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Sullivan VK, Chen J, Bernard L, Yu B, Michos ED, Appel LJ, Lichtenstein AH, Rebholz CM. Serum and urine metabolite correlates of vitamin D supplementation in the Atherosclerosis Risk in Communities (ARIC) study. Clin Nutr ESPEN 2025; 67:523-532. [PMID: 40189143 DOI: 10.1016/j.clnesp.2025.03.172] [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: 01/06/2025] [Revised: 03/07/2025] [Accepted: 03/30/2025] [Indexed: 04/12/2025]
Abstract
BACKGROUND & AIMS Vitamin D regulates calcium and phosphorus homeostasis, skeletal health, and potentially other aspects of health. There are limitations of existing vitamin D biomarkers. We aimed to discover novel vitamin D biomarkers by investigating serum and urine metabolites associated with vitamin D supplementation. METHODS We examined cross-sectional associations between vitamin D supplementation and serum and urine metabolites in Atherosclerosis Risk in Communities Study participants at visit 5 (2011-2013). Untargeted metabolomic profiling of serum and spot urine samples was performed by Metabolon, Inc. We analyzed associations between vitamin D supplementation and log2-transformed metabolites using linear regression models adjusted for demographic, lifestyle, and health covariates. RESULTS Of 5225 participants with serum metabolites analyzed (mean age 76 [SD 5] years, 57 % female, 20 % Black), 45 % reported taking vitamin D supplements. Eighty-two of 933 serum metabolites were associated with vitamin D supplementation (P < 0.05/933). Most were lipids (n = 36). Of 1565 participants with urine metabolites analyzed, one-third (37 %) used vitamin D. Nineteen of 946 urine metabolites were associated with vitamin D supplementation (P < 0.05/946). Most were cofactors and vitamins (n = 12). After adjusting for other supplement use (multivitamin/mineral, omega-3, B and C vitamins), 5 serum metabolites (pro-hydroxy-pro, pyroglutamine, sulfate, creatine, and 2-hydroxypalmitate) and no urine metabolites were significantly associated with vitamin D supplementation. CONCLUSIONS Many serum and urine metabolites were associated with vitamin D supplementation. Five serum metabolites remained associated with vitamin D after adjustment for other dietary supplements, including metabolites of bone collagen degradation, glutathione metabolism, and sphingolipid metabolism. These metabolites may reflect physiological activities of vitamin D and, thus, improve assessment of vitamin D adequacy to achieve functional outcomes. These merit further investigation as potential vitamin D biomarkers.
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Affiliation(s)
- Valerie K Sullivan
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; The Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA
| | - Jingsha Chen
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
| | - Lauren Bernard
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; University of Maryland School of Medicine, Baltimore, MD, USA
| | - Bing Yu
- Department of Epidemiology, University of Texas Health Sciences Center at Houston School of Public Health, Houston, TX, USA
| | - Erin D Michos
- Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lawrence J Appel
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; The Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA; The Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Alice H Lichtenstein
- Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA
| | - Casey M Rebholz
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; The Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD, USA; Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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Gao Y, Song XN, Wen ZP, Hu JZ, Du XZ, Zhang JH, Liu S. The association of vitamin deficiency with depression risk in late-life depression: a review. Front Nutr 2025; 12:1551375. [PMID: 40303879 PMCID: PMC12037377 DOI: 10.3389/fnut.2025.1551375] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Accepted: 03/18/2025] [Indexed: 05/02/2025] Open
Abstract
Late-life depression (LLD), a growing public health challenge in aging societies, profoundly impacts physical and mental health by exacerbating cognitive decline, functional disability, and comorbid chronic diseases. Emerging research highlights vitamin supplementation as a promising adjunctive therapy for LLD, targeting its multifactorial pathogenesis involving mitochondrial dysfunction, neuroinflammation, and oxidative stress. Specific vitamins, including B-complex vitamins (B1, B6, B9, B12), vitamin D, and antioxidants (C, E), demonstrate therapeutic potential through mechanisms ranging from neurotransmitter regulation to mitochondrial function enhancement. For instance, vitamin D modulates serotonin synthesis and calcium signaling, while B vitamins mitigate homocysteine-mediated neurotoxicity and support energy metabolism. Antioxidants counteract neural oxidative damage linked to depressive severity. Clinical studies reveal that vitamin D deficiency (<20 ng/mL) correlates with elevated depression risk, and combined B-vitamin supplementation shows symptom alleviation in nutritionally deficient subgroups. However, evidence remains heterogeneous due to variability in dosing protocols, bioavailability, and population-specific factors like comorbidities. Despite growing evidence, critical gaps persist regarding optimal dosages, bioavailability variations, and long-term outcomes in elderly populations. This review synthesizes current evidence on vitamin-mediated cellular pathways in LLD management, evaluates clinical efficacy across interventions, and proposes personalized nutritional strategies to optimize therapeutic outcomes. By integrating mechanistic insights with clinical data, this analysis aims to guide evidence-based vitamin supplementation protocols for LLD within geriatric care frameworks.
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Affiliation(s)
- Yao Gao
- Department of Psychiatry, First Clinical Medical College, First Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorders, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiao-Na Song
- Department of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China
| | - Zhong-Ping Wen
- Department of Psychiatry, First Clinical Medical College, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jian-Zhen Hu
- Department of Psychiatry, First Clinical Medical College, First Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorders, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Xin-Zhe Du
- Department of Psychiatry, First Clinical Medical College, First Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorders, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Ji-Hui Zhang
- Department of Mental Health, Sinopharm North Hospital, Baotou, China
| | - Sha Liu
- Department of Psychiatry, First Clinical Medical College, First Hospital of Shanxi Medical University, Taiyuan, China
- Shanxi Key Laboratory of Artificial Intelligence Assisted Diagnosis and Treatment for Mental Disorders, First Hospital of Shanxi Medical University, Taiyuan, China
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Long S, Mahfuz S, Piao X. Dietary 25-Hydroxycholecalciferol Supplementation from Day 85 of Gestation to Farrowing Enhances Performance, Antioxidant Capacity, and Immunoglobulins of Sows and Newborn Piglets. Animals (Basel) 2024; 14:3378. [PMID: 39682344 DOI: 10.3390/ani14233378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/16/2024] [Accepted: 11/19/2024] [Indexed: 12/18/2024] Open
Abstract
In this study, the aim was to evaluate the effects of dietary 25-hydroxycholecalciferol supplementation from day 85 of gestation on performance, antioxidant capacity, and immunoglobulin level of sows and newborn piglets. On day 85 of gestation, forty Landrace × Yorkshire gestating sows (average body weight of 241 ± 6.8 kg; average parity of 3.47 ± 0.6) were allotted into two treatments (20 replicates per treatment) based on parity, body weight, and back fat thickness. From day 85 of gestation to farrowing, sows were fed a normal vitamin D3 diet as control (containing 50 μg/kg vitamin D3; CON), or a 25-hydroxycholecalciferol-supplemented diet (containing 50 μg/kg 25-hydroxycholecalciferol). Compared with CON, dietary 25-hydroxycholecalciferol supplementation increased (p < 0.05) protein and fat content in colostrum and the average birth body weight of newborn piglets. Sows fed 25-hydroxycholecalciferol showed increased (p < 0.05) apparent total tract digestibility of crude protein compared with CON. Diets supplemented with 25-hydroxycholecalciferol also increased (p < 0.05) the content of superoxide dismutase (SOD), and tended to increase (p = 0.06) the total antioxidant capacity content and reduce (p = 0.09) the malondialdehyde (MDA) level in colostrum. An increase (p < 0.05) in the content of SOD and a reduction (p < 0.05) in the content of MDA in the serum of newborn piglets was also observed in the 25-hydroxycholecalciferol treatment compared with CON. Dietary 25-hydroxycholecalciferol supplementation also enhanced (p < 0.05) the immunoglobulin G content and reduced (p < 0.05) the concentration of tumor nuclear factor-α in the serum of sows, as well as reducing (p < 0.05) the content of immunoglobulin G and immunoglobulin A in the serum of newborn piglets compared with CON. Supplementation of 25-hydroxycholecalciferol in sow diets increased (p < 0.05) the content of alkaline phosphatase in the serum and colostrum of sows, the concentration of insulin and crosslap in serum of sows, and the serum calcium content of newborn piglets compared with CON. In conclusion, dietary 25-hydroxycholecalciferol supplementation from day 85 of gestation could enhance performance, antioxidant capacity, and immunoglobulin in sows and newborn piglets.
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Affiliation(s)
- Shenfei Long
- Beijing Jingwa Agricultural Science and Technology Innovation Center, Beijing 101205, China
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Shad Mahfuz
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - Xiangshu Piao
- Beijing Jingwa Agricultural Science and Technology Innovation Center, Beijing 101205, China
- State Key Laboratory of Animal Nutrition and Feeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
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Skv M, Abraham SM, Eshwari O, Golla K, Jhelum P, Maity S, Komal P. Tremendous Fidelity of Vitamin D3 in Age-related Neurological Disorders. Mol Neurobiol 2024; 61:7211-7238. [PMID: 38372958 DOI: 10.1007/s12035-024-03989-w] [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: 10/02/2023] [Accepted: 01/23/2024] [Indexed: 02/20/2024]
Abstract
Vitamin D3 (VD) is a secosteroid hormone and shows a pleiotropic effect in brain-related disorders where it regulates redox imbalance, inflammation, apoptosis, energy production, and growth factor synthesis. Vitamin D3's active metabolic form, 1,25-dihydroxy Vitamin D3 (1,25(OH)2D3 or calcitriol), is a known regulator of several genes involved in neuroplasticity, neuroprotection, neurotropism, and neuroinflammation. Multiple studies suggest that VD deficiency can be proposed as a risk factor for the development of several age-related neurological disorders. The evidence for low serum levels of 25-hydroxy Vitamin D3 (25(OH)D3 or calcidiol), the major circulating form of VD, is associated with an increased risk of Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), dementia, and cognitive impairment. Despite decades of evidence on low VD association with neurological disorders, the precise molecular mechanism behind its beneficial effect remains controversial. Here, we will be delving into the neurobiological importance of VD and discuss its benefits in different neuropsychiatric disorders. The focus will be on AD, PD, and HD as they share some common clinical, pathological, and epidemiological features. The central focus will be on the different attributes of VD in the aspect of its anti-oxidative, anti-inflammatory, anti-apoptotic, anti-cholinesterase activity, and psychotropic effect in different neurodegenerative diseases.
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Affiliation(s)
- Manjari Skv
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Sharon Mariam Abraham
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Omalur Eshwari
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Kishore Golla
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Priya Jhelum
- Centre for Research in Neuroscience and Brain Program, The Research Instituteof the, McGill University Health Centre , Montreal, QC, Canada
| | - Shuvadeep Maity
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India
| | - Pragya Komal
- Department of Biological Sciences, Birla Institute of Technology and Science-Pilani (BITS-Pilani) Hyderabad campus, Shameerpet-Mandal, Hyderabad, Telangana, India.
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Rafati M, Bazrafshan E, Shaki F, Ghalini-Moghaddam T, Moghimi M. The relationship between serum vitamin D, testosterone, and oxidative stress levels in women with sexual dysfunction: A case-controlled study. Taiwan J Obstet Gynecol 2024; 63:673-678. [PMID: 39266147 DOI: 10.1016/j.tjog.2024.06.004] [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] [Accepted: 06/21/2024] [Indexed: 09/14/2024] Open
Abstract
OBJECTIVE Female sexual dysfunction (FSD) is highly prevalent and can result from hypovitaminosis D. Besides the role of vitamin D in normal bone development, studies showed it could reduce oxidative stress and lipid peroxidation. This prospective study aims to evaluate the relationship between serum vitamin D, testosterone, and oxidative stress levels in women with FSD. MATERIALS AND METHODS In this cross-sectional study, a total of 40 women with FSD (age range: 18-45 years) were randomly assigned into two groups of intervention and control. In the intervention group, patients received vitamin D 300,000 IU intramuscularly (IM) and then 50,000 IU orally once a week for four weeks. We measured the serum vitamin D, testosterone, and oxidative stress levels, as well as the Female Sexual Function Index (FSFI) at baseline and monthly for three months. RESULTS Serum testosterone levels significantly increased in the intervention group at the end of the third month (P = 0.014). Also, FSFI scores significantly improved (P < 0.01) in the intervention group compared to the control group. While there was positive a correlation between serum vitamin D levels with glutathione, total antioxidant capacity (TAC), testosterone, and FSFI score, there was a negative correlation between serum vitamin D levels with malondialdehyde (MDA), protein carbonyl, and nitric oxide. CONCLUSION We witnessed that women with FSD had low serum vitamin D levels. So, modifying serum vitamin D levels must be considered as a treatment option. Moreover, vitamin D supplementation improved testosterone, serum oxidative stress, and sexual function.
