID: 36943910 PMCID: PMC11648553 DOI: 10.1161/circimaging.122.015055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/09/2023]
Affiliation(s)
- Charles Ginsberg
- Division of Nephrology-Hypertension, University of California, San Diego (C.G., J.H.C., J.H.I.)
| | - Andrew N Hoofnagle
- Departments of Laboratory Medicine and Medicine and the Kidney Research Institute (A.N.H.), University of Washington, Seattle
| | - Ronit Katz
- Department of Obstetrics and Gynecology (R.K.), University of Washington, Seattle
| | - Jonathan H Cheng
- Division of Nephrology-Hypertension, University of California, San Diego (C.G., J.H.C., J.H.I.)
| | - Simon Hsu
- Division of Nephrology and Kidney Research Institute (S.H., B.K., I.H.d.B.), University of Washington, Seattle
| | - Matthew J Budoff
- Cedars-Sinai Heart Institute and David Geffen School of Medicine UCLA, Los Angeles, CA (M.J.B.)
| | - Deborah M Kado
- Department of Medicine, Stanford University, Palo Alto, CA (D.M.K.)
| | - Bryan Kestenbaum
- Division of Nephrology and Kidney Research Institute (S.H., B.K., I.H.d.B.), University of Washington, Seattle
| | | | - Erin D Michos
- Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD (E.D.M.)
| | - Joachim H Ix
- Division of Nephrology-Hypertension, University of California, San Diego (C.G., J.H.C., J.H.I.)
- Nephrology Section, Veterans Affairs San Diego Healthcare System, CA (J.H.I.)
| | - Ian H de Boer
- Division of Nephrology and Kidney Research Institute (S.H., B.K., I.H.d.B.), University of Washington, Seattle
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15
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Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases. Nutrients 2023; 15:nu15020334. [PMID: 36678205 PMCID: PMC9864832 DOI: 10.3390/nu15020334] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 12/29/2022] [Accepted: 12/30/2022] [Indexed: 01/12/2023] Open
Abstract
Deficiency in vitamin D (VitD), a lipid-soluble vitamin and steroid hormone, affects approximately 24% to 40% of the population of the Western world. In addition to its well-documented effects on the musculoskeletal system, VitD also contributes importantly to the promotion and preservation of cardiovascular health via modulating the immune and inflammatory functions and regulating cell proliferation and migration, endothelial function, renin expression, and extracellular matrix homeostasis. This brief overview focuses on the cardiovascular and cerebrovascular effects of VitD and the cellular, molecular, and functional changes that occur in the circulatory system in VitD deficiency (VDD). It explores the links among VDD and adverse vascular remodeling, endothelial dysfunction, vascular inflammation, and increased risk for cardiovascular and cerebrovascular diseases. Improved understanding of the complex role of VDD in the pathogenesis of atherosclerotic cardiovascular diseases, stroke, and vascular cognitive impairment is crucial for all cardiologists, dietitians, and geriatricians, as VDD presents an easy target for intervention.
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16
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Guella A, Abduelkarem AR, Hassanein MM. The effects and safety of high dose vitamin D3 in hemodialysis patients. Pharm Pract (Granada) 2023; 21:2773. [PMID: 37090466 PMCID: PMC10117363 DOI: 10.18549/pharmpract.2023.1.2773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Accepted: 12/05/2022] [Indexed: 04/08/2023] Open
Abstract
Background Different studies have shown that hemodialysis patients require higher doses of Vitamin D3 (VD3) than the general population to achieve satisfactory replenishment. This study aims to assess the safety of such practice and its benefits on some of the parameters of Chronic Kidney Disease- Mineral and Bone Disorder (CKD-MBD). Methods A single-center clinical trial assessing the benefits of high dose VD3 in hemodialysis patients. The dose of VD3 (300,000 IU) was administered orally and monthly from April to December 2020 (9 months) at the dialysis unit. The data analyzed were blood levels of calcium, phosphorus, alkaline phosphatase, 25(OH)D, 1,25(OH)2D and intact parathyroid hormone (iPTH) done every three months. Results We could recruit a cohort of 23 patients. Blood levels of 25(OH)D increased significantly in 82.6% of the patients to above 30 ng/ml. A similar effect was observed with 1, 25(OH)2D levels. iPTH levels decreased significantly when levels of 25(OH)D exceeded 30ng/ml at the end of the nine months. Vitamin D serum levels were typically measured immediately before the next monthly dose was administered. Blood levels of calcium, phosphorus, and alkaline phosphatase were stable during the study period. No events of hypercalcemia were reported, and no patient discontinued the monthly VD3 supplementation. Conclusion Monthly administration of a high dose of VD3 over a long period of nine months in hemodialysis patients was found to be safe and beneficial in VD3 replenishment. It also allowed a significant decrease in iPTH levels. Further studies are warranted to identify the therapeutic target level of 25(OH)D in hemodialysis patients, allowing beneficial effects on iPTH.
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Affiliation(s)
- Adnane Guella
- Senior Consultant Nephrologist, University Hospital Sharjah, Department of Nephrology, P.O. Box 72772 Sharjah, United Arab Emirates.
| | - Abduelmula R Abduelkarem
- Pharmacy Practice and Pharmacotherapeutics Department, College of Pharmacy, The University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates.
| | - Mohammed M Hassanein
- Pharmacy Practice and Pharmacotherapeutics Department, College of Pharmacy University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates.
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17
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Latic N, Erben RG. Interaction of Vitamin D with Peptide Hormones with Emphasis on Parathyroid Hormone, FGF23, and the Renin-Angiotensin-Aldosterone System. Nutrients 2022; 14:nu14235186. [PMID: 36501215 PMCID: PMC9736617 DOI: 10.3390/nu14235186] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 12/12/2022] Open
Abstract
The seminal discoveries that parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are major endocrine regulators of vitamin D metabolism led to a significant improvement in our understanding of the pivotal roles of peptide hormones and small proteohormones in the crosstalk between different organs, regulating vitamin D metabolism. The interaction of vitamin D, FGF23 and PTH in the kidney is essential for maintaining mineral homeostasis. The proteohormone FGF23 is mainly secreted from osteoblasts and osteoclasts in the bone. FGF23 acts on proximal renal tubules to decrease production of the active form of vitamin D (1,25(OH)2D) by downregulating transcription of 1α-hydroxylase (CYP27B1), and by activating transcription of the key enzyme responsible for vitamin D degradation, 24-hydroxylase (CYP24A1). Conversely, the peptide hormone PTH stimulates 1,25(OH)2D renal production by upregulating the expression of 1α-hydroxylase and downregulating that of 24-hydroxylase. The circulating concentration of 1,25(OH)2D is a positive regulator of FGF23 secretion in the bone, and a negative regulator of PTH secretion from the parathyroid gland, forming feedback loops between kidney and bone, and between kidney and parathyroid gland, respectively. In recent years, it has become clear that vitamin D signaling has important functions beyond mineral metabolism. Observation of seasonal variations in blood pressure and the subsequent identification of vitamin D receptor (VDR) and 1α-hydroxylase in non-renal tissues such as cardiomyocytes, endothelial and smooth muscle cells, suggested that vitamin D may play a role in maintaining cardiovascular health. Indeed, observational studies in humans have found an association between vitamin D deficiency and hypertension, left ventricular hypertrophy and heart failure, and experimental studies provided strong evidence for a role of vitamin D signaling in the regulation of cardiovascular function. One of the proposed mechanisms of action of vitamin D is that it functions as a negative regulator of the renin-angiotensin-aldosterone system (RAAS). This finding established a novel link between vitamin D and RAAS that was unexplored until then. During recent years, major progress has been made towards a more complete understanding of the mechanisms by which FGF23, PTH, and RAAS regulate vitamin D metabolism, especially at the genomic level. However, there are still major gaps in our knowledge that need to be filled by future research. The purpose of this review is to highlight our current understanding of the molecular mechanisms underlying the interaction between vitamin D, FGF23, PTH, and RAAS, and to discuss the role of these mechanisms in physiology and pathophysiology.
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18
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Bouazza A, Tahar A, AitAbderrhmane S, Saidani M, Koceir EA. Modulation of cardiometabolic risk and CardioRenal syndrome by oral vitamin D 3 supplementation in Black and White Southern Sahara residents with chronic kidney disease Stage 3: focus on racial and ethnic disparities. Ren Fail 2022; 44:1243-1262. [PMID: 35930297 PMCID: PMC9359195 DOI: 10.1080/0886022x.2022.2106244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 06/20/2022] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVES Several studies have shown that cholecalciferol supplementation (25OHD-S) in chronic kidney disease (CKD) improves kidney injury by reducing fibrosis-related vascular calcification and declining apoptosis-linked nephron damage. METHODS The oral 25OHD-S was evaluated in 60,000 IU/month/36 weeks versus in 2000 IU/d/24 weeks in CKD Stage 3 with serum 25OHD level < 20 ng/mL. The study was undertaken on 156 black subjects and 150 white subjects Southern Sahara (SS). All biomarkers of cardiometabolic (CMet) and cardiorenal (CRenal) syndrome, Renin-angiotensin-aldosterone system (RAAS) profile, secondary hyperparathyroidism (SHPT), N-terminal pro B-type natriuretic peptide (NT-proBNP), Troponin T (cTnT) and atherogenicity risk were assessed by biochemical methods. Estimate glomerular filtration rate (eGFR) by chronic CKD-EPI equation formula. Total serum vitamin D by liquid chromatography-tandem mass spectrometry (MS). RESULTS Vitamin D deficiency alters in the same manner CMet, CRenal, and others biomarkers in both groups SS; however, these disorders are more acute in blacks compared to whites SS. Oral 25OHD-S a highlighted improvement of eGFR drop, SHPT decrease, decline proteinuria, and cardiac failure risk (NT-proBNP and cTnT) attenuation. Concomitantly, 25OHD-S normalizes Renin, Aldosterone, and Angiotensin System (RAAS) activity. Nevertheless, homocysteine and Lp (a) do not modulate by 25OHD-S. CONCLUSIONS The oral vitamin D3 supplementation, according the dose, and the treatment duration does not like in black-skinned people versus to white-skinned inhabitants, while the 02 groups are native to the same Saharan environment. It emerge that a high intermittent dose through an extensive supplementation (60,000 IU/36 weeks) was more effective in black subjects. At opposite, a lower dose during a short period supplementation is sufficient (2000 IU/24 weeks) in white subjects.
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Affiliation(s)
- Asma Bouazza
- Nutrition and Dietetics in Human Pathologies Post Graduate School, Bioenergetics, Intermediary Metabolism team, Biology and Organisms Physiology laboratory, USTHB, Algiers, Algeria
| | - Amina Tahar
- Nutrition and Dietetics in Human Pathologies Post Graduate School, Bioenergetics, Intermediary Metabolism team, Biology and Organisms Physiology laboratory, USTHB, Algiers, Algeria
| | | | - Messaoud Saidani
- Clinical Nephrology Exploration Unit, Dialysis and Kidney Transplantation Unit, University Hospital Center of Beni Messous, Algiers, Algeria
| | - Elhadj-Ahmed Koceir
- Nutrition and Dietetics in Human Pathologies Post Graduate School, Bioenergetics, Intermediary Metabolism team, Biology and Organisms Physiology laboratory, USTHB, Algiers, Algeria
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19
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Song S, Yuan Y, Wu X, Zhang D, Qi Q, Wang H, Feng L. Additive effects of obesity and vitamin D insufficiency on all-cause and cause-specific mortality. Front Nutr 2022; 9:999489. [PMID: 36337642 PMCID: PMC9634746 DOI: 10.3389/fnut.2022.999489] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 10/06/2022] [Indexed: 12/07/2022] Open
Abstract
Obesity and vitamin D deficiency are both considered risk factors for mortality, but the potential additive effects of vitamin D status and obesity on mortality has not been well-studied. We aimed to examine the possible additive effects of obesity and vitamin D status on all-cause and cause-specific mortality. The data from the NHANES III (1988–1994) and NHANES 2001–2014 surveys were used, and multivariate Cox regression models were performed to assess the additive effects of vitamin D status and overweight/obesity/abdominal obesity on the all-cause, cardiovascular and cancer mortality, by stratifying Cox Hazard Ratios (HRs) across different categories of vitamin D status and body mass index (BMI) and waist circumference (WC) categories. The models were adjusted for age, race/ethnicity, gender, educational level, family income to poverty ratio, leisure-time physical activity, smoking, and drinking. Across all BMI/WC categories, there was an additive effect of the vitamin D both insufficiency and deficiency on all mortality rates, with deficiency having much stronger effect than insufficiency. Interestingly, the effect of vitamin D deficiency overcame the effect of obesity on all mortality rates. The highest HRs for overall and cardiovascular mortality were observed among vitamin D deficient obese/abdominally obese subjects, while for cancer mortality among vitamin D deficient normal weight/non-abdominally obese subjects. In stratified analyses, regarding all-cause mortality, there was an additive effect of the vitamin D both insufficiency and deficiency in all BMI/WC categories. Regarding cardiovascular mortality, there was an additive effect of vitamin D deficiency in all BMI/WC categories, but the additive effect of vitamin D insufficiency reached significance only in normal weight subjects. Regarding cancer mortality, the effect did not reach significance among obese subjects for vitamin D deficiency, while for insufficiency, significance was reached only among non-abdominally obese subjects. Interestingly, vitamin D surplus was associated with increased risk for cancer mortality in obese subjects, but there was an inadequate number of subjects in this category to make proper judgment. In conclusion, vitamin D insufficiency and deficiency gradually increase risk for mortality across all BMI/WC categories. In our analyses, vitamin D deficiency overcame the effect of obesity on mortality rates.
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Affiliation(s)
- Shuaihua Song
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Yuan Yuan
- Department of Clinical Nutrition, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Xiaolong Wu
- The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
| | - Di Zhang
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Qianjin Qi
- Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
| | - Haoran Wang
- Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Li Feng
- Department of Clinical Nutrition, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- *Correspondence: Li Feng,
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20
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Kadham MJ, Abdullah RN, AL-Erjan AM. Relationship between Gene Polymorphism of Vitamin D Receptor with Coronary Heart Disease (CHD) in Baghdad Province /Iraq. 2022 INTERNATIONAL SYMPOSIUM ON MULTIDISCIPLINARY STUDIES AND INNOVATIVE TECHNOLOGIES (ISMSIT) 2022:340-344. [DOI: 10.1109/ismsit56059.2022.9932825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Affiliation(s)
| | - Rawaa najim Abdullah
- College of Health & Medical Technology, Middle technology university,Baghdad,Iraq
| | - Amran M. AL-Erjan
- College of Health & Medical Technology, AL- Ayen University,Thi-Qar,Iraq
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21
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The Association between Serum Vitamin D Concentration and New Inflammatory Biomarkers-Systemic Inflammatory Index (SII) and Systemic Inflammatory Response (SIRI)-In Patients with Ischemic Heart Disease. Nutrients 2022; 14:nu14194212. [PMID: 36235864 PMCID: PMC9570511 DOI: 10.3390/nu14194212] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 10/03/2022] [Accepted: 10/07/2022] [Indexed: 11/17/2022] Open
Abstract
The incidence of ischemic heart disease (IHD) increases every year. This cardiovascular disease has an inflammatory factor in its etiology due to different immune cells that influence atherogenesis. New inflammatory biomarkers—the Systemic Inflammatory Index (SII) and the Systemic Inflammatory Response (SIRI)—attempt to describe the pro- and anti-inflammatory balance and quantify the complex impact of the immune system on atherosclerosis, while vitamin D has a multidirectional impact on the human body, including the cardiovascular and immune systems. Hence, the objective of this research was to analyze the association between SII and SIRI and serum vitamin D concentrations in patients with IHD. A significant correlation was observed between SIRI and 25(OH)D in the whole group and between both biomarkers (SII and SIRI) and 25(OH)D in the group of patients with ACS but not in the group of patients with stable IHD. The role of vitamin D in IHD complications and its association with new inflammatory biomarkers requires further well-designed, large-scale research.
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22
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Vitamin D-Related Single Nucleotide Polymorphisms as Risk Biomarker of Cardiovascular Disease. Int J Mol Sci 2022; 23:ijms23158686. [PMID: 35955825 PMCID: PMC9368814 DOI: 10.3390/ijms23158686] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/01/2022] [Accepted: 08/01/2022] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels. In addition to environmental risk factors, genetic predisposition increases the risk; this includes alterations in the vitamin D receptor gene (VDR). These alterations play a key role in modifying vitamin D uptake, being able to modify its function and increasing susceptibility to cardiovascular disorders. The aim of this study was to evaluate the association of polymorphisms in the VDR gene and risk of CVD in a Caucasian population. A retrospective case-control study was conducted comprising 246 CVD patients and 246 controls of Caucasian origin from Southern Spain. The genetic polymorphisms BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232), FokI (rs2228570) and Cdx2 (rs11568820) were determined by means of real-time polymerase chain reaction (PCR) for allelic discrimination using TaqMan® probes. The logistic regression analysis adjusted for body mass index and diabetes revealed that the TT genotype was associated with a higher risk of CVD in both the genotypic model (p = 0.0430; OR = 2.30; 95% CI = 1.06–5.37; TT vs. CC) and the recessive model (p = 0.0099; OR = 2.71; 95% CI = 1.31–6.07; TT vs. C). Haplotype analysis revealed that the haplotype GAC (p = 0.047; OR = 0.34; 95% CI = 0.12–0.98) was associated with increased risk of CVD. The VDR polymorphisms FokI (rs2228570) was significantly associated with the development of CVD. No influence was observed of the VDR polymorphisms BsmI (rs1544410), TaqI (rs731236), ApaI (rs7975232) and Cdx2 (rs11568820) on the risk of developing CVD in the patients studied.
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Abstract
Purpose of the Review Results from epidemiological studies suggest that vitamin D (VD) deficiency (VDD) may be a cause of hypertension (HTN). However, the results of randomized clinical trials (RCTs) designed to address the impact of VD supplementation on reducing blood pressure (BP) remain equivocal. To determine whether VD might serve as a beneficial treatment option for a specific subset of hypertensive patients, we performed a stratified analysis of RCT data and addressed problems associated with some methodological issues. Recent Findings HTN is caused by multiple factors. VDD may be one of the factors contributing to the development of this disorder. There are more than 70 RCTs that examined the impact of VD supplementation on BP. These RCTs can be classified into four groups based on their respective study populations, including participants who are (1) VD-sufficient and normotensive, (2) VD-deficient and normotensive, (3) VD-sufficient and hypertensive, and (4) VD-deficient and hypertensive. Summary Our evaluation of these studies demonstrates that VD supplementation is ineffective when used to reduce BP in VD-sufficient normotensive subjects. VD supplementation for five years or more may reduce the risk of developing HTN specifically among those with VDD. Interestingly, findings from 12 RCTs indicate that daily or weekly supplementation, as opposed to large bolus dosing, results in the reduction of BP in VD-deficient hypertensive patients. Our ongoing research focused on elucidating the mechanisms of VDD-induced HTN will ultimately provide evidence to support the development of etiology-specific prevention and treatment strategies focused on HTN in the VD-deficient population.