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Affiliation(s)
- Mohammadreza Rafati
- Department of Clinical Pharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Elahe Bazrafshan
- Bu-Ali Sina Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Fatemeh Shaki
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Tahereh Ghalini-Moghaddam
- Department of Obstetrics and Gynecology, College of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
| | - Minoo Moghimi
- Department of Clinical Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
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Mohammed AI, Fedoruk L, Fisher N, Liu AX, Khanna S, Naylor K, Gong Z, Celentano A, Alrashdan MS, Cirillo N. Systemic Anti-Inflammatory Agents in the Prevention of Chemoradiation-Induced Mucositis: A Review of Randomised Controlled Trials. Biomolecules 2024; 14:560. [PMID: 38785967 PMCID: PMC11117894 DOI: 10.3390/biom14050560] [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: 03/13/2024] [Revised: 05/01/2024] [Accepted: 05/02/2024] [Indexed: 05/25/2024] Open
Abstract
Mucositis is a pathological condition characterised by inflammation and ulceration of the mucous membranes lining the alimentary canal, particularly in the mouth (oral mucositis) and the gastrointestinal tract. It is a common side effect of cancer treatments, including chemotherapy and radiotherapy, and it is sometimes responsible for treatment interruptions. Preventing mucositis throughout the alimentary tract is therefore crucial. However, current interventions mainly target either oral or gastrointestinal side effects. This review aimed to investigate the use of systemically administered anti-inflammatory agents to prevent mucositis in cancer patients undergoing cancer treatment. PubMed, Ovid, Scopus, Web of Science, WHO ICTRP and ClinicalTrials.gov were screened to identify eligible randomised controlled trials (RCTs). The published literature on anti-inflammatory agents provides mixed evidence regarding the degree of efficacy in preventing/reducing the severity of mucositis in most anticancer treatments; however, sample size continued to be a significant limitation, alongside others discussed. Our review yielded a list of several anti-inflammatory agents that exhibit potential mucositis-preventive effects in cancer patients undergoing cancer treatment, which can be used to inform clinical practice.
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Affiliation(s)
- Ali I. Mohammed
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Lexi Fedoruk
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Nicholas Fisher
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Andy Xiaoqian Liu
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Samar Khanna
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Kaelan Naylor
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Ziyi Gong
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Antonio Celentano
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
| | - Mohammad S. Alrashdan
- Department of Oral and Craniofacial Health Sciences, College of Dental Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates;
- Department of Oral Medicine and Oral Surgery, Faculty of Dentistry, Jordan University of Science and Technology, Irbid 22110, Jordan
| | - Nicola Cirillo
- Melbourne Dental School, Faculty of Medicine, Dentistry & Health Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; (A.I.M.); (L.F.); (N.F.); (A.X.L.); (S.K.); (K.N.); (Z.G.); (A.C.)
- School of Dentistry, University of Jordan, Amman 11942, Jordan
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Máčová L, Kancheva R, Bičíková M. Molecular Regulation of the CNS by Vitamin D. Physiol Res 2023; 72:S339-S356. [PMID: 38116771 DOI: 10.33549/physiolres.935248] [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: 01/05/2024] Open
Abstract
Vitamin D is a lipid-soluble vitamin that can be found in some foods. It is also produced endogenously (in the presence of ultraviolet light), transported through the blood to the targets organs and this is the reason to consider vitamin D as a hormone. It is known that vitamin D has genomic and non-genomic effects. This review is focused mainly on the vitamin D receptors, the importance of vitamin D as a neuromodulator, the role of vitamin D in the pathophysiology of devastating neurological disorders such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease and the benefit of vitamin D and its derivates in alleviating these disorders.
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Affiliation(s)
- L Máčová
- Department of Steroids and Proteofactors, Institute of Endocrinology, Prague, Czech Republic
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Ceolin G, Antunes LDC, Moretti M, Rieger DK, Moreira JD. Vitamin D and depression in older adults: lessons learned from observational and clinical studies. Nutr Res Rev 2023; 36:259-280. [PMID: 35022097 DOI: 10.1017/s0954422422000026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Depression is a mental disorder triggered by the interaction of social, psychological and biological factors that have an important impact on an individual's life. Despite being a well-studied disease with several established forms of treatment, its prevalence is increasing, especially among older adults. New forms of treatment and prevention are encouraged, and some researchers have been discussing the effects of vitamin D (VitD) on depression; however, the exact mechanism by which VitD exerts its effects is not yet conclusive. In this study, we aimed to discuss the possible mechanisms underlying the association between VitD and depression in older adults. Therefore, we conducted a systematic search of databases for indexed articles published until 30 April 2021. The primary focus was on both observational studies documenting the association between VitD and depression/depressive symptoms, and clinical trials documenting the effects of VitD supplementation on depression/depressive symptoms, especially in older adults. Based on pre-clinical, clinical and observational studies, it is suggested that the maintenance of adequate VitD concentrations is an important issue, especially in older adults, which are a risk population for both VitD deficiency and depression. Nevertheless, it is necessary to carry out more studies using longitudinal approaches in low- and middle-income countries to develop a strong source of evidence to formulate guidelines and interventions.
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Affiliation(s)
- Gilciane Ceolin
- Postgraduate Program in Nutrition, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
- Translational Nutritional Neuroscience working Group, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Luciana da Conceição Antunes
- Department of Nutrition, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
- Translational Nutritional Neuroscience working Group, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Morgana Moretti
- Postgraduate Program in Biochemistry, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Débora Kurrle Rieger
- Department of Nutrition, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
- Translational Nutritional Neuroscience working Group, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
| | - Júlia Dubois Moreira
- Department of Nutrition, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
- Translational Nutritional Neuroscience working Group, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil
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Kalejahi P, Kheirouri S, Noorazar SG. A randomized controlled trial of Vitamin D supplementation in Iranian patients with schizophrenia: Effects on serum levels of glycogen synthase kinase-3β and symptom severity. Int J Psychiatry Med 2023; 58:559-575. [PMID: 37545122 DOI: 10.1177/00912174231193303] [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] [Indexed: 08/08/2023]
Abstract
BACKGROUND Growing evidence has shown that hypovitaminosis D is a risk factor for developing schizophrenia and comorbid conditions. Therefore, this study aimed to examine the effect of vitamin D supplementation on serum levels of vitamin D, metabolic factors related to insulin resistance (IR) and the severity of the disorder in patients with schizophrenia. METHODS Forty-eight chronic male patients with schizophrenia with vitamin D deficiency (≤20 ng/mL= (≤50 nmol/l) were selected and randomly assigned to vitamin D treatment and placebo groups. Subjects were supplemented for 8 weeks with vitamin D (2000 IU/day) or placebo. RESULTS Within-group comparison revealed that the vitamin D group had a significant reduction in waist circumference, Positive and Negative Syndrome Scale - total score (PANSS-TS), and glycogen synthase kinase 3 beta (GSK-3β) levels (P = .022, P = <.001 and P = .013, respectively). On the other hand, the placebo group showed a significant increase in the level of fasting serum insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (P = .003 and P = .003). The between-group comparison showed a significant difference in terms of PANSS-TS, GSK-3β, fasting serum insulin (FSI), and HOMA-IR (P = .022, P = .048, P = .013 and P = .014 respectively). CONCLUSIONS Among vitamin D deficient patients with schizophrenia, vitamin D supplementation may affect GSK-3 β, an important biomarker in schizophrenia and insulin resistance. In addition, vitamin D supplementation in such patients may reduce the disorder's symptom severity.
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Affiliation(s)
- Parinaz Kalejahi
- Department of Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sorayya Kheirouri
- Department of Nutrition, Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Seyed Gholamreza Noorazar
- Research Center of Psychiatry and Behavioral Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
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Korkut O, Aydin H. Neurological Symptoms That May Represent a Warning in Terms of Diagnosis and Treatment in a Group of Children and Adolescents with Vitamin D Deficiency. CHILDREN (BASEL, SWITZERLAND) 2023; 10:1251. [PMID: 37508748 PMCID: PMC10377780 DOI: 10.3390/children10071251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 07/04/2023] [Accepted: 07/13/2023] [Indexed: 07/30/2023]
Abstract
AIM This research was intended to evaluate the clinical and laboratory findings of children presenting to our pediatric neurology clinic with symptoms potentially linked to vitamin D deficiency and with low vitamin D levels and the distribution of those findings by sex, age groups, and vitamin D levels. METHODS This retrospective study involved patients presenting to our clinic with symptoms potentially associated with vitamin D deficiency and low serum concentrations of 25 OH vitamin D (25 OH D) (<75 nmol/L, 30 µg/mL). Patients' movement disorders and central nervous system-related symptoms at the time of presentation and serum 25 OH D, calcium (Ca), phosphorus (P), and magnesium (Mg) levels were recorded and evaluated in terms of age, sex, and vitamin D levels. RESULTS Eight hundred twenty-two cases of vitamin D deficiency were included in the study, 50.2% (n = 413) boys and 49.8% (n = 409) girls. Although cases of vitamin D deficiency were present across all the age groups between 1 and 18, they were most common in the 5-14 age range (n = 372, 45.3%). Movement disorders were observed in 14.6% (n = 120) of our cases, and neurological findings associated with the central nervous system were observed in 52.6% (n = 432). The most common accompanying movement in our cases was difficulty remaining in balance (n = 42, 35%), while the most frequent accompanying central nervous system finding was vertigo (n = 99, 22.92%). Other movement disorders encountered included limb shaking (n = 32, 26.7%), abnormal posture (n = 20, 16.67%), easy falling (n = 16, 13.33%), body rigidity (n = 15, 12.5%), and hand clenching (n = 5, 4.17%). Other frequently encountered neurological findings were headache (n = 88, 20.37%), epileptic seizures (n = 83, 19.21%), fainting (n = 58, 13.43%), developmental delay (n = 41, 9.49%), febrile seizures (n = 33, 7.64%), and numbness in the fingers (n = 20, 4.63%). Other neurological findings were sleep disorders (n = 10, 2.31%), nightmares (n = 8, 1.85%), pain in the extremities (n = 7, 1.62%), and sweating and frailty (n = 4, 0.93% for both). Ca, P, and Mg levels were lower in cases with vitamin D levels < 12 µg/mL. The prevalences of both movement disorders and central nervous system findings varied according to age groups, sex, and vitamin D levels. CONCLUSIONS Our study results show that vitamin D deficiency can present with different neurological findings and that these may vary according to age group, sex, and vitamin D levels. Clinicians must take particular care in pediatric cases with neurological findings in terms of the early diagnosis and treatment of vitamin D deficiency.
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Affiliation(s)
- Oguzhan Korkut
- Department of Medical Pharmacology, Faculty of Medicine, Balikesir University, 10145 Balikesir, Turkey
| | - Hilal Aydin
- Department of Pediatrics, Faculty of Medicine, Balikesir University, 10145 Balikesir, Turkey
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11
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Holton K. The potential role of dietary intervention for the treatment of neuroinflammation. TRANSLATIONAL NEUROIMMUNOLOGY, VOLUME 7 2023:239-266. [DOI: 10.1016/b978-0-323-85841-0.00022-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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12
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Wang W, Li Y, Meng X. Vitamin D and neurodegenerative diseases. Heliyon 2023; 9:e12877. [PMID: 36820164 PMCID: PMC9938420 DOI: 10.1016/j.heliyon.2023.e12877] [Citation(s) in RCA: 23] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 11/23/2022] [Accepted: 01/05/2023] [Indexed: 01/13/2023] Open
Abstract
Neurodegenerative diseases, featured by progressive loss of structure or function of neurons, are considered incurable at present. Movement disorders like tremor and postural instability, cognitive or behavioral disorders such as memory impairment are the most common symptoms of them and the growing patient population of neurodegenerative diseases poses a serious threat to public health and a burden on economic development. Hence, it is vital to prevent the occurrence of the diseases and delay their progress. Vitamin D can be transformed into a hormone in vivo with both genomic and non-genomic actions, exerting diverse physiological effects. Cumulative evidence indicates that vitamin D can ameliorate neurodegeneration by regulating pertinent molecules and signaling pathways including maintaining Ca2+ homeostasis, reducing oxidative stress, inhibiting inflammation, suppressing the formation and aggregation of the pathogenic protein, etc. This review updates discoveries of molecular mechanisms underlying biological functions of vitamin D in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and vascular dementia. Clinical trials investigating the influence of vitamin D supplementation in patients with neurodegenerative diseases are also summarized. The synthesized information will probably provoke an enhanced understanding of the neuroprotective roles of vitamin D in the nervous system and provide therapeutic options for patients with neurodegenerative diseases in the future.
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13
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Behl T, Arora A, Singla RK, Sehgal A, Makeen HA, Albratty M, Meraya AM, Najmi A, Bungau SG. Understanding the role of "sunshine vitamin D " in Parkinson's disease: A review. Front Pharmacol 2022; 13:993033. [PMID: 36601055 PMCID: PMC9807223 DOI: 10.3389/fphar.2022.993033] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 12/01/2022] [Indexed: 12/23/2022] Open
Abstract
Next to Alzheimer's disease, Parkinson's disease constitutes the second most widespread neurological disorder, primarily affecting the older population. Its symptoms are noticeable with advancing age including tremors, postural imbalance, and slow movements, and over time, these symptoms get aggravated, progressing to osteoporosis, osteopenia, and risk of fractures. These symptoms correlate to low bone density and hence weakened bones; thus, vitamin D proves to be an intricate component of the pathogenesis of the disease. Moreover, lower serum concentrations of vitamin D have been found in diseased subjects. Supplementation with vitamin D can retard the aggravation of non-motor as well as motor symptoms of Parkinson's disease that include cognitive improvement along with the decline in risk of fractures. Also, vitamin D is extremely crucial for brain functioning, targeting dopaminergic neurons, and almost the entire functioning of the brain is affected. However, further exploration is required to determine the toxic dose of vitamin D in Parkinson's subjects. This "sunshine vitamin" surely can be a ray of sunshine for neurologically diseased subjects.