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Zhou A, Selvanayagam JB, Hyppönen E. Non-linear Mendelian randomization analyses support a role for vitamin D deficiency in cardiovascular disease risk. Eur Heart J 2022; 43:1731-1739. [PMID: 34891159 DOI: 10.1093/eurheartj/ehab809] [Citation(s) in RCA: 119] [Impact Index Per Article: 39.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2021] [Revised: 09/28/2021] [Accepted: 11/12/2021] [Indexed: 11/14/2022] Open
Abstract
AIMS Low vitamin D status is associated with a higher risk for cardiovascular diseases (CVDs). Although most existing linear Mendelian randomization (MR) studies reported a null effect of vitamin D on CVD risk, a non-linear effect cannot be excluded. Our aim was to apply the non-linear MR design to investigate the association of serum 25-hydroxyvitamin D [25(OH)D] concentration with CVD risk. METHODS AND RESULTS The non-linear MR analysis was conducted in the UK Biobank with 44 519 CVD cases and 251 269 controls. Blood pressure (BP) and cardiac-imaging-derived phenotypes were included as secondary outcomes. Serum 25(OH)D concentration was instrumented using 35 confirmed genome-wide significant variants.We also estimated the potential reduction in CVD incidence attributable to correction of low vitamin D status. There was a L-shaped association between genetically predicted serum 25(OH)D and CVD risk (Pnon-linear = 0.007), where CVD risk initially decreased steeply with increasing concentrations and levelled off at around 50 nmol/L. A similar association was seen for systolic (Pnon-linear = 0.03) and diastolic (Pnon-linear = 0.07) BP. No evidence of association was seen for cardiac-imaging phenotypes (P = 0.05 for all). Correction of serum 25(OH)D level below 50 nmol/L was predicted to result in a 4.4% reduction in CVD incidence (95% confidence interval: 1.8- 7.3%). CONCLUSION Vitamin D deficiency can increase the risk of CVD. Burden of CVD could be reduced by population-wide correction of low vitamin D status.
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Affiliation(s)
- Ang Zhou
- Australian Center for Precision Health, University of South Australia Cancer Research Institute, GPO Box 2471, Adelaide, SA 5001, Australia
- South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia
| | - Joseph B Selvanayagam
- South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia
- Department of Cardiovascular Medicine, Flinders Medical Centre, Bedford Park, Adelaide, SA 5042, Australia
| | - Elina Hyppönen
- Australian Center for Precision Health, University of South Australia Cancer Research Institute, GPO Box 2471, Adelaide, SA 5001, Australia
- South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia
- Population, Policy and Practice, UCL Great Ormond Street Institute of Child Health, 30 Guilford Street, London, UK
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Jafarzadeh J, Payahoo L, Yousefi M, Barzegar A. The comprehensive mechanistic insight into the effects of vitamin D on dementia – a review. NUTRITION & FOOD SCIENCE 2022; 52:698-721. [DOI: 10.1108/nfs-08-2021-0256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
PurposeThis paper aims to depict the mechanistic role of vitamin D on dementia prevention, relief of the severity and the complication of the disease. All papers indexed in scientific databases, including Scopus, Elsevier, PubMed, Embase and Google Scholar between 2000 and 2021 were extracted and discussed. To present the mechanistic role of vitamin D in declining the severity of dementia, keywords including dementia, vitamin D, oxidative stress, inflammation, amyloid beta-Peptides were used.Design/methodology/approachDementia is a prevalent cognitive disorder worldwide, especially in elderly people, which is accompanied by serious disabilities. Besides genetic, biological and lifestyle factors are involved in the incidence of dementia. An unhealthy diet along with micronutrient deficiencies are among modifiable factors. Vitamin D is one of the important micronutrients in brain health. Besides the involvement in gene expression, bone mineralization, apoptosis, inflammation, skeletal maturation, neurotropic action and hemostasis of phosphate and calcium, vitamin D also exerts neuroprotective effects via genomic and non-genomic pathways.FindingsVitamin D up-regulates the expression of various genes involved in dementia incidence via various mechanisms. Decreasing oxidative stress and the neuro-inflammatory cytokines levels, regulation of the expression of alternated Proteins including Tau and Amyloid-ß, calcium homeostasis in the central nervous system and also vascular are considered main mechanisms.Originality/valueConsidering the importance of diet in preventing dementia, adherence to a healthy diet that provides essential nutrients to brain function seems to be urgent. Controlling serum levels of vitamin D periodically and providing vitamin D by related sources or supplements, if there is a deficiency, is recommended. Future studies are needed to clarify other related mechanisms.
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Janus SE, Durieux JC, Hajjari J, Carneiro H, McComsey GA. Inflammation-mediated vitamin K and vitamin D effects on vascular calcifications in people with HIV on active antiretroviral therapy. AIDS 2022; 36:647-655. [PMID: 34907958 DOI: 10.1097/qad.0000000000003149] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND People with HIV (PWH) experience increased systemic inflammation and monocyte activation, leading to increased risk of cardiovascular events (death, stroke, and myocardial infarction) and higher coronary artery calcium scores (CACs). Vitamins D and K2 have significant anti-inflammatory effects; in addition, vitamin K2 is involved in preventing vascular calcifications in the general population. The roles of vitamins D and K in increased coronary calcifications in successfully treated PWH is less understood. METHODS We prospectively recruited 237 PWH on antiretroviral treatment (ART) and 67 healthy controls. CACs were derived from noncontrast chest computed tomography (CT) and levels of 25-hydroxyvitamin D (vitamin D) and inactive vitamin K-dependent dephosphorylated-uncarboxylated matrix Gla protein (dp-uc MGP, marker of vitamin K deficiency) were measured in plasma during a fasting state. The relationship between inflammation markers, dp-uc MGP, and vitamin D on CACs were estimated using zero-inflated negative binomial regression. Adjusted models included 25(OH)D, MGP, sex, race, age, and markers of inflammation or monocyte activation. RESULTS Overall, controls had lower median age (45.8 vs. 48.8; P = 0.03), a larger proportion of female individuals (55.2 vs. 23.6%; P < 0.0001), and nonwhite (33.8 vs. 70%; P < 0.0001). Among PWH, less than 1% had detectable viral load and the median CD4+ cell count was 682 (IQR: 473.00-899.00). 62.17% of the participants had zero CACs and 51.32% were vitamin D-deficient (<20 ng/ml). There was no difference in detectable CACs (P = 0.19) or dp-uc MGP (P = 0.42) between PWH and controls. In adjusted models, PWH with nonzero CACs have three times greater expected CAC burden compared with controls. Every 1% increase in MGP (worse K status) decreases the probability of having CACs equal to zero by 21.33% (P = 0.01). Evidence suggests that the effects of 25(OH)D and MGP are inflammation-mediated, specifically through sVCAM, TNF-αRI, and TNF-αRII. CONCLUSION Vitamin K deficiency is a modifiable preventive factor against coronary calcification in PWH. Further research should determine whether vitamin K supplementation would reduce systemic inflammation, vascular calcification, and risk of cardiovascular events in PWH.
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Affiliation(s)
| | | | | | | | - Grace A McComsey
- Clinical Research Center
- Department of Medicine and Pediatrics, University Hospital Cleveland Medical Center
- Case Western Reserve University, Cleveland, Ohio, USA
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Trimarco V, Manzi MV, Mancusi C, Strisciuglio T, Fucile I, Fiordelisi A, Pilato E, Izzo R, Barbato E, Lembo M, Morisco C. Insulin Resistance and Vitamin D Deficiency: A Link Beyond the Appearances. Front Cardiovasc Med 2022; 9:859793. [PMID: 35369303 PMCID: PMC8968037 DOI: 10.3389/fcvm.2022.859793] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 02/17/2022] [Indexed: 12/23/2022] Open
Abstract
Vitamin D is a steroid hormone that plays a key role in the regulation of body homeostasis, including cardiovascular function. Although the chronic deficiency of vitamin D is associated with cardiovascular risk factors, as well as with an adverse prognosis, randomized controlled trials have failed in demonstrating that dietary vitamin D supplementation could ameliorate the prognosis of patients with cardiovascular diseases, and suggested that vitamin D deficiency is the expression of the effects of other determinants of cardiovascular risk. Thus, the supplementation of vitamin D is not sufficient to improve the cardiovascular risk profile and prognosis. Insulin resistance is a complex phenomenon that plays a key role in the pathogenesis of conventional cardiovascular risk factors. Interestingly, defects of vitamin D and insulin resistance have a superimposable epidemiological distribution. According to the common view, Insulin resistance is considered the direct or indirect consequence of vitamin D deficiency. However, it is also reasonable to speculate that the deficit or the impaired action of vitamin D, in some circumstances, could be the result of the same pathogenic mechanisms responsible of insulin resistance development. In this case, vitamin D deficiency could be considered an epiphenomenon of insulin resistance. Insulin resistance is a reversible condition, being possibly ameliorated by physical activity and hypocaloric diets. Notably, both physical exercise and energy-restricted dietary regimens are associated with an increase of vitamin D levels. These findings indicate that improving insulin resistance condition is a necessary step to ameliorate vitamin D supplementation-based strategies in cardiovascular prevention.