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Affiliation(s)
- Tapan Behl
- School of Health Science and Technology, University of Petroleum and Energy Studies, Bidholi, Uttarakhand, India
| | - Arpita Arora
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Rajeev K. Singla
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
| | - Aayush Sehgal
- GHG Khalsa College of Pharmacy, Gurusar Sadhar, Ludhiana, Punjab, India
| | - Hafiz A. Makeen
- Pharmacy Practice Research Unit, Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Mohammed Albratty
- Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Abdulkarim M. Meraya
- Pharmacy Practice Research Unit, Clinical Pharmacy Department, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Asim Najmi
- Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Simona Gabriela Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
- Doctoral School of Biomedical Sciences, University of Oradea, Oradea, Romania
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14
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Rihal V, Khan H, Kaur A, Singh TG, Abdel-Daim MM. Therapeutic and mechanistic intervention of vitamin D in neuropsychiatric disorders. Psychiatry Res 2022; 317:114782. [PMID: 36049434 DOI: 10.1016/j.psychres.2022.114782] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 08/08/2022] [Accepted: 08/09/2022] [Indexed: 11/19/2022]
Abstract
Vitamin D deficiency is believed to affect between 35 and 55% of the world's population, making it a hidden pandemic. In addition to its role in bone and calcium homeostasis, vitamin D has also been linked in preclinical and clinical research to brain function. These outcomes have also been used for a variety of neuropsychiatric and neurodevelopmental problems. Nevertheless, these individuals are more prone to develop signs of cognitive decline. This review will emphasize the association between vitamin D and neuropsychiatric illnesses such as autism, schizophrenia, depression, and Attention Deficit Hyperactivity Disorder (ADHD). While numerous research show vitamin D's essential role in cognitive function in neuropsychiatric illnesses, it is too early to propose its effect on cognitive symptoms with certainty. It is necessary to conduct additional research into the associations between vitamin D deficiency and cognitive abnormalities, particularly those found in autism, schizophrenia, depression, and ADHD, to develop initiatives that address the pressing need for novel and effective preventative therapeutic strategies.
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Affiliation(s)
- Vivek Rihal
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | - Heena Khan
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | - Amarjot Kaur
- Chitkara College of Pharmacy, Chitkara University, Punjab 140401, India
| | | | - Mohamed M Abdel-Daim
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231 Jeddah 21442, Saudi Arabia; Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt
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15
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Ren ZL, Li CX, Ma CY, Chen D, Chen JH, Xu WX, Chen CA, Cheng FF, Wang XQ. Linking Nonalcoholic Fatty Liver Disease and Brain Disease: Focusing on Bile Acid Signaling. Int J Mol Sci 2022; 23:13045. [PMID: 36361829 PMCID: PMC9654021 DOI: 10.3390/ijms232113045] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 10/21/2022] [Accepted: 10/25/2022] [Indexed: 11/01/2023] Open
Abstract
A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world's population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood-brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently.
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Affiliation(s)
- Zi-Lin Ren
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chang-Xiang Li
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Chong-Yang Ma
- School of Traditional Chinese Medicine, Capital Medical University, Beijing 100069, China
| | - Dan Chen
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Jia-Hui Chen
- Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing 100700, China
| | - Wen-Xiu Xu
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Cong-Ai Chen
- Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing 100700, China
| | - Fa-Feng Cheng
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xue-Qian Wang
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China
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16
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Zhang J, Zhang X, Yang Y, Zhao J, Hu W, Yu Y. Effect of Different Vitamin D Levels on Cognitive Function in Aged Mice After Sevoflurane Anesthesia. Front Aging Neurosci 2022; 14:940106. [PMID: 35754958 PMCID: PMC9226433 DOI: 10.3389/fnagi.2022.940106] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2022] [Accepted: 05/23/2022] [Indexed: 11/13/2022] Open
Abstract
Although the biological relationship between vitamin D (VD) deficiency and cognitive function has been recognized by many scholars, the theoretical mechanisms involved are still not well-understood. In this study, we demonstrated the role of VD in alleviating the cognitive dysfunction in aged mice caused by sevoflurane anesthesia. Forty female C57BL/6 mice aged 12 months were selected for the experiment. VD (-) and VD (+) mouse models and sevoflurane anesthesia models were established. Mice were randomly divided into normal elderly group (NC group), normal aged mice + sevoflurane anesthesia treatment group (NS group), aged VD (-) mice + sevoflurane anesthesia treatment group [VD (-) group], and aged VD (+) + sevoflurane anesthesia treatment group [VD (+) group]. To compare the emergence time after sevoflurane anesthesia in aged mice with different levels of VD and to test the cognitive function of four groups through the water maze. Inflammatory factor expression and cholinergic activity in hippocampus tissue of all mice were measured at the end of behavioral tests. These data show that, low levels of VD aggravated the delayed emergence and cognitive dysfunction in aged mice caused by sevoflurane anesthesia, while higher levels of VD mitigated this impairment by enhancing cholinergic activity and reducing inflammatory factor expression in the hippocampus.
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Affiliation(s)
- Jialei Zhang
- Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.,Department of Anesthesiology, Changzhi People's Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Xiaoling Zhang
- Department of Oncology, Changzhi People's Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Yongyan Yang
- Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jun Zhao
- Department of Oncology, Changzhi People's Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Wenqing Hu
- Department of Gastrointestinal Surgery, Changzhi People's Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Yonghao Yu
- Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China
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17
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Vitamin D and Parkinson's Disease. Nutrients 2022; 14:nu14061220. [PMID: 35334877 PMCID: PMC8953648 DOI: 10.3390/nu14061220] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Revised: 03/04/2022] [Accepted: 03/08/2022] [Indexed: 02/04/2023] Open
Abstract
Vitamin D is a fat-soluble secosteroid, traditionally considered a key regulator of bone metabolism, calcium and phosphorous homeostasis. Its action is made possible through the binding to the vitamin D receptor (VDR), after which it directly and indirectly modulates the expression of thousands of genes. Vitamin D is important for brain development, mature brain activity and associated with many neurological diseases, including Parkinson’s disease (PD). High frequency of vitamin D deficiency in patients with Parkinson’s disease compared to control population was noted nearly twenty years ago. This finding is of interest given vitamin D’s neuroprotective effect, exerted by the action of neurotrophic factors, regulation of nerve growth or through protection against cytotoxicity. Vitamin D deficiency seems to be related to disease severity and disease progression, evaluated by Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr (H&Y) scale, but not with age of PD onset and duration of disease. Additionally, fall risk has been associated with lower vitamin D levels in PD. However, while the association between vitamin D and motor-symptoms seems to be possible, results of studies investigating the association with non-motor symptoms are conflicting. In addition, very little evidence exists regarding the possibility to use vitamin D supplementation to reduce clinical manifestations and disability in patients with PD. However, considering the positive balance between potential benefits against its limited risks, vitamin D supplementation for PD patients will probably be considered in the near future, if further confirmed in clinical studies.
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18
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Rihal V, Khan H, Kaur A, Singh TG. Vitamin D as therapeutic modulator in cerebrovascular diseases: a mechanistic perspectives. Crit Rev Food Sci Nutr 2022; 63:7772-7794. [PMID: 35285752 DOI: 10.1080/10408398.2022.2050349] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Vitamin D deficiency has been linked to several major chronic diseases, such as cardiovascular and neurodegenerative diseases, diabetes, and cancer, linked to oxidative stress, inflammation, and aging. Vitamin D deficiency appears to be particularly harmful to the cardiovascular system, as it can cause endothelial dysfunctioning and vascular abnormalities through the modulation of various downstream mechanisms. As a result, new research indicates that therapeutic approaches targeting vitamin D inadequacies or its significant downstream effects, such as impaired autophagy, abnormal pro-inflammatory and pro-oxidant reactions, may delay the onset and severity of major cerebrovascular disorders such as stroke and neurologic malformations. Vitamin D modulates the various molecular pathways, i.e., Nitric Oxide, PI3K-Akt Pathway, cAMP pathway, NF-kB Pathway, Sirtuin 1, Nrf2, FOXO, in cerebrovascular disorder. The current review shows evidence for vitamin D's mitigating or slowing the progression of these cerebrovascular disorders, which are significant causes of disability and death worldwide.
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Affiliation(s)
- Vivek Rihal
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Heena Khan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
| | - Amarjot Kaur
- Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
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19
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Arosio B, Rossi PD, Ferri E, Cesari M, Vitale G. Characterization of Vitamin D Status in Older Persons with Cognitive Impairment. Nutrients 2022; 14:nu14061142. [PMID: 35334800 PMCID: PMC8949190 DOI: 10.3390/nu14061142] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/24/2022] [Accepted: 03/03/2022] [Indexed: 01/13/2023] Open
Abstract
Vitamin D exerts a role in the maintenance of cognitive abilities and in frailty. Although several studies evaluated the interactions between vitamin D and cognitive impairment, results were conflicting. In a cohort of community-dwelling older persons, we described the association between vitamin D levels and cognitive decline and all-cause dementia evaluating frailty’s contribution. Our cohort included 509 adults, aged 64–92 years: 176 patients with mild cognitive impairment (MCI), 59 with Alzheimer’s Disease (AD), 26 with idiopathic Normal Pressure Hydrocephalus (iNPH), 133 with mixed dementia (MD) and 115 without cognitive decline. Frailty was measured by frailty index, and serum 25-hydroxyvitamin D concentrations through electrochemiluminescence immunoassays. We found a significant association between vitamin D levels and Mini Mental State Examination independently of cognitive impairment, age, sex and frailty. The patients with dementia (AD and MD) showed the lowest vitamin D levels, while MCI patients showed higher levels than the other groups. The most severe deficiency was observed in MD patients, the most aged as well as cognitively and functionally impaired. In conclusion, in our community-dwelling older persons investigated for a suspected cognitive impairment, we observed an association between vitamin D levels and cognitive decline, regardless of the frailty status.
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Affiliation(s)
- Beatrice Arosio
- Department of Clinical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy;
- Correspondence: ; Tel.: +39-02-55035405; Fax: +39-02-50320734
| | - Paolo Dionigi Rossi
- Geriatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy; (P.D.R.); (E.F.)
| | - Evelyn Ferri
- Geriatric Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Pace 9, 20122 Milan, Italy; (P.D.R.); (E.F.)
| | - Matteo Cesari
- Department of Clinical Sciences and Community Health, University of Milan, Via Pace 9, 20122 Milan, Italy;
- Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, Via Camaldoli 64, 20138 Milan, Italy
| | - Giovanni Vitale
- Department of Medical Biotechnology and Translational Medicine, University of Milan, Via Vanvitelli 32, 20133 Milan, Italy;
- Istituto Auxologico Italiano IRCCS, Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Via Zucchi 18, 20095 Cusano Milanino, Italy
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Mohammadzadeh Honarvar N, Samadi M, Seyedi Chimeh M, Gholami F, Bahrampour N, Jalali M, Effatpanah M, Yekaninejad MS, Abdolahi M, Chamari M. Effect of Vitamin D on Paraxonase-1, Total Antioxidant Capacity, and 8-Isoprostan in Children with Attention Deficit Hyperactivity Disorder. Int J Clin Pract 2022; 2022:4836731. [PMID: 35685610 PMCID: PMC9159115 DOI: 10.1155/2022/4836731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 12/19/2021] [Accepted: 12/25/2021] [Indexed: 11/17/2022] Open
Abstract
METHOD In this double-blind, randomized, placebo-controlled trial, 75 children (aged 6-12) diagnosed with ADHD were randomly assigned into two groups. The supplementation group received vitamin D3 (2000 IU), and the control group received a placebo for 3 months. Blood samples were collected at baseline and after intervention to analyze the 25(OH)D, paraxonase-1 activity (PON-1), Total Antioxidant Capacity (TAC), and 8-isoprostan levels. RESULTS A significant rise in circulating 25(OH)D was observed in the vitamin D group versus the placebo group at the end of the study. There was no reduction in 8-isoprostan levels in the vitamin D group compared to the placebo group. Serum paraxonase-1 and TAC concentration decreased in both groups, but these alterations were not statistically significant in the treatment group versus the placebo group at the end of the intervention. CONCLUSION Vitamin D supplementation for 3 months did not have beneficial effects on biomarkers of oxidative stress status. To confirm these findings, further studies on children are suggested.
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Affiliation(s)
- Niyaz Mohammadzadeh Honarvar
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahsa Samadi
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Marzieh Seyedi Chimeh
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Gholami
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Niki Bahrampour
- Department of Nutrition, Science and Research Branch Islamic Azad University (SRBIAU), Tehran, Iran
| | - Mahmoud Jalali
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Effatpanah
- School of Medicine, Ziaeian Hospital, International Campus, Tehran University of Medical Sciences, Tehran, Iran
| | - Mir Saeid Yekaninejad
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Science, Tehran, Iran
| | - Mina Abdolahi
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Chamari
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
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The Role of Vitamin D in Sleep Disorders of Children and Adolescents: A Systematic Review. Int J Mol Sci 2022; 23:ijms23031430. [PMID: 35163353 PMCID: PMC8835880 DOI: 10.3390/ijms23031430] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2021] [Revised: 01/21/2022] [Accepted: 01/25/2022] [Indexed: 02/07/2023] Open
Abstract
This review investigates the association between vitamin D and sleep disorders. Vitamin D is an essential nutrient known to play an important role in the growth and bone health of the human body, but it also appears to play a role in sleep. The goal of our review is to examine the association between vitamin D and sleep disorders in children and adolescents. We summarize the evidence about the role and the mechanism of action of vitamin D in children and adolescents with sleep disorders such as insomnia, obstructive sleep apnea (OSA), restless legs syndrome (RLS), and other sleep disorders. Systematic electronic database searches were conducted using Pubmed and Cochrane Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. The studies that met the established inclusion criteria were analyzed and compared. Results suggest a strict relationship between vitamin D deficiency in children and sleep disorders. There is evidence that vitamin D is implicated in the different neurochemical mechanisms involved in sleep regulation and mainly in the serotonergic and dopaminergic pathways. This might be responsible for the association of vitamin D deficiency and restless sleep, sleep hyperhidrosis, OSA, and RLS.