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Affiliation(s)
- Valentina Trimarco
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Maria Virginia Manzi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Costantino Mancusi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Teresa Strisciuglio
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Ilaria Fucile
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Antonella Fiordelisi
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuele Pilato
- Department of Cardiac Surgery, School of Medicine, University of Naples Federico II, Naples, Italy
| | - Raffaele Izzo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Emanuele Barbato
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
| | - Maria Lembo
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
- *Correspondence: Maria Lembo
| | - Carmine Morisco
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy
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Small Differences in Vitamin D Levels between Male Cardiac Patients in Different Stages of Coronary Artery Disease. J Clin Med 2022; 11:jcm11030779. [PMID: 35160231 PMCID: PMC8836728 DOI: 10.3390/jcm11030779] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/27/2022] [Accepted: 01/28/2022] [Indexed: 12/19/2022] Open
Abstract
Cardiovascular diseases are the main cause of mortality in males older than 65 years of age. The prevalent vitamin D deficiency in the worldwide population may have multiple effects on the cardiovascular system. This study sought to determine the association between serum levels of 25-hydroxyvitamin D (25(OH)D) and the stage of coronary artery disease (CAD) in Polish male subjects. Additionally, subjects with a history of myocardial infarction (MI) were analyzed for potential differences in 25(OH)D levels in comparison with those diagnosed with stable CAD. The study was conducted prospectively in a group of 669 male patients subjected to coronarography examination. CAD stage was defined using the Coronary Artery Surgery Study Score. Patients without significant coronary lesions had significantly higher 25(OH)D levels than patients with single-, double-, or triple-vessel disease (median, 17 vs. 15 ng/mL; p < 0.01). Significantly lower levels of 25(OH)D were apparent when MI was identified as the cause of the then-current hospitalization in comparison with stable CAD, as well as in patients with a history of MI; all of these cases had lower levels of 25(OH)D in comparison with patients with no such history. Male patients with single-, double-, or triple-vessel CAD, acute coronary syndrome, or a history of MI presented lower serum 25(OH)D.
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Poniedziałek-Czajkowska E, Mierzyński R. Could Vitamin D Be Effective in Prevention of Preeclampsia? Nutrients 2021; 13:nu13113854. [PMID: 34836111 PMCID: PMC8621759 DOI: 10.3390/nu13113854] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 10/21/2021] [Accepted: 10/26/2021] [Indexed: 12/23/2022] Open
Abstract
Prevention of preeclampsia (PE) remains one of the most significant problems in perinatal medicine. Due to the possible unpredictable course of hypertension in pregnancy, primarily PE and the high complication rate for the mother and fetus/newborn, it is urgent to offer pregnant women in high-risk groups effective methods of preventing the PE development or delaying its appearance. In addition, due to the association of PE with an increased risk of developing cardiovascular diseases (CVD) in later life, effective preeclampsia prevention could also be important in reducing their incidence. Ideal PE prophylaxis should target the pathogenetic changes leading to the development of PE and be safe for the mother and fetus, inexpensive and freely available. Currently, the only recognized method of PE prevention recommended by many institutions around the world is the use of a small dose of acetylsalicylic acid in pregnant women with risk factors. Unfortunately, some cases of PE are diagnosed in women without recognized risk factors and in those in whom prophylaxis with acetylsalicylic acid is not adequate. Hence, new drugs which would target pathogenetic elements in the development of preeclampsia are studied. Vitamin D (Vit D) seems to be a promising agent due to its beneficial effect on placental implantation, the immune system, and angiogenic factors. Studies published so far emphasize the relationship of its deficiency with the development of PE, but the data on the benefits of its supplementation to reduce the risk of PE are inconclusive. In the light of current research, the key issue is determining the protective concentration of Vit D in a pregnant woman. The study aims to present the possibility of using Vit D to prevent PE, emphasizing its impact on the pathogenetic elements of preeclampsia development.
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Murni IK, Sulistyoningrum DC, Gasevic D, Susilowati R, Julia M. Sex differences in the association of vitamin D and metabolic risk factors with carotid intima-media thickness in obese adolescents. PLoS One 2021; 16:e0258617. [PMID: 34653200 PMCID: PMC8519449 DOI: 10.1371/journal.pone.0258617] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 10/02/2021] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND It has been shown that vitamin D is associated with obesity and the development of atherosclerosis. Less is known about this association among adolescents with obesity. OBJECTIVES To determine the association of vitamin D level and metabolic risk factors with carotid intima-media thickness (CIMT) among obese adolescents. METHODS We conducted a cross-sectional study among obese children aged 15 to 17 years in Yogyakarta, Indonesia. The association of vitamin D and other metabolic risk factors (triglyceride, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR)) with CIMT was explored by multivariable linear regression models. RESULTS Out of 156 obese adolescents, 55.8% were boys. Compared to girls, boys had higher BMI z-score, waist circumference, and HDL-cholesterol. After adjustment for age, sex and second-hand smoke exposure, high HOMA-IR, total cholesterol, LDL-cholesterol and triglyceride levels were associated with higher odds of elevated CIMT. In analyses stratified by sex, a similar trend was observed in boys, while none of the risk factors were associated with CIMT in girls. We observed no association between vitamin D and CIMT. CONCLUSIONS Hyperinsulinemia, higher total cholesterol and LDL cholesterol were associated with greater odds of elevated CIMT among obese adolescent boys.
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Affiliation(s)
- Indah K. Murni
- Department of Child Health, Dr. Sardjito Hospital/Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
- Center for Child Health—Pediatric Research Office, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
- * E-mail:
| | - Dian C. Sulistyoningrum
- Department of Nutrition and Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Danijela Gasevic
- School of Public Health and Preventive Medicine, Monash University, Victoria, Australia
| | - Rina Susilowati
- Department of Histology and Cell Biology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
| | - Madarina Julia
- Department of Child Health, Dr. Sardjito Hospital/Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
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Abouzid M, Kruszyna M, Burchardt P, Kruszyna Ł, Główka FK, Karaźniewicz-Łada M. Vitamin D Receptor Gene Polymorphism and Vitamin D Status in Population of Patients with Cardiovascular Disease-A Preliminary Study. Nutrients 2021; 13:3117. [PMID: 34578994 PMCID: PMC8465937 DOI: 10.3390/nu13093117] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/31/2021] [Accepted: 09/03/2021] [Indexed: 02/07/2023] Open
Abstract
The association between vitamin D receptor (VDR) polymorphism and the risk of cardiovascular diseases (CVD) remains unclear. This study aimed to assess a relationship between the VDR genotypes, plasma concentrations of vitamin D metabolites, and the occurrence of cardiovascular and metabolic disorders. Fifty-eight patients treated for various cardiological afflictions were included. Identification of VDR polymorphisms: ApaI, TaqI, BsmI, and FokI were carried out using the PCR-RFLP method. Plasma concentrations of 25-hydroxyvitamin-D2, 25-hydroxyvitamin-D3, and 3-epi-25-hydroxyvitamin D3 were assessed by the UPLC-MS/MS method. Lower incidence of BsmI AA genotype in the studied patients was observed compared with healthy controls, but the difference was insignificant. Among patients with the TT genotype, frequency of hypertension was higher than among carriers of other ApaI genotypes (p < 0.01). In addition, carriers of the TT ApaI, TC TaqI, and GA BsmI genotypes had an increased risk of obesity, while the presence of the FokI TT genotype was associated with a higher incidence of heart failure and hypertension. In conclusion, the BsmI AA genotype can be protective against CVD, but this observation needs study on a larger group of patients. Particular VDR genotypes were associated with 25-hydroxyvitamin-D levels, and the mechanism of this association should be further investigated.
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Affiliation(s)
- Mohamed Abouzid
- Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego Street, 60-781 Poznan, Poland; (M.A.); (F.K.G.)
| | - Marlena Kruszyna
- Department of Hypertension, Angiology, and Internal Medicine, Poznan University of Medical Sciences, Długa ½, 60-848 Poznan, Poland; (M.K.); (P.B.)
| | - Paweł Burchardt
- Department of Hypertension, Angiology, and Internal Medicine, Poznan University of Medical Sciences, Długa ½, 60-848 Poznan, Poland; (M.K.); (P.B.)
- Department of Cardiology, J. Struś Hospital, Szwajcarska 3, 61-285 Poznan, Poland
| | - Łukasz Kruszyna
- Department of Vascular and Endovascular Surgery, Angiology and Phlebology, Poznan University of Medical Sciences, Długa ½, 60-848 Poznan, Poland;
| | - Franciszek K. Główka
- Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego Street, 60-781 Poznan, Poland; (M.A.); (F.K.G.)
| | - Marta Karaźniewicz-Łada
- Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego Street, 60-781 Poznan, Poland; (M.A.); (F.K.G.)
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Tintut Y, Demer LL. Potential impact of the steroid hormone, vitamin D, on the vasculature. Am Heart J 2021; 239:147-153. [PMID: 34051171 DOI: 10.1016/j.ahj.2021.05.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 05/20/2021] [Indexed: 02/06/2023]
Abstract
The role of vitamin D in the cardiovascular system is complex because it regulates expression of genes involved in diverse metabolic processes. Although referred to as a vitamin, it is more accurately considered a steroid hormone, because it is produced endogenously in the presence of ultraviolet light. It occurs as a series of sequentially activated forms, here referred to as vitamin D-hormones. A little-known phenomenon, based on pre-clinical data, is that its biodistribution and potential effects on vascular disease likely depend on whether it is derived from diet or sunlight. Diet-derived vitamin D-hormones are carried in the blood, at least in part, in chylomicrons and lipoprotein particles, including low-density lipoprotein. Since low-density lipoprotein is known to accumulate in the artery wall and atherosclerotic plaque, diet-derived vitamin D-hormones may also collect there, and possibly promote the osteochondrogenic mineralization associated with plaque. Also, little known is the fact that the body stores vitamin D-hormones in adipose tissue with a half-life on the order of months, raising doubts about whether the use of the term "daily requirement" is appropriate. Cardiovascular effects of vitamin D-hormones are controversial, and risk appears to increase with both low and high blood levels. Since low serum vitamin D-hormone concentration is reportedly associated with increased cardiovascular and orthopedic risk, oral supplementation is widely used, often together with calcium supplements. However, meta-analyses show that oral vitamin D-hormone supplementation does not protect against cardiovascular events, findings that are also supported by a randomized controlled trial. These considerations suggest that prevalent recommendations for vitamin D-hormone supplementation for the purpose of cardiovascular protection should be carefully reconsidered.
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Affiliation(s)
- Yin Tintut
- Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA; Department of Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA; Department of Orthopaedic Surgery, University of California, Los Angeles (UCLA), Los Angeles, CA
| | - Linda L Demer
- Department of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA; Department of Physiology, University of California, Los Angeles (UCLA), Los Angeles, CA; Department of Bioengineering, University of California, Los Angeles (UCLA), Los Angeles, CA; VA Greater Los Angeles Healthcare System, Los Angeles, Los Angeles, CA.
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Vitamin D, Calcium Supplements, and Implications for Cardiovascular Health: JACC Focus Seminar. J Am Coll Cardiol 2021; 77:437-449. [PMID: 33509400 DOI: 10.1016/j.jacc.2020.09.617] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 08/10/2020] [Accepted: 09/01/2020] [Indexed: 02/07/2023]
Abstract
Vitamin D and calcium supplements are commonly used, often together, to optimize bone health. Multiple observational studies have linked low serum 25-hydroxyvitamin D concentrations with increased cardiovascular risk. However, subsequent randomized controlled trials (RCTs) failed to demonstrate cardiovascular benefit with vitamin D supplementation. Although vitamin D supplements do not appear to be harmful for cardiovascular health, the lack of benefit in RCTs should discourage their use for this purpose, favoring optimizing vitamin D status through healthy lifestyles such as specific foods and modest sunlight exposure. Furthermore, some (but not all) observational and RCT studies of calcium supplementation have suggested potential for cardiovascular harm. Therefore, calcium supplementation should be used cautiously, striving for recommended intake of calcium predominantly from food sources. In this review, the authors examine the currently available evidence investigating whether vitamin D and calcium supplements are helpful, harmful, or neutral for cardiovascular health.
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Subber Z, Al-Shamma G, Hashim H. total and free vitamin D in type 2 diabetes mellitus patients in Baghdad city. BAGHDAD JOURNAL OF BIOCHEMISTRY AND APPLIED BIOLOGICAL SCIENCES 2021. [DOI: 10.47419/bjbabs.v2i02.41] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background: The free-form of vitamin D has been used by many researchers as an index of vitamin D status in health and disease. Several methods are there to estimate free, total, and even bioavailable vitamin D.
Objective: The present work was carried out to measure free vitamin D using a special formula suggested by Bikle and Schwartz in 2019, which includes the vitamin D binding protein (VDBP). The results will be used to evaluate the vitamin D status in patients with type 2 diabetes mellitus (T2DM), and its relation to the disease progression.
Methods: Sixty-four patients with T2DM and 73 healthy subjects, all from Baghdad city, were enrolled in the current study from March to October 2020. For each participant, fasting blood glucose, hemoglobin (HbA1c), insulin resistance HOMA-IR, and body mass index (BMI) were measured in addition to the total vitamin D and VDBP. Moreover, free vitamin D was calculated by the formula of Bikle & Schwartz.
Results: There were highly significant correlations between total vitamin D and absolute values of free vitamin D or its percentage. The difference in total vitamin D was significant between patients and healthy controls with no significant change in VDBP, free and bio-available vitamin D, while free vitamin D% was higher in the patient’s group. Correlations between vitamin D and each of BMI, fasting glucose, HbA1c, and HOMA-IR were not significant; however, there was a negative correlation with BMI and fasting glucose in the healthy control subjects only. The Receiver Operating Characteristic (ROC) curve analysis of vitamin D in the diagnosis of diabetes mellitus was poor.
Conclusion: Total vitamin D can represent vitamin D status, but it cannot be used as a factor for diagnosing T2DM. However, it could be of importance to change the glycemic status.
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Gouni-Berthold I, Berthold HK. Vitamin D and Vascular Disease. Curr Vasc Pharmacol 2021; 19:250-268. [PMID: 32183681 DOI: 10.2174/1570161118666200317151955] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Revised: 02/24/2020] [Accepted: 03/01/2020] [Indexed: 12/20/2022]
Abstract
Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide. Vitamin D deficiency has been identified as a potential risk factor for a number of diseases unrelated to the classical skeletal pathophysiology, such as cancer and CVD, but the effects of vitamin D supplementation are less clear. Purpose of this narrative review is to discuss the evidence suggesting an association between vitamin D status and CVD as well as the results of supplementation studies. Vitamin D deficiency has been associated with CVD risk factors such as hypertension, dyslipidemia and diabetes mellitus as well as with cardiovascular events such as myocardial infarction, stroke and heart failure. While vitamin D deficiency might contribute to the development of CVD through its association with risk factors, direct effects of vitamin D on the cardiovascular system may also be involved. Vitamin D receptors are expressed in a variety of tissues, including cardiomyocytes, vascular smooth muscle cells and endothelial cells. Moreover, vitamin D has been shown to affect inflammation, cell proliferation and differentiation. While observational studies support an association between low plasma vitamin D levels and increased risk of CVD, Mendelian randomization studies do not support a causal association between the two. At present, high quality randomized trials do not find evidence of significant effects on CVD endpoints and do not support supplementation of vitamin D to decrease CVD events.
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Affiliation(s)
- Ioanna Gouni-Berthold
- Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany
| | - Heiner K Berthold
- Department of Internal Medicine and Geriatrics, Bethel Clinic (EvKB), Bielefeld, Germany
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Han YY, Hsu SHJ, Su TC. Association between Vitamin D Deficiency and High Serum Levels of Small Dense LDL in Middle-Aged Adults. Biomedicines 2021; 9:464. [PMID: 33923190 PMCID: PMC8145029 DOI: 10.3390/biomedicines9050464] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 04/20/2021] [Accepted: 04/21/2021] [Indexed: 11/29/2022] Open
Abstract
Recent studies suggested a potential link between vitamin D deficiency and cardiovascular risk factors, including dyslipidemia. This study aimed to investigate the association between serum 25(OH)D levels and atherogenic lipid profiles, specifically, that of small dense low-density lipoprotein-cholesterol (sdLDL-C). From 2009 to 2011, a total of 715 individuals aged 35-65 without evident cardiovascular disease (CVD) were enrolled. Their levels of serum 25(OH)D and lipid profiles were measured. Vitamin D deficiency was found to be more common in females, smokers, alcohol drinkers, individuals at a younger age, and those who do not exercise regularly. The analysis of lipid profiles revealed that high sdLDL-C levels were associated with low serum vitamin D levels and were more common among cigarette smokers; alcohol drinkers; individuals with hypertension; individuals with high BMI; and those with high levels of fasting blood glucose, triglycerides, LDL-C, and VLDL-C. The use of multivariate logistic regression verified a strong negative correlation between low vitamin D status (serum 25(OH)D < 15 ng/mL) and the three identified biomarkers of atherogenic dyslipidemia: high serum levels of sdLDL-C, triglycerides, and VLDL-C. This study provides strong evidence that vitamin D deficiency is associated with atherogenic dyslipidemia, and in particular, high sdLDL-C levels in middle-aged adults without CVD.
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Affiliation(s)
- Yin-Yi Han
- Department of Anesthesiology, National Taiwan University Hospital, Taipei 100225, Taiwan;
- Department of Traumatology, National Taiwan University Hospital, Taipei 100225, Taiwan
| | - Sandy Huey-Jen Hsu
- Department of Laboratory Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei 100225, Taiwan;
| | - Ta-Chen Su
- Department of Environmental and Occupational Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan
- Department of Internal Medicine and Cardiovascular Center, National Taiwan University Hospital, Taipei 100225, Taiwan
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Soh V, Tan SJX, Sehgal R, Shirke MM, Ashry A, Harky A. The Relationship Between Vitamin D Status and Cardiovascular Diseases. Curr Probl Cardiol 2021; 46:100836. [PMID: 33848960 DOI: 10.1016/j.cpcardiol.2021.100836] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 03/08/2021] [Indexed: 12/14/2022]
Abstract
With cardiovascular conditions being a leading cause of mortality and morbidity globally, several studies have identified that there is an important correlation between the level of Vitamin D and cardiovascular diseases, including an increased risk of hypertension, heart failure, and coronary artery diseases. Current published studies are in the form of both in vivo and in vitro studies and they primarily showed the evidence of how Vitamin D can downregulate Renin-Angiotensin-Aldosterone system activity and therefore providing a cardioprotective role. Nevertheless, most of these studies are observational, and there yet to be large-scale randomized controlled trials which would increase the evidence of the findings.This review aims to capture the current evidence of Vitamin D as a metabolite which is critical in reducing cardiovascular conditions and the possible physiological pathways that it works via.