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Al-Amin MM, Sullivan RKP, Alexander S, Carter DA, Bradford D, Burne THJ, Burne THJ. Impaired spatial memory in adult vitamin D deficient BALB/c mice is associated with reductions in spine density, nitric oxide, and neural nitric oxide synthase in the hippocampus. AIMS Neurosci 2022; 9:31-56. [PMID: 35434279 PMCID: PMC8941191 DOI: 10.3934/neuroscience.2022004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2021] [Revised: 01/11/2022] [Accepted: 01/20/2022] [Indexed: 02/01/2023] Open
Abstract
Vitamin D deficiency is prevalent in adults and is associated with cognitive impairment. However, the mechanism by which adult vitamin D (AVD) deficiency affects cognitive function remains unclear. We examined spatial memory impairment in AVD-deficient BALB/c mice and its underlying mechanism by measuring spine density, long term potentiation (LTP), nitric oxide (NO), neuronal nitric oxide synthase (nNOS), and endothelial NOS (eNOS) in the hippocampus. Adult male BALB/c mice were fed a control or vitamin D deficient diet for 20 weeks. Spatial memory performance was measured using an active place avoidance (APA) task, where AVD-deficient mice had reduced latency entering the shock zone compared to controls. We characterised hippocampal spine morphology in the CA1 and dentate gyrus (DG) and made electrophysiological recordings in the hippocampus of behaviourally naïve mice to measure LTP. We next measured NO, as well as glutathione, lipid peroxidation and oxidation of protein products and quantified hippocampal immunoreactivity for nNOS and eNOS. Spine morphology analysis revealed a significant reduction in the number of mushroom spines in the CA1 dendrites but not in the DG. There was no effect of diet on LTP. However, hippocampal NO levels were depleted whereas other oxidation markers were unaltered by AVD deficiency. We also showed a reduced nNOS, but not eNOS, immunoreactivity. Finally, vitamin D supplementation for 10 weeks to AVD-deficient mice restored nNOS immunoreactivity to that seen in in control mice. Our results suggest that lower levels of NO and reduced nNOS immunostaining contribute to hippocampal-dependent spatial learning deficits in AVD-deficient mice.
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Affiliation(s)
- Md. Mamun Al-Amin
- Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia
| | | | - Suzy Alexander
- Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia,Queensland Centre for Mental Health Research, Wacol 4076, Australia
| | - David A. Carter
- Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia
| | - DanaKai Bradford
- Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia,Australian E-Health Research Centre, CSIRO, Pullenvale 4069, Australia
| | - Thomas H. J. Burne
- Queensland Brain Institute, The University of Queensland, Brisbane 4072, Australia,Queensland Centre for Mental Health Research, Wacol 4076, Australia,* Correspondence: ; Tel: +61 733466371; Fax: +61 733466301
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Lv L, Zhang H, Tan X, Qin L, Peng X, Bai R, Xiao Q, Tan C, Liao H, Yan W, Tan J, Tang B, Wang C. Assessing the Effects of Vitamin D on Neural Network Function in Patients With Parkinson's Disease by Measuring the Fraction Amplitude of Low-Frequency Fluctuation. Front Aging Neurosci 2022; 13:763947. [PMID: 34987377 PMCID: PMC8721225 DOI: 10.3389/fnagi.2021.763947] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 11/17/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Recently, many studies have shown that low vitamin D (VD) levels may be related to an increased risk of Parkinson's disease (PD), but the underlying mechanisms remain unclear. Objective: To explore the relationship between PD and VD levels, as well as to analyze the effects of VD on spontaneous brain activity and explore the possible mechanism of its involvement in PD risk. Methods: In a cross-sectional study, we quantified the difference in VD levels between 330 PD patients and 209 healthy controls (HC) to explore the correlation between VD and PD risk. We also acquired resting-state Functional Magnetic Resonance Imaging (rs-fMRI) data from 46 PD patients and 21 HC. The PD patients were divided into three groups according to 25(OH)D levels: PD patients with VD deficiency (PD + VDD), PD patients with VD insufficiency (PD + VDI), and PD patients with normal VD (PD + NVD). The effect of VD status on spontaneous neuronal activity in the whole brain was analyzed by measuring the fraction amplitude of low-frequency fluctuation (fALFF). Results: Compared with HC, the PD patients had lower serum 25(OH)D levels (23.60 ± 7.27 vs. 25.60 ± 5.78, P < 0.001). The 25(OH)D level may have a potential dose-dependent effect on the risk of PD (P trend = 0.007). A high risk of PD was associated with VD deficiency [25(OH)D < 20 ng/mL, OR = 2.319], and the lowest quartile of 25(OH)D concentration was associated with a high risk of PD (OR = 1.941). In the rs-fMRI study, PD + VDD patients had wider brain regions with altered fALFF than other PD groups when compared with the corresponding HC groups. Both PD + VDD and PD + VDI showed higher fALFF in the cuneus, left precuneus, calcarine cortex and right lingual, as well as lower fALFF in the left middle temporal gyrus. PD + VDD patients also showed higher fALFF in the left superior, middle and inferior frontal gyri, as well as the left precentral gyrus than HC. Among PD patients, there was only a statistically significant difference in fALFF between the PD + VDD and PD + NVD groups. Compared with the PD + NVD group, PD + VDD patients exhibited higher fALFF in the left precentral and left postcentral gyrus, as well as the left inferior parietal lobule. Conclusion: These results demonstrate that PD patients had lower serum VD levels than HC, and VD may have a potential dose-dependent effect on PD risk. Lower serum VD levels can affect the spontaneous neuronal activity of default-mode network (DMN) and visual pathway neurons in PD patients, providing a possible mechanism for its effect on PD risk.
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Affiliation(s)
- Lingling Lv
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Hainan Zhang
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xuling Tan
- Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Lixia Qin
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Xinke Peng
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Rongrong Bai
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Qile Xiao
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Changlian Tan
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Haiyan Liao
- Department of Radiology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Weiqian Yan
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China
| | - Jieqiong Tan
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.,Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, China.,Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, China
| | - Beisha Tang
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China.,Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.,Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China
| | - Chunyu Wang
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, China.,Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, China
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24
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Zhang J, Zhang X, Yang Y, Zhao J, Yu Y. Correlation Analysis of Serum Vitamin D Levels and Postoperative Cognitive Disorder in Elderly Patients With Gastrointestinal Tumor. Front Psychiatry 2022; 13:893309. [PMID: 35492737 PMCID: PMC9051327 DOI: 10.3389/fpsyt.2022.893309] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 03/28/2022] [Indexed: 12/19/2022] Open
Abstract
PURPOSE Vitamin D prevents hypocalcaemia, osteoporosis, and infections, among other problems, and is involved in the prevention and treatment of cardiovascular and neurological diseases. Recently, vitamin D was shown to improve cognitive dysfunction caused by Alzheimer's disease and vascular dementia. This study aims to explore the correlation between preoperative serum vitamin D and postoperative cognitive disorder (POCD) occurrence in elderly patients with gastrointestinal tumors to guide perioperative medication use and promote early patient recovery. METHODS This study recruited 238 elderly patients (65 ≤ age ≤ 85) who underwent gastrointestinal tumor surgery; 117 cases were enrolled, and 55 controls of the same age and education level as the cases were included. Blood samples were taken preoperatively and at 7, 15, 30, and 90 days postoperatively, and plasma vitamin D (25OH-D3) and glutathione (GSH) was measured. Different from the previous diagnosis of POCD was obtained by telephone interview through Cognitive Status Modified Telephone Interview (TICS-m), mainly for memory impairment, a series of neuropsychological tests was used to evaluate cognitive function, Picture Recollect Test, Stroop Color-word Test, and Digit Symbol Substitution Test were used to comprehensively evaluate the three domains of cognitive function of patients, namely memory, attention and information processing ability. All neuropsychiatric assessments were performed at the bedside and completed face-to-face by the assessment staff and the patient. RESULTS A total of 65.8% (77/117) of elderly patients undergoing gastrointestinal tumor surgery had preoperative vitamin D deficiency (serum 25OH-D concentration < 12 ng/ml), of whom 46.7% (36/77, 7 days after surgery), 31.2% (24/77, 15 days after surgery), 15.6% (12/77, 30 days after surgery), and 9% (7/77, 90 days after surgery) of patients developed POCD; 7.5% (3/40) of patients without vitamin D deficiency developed PNDs, which was detected only on the 7th day after surgery. CONCLUSIONS Vitamin D deficiency can increase neurocognitive disorder risk in elderly patients during the perioperative period, possibly because low vitamin D levels cannot effectively inhibit the postoperative oxidative stress increase. TRIAL REGISTRATION This experiment was approved and registered by the China Clinical Trial Registration Center, registration number ChiCTR2100046900 (30/05/2021).
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Affiliation(s)
- Jialei Zhang
- Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.,Department of Anesthesiology, Changzhi People's Hospital Affiliated to Shanxi Medical University, Changzhi, China
| | - Xiaoling Zhang
- Department of Oncology, Changzhi People's Hospital Affiliated to Shanxi Medical University, Changzhi, China
| | - Yongyan Yang
- Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China
| | - Jun Zhao
- Department of Oncology, Changzhi People's Hospital Affiliated to Shanxi Medical University, Changzhi, China
| | - Yonghao Yu
- Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China
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25
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Atanasovska E, Petrusevska M, Zendelovska D, Spasovska K, Stevanovikj M, Kasapinova K, Gjorgjievska K, Labachevski N. Vitamin D levels and oxidative stress markers in patients hospitalized with COVID-19. Redox Rep 2021; 26:184-189. [PMID: 34727009 PMCID: PMC8567917 DOI: 10.1080/13510002.2021.1999126] [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] [Indexed: 12/15/2022] Open
Abstract
Background COVID-19 is characterized by the presence of oxidative stress. Vitamin D status has been reviewed as one of the factors that may affect disease severity. The aim of this study was to assess the relationship between serum vitamin D levels, oxidative stress markers and disease severity in hospitalized COVID-19 patients. Methods Vitamin D levels were measured in 33 patients with COVID-19. The total antioxidant power and plasma peroxides were determined in serum. Results Severe COVID-19 patients have lower vitamin D levels (18.39 ± 2.29 ng/mL vs. 28.47 ± 3.05 ng/mL, p < .05) and higher oxidative stress compared to the moderate group. When divided according to serum vitamin D levels, significantly higher values of LDH (604.8 ± 76.98 IU/mL vs. 261.57 ± 47.33 IU/mL) and D-dimer (5978 ± 2028ng/mL vs. 977.7 ± 172 ng/mL) were obtained in the group with vitamin D below 30 ng/mL, followed with significantly higher levels of plasma peroxides (d-ROMs: 414.9 ± 15.82 U.Carr vs. 352.4 ± 18.77 U.Carr; p < .05) and oxidative stress index (OSI: 92.25 ± 6.60 vs. 51.89 ± 6.45; p < .001). Conclusion The presented data provide a justification to consider vitamin D as an important factor that could ameliorate disease severity through its anti-inflammatory and antioxidant effects.