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Affiliation(s)
- Vernie Soh
- Department of Medicine, Queen's University Belfast, School of Medicine, Belfast, UK
| | - Shawn Jia Xiang Tan
- Department of Medicine, Queen's University Belfast, School of Medicine, Belfast, UK
| | - Rijuvani Sehgal
- Department of Medicine, Queen's University Belfast, School of Medicine, Belfast, UK
| | - Manasi Mahesh Shirke
- Department of Medicine, Queen's University Belfast, School of Medicine, Belfast, UK
| | - Amr Ashry
- Department of Paediatric Cardiac Surgery, Alder Hey Children Hospital, Liverpool, UK; Department of Cardiothoracic Surgery, Assiut University Hospital, Assiut, Egypt
| | - Amer Harky
- Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, UK; Department of Cardiothoracic Surgery, Liverpool Heart and Chest Hospital, Liverpool, UK.
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Vitamin D and Cardiovascular Disease: An Updated Narrative Review. Int J Mol Sci 2021; 22:ijms22062896. [PMID: 33809311 PMCID: PMC7998446 DOI: 10.3390/ijms22062896] [Citation(s) in RCA: 73] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2021] [Revised: 03/10/2021] [Accepted: 03/10/2021] [Indexed: 12/16/2022] Open
Abstract
During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.
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Liu K, Han B, Hou J, Zhang J, Su J, Meng H. Expression of vitamin D 1α-hydroxylase in human gingival fibroblasts in vivo. PeerJ 2021; 9:e10279. [PMID: 33505780 PMCID: PMC7789863 DOI: 10.7717/peerj.10279] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 10/09/2020] [Indexed: 11/20/2022] Open
Abstract
Background Vitamin D 1α-hydroxylase CYP27B1 is the key factor in the vitamin D pathway. Previously, we analyzed the expression of CYP27B1 in human gingival fibroblasts in vitro. In the present study, we analyzed the gingival expression of CYP27B1 in vivo. Methods Forty-two patients with periodontitis Stage IV Grade C and 33 controls were recruited. All patients with periodontitis had unsalvageable teeth and part of the wall of the periodontal pocket was resected and obtained after tooth extraction. All controls needed crown-lengthening surgery, and samples of gingiva resected during surgery were also harvested. All the individuals' gingivae were used for immunohistochemistry and immunofluorescence. In addition, gingivae from seventeen subjects of the diseased group and twelve subjects of the control group were analyzed by real-time PCR. Results Expression of CYP27B1 was detected both in gingival epithelia and in gingival connective tissues, and the expression in connective tissues colocalized with vimentin, indicating that CYP27B1 protein is expressed in gingival fibroblasts. The expression of CYP27B1 mRNA in gingival connective tissues and the CYP27B1 staining scores in gingival fibroblasts in the diseased group were significantly higher than those in the control group. Conclusions Expression of CYP27B1 in human gingival tissues was detected, not only in the fibroblasts of gingival connective tissues, but also in the gingival epithelial cells, and might be positively correlated with periodontal inflammation.
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Affiliation(s)
- Kaining Liu
- Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.,National Clinical Research Center for Oral Diseases, Beijing, China.,National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China.,Beijing Key Laboratory of Digital Stomatology, Beijing, China
| | - Bing Han
- National Clinical Research Center for Oral Diseases, Beijing, China.,National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China.,Beijing Key Laboratory of Digital Stomatology, Beijing, China.,Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Jianxia Hou
- Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.,National Clinical Research Center for Oral Diseases, Beijing, China.,National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China.,Beijing Key Laboratory of Digital Stomatology, Beijing, China
| | - Jianyun Zhang
- National Clinical Research Center for Oral Diseases, Beijing, China.,National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China.,Beijing Key Laboratory of Digital Stomatology, Beijing, China.,Department of Oral Pathology, Peking University School and Hospital of Stomatology, Beijing, China
| | - Jing Su
- Department of Pathology, Peking University Health Science Center, Beijing, China
| | - Huanxin Meng
- Department of Periodontology, Peking University School and Hospital of Stomatology, Beijing, China.,National Clinical Research Center for Oral Diseases, Beijing, China.,National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, China.,Beijing Key Laboratory of Digital Stomatology, Beijing, China
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40
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Panahi Y, Namazi S, Rostami-Yalmeh J, Sahebi E, Khalili N, Jamialahmadi T, Sahebkar A. Effect of Vitamin D Supplementation on the Regulation of Blood Pressure in Iranian Patients with Essential Hypertension: A Clinical Trial. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1328:501-511. [PMID: 34981501 DOI: 10.1007/978-3-030-73234-9_35] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND Low serum vitamin D level is associated with both high blood pressure and incidence of primary hypertension. Experimental studies suggest that vitamin D supplements may reduce blood pressure. OBJECTIVE The aim of this study was to investigate whether vitamin D supplementation reduces systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) in Iranian patients with essential hypertension. METHOD A total of 173 patients with essential hypertension participated in this open-label clinical trial. SBP, DBP, and serum vitamin D levels were measured at baseline and at the end of the study. Vitamin D was administered at a dose of 50,000 IU/week, and 1000 IU/day in patients with serum vitamin D levels <20 ng/mL and 20-30 ng/mL, respectively, for 8 weeks. RESULTS Based on serum vitamin D levels, 45.1%, 17.3%, and 29.5% of patients were deficient, insufficient, and sufficient for vitamin D intake, respectively. Baseline serum levels of vitamin D were not correlated with SBP, DBP, and MAP at the beginning of the study (p = ns). Multiple logistic regression analysis revealed that the risk of vitamin D deficiency was 2.5-fold times higher in women than in men (p = 0.03). After 8 weeks of supplementation with vitamin D, mean SBP and MAP were significantly reduced by 5.5 ± 16.16 (p = 0.01) and 3.7 ± 9.24 (p = 0.004) mmHg, respectively. Neither sex nor age could significantly predict BP response to vitamin D supplementation. CONCLUSION Vitamin D supplementation may significantly reduce SBP and MAP but not DBP in patients with essential hypertension.
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Affiliation(s)
- Yunes Panahi
- Faculty of Pharmacy, Pharmacotherapy Department, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Soha Namazi
- Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Javad Rostami-Yalmeh
- Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ebrahim Sahebi
- Department of Pharmacotherapy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nahid Khalili
- Department of Endocrinology, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Tannaz Jamialahmadi
- Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran
- Faculty of Medicine, Department of Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- School of Medicine The University of Western Australia, Perth, Australia.
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Sangha GS, Goergen CJ, Prior SJ, Ranadive SM, Clyne AM. Preclinical techniques to investigate exercise training in vascular pathophysiology. Am J Physiol Heart Circ Physiol 2021; 320:H1566-H1600. [PMID: 33385323 PMCID: PMC8260379 DOI: 10.1152/ajpheart.00719.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Atherosclerosis is a dynamic process starting with endothelial dysfunction and inflammation and eventually leading to life-threatening arterial plaques. Exercise generally improves endothelial function in a dose-dependent manner by altering hemodynamics, specifically by increased arterial pressure, pulsatility, and shear stress. However, athletes who regularly participate in high-intensity training can develop arterial plaques, suggesting alternative mechanisms through which excessive exercise promotes vascular disease. Understanding the mechanisms that drive atherosclerosis in sedentary versus exercise states may lead to novel rehabilitative methods aimed at improving exercise compliance and physical activity. Preclinical tools, including in vitro cell assays, in vivo animal models, and in silico computational methods, broaden our capabilities to study the mechanisms through which exercise impacts atherogenesis, from molecular maladaptation to vascular remodeling. Here, we describe how preclinical research tools have and can be used to study exercise effects on atherosclerosis. We then propose how advanced bioengineering techniques can be used to address gaps in our current understanding of vascular pathophysiology, including integrating in vitro, in vivo, and in silico studies across multiple tissue systems and size scales. Improving our understanding of the antiatherogenic exercise effects will enable engaging, targeted, and individualized exercise recommendations to promote cardiovascular health rather than treating cardiovascular disease that results from a sedentary lifestyle.
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Affiliation(s)
- Gurneet S Sangha
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland
| | - Craig J Goergen
- Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana.,Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana
| | - Steven J Prior
- Department of Kinesiology, University of Maryland School of Public Health, College Park, Maryland.,Baltimore Veterans Affairs Geriatric Research, Education, and Clinical Center, Baltimore, Maryland
| | - Sushant M Ranadive
- Department of Kinesiology, University of Maryland School of Public Health, College Park, Maryland
| | - Alisa M Clyne
- Fischell Department of Bioengineering, University of Maryland, College Park, Maryland
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Čečrle M, Černý D, Sedláčková E, Míková B, Dudková V, Drncová E, Pokusová M, Skalský I, Tamášová J, Halačová M. Vitamin D for prevention of sternotomy healing complications: REINFORCE-D trial. Trials 2020; 21:1018. [PMID: 33308291 PMCID: PMC7731517 DOI: 10.1186/s13063-020-04920-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 11/19/2020] [Indexed: 11/29/2022] Open
Abstract
Background Most cardiac surgery patients undergo median sternotomy during open heart surgery. Sternotomy healing is an arduous, very complex, and multifactorial process dependent on many independent factors affecting the sternum and the surrounding soft tissues. Complication rates for median sternotomy range from 0.5 to 5%; however, mortality rates from complications are very variable at 7–80%. Low calcidiol concentration below 80 nmol/L results in calcium absorptive impairment and carries a risk of bone loss, which is considered as a risk factor in the sternotomy healing process. The primary objective of this clinical trial is to compare the incidence of all postoperative sternotomy healing complications in two parallel patient groups administered cholecalciferol or placebo. The secondary objectives are focused on general patient recovery process: sternal bone healing grade at the end of the trial, length of hospitalization, number of days spent in the ICU, number of days spent on mechanical lung ventilation, and number of hospital readmissions for sternotomy complications. Methods This clinical trial is conducted as monocentric, randomized, double-blind, placebo-controlled, with planned enrollment of 600 patients over 4 years, approximately 300 in the placebo arm and 300 in the treatment arm. Males and females from 18 to 95 years of age who fulfill the indication criteria for undergoing cardiac surgery with median sternotomy can be included in this clinical trial, if they meet the eligibility criteria. Discussion REINFORCE-D is the first monocentric trial dividing patients into groups based on serum calcidiol levels, and with dosing based on serum calcidiol levels. This trial may help to open up a wider range of postoperative healing issues. Trial registration EU Clinical Trials Register, EUDRA CT No: 2016-002606-39. Registered on September 8, 2016.
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Affiliation(s)
- Michal Čečrle
- Department of Clinical Pharmacy, Na Homolce Hospital, Prague, Czech Republic.,Institute of Pharmacology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Dalibor Černý
- Department of Clinical Pharmacy, Na Homolce Hospital, Prague, Czech Republic. .,Institute of Pharmacology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
| | - Eva Sedláčková
- Department of Cardiac Surgery, Na Homolce Hospital, Prague, Czech Republic
| | - Barbora Míková
- Department of Radiology, Na Homolce Hospital, Prague, Czech Republic
| | - Vlasta Dudková
- Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague, Czech Republic
| | - Eva Drncová
- Department of Clinical Biochemistry, Hematology and Immunology, Na Homolce Hospital, Prague, Czech Republic
| | | | - Ivo Skalský
- Department of Cardiac Surgery, Na Homolce Hospital, Prague, Czech Republic
| | - Jana Tamášová
- Department of Medical Physics, Na Homolce Hospital, Prague, Czech Republic
| | - Milada Halačová
- Department of Clinical Pharmacy, Na Homolce Hospital, Prague, Czech Republic.,Department of Pharmacology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic
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Lim K, Molostvov G, Lubczanska M, Fletcher S, Bland R, Hiemstra TF, Zehnder D. Impaired arterial vitamin D signaling occurs in the development of vascular calcification. PLoS One 2020; 15:e0241976. [PMID: 33211721 PMCID: PMC7676703 DOI: 10.1371/journal.pone.0241976] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 10/24/2020] [Indexed: 01/10/2023] Open
Abstract
Conflicting data exists as to whether vitamin D receptor agonists (VDRa) are protective of arterial calcification. Confounding this, is the inherent physiological differences between human and animal experimental models and our current fragmented understanding of arterial vitamin D metabolism, their alterations in disease states and responses to VDRa's. Herein, the study aims to address these problems by leveraging frontiers in human arterial organ culture models. Human arteries were collected from a total of 24 patients (healthy controls, n = 12; end-stage CKD, n = 12). Cross-sectional and interventional studies were performed using arterial organ cultures treated with normal and calcifying (containing 5mmol/L CaCl2 and 5mmol/L β-glycerophosphate) medium, ex vivo. To assess the role of VDRa therapy, arteries were treated with either calcitriol or paricalcitol. We found that human arteries express a functionally active vitamin D system, including the VDR, 1α-hydroxylase and 24-hydroxylase (24-OHase) components and these were dysregulated in CKD arteries. VDRa therapy increased VDR expression in healthy arteries (p<0.01) but not in CKD arteries. Arterial 1α-OHase (p<0.05) and 24-OHase mRNA and protein expression were modulated differentially in healthy and CKD arteries by VDRa therapy. VDRa exposure suppressed Runx2 and MMP-9 expression in CKD arteries, however only paricalcitol suppressed MMP-2. VDRa exposure did not modulate arterial calcification in all organ culture models. However, VDRa reduced expression of senescence associated β-galactosidase (SAβG) staining in human aortic-smooth muscle cells under calcifying conditions, in vitro. In conclusion, maladaptation of arterial vitamin D signaling components occurs in CKD. VDRa exposure can exert vasculo-protective effects and seems critical for the regulation of arterial health in CKD.
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Affiliation(s)
- Kenneth Lim
- Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States of America
| | - Guerman Molostvov
- Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom
| | - Maria Lubczanska
- Divisions of Biomedical Sciences, University of Warwick, Coventry, United Kingdom
| | - Simon Fletcher
- Department of Nephrology, University Hospital Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
| | - Rosemary Bland
- Divisions of Biomedical Sciences, University of Warwick, Coventry, United Kingdom
| | - Thomas F. Hiemstra
- Cambridge Clinical Trials Unit and School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
| | - Daniel Zehnder
- Department of Nephrology and Department of Acute Medicine, North Cumbria Integrated Care University Hospital NHS Trust, Carlisle, United Kingdom
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Vitamin D and Cardiovascular Disease, with Emphasis on Hypertension, Atherosclerosis, and Heart Failure. Int J Mol Sci 2020; 21:ijms21186483. [PMID: 32899880 PMCID: PMC7555466 DOI: 10.3390/ijms21186483] [Citation(s) in RCA: 157] [Impact Index Per Article: 31.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 08/24/2020] [Accepted: 08/31/2020] [Indexed: 12/14/2022] Open
Abstract
Vitamin D deficiency is the most common nutritional deficiency, affecting almost one billion people worldwide. Vitamin D is mostly known for its role in intestinal calcium absorption and bone mineralization. However, the observation of seasonal changes in blood pressure and the subsequent identification of vitamin D receptor (VDR) and 1α-hydroxylase in cardiomyocytes, as well as endothelial and vascular smooth muscle cells, implicated a role of vitamin D in the cardiovascular system. Animal studies provided compelling evidence that vitamin D signaling is essential for cardiovascular integrity, especially for the regulation of vascular tone and as an antifibrotic and antihypertrophic signaling pathway in the heart. In addition, observational studies reported an association between vitamin D deficiency and risk of hypertension, atherosclerosis, and heart failure. However, recent clinical intervention studies failed to prove the causal relationship between vitamin D supplementation and beneficial effects on cardiovascular health. In this review, we aim to highlight our current understanding of the role of vitamin D in the cardiovascular system and to find potential explanations for the large discrepancies between the outcome of experimental studies and clinical intervention trials.
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Silent myocardial dysfunction in vitamin D deficiency. ARCHIVES OF MEDICAL SCIENCES. ATHEROSCLEROTIC DISEASES 2020; 5:e153-e162. [PMID: 32832715 PMCID: PMC7433788 DOI: 10.5114/amsad.2020.97110] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Accepted: 05/28/2020] [Indexed: 01/31/2023]
Abstract
Introduction Vitamin D (VD) deficiency is a common disease that occurs in all stages of life. A growing number of studies call attention to the relationship between VD deficiency and cardiovascular disease. The aim of this study was to investigate the effect of VD on subclinical left ventricular (LV) function in diabetic and non-diabetic patients with no significant coronary artery disease. Material and methods We recruited 140 patients (80 diabetics and 60 non-diabetics) with symptoms of stable ischemic heart disease who underwent coronary angiography and who had no significant coronary artery disease in our clinic. The 25(OH)D3 levels were measured and patients who had 25-(OH)D3 levels below 20 ng/dl were defined as the VD deficient group. In addition to conventional echocardiographic parameters, tissue Doppler echocardiography was used for LV diastolic functions and 2D speckle tracking strain echocardiography (2D STE) for evaluating the longitudinal deformation indices of the LV myocardium. Results In all groups, LV global longitudinal strain (GLS) was significantly impaired in patients with VD deficiency (p < 0.001) compared to patients without VD deficiency. LV global longitudinal strain rate (GLSR) was significantly impaired in patients with VD deficiency (p = 0.003). The GLS was negatively associated with 25-(OH)D3 in the VD deficiency group (r = –0.52623, p < 0.001). Conversely, GLS was positively associated with 25-(OH)D3 levels in the normal VD group (r = 0.28, p = 0.048). Conclusions VD deficiency is associated with impaired myocardial GLS. The present study demonstrated that VD deficiency may be the cause of subclinical myocardial dysfunction in patients with or without diabetes mellitus and no history of significant coronary artery disease.
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Bauer P, Kraushaar L, Dörr O, Bauer T, Nef H, Hamm CW, Most A. Association of 25-hydroxy vitamin D level with the blood pressure response to a maximum exercise test among professional indoor athletes. Eur J Appl Physiol 2020; 120:1931-1941. [PMID: 32588193 PMCID: PMC7340632 DOI: 10.1007/s00421-020-04421-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 06/13/2020] [Indexed: 12/17/2022]
Abstract
Purpose Low vitamin D levels have been associated with elevated blood pressure (BP) in the general population. However, whether there is an association of vitamin D insufficiency with BP changes during maximum exercise in athletes is currently unclear.
Methods A total of 120 male professional indoor athletes (age 26 ± 5 years) were examined. BP was measured at rest and during a graded cycling test. We assessed the BP response (BPR) during maximum exercise and the respective load. BP and BPR (peak-baseline BP) were analysed with respect to 25-OH vitamin D levels, with levels < 30 ng/mL defining vitamin D insufficiency.