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Affiliation(s)
- Emilija Atanasovska
- Faculty of Medicine, University of Ss Cyril and Methodius, Institute of Preclinical and Clinical Pharmacology and Toxicology, Skopje, Republic of North Macedonia
| | - Marija Petrusevska
- Faculty of Medicine, University of Ss Cyril and Methodius, Institute of Preclinical and Clinical Pharmacology and Toxicology, Skopje, Republic of North Macedonia
| | - Dragica Zendelovska
- Faculty of Medicine, University of Ss Cyril and Methodius, Institute of Preclinical and Clinical Pharmacology and Toxicology, Skopje, Republic of North Macedonia
| | - Katerina Spasovska
- Intensive Care Unit, University Clinic for Infectious Diseases and Febrile Conditions, Skopje, Republic of North Macedonia
| | - Milena Stevanovikj
- Intensive Care Unit, University Clinic for Infectious Diseases and Febrile Conditions, Skopje, Republic of North Macedonia
| | - Katerina Kasapinova
- Intensive Care Unit, University Surgery Clinic 'St.Naum Ohridski', Skopje, Republic of North Macedonia
| | - Kalina Gjorgjievska
- Faculty of Medicine, University of Ss Cyril and Methodius, Institute of Preclinical and Clinical Pharmacology and Toxicology, Skopje, Republic of North Macedonia
| | - Nikola Labachevski
- Faculty of Medicine, University of Ss Cyril and Methodius, Institute of Preclinical and Clinical Pharmacology and Toxicology, Skopje, Republic of North Macedonia
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Jenkins DD, Moss HG, Brown TR, Yazdani M, Thayyil S, Montaldo P, Vento M, Kuligowski J, Wagner C, Hollis BW, Wiest DB. NAC and Vitamin D Improve CNS and Plasma Oxidative Stress in Neonatal HIE and Are Associated with Favorable Long-Term Outcomes. Antioxidants (Basel) 2021; 10:1344. [PMID: 34572976 PMCID: PMC8466838 DOI: 10.3390/antiox10091344] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 08/11/2021] [Accepted: 08/23/2021] [Indexed: 12/15/2022] Open
Abstract
N-acetylcysteine (NAC) and vitamin D provide effective neuroprotection in animal models of severe or inflammation-sensitized hypoxic ischemic encephalopathy (HIE). To translate these FDA-approved drugs to HIE neonates, we conducted an early phase, open-label trial of 10 days of NAC (25, 40 mg/kg q12h) + 1,25(OH)2D (calcitriol 0.05 mg/kg q12h, 0.03 mg/kg q24h), (NVD), for pharmacokinetic (PK) estimates during therapeutic hypothermia and normothermia. We paired PK samples with pharmacodynamic (PD) targets of plasma isoprostanoids, CNS glutathione (GSH) and total creatine (tCr) by serial MRS in basal ganglia (BG) before and after NVD infusion at five days. Infants had moderate (n = 14) or severe HIE (n = 16), funisitis (32%), and vitamin D deficiency (75%). NVD resulted in rapid, dose-responsive increases in CNS GSH and tCr that correlated positively with plasma [NAC], inversely with plasma isofurans, and was greater in infants with lower baseline [GSH] and [tCr], suggesting increases in these PD markers were titrated by neural demand. Hypothermia and normothermia altered NAC PK estimates. NVD was well tolerated. Excluding genetic syndromes (2), prolonged ECMO (2), lost-to-follow-up (1) and SIDS death (1), 24 NVD treated HIE infants have no evidence of cerebral palsy, autism or cognitive delay at 24-48 months. These data confirm that low, safe doses of NVD in HIE neonates decreased oxidative stress in plasma and CNS, improved CNS energetics, and are associated with favorable developmental outcomes at two to four years.
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Affiliation(s)
- Dorothea D Jenkins
- Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, 10 McClennan Banks Drive, Charleston, SC 29425, USA; (C.W.); (B.W.H.)
| | - Hunter G Moss
- Center for Biomedical Imaging, Department of Radiology, Medical University of South Carolina, Charleston, SC 29425, USA; (H.G.M.); (T.R.B.); (M.Y.)
| | - Truman R Brown
- Center for Biomedical Imaging, Department of Radiology, Medical University of South Carolina, Charleston, SC 29425, USA; (H.G.M.); (T.R.B.); (M.Y.)
| | - Milad Yazdani
- Center for Biomedical Imaging, Department of Radiology, Medical University of South Carolina, Charleston, SC 29425, USA; (H.G.M.); (T.R.B.); (M.Y.)
| | - Sudhin Thayyil
- Centre for Perinatal Neuroscience, Imperial College London, London W12 0HS, UK; (S.T.); (P.M.)
| | - Paolo Montaldo
- Centre for Perinatal Neuroscience, Imperial College London, London W12 0HS, UK; (S.T.); (P.M.)
| | - Maximo Vento
- Neonatal Research Group, Health Research Institute Hospital La Fe, 46026 Valencia, Spain; (M.V.); (J.K.)
| | - Julia Kuligowski
- Neonatal Research Group, Health Research Institute Hospital La Fe, 46026 Valencia, Spain; (M.V.); (J.K.)
| | - Carol Wagner
- Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, 10 McClennan Banks Drive, Charleston, SC 29425, USA; (C.W.); (B.W.H.)
| | - Bruce W Hollis
- Division of Neonatology, Department of Pediatrics, Medical University of South Carolina, 10 McClennan Banks Drive, Charleston, SC 29425, USA; (C.W.); (B.W.H.)
| | - Donald B Wiest
- Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, SC 29425, USA;
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Effects of dietary 25-hydroxyvitamin D3 on the lactation performance, blood metabolites, antioxidant and immune function in dairy cows. Livest Sci 2021. [DOI: 10.1016/j.livsci.2021.104497] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Zhang L, Liu S, Piao X. Dietary 25-hydroxycholecalciferol supplementation improves performance, immunity, antioxidant status, intestinal morphology, and bone quality in weaned piglets. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2021; 101:2592-2600. [PMID: 33063320 DOI: 10.1002/jsfa.10889] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 10/08/2020] [Accepted: 10/16/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND 25-Hydroxycholecalciferol (25OHD3 ) is a new feed additive, which is a potential alternative to vitamin D3 in swine nutrition. The objective of this study was to determine the effects of different doses of 25OHD3 supplementation on performance, immunity, antioxidant capacity, intestinal morphology and bone quality in piglets. RESULTS As dietary 25OHD3 supplementation increased, the average daily gain (ADG) improved (P < 0.05) quadratically during days 1-14, and tended to increase (P = 0.06) quadratically during the overall period of the experiment. Increasing 25OHD3 supplementation increased (linear effect, P < 0.05) the serum 25OHD3 level and serum glutathione peroxidase (GSH-Px) activity. On day 14, serum immunoglobulin A (IgA) was increased (linear and quadratic effects, P < 0.05) as dietary 25OHD3 supplementation increased. On day 28, serum IgA level was higher (P < 0.05) linearly and the complement 3 (C3) level was reduced (P < 0.05) linearly as dietary supplementation of 25OHD3 increased. The mucosal GSH-Px activity of the small intestine was higher (quadratic effect, P < 0.05) with increasing 25OHD3 supplementation. Jejunal villus height (P = 0.06) and villus height to crypt depth ratio (P = 0.07) tended to increase quadratically, and the villus height to crypt-depth ratio of the ileum increased (P < 0.05) linearly and quadratically with increasing 25OHD3 supplementation. Dietary supplementation with an increasing level of 25OHD3 increased breaking strength of tibias and femurs (quadratic effect, P < 0.05). CONCLUSION Increasing dietary 25OHD3 supplementation partly improved performance, immunity, antioxidant status, intestinal morphology, and bone properties of weaned piglets. © 2020 Society of Chemical Industry.
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Affiliation(s)
- Lianhua Zhang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Sujie Liu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Xiangshu Piao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing, China
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Adams LE, Moss HG, Lowe DW, Brown T, Wiest DB, Hollis BW, Singh I, Jenkins DD. NAC and Vitamin D Restore CNS Glutathione in Endotoxin-Sensitized Neonatal Hypoxic-Ischemic Rats. Antioxidants (Basel) 2021; 10:489. [PMID: 33804757 PMCID: PMC8003885 DOI: 10.3390/antiox10030489] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/15/2021] [Accepted: 03/17/2021] [Indexed: 01/31/2023] Open
Abstract
Therapeutic hypothermia does not improve outcomes in neonatal hypoxia ischemia (HI) complicated by perinatal infection, due to well-described, pre-existing oxidative stress and neuroinflammation that shorten the therapeutic window. For effective neuroprotection post-injury, we must first define and then target CNS metabolomic changes immediately after endotoxin-sensitized HI (LPS-HI). We hypothesized that LPS-HI would acutely deplete reduced glutathione (GSH), indicating overwhelming oxidative stress in spite of hypothermia treatment in neonatal rats. Post-natal day 7 rats were randomized to sham ligation, or severe LPS-HI (0.5 mg/kg 4 h before right carotid artery ligation, 90 min 8% O2), followed by hypothermia alone or with N-acetylcysteine (25 mg/kg) and vitamin D (1,25(OH)2D3, 0.05 μg/kg) (NVD). We quantified in vivo CNS metabolites by serial 7T MR Spectroscopy before, immediately after LPS-HI, and after treatment, along with terminal plasma drug concentrations. GSH was significantly decreased in all LPS-HI rats compared with baseline and sham controls. Two hours of hypothermia alone did not improve GSH and allowed glutamate + glutamine (GLX) to increase. Within 1 h of administration, NVD increased GSH close to baseline and suppressed GLX. The combination of NVD with hypothermia rapidly improved cellular redox status after LPS-HI, potentially inhibiting important secondary injury cascades and allowing more time for hypothermic neuroprotection.
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Affiliation(s)
- Lauren E. Adams
- Department of Pediatrics, 10 McLellan Banks Dr, Medical University of South Carolina, Charleston, SC 29425, USA; (L.E.A.); (B.W.H.); (I.S.)
| | - Hunter G. Moss
- Center for Biomedical Imaging, Department of Radiology, Medical University of South Carolina, 68 President St. Room 205, Charleston, SC 29425, USA; (H.G.M.); (T.B.)
| | - Danielle W. Lowe
- Department of Psychiatry, Medical University of South Carolina, 67 Presidents St., MSC 861, Charleston, SC 29425, USA;
| | - Truman Brown
- Center for Biomedical Imaging, Department of Radiology, Medical University of South Carolina, 68 President St. Room 205, Charleston, SC 29425, USA; (H.G.M.); (T.B.)
| | - Donald B. Wiest
- Department of Pharmacy and Clinical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, SC 29425, USA;
| | - Bruce W. Hollis
- Department of Pediatrics, 10 McLellan Banks Dr, Medical University of South Carolina, Charleston, SC 29425, USA; (L.E.A.); (B.W.H.); (I.S.)
| | - Inderjit Singh
- Department of Pediatrics, 10 McLellan Banks Dr, Medical University of South Carolina, Charleston, SC 29425, USA; (L.E.A.); (B.W.H.); (I.S.)
| | - Dorothea D. Jenkins
- Department of Pediatrics, 10 McLellan Banks Dr, Medical University of South Carolina, Charleston, SC 29425, USA; (L.E.A.); (B.W.H.); (I.S.)
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Abstract
OBJECTIVE Vitamin D deficiency may be a clinical problem in patients with addictions. The authors systematically searched for studies addressing vitamin D and addiction and develop a hypothesis which can direct future research of the possible mechanistic role of vitamin D in the process of addiction. METHODS Systematic review of the literature found in PubMed and EMBASE followed by narrative review combined with clinical experiences leading to hypotheses for future research. RESULTS Only five articles were identified about a role of vitamin D in the pathophysiology of addiction. Their results are in line with a possible influence of vitamin D in dopaminergic transmission. The cerebral vitamin D status depends on the functionality of genetic variants of vitamin D receptor and other involved genes. Routine serum calcidiol levels may not adequately reflect cerebral vitamin D status. Uncertainty exists regarding appropriate calcidiol blood levels and proper dosages for affecting the central nervous system (CNS). CONCLUSIONS The putative pathophysiological role of vitamin D in substance abuse has been insufficiently studied which calls to more studies how to measure cerebral vitamin D status in clinical practice. Research is indicated whether vitamin D supplementation should use higher dosages and aim to reach higher calcidiol serum levels. Measuring dopaminergic functioning within the prefrontal cortex as reflected by neuropsychological tests selected as suitable could be a appropriate proxy for the cerebral vitamin D status when studying the pharmacogenomics of this functionality in patients.
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Demir F, Demir M, Aygun H. Evaluation of the protective effect of paricalcitol and vitamin D 3 at doxorubicin nephrotoxicity in rats with 99mTechnetium-dimercaptosuccinic acid renal scintigraphy and biochemical methods. Hum Exp Toxicol 2021; 40:274-283. [PMID: 32812453 DOI: 10.1177/0960327120950010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
AIM The present study aimed to examine the effect of paricalcitol (PRC) and vitamin D3 (vit D3) on doxorubicin (DOX)-induced nephrotoxicity in rats. MATERIALS AND METHODS Forty-two Wistar rats were randomly categorized into six groups: control; 2) PRC(0.5 µg/kg) and 3) vit D3(5.000 IU/kg) administered for 14 days; 4) DOX, 18 mg/kg administered on the 12th, 13th and 14th days of the study; 5) PRC (0.5 µg/kg, +DOX(18 mg/kg); vit D3(5.000 IU)+DOX(18 mg/kg). On the 15th day of the experiment, 99mTc-DMSA uptake level and biochemical parameter in serum and tissue were assay. RESULTS Activities of 99mTechnetium-Dimercaptosuccinic Acid (99mTc-DMSA) were lower in groups receiving DOX and/or PRC+DOX, vit D3+DOX than in control groups. The 99mTc-DMSA level in the group PRC+DOX and vit D3+DOX were importantly higher than DOX group. DOX caused an important increase in blood urea nitrogen (BUN), creatinine, Tumor Necrosis Factor-α(TNF- α), interleukin-6(IL-6) and nitric oxide(NO) levels compared to control groups. However, PRC and vit D3 pretreatments lowered them. Uptake of 99mTc-DMSA level was higher in groups PRC+DOX than in vit D3+DOX group. Administration of PRC and vit D3 alone did not change alterations all of parameters. CONCLUSION The results indicated that PRC administration protects kidney in DOX-induced nephrotoxic rats. In addition, PRC has a stronger nephroprotective effect than vit D3.