Results 35 athletes were classified as being vitamin D insufficient. BP was not different between sufficient and insufficient vitamin D groups (122 ± 10/75 ± 7 vs. 120 ± 12/77 ± 9 mmHg). At maximum exercise, however, systolic BP (198 ± 17 vs. 189 ± 19, p = 0.026) and the pulse pressure (118 ± 18 vs. 109 ± 21 mmHg, p = 0.021) were higher in the sufficient group; the BPR was not different between groups (76 ± 20/5 ± 6 vs. 69 ± 22/3 ± 6 mmHg, p = 0.103). Athletes with sufficient levels had a higher maximum power output (3.99 ± 0.82 vs. 3.58 ± 0.78 W/kg, p = 0.015) and achieved higher workloads (367 ± 78 vs. 333 ± 80 W, p = 0.003). The workload-adjusted BPR (maximum systolic BP/MPO) was not different between athletes with sufficient and insufficient vitamin D levels (51 ± 10 vs. 56 ± 14 mmHg × kg/W, p = 0.079).
Conclusion Athletes with sufficient vitamin D achieved a higher maximum systolic BP and a higher maximum power output. The workload-adjusted BPR was not different between groups, which suggests that this finding reflects a better performance of athletes with sufficient vitamin D.
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Affiliation(s)
- Pascal Bauer
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Giessen, Germany.
| | | | - Oliver Dörr
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Giessen, Germany
| | - Timm Bauer
- Department of Cardiology and Intensive Care Medicine, Sana Clinic Offenbach, Offenbach, Germany
| | - Holger Nef
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Giessen, Germany
| | - Christian W Hamm
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Giessen, Germany.,Department of Cardiology, Kerckhoff Clinic GmbH, Bad Nauheim, Germany
| | - Astrid Most
- Department of Cardiology and Angiology, Justus- Liebig- University Giessen, Giessen, Germany
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Çakır OM. Low vitamin D levels predict left atrial thrombus in nonvalvular atrial fibrillation. Nutr Metab Cardiovasc Dis 2020; 30:1152-1160. [PMID: 32456946 DOI: 10.1016/j.numecd.2020.03.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 03/14/2020] [Accepted: 03/27/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND AND AIMS We determined the association between left atrial (LA) thrombus occurrence and a non-classic risk marker, plasma levels of vitamin D, in atrial fibrillation (AF) patients on continuous non-vitamin K antagonist oral anticoagulant (NOAC) therapy for ≥4 weeks. Low levels of plasma 25-hydroxy vitamin D (25-OHD) are predictive of fatal stroke. Vitamin D has anticoagulant effects on the coagulation cascade, which are indirectly targeted by NOAC therapy. The impact of plasma levels of vitamin D on the rate of LA thrombus detected by transesophageal echocardiography (TEE) in AF patients is unknown. METHODS AND RESULTS We enrolled 201 (133 female) AF patients who were using continuous NOAC therapy for ≥4 weeks. All patients underwent transthoracic and TEE examination. Serum concentrations of 25-OHD, C-reactive protein (CRP) levels, CHA2DS2-VASc scores and parameters, LA size, and left ventricle ejection fraction (LVEF) were examined before the TEE procedure. LA thrombus occurrence was independently associated with serum levels of 25-OHD (OR: 0.884; 95% CI: 0.839-0.932; P < 0.001), LA diameter (OR: 1.120; 95% CI: 1.038-1.209; P = 0.003), and LVEF(OR: 0.944; 95% CI: 0.896-0.995; P = 0.032). Dense spontaneous echo contrast (SEC) presence was also inversely associated with 25-OHD concentrations. CONCLUSIONS Low 25-OHD levels, as a non-classic risk factor, were independently and significantly associated with dense SEC and LA thrombus occurrence in AF patients under NOAC therapy, as well as LA enlargement and decreased LVEF. Further large-scale studies are needed to explain the role of vitamin D deficiency, or efficacy of replacement, on LA thrombus occurrence.
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Affiliation(s)
- Ozan M Çakır
- Department of Cardiology, Bülent Ecevit University Faculty of Medicine Medical Center, Zonguldak, Turkey.
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SİNAN ÜY, CANBOLAT İP, KAYA A, KÜÇÜKOĞLU MS. Pulmoner Arteriyal Hipertansiyon Hastalarında Serum D vitamini Düzeyleri. DICLE MEDICAL JOURNAL 2020. [DOI: 10.5798/dicletip.706143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Atamañuk AN, Litewka DF, Baratta SJ, Seropian IM, Perez Prados G, Payaslian MO, Ortiz Fragola JP, Escribano Subias P. Vitamin D deficiency among patients with pulmonary hypertension. BMC Pulm Med 2019; 19:258. [PMID: 31864342 PMCID: PMC6925472 DOI: 10.1186/s12890-019-1011-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Accepted: 11/25/2019] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND There is little information about vitamin D (Vit D) deficiency in patients with pulmonary hypertension (PH). The objective of this study was: 1) compare Vit D levels between patients with PH, left ventricular failure (LVF) and healthy subjects (HS); 2) correlate, in patients with PH, Vit D levels with prognosis-related variables, such as the 6-min walk test (6MWT). METHODS Vitamin D levels were measured in a cross-sectional study in 126 patients from one of three groups: patients with PH (n = 53), patients with LVF (n = 42) and healthy subjects (n = 31). In all groups, 8-h fasting blood samples were obtained in the morning. In the PH and the LVF group, functional class (WHO criteria), metres covered in the 6MWT and echocardiographic parameters were analysed. In the PH group, plasma N terminal pro B type natriuretic peptide (NT-proBNP) level was analysed and a complete haemodynamic evaluation by right heart catheterisation was made. RESULTS Mean Vit D levels were lower in PH than in both other groups (ng/ml, mean ± SD): PH 19.25 ± 10, LVF 25.68 ± 12, HS 28.8 ± 12 (PH vs LVF p = 0.017, PH vs HS p = 0.001 and HS vs LVF p = 0.46). Vit D deficiency prevalence was higher in PH as compared to the other groups (PH 53.8%, LVF 45.2%, HS 25%, p = 0.01). Patients with PH in functional class (FC; WHO criteria) III-IV had higher Vit D deficiency prevalence than those in FC I-II (86.7% vs 40.5%, p = 0.003). There was a significant linear correlation between the 6MWT and Vit D levels in PH (p < 0.01), but not in LVF (p = 0.69). CONCLUSIONS Vit D levels were lower in patients with PH as compared to patients with LVF and HS and correlated directly with 6-min walk distance.
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Affiliation(s)
- Andrés N. Atamañuk
- División Cardiología y Servicio de Neumonología, Hospital General de Agudos “Juan A. Fernández”, Ciudad Autónoma de Buenos Aires, Argentina
- Instituto de Cardiología y Terapéutica Cardiovascular, Hospital Universitario Austral, Buenos Aires, Argentina
| | - Diego F. Litewka
- División Cardiología y Servicio de Neumonología, Hospital General de Agudos “Juan A. Fernández”, Ciudad Autónoma de Buenos Aires, Argentina
| | - Sergio J. Baratta
- Instituto de Cardiología y Terapéutica Cardiovascular, Hospital Universitario Austral, Buenos Aires, Argentina
| | - Ignacio M. Seropian
- Servicio de Hemodinamia, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
| | - Graciela Perez Prados
- División Cardiología y Servicio de Neumonología, Hospital General de Agudos “Juan A. Fernández”, Ciudad Autónoma de Buenos Aires, Argentina
| | - Miguel O. Payaslian
- División Cardiología y Servicio de Neumonología, Hospital General de Agudos “Juan A. Fernández”, Ciudad Autónoma de Buenos Aires, Argentina
| | - Juan P. Ortiz Fragola
- División Cardiología y Servicio de Neumonología, Hospital General de Agudos “Juan A. Fernández”, Ciudad Autónoma de Buenos Aires, Argentina
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Vitamin D as A Protector of Arterial Health: Potential Role in Peripheral Arterial Disease Formation. Int J Mol Sci 2019; 20:ijms20194907. [PMID: 31623356 PMCID: PMC6801787 DOI: 10.3390/ijms20194907] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 09/27/2019] [Accepted: 09/28/2019] [Indexed: 12/14/2022] Open
Abstract
Atherosclerotic occlusive diseases and aneurysms that affect large and medium-sized arteries outside the cardiac and cerebral circulation are collectively known as peripheral arterial disease (PAD). With a rise in the rate of aging population worldwide, the number of people diagnosed with PAD is rapidly increasing. The micronutrient vitamin D is an important steroid hormone that acts on many crucial cellular mechanisms. Experimental studies suggest that optimal levels of vitamin D have beneficial effects on the heart and blood vessels; however, high vitamin D concentrations have been implicated in promoting vascular calcification and arterial stiffness. Observations from various clinical studies shows that deficiency of vitamin D has been associated with a greater risk of PAD. Epidemiological studies have often reported an inverse relation between circulating vitamin D status measured in terms of 25-hydroxivitamin D [25(OH)D] levels and increased cardiovascular disease risk; however, randomized controlled trials did not show a consistent positive effect of vitamin D supplementation on cardiovascular disease risk or events. Even though PAD shares all the major risk factors with cardiovascular diseases, the effect of vitamin D deficiency in PAD is not clear. Current evidence suggests a strong role of vitamin D in promoting genomic and epigenomic changes. This review summarises the current literature that supports the notion that vitamin D deficiency may promote PAD formation. A better understanding of underlying pathological mechanisms will open up new therapeutic possibilities which is the main unmet need in PAD management. Furthermore, epigenetic evidence shows that a more holistic approach towards PAD prevention that incorporates a healthy lifestyle, adequate exercise and optimal nutrition may be more effective in protecting the genome and maintaining a healthy vasculature.
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