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Affiliation(s)
- Fadime Demir
- Department of Nuclear Medicine, 218488Tokat Gaziosmanpasa University, Faculty of Medicine, Tokat, Turkey
| | - Mustafa Demir
- Department of Nephrology, 64177Firat University, Faculty of Medicine, Elazig, Turkey
| | - Hatice Aygun
- Department of Physiology, 218488Tokat Gaziosmanpasa University, Faculty of Medicine, Tokat, Turkey
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Lisi G, Ribolsi M, Siracusano A, Niolu C. Maternal Vitamin D and its Role in Determining Fetal Origins of Mental Health. Curr Pharm Des 2020; 26:2497-2509. [PMID: 32370709 DOI: 10.2174/1381612826666200506093858] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 04/26/2020] [Indexed: 12/21/2022]
Abstract
There is evidence that mental health disorders may have roots in fetal life and are associated with deficiencies in various micronutrients, including vitamin D. During pregnancy, vitamin D balance is influenced by an increase in maternal calcitriol and a substantial increase in maternal Vitamin D Binding Protein concentrations. In the early stages of life, vitamin D is necessary to mediate numerous brain processes such as proliferation, apoptosis, and neurotransmission. Furthermore, Vitamin D has a recognized anti-inflammatory activity that normally suppresses inflammation. Increased activation of hypothalamo-pituitary-adrenal axis (HPA) and inflammation during gestation may influence maternal health and fetal neurodevelopment during and beyond pregnancy. A deficit of Vitamin D and maternal stressful events during gestation, such as perinatal depression, could influence the efficacy of the immune system altering its activity. Vitamin D deficiency during gestation associated with a reduction in fetal brain development has been widely described and correlated with alteration in the production of the brain-derived neurotrophic factor. To this regard, many studies highlights that low maternal vitamin D dosage during gestation has been related to a significantly greater risk to develop schizophrenia and other severe mental illnesses in later life. The objective of this paper is a comprehensive overview of maternal vitamin D balance in determining the fetal origins of mental health with some references to the link between vitamin D levels, inflammatory responses to stress and mental disorders in adult life.
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Affiliation(s)
- Giulia Lisi
- Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.,Department of Mental Health, ASL ROMA 1, Rome, Italy
| | - Michele Ribolsi
- Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.,Policlinico Tor Vergata Foundation, Rome, Italy
| | - Alberto Siracusano
- Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.,Policlinico Tor Vergata Foundation, Rome, Italy
| | - Cinzia Niolu
- Chair of Psychiatry, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.,Policlinico Tor Vergata Foundation, Rome, Italy
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Mansourian M, Rafie N, Khorvash F, Hadi A, Arab A. Are serum vitamin D, calcium and phosphorous associated with restless leg syndrome? A systematic review and meta-analysis. Sleep Med 2020; 75:326-334. [PMID: 32950014 DOI: 10.1016/j.sleep.2020.08.022] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 06/29/2020] [Accepted: 08/21/2020] [Indexed: 11/26/2022]
Abstract
BACKGROUND It is hypothesized that vitamin D deficiency, and calcium/phosphate imbalance could be involved in the pathophysiology of restless leg syndrome (RLS). This systematic review and meta-analysis of observational studies were carried out to reach a firm conclusion regarding the possible association between vitamin D, calcium and phosphorous levels with RLS in end-stage renal disease (ESRD) patients, other comorbidities and healthy population. METHODS PubMed, Scopus, ISI Web of Science, and Cochrane's library were systematically searched up to June 2020. Quality assessment of the included observational studies was performed using Newcastle-Ottawa Quality Assessment Scale. Statistical analyses were done using STATA 11.2. A P-value <0.05 were considered statistically significant. RESULTS A total of 36 studies involving 9590 participants were included in this systematic review and meta-analysis. We found that serum vitamin D level is significantly lower (WMD -3.39 ng/mL; 95% CI, -5.96 to -0.81; P = 0.010; I2 = 86.2%) and phosphorous (SMD 0.19; 95% CI, 0.04-0.34; P = 0.011; I2 = 83.6%) is significantly higher in RLS individuals compared to the non-RLS individuals. However, the mean difference of serum calcium was not significant in comparison between RLS and control groups (SMD -0.01; 95% CI, -0.19 to 0.18; P = 0.957; I2 = 89.2%). CONCLUSION Results revealed a significant association between serum vitamin D and phosphorous with RLS. However, further prospective cohort studies and clinical trials are needed for better understanding of the relationship between these variables.
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Affiliation(s)
- Marjan Mansourian
- Pediatric Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nahid Rafie
- Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Fariborz Khorvash
- Department of Neurology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Amir Hadi
- Halal Research Center of IRI, FDA, Tehran, Iran.
| | - Arman Arab
- Department of Community Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
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Zhang L, Liu S, Li M, Piao X. Effects of maternal 25-hydroxycholecalciferol during the last week of gestation and lactation on serum parameters, intestinal morphology and microbiota in suckling piglets. Arch Anim Nutr 2020; 74:445-461. [PMID: 33198510 DOI: 10.1080/1745039x.2020.1822710] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
This study was conducted to test the effects of maternal 25-hydroxycholecalciferol (25OHD3) supplementation on serum parameters, intestinal morphology and microbiota in suckling piglets. The experiment started on day 107 of gestation and lasted until piglets were weaned on day 21 of lactation. Thirty-two sows were allocated randomly to two treatments (ND diet, basal diet with 2000 IU/kg of vitamin D3; 25-D diet, basal diet with 50 μg/kg 25OHD3). Results showed that maternal 25-D treatment increased (p < 0.05) serum 25OHD3 concentration in the umbilical cords, which led to higher (p < 0.05) serum 25OHD3 concentration of suckling piglets from 25-D sows. The GSH-Px activity in colostrum was higher (p < 0.05), as well as SOD and GSH-Px activities in milk, were higher (p < 0.05) in 25-D sows than ND sows. Compared with piglets suckling ND sows, piglets suckling 25-D sows had higher (p < 0.05) serum SOD activity on day 7, 14 and 21 of lactation. On day 21 of lactation, piglets form 25-D sows had greater (p < 0.05) serum levels of GH and IGF-I and lower (p < 0.05) serum DAO activity than those from ND sows. Piglets from 25-D sows had higher (p < 0.05) jejunal villus height than those from ND sows. Feeding 25OHD3 to sows tended to increase (p < 0.10) the species richness in the colonic digesta of suckling piglets, as reflected by the α-diversity index of Chao-1. In the caecal digesta, the α-diversity for bacterial community analysis of Simpson and Shannon was lower (p < 0.05) in 25-D piglets than ND piglets. The relative abundances of colonic Alloprevotella and caecal Lactobacillus were significantly higher, while the population of caecal [Eubacterium]_coprostanoligenes_group was lower (p < 0.05) in 25-D piglets than ND piglets. In conclusion, maternal 25OHD3 supplementation partly improved antioxidant status in sows and suckling piglets and altered gut microbiota in the hindgut of piglets.
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Affiliation(s)
- Lianhua Zhang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University , Beijing, China
| | - Sujie Liu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University , Beijing, China
| | - Miao Li
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University , Beijing, China
| | - Xiangshu Piao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University , Beijing, China
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Farghali M, Ruga S, Morsanuto V, Uberti F. Can Brain Health Be Supported by Vitamin D-Based Supplements? A Critical Review. Brain Sci 2020; 10:brainsci10090660. [PMID: 32972010 PMCID: PMC7563709 DOI: 10.3390/brainsci10090660] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 09/10/2020] [Accepted: 09/15/2020] [Indexed: 02/07/2023] Open
Abstract
This review presents recent knowledge on the neuroprotective effects of vitamin D and their usefulness as oral supplementation when combined with other molecules, such as curcumin. A critical look at the effectiveness of vitamin D in this field is also provided. Vitamin D plays a crucial role in neuroprotection and in the cognitive decline associated with aging, where vitamin D’s levels are related to the levels of several neurotrophic factors. An important role of vitamin D has also been observed in the mechanism of neuroinflammation, which is the basis of several aging conditions, including cognitive decline and neurodegeration; furthermore, the neuroprotective effect of vitamin D in the cognitive decline of aging has recently been reported. For this reason, many food supplements created for humans contain vitamin D alone or combined with other molecules with antioxidant properties. However, recent studies also explored negative consequences of the use at a high dosage of vitamin D. Vitamin D in tissues or brain cells can also modulate calbindin-D28K, parvalbumin, and calretinin, and is involved in immune function, thanks also to the combination with curcumin. Curcumin acts as a free radical scavenger and antioxidant, inhibiting lipid peroxidation and oxidative DNA damage. In particular, curcumin is a potent immune-regulatory agent and its administration has been reported to attenuate cognitive impairments. These effects could be exploited in the future to control the mechanisms that lead to the brain decay typical of neurodegenerative diseases.
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The Molecular Mechanisms by Which Vitamin D Prevents Insulin Resistance and Associated Disorders. Int J Mol Sci 2020; 21:ijms21186644. [PMID: 32932777 PMCID: PMC7554927 DOI: 10.3390/ijms21186644] [Citation(s) in RCA: 110] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 09/07/2020] [Accepted: 09/09/2020] [Indexed: 02/06/2023] Open
Abstract
Numerous studies have shown that vitamin D deficiency is very common in modern societies and is perceived as an important risk factor in the development of insulin resistance and related diseases such as obesity and type 2 diabetes (T2DM). While it is generally accepted that vitamin D is a regulator of bone homeostasis, its ability to counteract insulin resistance is subject to debate. The goal of this communication is to review the molecular mechanism by which vitamin D reduces insulin resistance and related complications. The university library, PUBMED, and Google Scholar were searched to find relevant studies to be summarized in this review article. Insulin resistance is accompanied by chronic hyperglycaemia and inflammation. Recent studies have shown that vitamin D exhibits indirect antioxidative properties and participates in the maintenance of normal resting ROS level. Appealingly, vitamin D reduces inflammation and regulates Ca2+ level in many cell types. Therefore, the beneficial actions of vitamin D include diminished insulin resistance which is observed as an improvement of glucose and lipid metabolism in insulin-sensitive tissues.
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Relationship between suicidal patients and vitamin D: A prospective case-control study. JOURNAL OF SURGERY AND MEDICINE 2020. [DOI: 10.28982/josam.727963] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Lv L, Tan X, Peng X, Bai R, Xiao Q, Zou T, Tan J, Zhang H, Wang C. The relationships of vitamin D, vitamin D receptor gene polymorphisms, and vitamin D supplementation with Parkinson's disease. Transl Neurodegener 2020; 9:34. [PMID: 32867847 PMCID: PMC7460797 DOI: 10.1186/s40035-020-00213-2] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 08/06/2020] [Indexed: 12/13/2022] Open
Abstract
In recent years, many studies have investigated the correlations between Parkinson's disease (PD) and vitamin D status, but the conclusion remains elusive. The present review focuses on the associations between PD and serum vitamin D levels by reviewing studies on the associations of PD with serum vitamin D levels and vitamin D receptor (VDR) gene polymorphisms from PubMed, Web of Science, Cochrane Library, and Embase databases. We found that PD patients have lower vitamin D levels than healthy controls and that the vitamin D concentrations are negatively correlated with PD risk and severity. Furthermore, higher vitamin D concentrations are linked to better cognitive function and mood in PD patients. Findings on the relationship between VDR gene polymorphisms and the risk of PD are inconsistent, but the FokI (C/T) polymorphism is significantly linked with PD. The occurrence of FokI (C/T) gene polymorphism may influence the risk, severity, and cognitive ability of PD patients, while also possibly influencing the effect of Vitamin D3 supplementation in PD patients. In view of the neuroprotective effects of vitamin D and the close association between vitamin D and dopaminergic neurotransmission, interventional prospective studies on vitamin D supplementation in PD patients should be conducted in the future.
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Affiliation(s)
- Lingling Lv
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Xuling Tan
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Xinke Peng
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Rongrong Bai
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Qile Xiao
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Ting Zou
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Jieqiong Tan
- Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, 410078, China
- Hunan Key Laboratory of Animal Models for Human Diseases, Central South University, Changsha, 410078, China
- Hunan Key Laboratory of Medical Genetics, Central South University, Changsha, 410078, China
| | - Hainan Zhang
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Chunyu Wang
- Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
- Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
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Zhang LH, He TF, Hu JX, Li M, Piao XS. Effects of normal and low calcium and phosphorus levels and 25-hydroxycholecalciferol supplementation on performance, serum antioxidant status, meat quality, and bone properties of broilers. Poult Sci 2020; 99:5663-5672. [PMID: 33142484 PMCID: PMC7647707 DOI: 10.1016/j.psj.2020.07.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 06/24/2020] [Accepted: 07/09/2020] [Indexed: 12/14/2022] Open
Abstract
To determine the effects of normal and low dietary calcium (Ca) and phosphorus (P) levels and 25-hydroxycholecalciferol (25-OH-D3) supplementation on performance, serum antioxidant status, meat quality, and bone properties of broilers, 224 1-day-old Arbor Acre male broilers were used in this study. Broilers were allotted randomly to 1 of 4 treatments in a 2 × 2 factorial arrangement that included normal or low Ca and P diet with or without 69 μg/kg 25-OH-D3. The trial consists of a starter phase from day 1 to 21 and a grower phase from day 22 to 42. Dietary 25-OH-D3 supplementation increased (P < 0.05) average daily weight gain from day 22 to 42 and decreased feed conversation ratio from day 22 to 42 and day 0 to 42. On day 21, 25-OH-D3 increased serum concentrations of total antioxidant capacity (T-AOC), catalase (CAT), and glutathione peroxidase in broilers fed low Ca and P diet (Interaction, P < 0.05). 25-hydroxycholecalciferol significantly decreased serum malondialdehyde concentration. Dietary Ca and P deficiencies significantly decreased serum Ca and P concentrations and increased serum parathyroid hormone (PTH) concentration, and serum Ca and 25-OH-D3 concentrations were significantly increased by 25-OH-D3 supplementation. On day 42, serum T-AOC and CAT concentrations were decreased by dietary Ca and P deficiencies without 25-OH-D3 (Interaction, P < 0.05) and unaffected by dietary Ca and P deficiencies with 25-OH-D3. Dietary Ca and P deficiencies significantly decreased Ca, P, and alkaline phosphatase concentrations and increased PTH concentration in serum. Dietary 25-OH-D3 increased (P < 0.05) serum Ca and 25-OH-D3 concentrations and decreased (P < 0.05) serum tartrate-resistant acid phosphatase concentration. The interaction between CaP level and 25-OH-D3 was observed (P < 0.05) for tibial Ca content and femoral bone density. 25-hydroxycholecalciferol significantly increased tibial breaking strength. These data indicated that 25-OH-D3 supplementation at 69 μg/kg increased growth performance in some periods, enhanced serum antioxidant capacity, and improved bone mineralization and breaking strength of broilers.
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Affiliation(s)
- L H Zhang
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - T F He
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - J X Hu
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - M Li
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China
| | - X S Piao
- State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.
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di Michele F, Talamo A, Niolu C, Siracusano A. Vitamin D and N-Acetyl Cysteine Supplementation in Treatment-Resistant Depressive Disorder Patients: A General Review. Curr Pharm Des 2020; 26:2442-2459. [PMID: 32250212 DOI: 10.2174/1381612826666200406090051] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 03/31/2020] [Indexed: 12/20/2022]
Abstract
:
Major Depressive Disorder (MDD) is often a lifetime disabling mental illness as individuals with
MDD might not benefit from standard-therapy, including both pharmacological and psychosocial interventions.
Novel therapies are, therefore, required.
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It was shown by recent preclinical and clinical studies that the dysfunction of glutamatergic neurotransmission
might be involved in the pathophysiology of MDD. Furthermore, neuroimmune alterations could have a significant
role in the pathogenesis of MDD.
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Vitamin D is a neurosteroid hormone essential for several metabolic processes, immune responses, and for regulating
neurotrophic-neuroprotective processes, neurotransmission and synaptic plasticity. Recent studies have also
shown Vitamin D deficiency in patients with severe psychiatric disorders, including MDD.
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Lately, clinical studies have shown the neuroprotective action of N-acetyl cysteine (NAC) through the modulation
of inflammatory pathways and via the modulation of synaptic release of glutamate in cortico-subcortical
brain regions; the cysteine-glutamate antiporter.
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This paper reviews the therapeutic use of Vitamin D and NAC and among individuals with refractory MDD to the
first- line pharmacological interventions, reviewing the clinical studies published in the last decade.
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A detailed summary of the current evidence in this area aims to better inform psychiatrists and general practitioners
on the potential benefits of Vitamin D and NAC supplementation for this disorder.
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Nutraceutical supplementation with Vitamin D and NAC in treatment-resistant MDD patients may be important
not only for improving depressive clinical manifestations but also for their safety and tolerability profile. This is
of great interest, especially considering the need for treating special populations affected by MDD, such as
youngsters and elders. Finally, the nutraceutical approach represents a good choice, considering its better compliance
by the patients compared to traditional psychopharmacological treatment.
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Affiliation(s)
- Flavia di Michele
- Acute Psychiatric Unit, PTV Foundation - Policlinico Tor Vergata, Rome, Italy
| | - Alessandra Talamo
- Acute Psychiatric Unit, PTV Foundation - Policlinico Tor Vergata, Rome, Italy
| | - Cinzia Niolu
- Acute Psychiatric Unit, PTV Foundation - Policlinico Tor Vergata, Rome, Italy
| | - Alberto Siracusano
- Acute Psychiatric Unit, PTV Foundation - Policlinico Tor Vergata, Rome, Italy
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Kim SW, Oh JS, Park J, Jeong HH, Oh YM, Choi S, Choi KH. Neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia. Int J Emerg Med 2020; 13:30. [PMID: 32522270 PMCID: PMC7288434 DOI: 10.1186/s12245-020-00289-7] [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: 04/07/2020] [Accepted: 05/26/2020] [Indexed: 12/04/2022] Open
Abstract
Background Paricalcitol is known to attenuate ischemic-reperfusion injury of various organs. However, it is not known whether paricalcitol prevents neuronal injury after global cerebral ischemia. The purpose of this study is to investigate the neuroprotective effect of paricalcitol in a rat model of transient global cerebral ischemia. Methods This is a prospective, randomized experimental study. Male Sprague-Dawley rats that survived 10 min of four-vessel occlusion were randomly assigned to two treatment groups: one group was treated with paricalcitol 1 μg/kg IP, and the other was given an equivalent volume of normal saline IP. Drugs were administered at 5 min, 1 day, 2 days, and 3 days after ischemia. Neurologic function was assessed at 2 h, 1 day, 2 days, 3 days, and 4 days after ischemia. We tested motor function 3 days after ischemia using the rotarod test. Also, we tested memory function 4 days after ischemia using the passive avoidance test. We assessed neuronal degeneration in the hippocampus of surviving rats 4 days after ischemia. Results Eight rats were allocated to each group. No significant differences were found between the groups in terms of survival rate, motor coordination, or memory function. The neurological function score 2-h post-ischemia was significantly higher in the paricalcitol group (p = 0.04). Neuronal degeneration was significantly less in the paricalcitol group compared with the control group (p = 0.01). Conclusions Paricalcitol significantly attenuated neuronal injury in the hippocampus. Although motor coordination, memory function, and survival rate were not significantly improved by paricalcitol treatment in this study, paricalcitol remains a potential neuroprotective drug after global cerebral ischemia.
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Affiliation(s)
- Sung Wook Kim
- Department of Emergency Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 1021 Tongil-Ro, Eunpyeong-gu, Seoul, 03312, Republic of Korea
| | - Joo Suk Oh
- Department of Emergency Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea.
| | - Jungtaek Park
- Department of Emergency Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea
| | - Hyun Ho Jeong
- Department of Emergency Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea
| | - Young Min Oh
- Department of Emergency Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea
| | - Semin Choi
- Department of Emergency Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea
| | - Kyoung Ho Choi
- Department of Emergency Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 271, Cheonbo-Ro, Uijeongbu-si, Gyeonggi-do, 11765, Republic of Korea
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Siracusano M, Riccioni A, Abate R, Benvenuto A, Curatolo P, Mazzone L. Vitamin D Deficiency and Autism Spectrum Disorder. Curr Pharm Des 2020; 26:2460-2474. [PMID: 32294031 DOI: 10.2174/1381612826666200415174311] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 04/08/2020] [Indexed: 12/24/2022]
Abstract
Vitamin D is a neurosteroid hormone crucially involved in neurodevelopment. Neural cell proliferation, neurotransmission, oxidative stress and immune function represent the main mechanisms mediated by vitamin D in the Central Nervous System. Therefore, its deficiency during pregnancy and early childhood may significantly impact on a developing brain, leading to possible adverse neuropsychological outcomes including Autism Spectrum Disorder (ASD). Significant vitamin D deficiency is described within children affected by ASD and in pregnant mothers whose offspring will later develop ASD, suggesting a possible role of the hormone as a contributing risk factor in the etiopathogenesis of ASD. We reviewed the actual literature on the potential contributing role of prenatal and early postnatal vitamin D deficiency in ASD etiopathogenesis, at both genetic and environmental levels, and the possible effect of vitamin D supplementation in autistic children. Conflicting but promising results emerged on the topic. Further Randomized Controlled Trials studies carried out during pregnancy and early infancy are necessary for better understanding the possible contribution of vitamin D deficiency in the etiopathogenesis of autism and the potential efficacy of the hormone supplementation in the improvement of ASD core symptoms.
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Affiliation(s)
- Martina Siracusano
- Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy.,PHD Student in Experimental Medicine- Neuroscience, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila AQ, Italy
| | - Assia Riccioni
- Child Neurology and Psychiatry Unit, System Medicine Department, Tor Vergata University Hospital of Rome, Rome, Italy
| | - Roberta Abate
- Child Neurology and Psychiatry Unit, System Medicine Department, Tor Vergata University Hospital of Rome, Rome, Italy
| | - Arianna Benvenuto
- Child Neurology and Psychiatry Unit, System Medicine Department, Tor Vergata University Hospital of Rome, Rome, Italy
| | - Paolo Curatolo
- Child Neurology and Psychiatry Unit, System Medicine Department, Tor Vergata University Hospital of Rome, Rome, Italy
| | - Luigi Mazzone
- Child Neurology and Psychiatry Unit, System Medicine Department, Tor Vergata University Hospital of Rome, Rome, Italy
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Ghorbani Z, Rafiee P, Fotouhi A, Haghighi S, Rasekh Magham R, Ahmadi ZS, Djalali M, Zareei M, Razeghi Jahromi S, Shahemi S, Mahmoudi M, Togha M. The effects of vitamin D supplementation on interictal serum levels of calcitonin gene-related peptide (CGRP) in episodic migraine patients: post hoc analysis of a randomized double-blind placebo-controlled trial. J Headache Pain 2020; 21:22. [PMID: 32093657 PMCID: PMC7041277 DOI: 10.1186/s10194-020-01090-w] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Accepted: 02/13/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Emerging evidence showed promising effects of vitamin D on headaches characteristics. Thus, it seems there is still a need for more researches to clarify the mechanisms by which this vitamin exerts anti-migraine effects. METHODS The present study was conducted as a 16-week randomized double-blind placebo-controlled trial on 80 episodic migraine patients allocated in 2 parallel groups each consisted of 40 patients who received vitamin D 2000 IU/d or placebo. At baseline and after the intervention completion, headache diaries and migraine disability assessment questionnaire (MIDAS) were used to assess migraine related variables in patients. Also, interictal serum concentration of calcitonin gene-related peptide (CGRP) (as the dominant mediator of migraine pain pathogenesis) was evaluated using ELISA method. RESULTS The mean (SD) of age in the vitamin D and placebo groups was 37 (8) and 38 (12) years, respectively. ANCOVA test adjusted for baseline values, and confounders showed vitamin D supplementation resulted in a significant improvement in MIDAS score after 12 weeks in the intervention group (21.49 (16.22-26.77)) compared to placebo (31.16 (25.51-36.82) P value: 0.016). Moreover, after controlling for baseline levels, and other variables using ANCOVA, CGRP level was appeared to be significantly lower following vitamin D supplementation (153.26 (133.03-173.49) ng/L) than the patients in the placebo arm (188.35 (167.15-209.54) ng/L) (P value = 0.022). CONCLUSION According to the current findings, vitamin D supplementation in episodic migraineurs, particularly in those with migraine with aura, may potentially improve migraine headache characteristics and disability probably through attenuating CGRP levels. Therefore, these results could provide a new insight into anti-nociceptive effects of vitamin D; however, more studies are required to confirm our findings. TRIAL REGISTRATION The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6.
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Affiliation(s)
- Zeinab Ghorbani
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Pegah Rafiee
- Student Research Committee, Department and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Akbar Fotouhi
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Samane Haghighi
- Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Reyhaneh Rasekh Magham
- Department of Nutrition, Faculty of Medical Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Zeynab Sadat Ahmadi
- Department of Nutrition, School of Health, Iran University of Medical Sciences, Tehran, Iran
| | - Mahmoud Djalali
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahnaz Zareei
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
| | - Soodeh Razeghi Jahromi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sahar Shahemi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Department of Clinical Nutrition and Dietetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Mahmoudi
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
- Pediatric Gastroenterology and Hepatology Research Center, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
- Dietitians and Nutrition Experts Team (DiNET), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Mansoureh Togha
- Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
- Headache Department, Neurology Ward, Sina University Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
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Alzghoul L. Role of Vitamin D in Autism Spectrum Disorder. Curr Pharm Des 2020; 25:4357-4367. [DOI: 10.2174/1381612825666191122092215] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 11/15/2019] [Indexed: 12/19/2022]
Abstract
:
Autism spectrum disorder (ASD) is a pervasive developmental disorder with heterogeneous etiology.
Vitamin D can function as a fat-soluble vitamin as well as a hormone, and can exert its effect through both genomic
and non-genomic mechanisms. In the last decades, several studies have examined the relationship between
vitamin D levels and ASD. These studies demonstrated that low vitamin D status in early development has been
hypothesized as an environmental risk factor for ASD. Both in vivo and in vitro studies have demonstrated that
vitamin D deficiency in early life can alter brain development, dysregulates neurotransmitter balance in the brain,
decreases body and brain antioxidant ability, and alters the immune system in ways that resemble pathological
features commonly seen in ASD. In this review, we focused on the association between vitamin D and ASD. In
addition, the above-mentioned mechanisms of action that link vitamin D deficiency with ASD were also discussed.
Finally, clinical trials of vitamin D supplementation treatment of ASD have also been discussed.
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Affiliation(s)
- Loai Alzghoul
- Department of Physiology and Biochemistry, School of Medicine, The University of Jordan, Amman, Jordan
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Kasatkina LA, Tarasenko AS, Krupko OO, Kuchmerovska TM, Lisakovska OO, Trikash IO. Vitamin D deficiency induces the excitation/inhibition brain imbalance and the proinflammatory shift. Int J Biochem Cell Biol 2019; 119:105665. [PMID: 31821883 DOI: 10.1016/j.biocel.2019.105665] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 11/25/2019] [Accepted: 12/05/2019] [Indexed: 12/16/2022]
Abstract
Vitamin D3 is among the major neurosteroids whose role in developing and adult brain is intensively studied now. Its active form 1,25(OH)2D3 regulates the expression and functioning of a range of brain-specific proteins, which orchestrate the neurotransmitter turnover, neurogenesis and neuroplasticity. Despite numerous studies of the vitamin D role in normal and pathological brain function, there is little evidence on the mechanisms of alterations in excitatory and inhibitory neurotransmission under vitamin D deficiency (VDD). Using the animal model we characterized the dysfunction of excitatory and inhibitory neurotransmission under alimentary VDD. The shift between unstimulated and evoked GABA release under VDD was largely reversed after treatment of VDD, whereas the impairments in glutamatergic system were only partially recovered after 1-month vitamin D3 supplementation. The increase of the external glutamate level and unstimulated GABA release in brain nerve terminals was associated with intensified ROS production and higher [Ca2+]i in presynapse. The negative allosteric modulation of presynaptic mGlu7 receptors significantly enhanced exocytotic GABA release, which was decreased under VDD, thereby suggesting the neuroprotective effect of such modulation of inhibitory neurotransmission. Synaptic plasma membranes and cytosolic proteins contribute to the decreased stimulated release of neurotransmitter, by being the crucial components, whose functional state is impaired under VDD. The critical changes with synaptic vesicles occurred at the docking step of the process, whereas malfunctioning of synaptic cytosolic proteins impacted the fusion event foremost. The decreased amplitude of exocytosis was inherent for non-excitable cells as well, as evidenced by lower platelet degranulation. Our data suggest the presynaptic dysfunction and proinflammatory shift as the early events in the pathogenesis of VDD-associated disorders and provide evidences for the neuroprotective role of vitamin D3.
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Affiliation(s)
- Ludmila A Kasatkina
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9, Leontovycha Street, Kyiv, 01030, Ukraine
| | - Alla S Tarasenko
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9, Leontovycha Street, Kyiv, 01030, Ukraine
| | - Olga O Krupko
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9, Leontovycha Street, Kyiv, 01030, Ukraine
| | - Tamara M Kuchmerovska
- The Department of Biochemistry of Vitamins and Coenzymes, Palladin Institute of Biochemistry, NAS of Ukraine, 9, Leontovycha Street, Kyiv, 01030 Ukraine
| | - Olha O Lisakovska
- The Department of Biochemistry of Vitamins and Coenzymes, Palladin Institute of Biochemistry, NAS of Ukraine, 9, Leontovycha Street, Kyiv, 01030 Ukraine
| | - Irene O Trikash
- The Department of Neurochemistry, Palladin Institute of Biochemistry, NAS of Ukraine, 9, Leontovycha Street, Kyiv, 01030, Ukraine.
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Ghorbani Z, Togha M, Rafiee P, Ahmadi ZS, Rasekh Magham R, Haghighi S, Razeghi Jahromi S, Mahmoudi M. Vitamin D in migraine headache: a comprehensive review on literature. Neurol Sci 2019; 40:2459-2477. [PMID: 31377873 DOI: 10.1007/s10072-019-04021-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Accepted: 07/19/2019] [Indexed: 12/13/2022]
Abstract
INTRODUCTION As a primary headache, migraine has been established as the first leading disability cause worldwide in the subjects who aged less than 50 years. A variety of dietary supplements have been introduced for migraine complementary treatment. As an anti-inflammatory and antioxidant agent, vitamin D is one of these agents which has been of interest in recent years. Although higher prevalence of vitamin D deficiency/insufficiency has been highlighted among migraineurs compared to controls, there is not any consensus in prescribing vitamin D in clinical practice. Therefore, in the current review, in addition to observational and case-control studies, we also included clinical trials concerning the effects of vitamin D supplementation on migraine/headache. METHODS Based on a PubMed/MEDLINE and ScienceDirect database search, this review study includes published articles up to June 2019 concerning the association between migraine/headache and vitamin D status or supplementation. RESULTS The percentage of subjects with vitamin D deficiency and insufficiency among migraineurs and headache patients has been reported to vary between 45 and 100%. In a number of studies, vitamin D level was negatively correlated with frequency of headaches. The present findings show that supplementation with this vitamin in a dose of 1000-4000 IU/d could reduce the frequency of attacks in migraineurs. CONCLUSION It seems a high proportion of migraine patients might suffer from vitamin D deficiency/insufficiency. Further, the current evidence shows that in addition to routine drug therapy, vitamin D administration might reduce the frequency of attacks in migraineurs. However, these results have yet to be confirmed.
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Affiliation(s)
- Zeinab Ghorbani
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran
- Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mansoureh Togha
- Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Pegah Rafiee
- Student Research Committee, Department and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zeynab Sadat Ahmadi
- Department of Nutrition, School of Health, Iran University of Medical Sciences, Tehran, Iran
| | - Reyhaneh Rasekh Magham
- Department of Nutrition, Faculty of Medical Sciences, Science & Research Branch, Islamic Azad University, Tehran, Iran
| | - Samane Haghighi
- Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Soodeh Razeghi Jahromi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Mahmoudi
- Department of Cellular and Molecular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
- Pediatric Gastroenterology and Hepatology Research Center, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
- Dietitians and Nutrition Experts Team (DiNET), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
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Bivona G, Gambino CM, Iacolino G, Ciaccio M. Vitamin D and the nervous system. Neurol Res 2019; 41:827-835. [PMID: 31142227 DOI: 10.1080/01616412.2019.1622872] [Citation(s) in RCA: 99] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 05/19/2019] [Indexed: 12/19/2022]
Abstract
Objective: to summarise the activities that Vitamin D (VD) carries out in the brain and to clarify the potential role of VD in neurological diseases. Methods: a literature research has been performed in Pubmed using the following keywords: 'Vitamin D', 'nervous system', 'brain'. Results: the studies reviewed show that VD contributes to cerebral activity in both embryonic and adult brain, helping the connectivity of neural circuits responsible for locomotor, emotional and reward-dependent behavior. Low VD serum levels have been found in patients affected by Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Autism Spectrum Disorders, Sleep Disorders and Schizophrenia. Discussion: findings are controversial and should be interpreted with caution, since most of the studies performed have observational study set and few interventional studies are available, producing conflicting results. Overall, it can be stated that the potential role of Vitamin D in neurological diseases is mostly unclear and further randomised controlled trials are needed to understand better whether Vitamin D supplementation treatment can be useful in brain disorders.
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Affiliation(s)
- Giulia Bivona
- Section of Clinical Biochemistry and Clincal Molecular Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo , Palermo , Italy
| | - Caterina Maria Gambino
- Section of Clinical Biochemistry and Clincal Molecular Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo , Palermo , Italy
| | - Giorgia Iacolino
- Section of Clinical Biochemistry and Clincal Molecular Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo , Palermo , Italy
| | - Marcello Ciaccio
- Section of Clinical Biochemistry and Clincal Molecular Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo , Palermo , Italy
- Department and U.O.C. Laboratory Medicine, University Hospital "Paolo Giaccone" of Palermo , Palermo , Italy
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Goodarzi P, Akhlaghi A, Zamiri MJ, Shirazi MRJ, Akhlaghi AA, Habibi M, Daryabari H, Saemi F, Peebles ED. Sperm characteristics of Chukar partridge (Alectoris chukar) breeders as affected by the addition of calcitriol to the semen extender. Poult Sci 2019; 98:3292-3297. [PMID: 30944932 DOI: 10.3382/ps/pez158] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Accepted: 03/09/2019] [Indexed: 12/26/2022] Open
Abstract
This study was carried out to determine the effect of supplementing the semen extender with calcitriol on in vitro sperm characteristics in Chukar partridges. A total of 60 male Chukar partridges were habituated for semen collection by abdominal massage. Pooled ejaculates from several males were extended (1 to 5 v/v ratio) in the Sexton's diluent containing 0, 24, 48, 96, or 192 μg calcitriol/mL. These concentrations represented 0-, 2-, 4-, 8-, and 16-fold levels of the mean seminal calcitriol concentration, respectively. A total of 12 subsamples from each treatment group were kept at 4 to 5°C or 19 to 24°C for 4, 24, or 48 h. The percentages of motile sperm, live sperm, abnormal sperm, incidence of hypoosmotic swelling (HOS), and thiobarbituric acid reactive species (TBARS) concentrations were determined. The data were analyzed by the xtmixed procedure of STATA software. The percentages of motile sperm, live sperm, abnormal sperm, and seminal TBARS were affected by calcitriol (P < 0.05). There was no effect of treatments on HOS (P > 0.05). There was an interaction effect between calcitriol, storage time, and storage temperature on sperm motility, sperm viability, and seminal TBARS. Supplementation of the diluent with 96 μg calcitriol/mL resulted in the highest sperm motility at 4°C. Also, the same treatment group recorded the highest sperm viability and lowest seminal TBARS at 19 to 24°C. Supplementing the diluent with calcitriol had beneficial effects on spermatozoa; however, the fertility rate of spermatozoa extended in calcitriol-supplemented diluent needs to be determined before the procedure can be recommended for use in artificial insemination programs.
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Affiliation(s)
- P Goodarzi
- Department of Animal Science, School of Agriculture, Shiraz University, Shiraz 71441-65186, Iran
| | - A Akhlaghi
- Department of Animal Science, School of Agriculture, Shiraz University, Shiraz 71441-65186, Iran
| | - M J Zamiri
- Department of Animal Science, School of Agriculture, Shiraz University, Shiraz 71441-65186, Iran
| | - M R Jafarzadeh Shirazi
- Department of Animal Science, School of Agriculture, Shiraz University, Shiraz 71441-65186, Iran
| | - A A Akhlaghi
- Department of Epidemiology and Reproductive Health, Reproductive Epidemiology Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran 16635-148, Iran
| | - M Habibi
- Department of Animal and Food Sciences, Oklahoma State University, Stillwater, OK 74078
| | - H Daryabari
- Department of Animal Science, School of Agriculture, Shiraz University, Shiraz 71441-65186, Iran
| | - F Saemi
- Department of Animal Science, School of Agriculture, Shiraz University, Shiraz 71441-65186, Iran
| | - E D Peebles
- Department of Poultry Science, Mississippi State University, MS 39762
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Haq SH, AlAfaleq NO, Johari RA. Vitamin D Treatment Reverses the Induced Oxidative Stress Damage to DNA. Pak J Biol Sci 2019; 22:8-14. [PMID: 30796763 DOI: 10.3923/pjbs.2019.8.14] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND OBJECTIVE The aim of the current study was to investigate in detail the effect of the active metabolite of vitamin D3 [1, 25 (OH)2 D3] in ameliorating the induced oxidative damage to DNA. MATERIALS AND METHODS Primary cortical neuron cultures from one week old Wister rats were set up in sterile conditions. The neuron cultures were maintained for up to 72 h in culture in the presence of varying doses of vitamin D. Cells were exposed to (0.5 mM H2O2) for 2 h prior to collection of condition medium and cell pellet for Biochemical Assays. Control and H2O2 treated cultures were maintained without any treatment with vitamin D. RESULTS Pre-treatment with 0.25 μg mL-1 for 24 and 48 h significantly reduced the oxidative stress. 8-hydroxydeoxyguanosine a ubiquitous marker of oxidative stress had also shown to be significantly reduced. The DNA damage marker PolyUB of histones was observed in the neuron treated with H2O2 only. CONCLUSION This study revealed that oxidation of DNA by hydrogen peroxide caused extensive DNA damage, resulting in polyubiquitination of histones. The pre-treatment with vitamin D3 however completely reversed the DNA damage cascade induced by hydrogen peroxide and protected the DNA.
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50
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Bivona G, Agnello L, Bellia C, Iacolino G, Scazzone C, Lo Sasso B, Ciaccio M. Non-Skeletal Activities of Vitamin D: From Physiology to Brain Pathology. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:341. [PMID: 31284484 PMCID: PMC6680897 DOI: 10.3390/medicina55070341] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 06/27/2019] [Accepted: 07/02/2019] [Indexed: 12/17/2022]
Abstract
Vitamin D is a secosteroid hormone regulating the expression of almost 900 genes, and it is involved in the regulation of calcium and phosphate metabolism, immune response, and brain development. Low blood vitamin D levels have been reported in patients affected by various diseases. Despite a large amount of literature data, there is uncertainty surrounding the role of vitamin D as a serum biomarker in Alzheimer's disease (AD) and Parkinson's disease (PD). Indeed, the lack of internationally recognized 25(OH)D3 reference measurement procedures and standard materials in the past led to unstandardized serum total 25(OH)D3 results among research and clinical care laboratories. Thus, most of the literature studies reported unstandardized data, which are of little use and make it difficult to draw conclusions of the role of vitamin D in AD and PD. This review summarizes the extra-skeletal actions of vitamin D, focusing its role in immunomodulation and brain function, and reports the issue of lacking standardized literature data concerning the usefulness of vitamin D as a biomarker in AD and PD.
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Affiliation(s)
- Giulia Bivona
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Luisa Agnello
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Chiara Bellia
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Giorgia Iacolino
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Concetta Scazzone
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Bruna Lo Sasso
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy
| | - Marcello Ciaccio
- Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy.
- Department and U.O.C. Laboratory Medicine, University Hospital "Paolo Giaccone" of Palermo, 90127 Palermo, Italy.
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