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Ptaszek B, Podsiadło S, Czerwińska-Ledwig O, Teległów A. Whole-Body Cryotherapy Affects Blood Vitamin D Levels in People with Multiple Sclerosis. J Clin Med 2025; 14:3086. [PMID: 40364117 PMCID: PMC12072845 DOI: 10.3390/jcm14093086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 04/22/2025] [Accepted: 04/28/2025] [Indexed: 05/15/2025] Open
Abstract
Background: The aim of this study was to investigate and evaluate the effect of a series of 20 whole-body cryotherapy (WBC) treatments on the level of vitamin D in the blood of women with multiple sclerosis and healthy women. Methods: This study involved three participant groups. The experimental group included 15 women, aged 34 to 55 years and diagnosed with multiple sclerosis (MS), who received whole-body cryotherapy. The first control group comprised 20 women with MS who did not undergo cryotherapy. The second control group consisted of 15 women, aged 30 to 49 years, who did not have neurological or chronic conditions and who also participated in whole-body cryotherapy. Venous blood samples were taken from all participants at two points: on the first day of cryotherapy and after completing 20 sessions. These samples were analyzed to evaluate their key parameters and assess the differences between the groups. The electrochemiluminescence (ELISA) technique was employed using the 25(OH)D (total) competitive assay, which is designed to measure vitamin D concentration [ng/mL] in the human body. Results: In women with MS, a significant increase in vitamin D levels was observed after the use of WBC (CRYO-MS), while in healthy women the increase was statistically insignificant after WBC (CONTROL-CRYO). Conclusions: After 20 whole-body cryotherapy sessions, an increase in vitamin D levels was observed in women with multiple sclerosis. A trend towards an increase in vitamin D levels was observed in healthy women after WBC.
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Affiliation(s)
- Bartłomiej Ptaszek
- Institute of Applied Sciences, University of Physical Culture in Krakow, 31-571 Krakow, Poland
| | - Szymon Podsiadło
- Institute of Clinical Rehabilitation, University of Physical Culture in Krakow, 31-571 Krakow, Poland;
| | - Olga Czerwińska-Ledwig
- Institute of Basic Sciences, University of Physical Culture in Krakow, 31-571 Krakow, Poland; (O.C.-L.); (A.T.)
| | - Aneta Teległów
- Institute of Basic Sciences, University of Physical Culture in Krakow, 31-571 Krakow, Poland; (O.C.-L.); (A.T.)
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Gill A, Orji C, Reghefaoui M, Peresuodei TS, Thota P, Saavedra Palacios MS, Arcia Franchini AP. The Effectiveness of Vitamin D Intake in Improving Symptoms and Relapses of Multiple Sclerosis: A Systematic Review. Cureus 2024; 16:e68565. [PMID: 39364460 PMCID: PMC11449499 DOI: 10.7759/cureus.68565] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 09/03/2024] [Indexed: 10/05/2024] Open
Abstract
There are disagreements over the effectiveness of vitamin D supplementation in treating multiple sclerosis (MS) patients' symptoms and reducing relapses. The goal of this systematic review is to assess the effect of vitamin D supplements on improving symptoms and relapses in MS patients. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted by searching eight databases: Embase, PubMed, Cochrane Library, MEDLINE, CINAHL, Web of Science, Scopus, and Google Scholar. The RoB 2 tool was used to evaluate the quality of the studies that were included in the analysis. From the 1,345 studies identified, 16 randomized controlled trials were selected. All studies reported that vitamin D administration significantly increased the mean serum 25(OH)D compared with the placebo group. Also, most included studies revealed a significant improvement in magnetic resonance imaging (MRI) brain lesion markers. However, most studies showed that being treated with vitamin D instead of placebo showed no significant effect on relapse rates, fatigue, Expanded Disability Status Scale (EDSS), serum neurofilament light chain (NfL), calcium, and cytokine levels, except for quality-of-life transforming growth factor beta (TGF-β). This systematic review shows that the effect of vitamin D supplements on improving symptoms and relapses during treatment in MS patients remains inconclusive.
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Affiliation(s)
- Abhishek Gill
- Internal Medicine, Christian Medical College & Hospital, Ludhiana, IND
- Internal Medicine and Neurology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Chijioke Orji
- Orthopedics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | | | - Tariladei S Peresuodei
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Priyanka Thota
- College of Medicine, Siddhartha Medical College, Vijayawada, IND
| | | | - Ana P Arcia Franchini
- Psychiatry and Behavioral Sciences, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Lis M, Niedziela N, Adamczyk-Zostawa J, Wierzbicki K, Czuba Z, Zalejska-Fiolka J, Bartman W, Świętek A, Adamczyk-Sowa M. Can Vitamin D Supplementation Improve Inflammation in Relapsing-Remitting Multiple Sclerosis Patients? Biomedicines 2024; 12:1580. [PMID: 39062153 PMCID: PMC11274703 DOI: 10.3390/biomedicines12071580] [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: 05/18/2024] [Revised: 07/10/2024] [Accepted: 07/11/2024] [Indexed: 07/28/2024] Open
Abstract
(1) Background: Studies indicate that vitamin D (VitD) may reduce inflammation in multiple sclerosis (MS). The aim of the study was to assess the effect of supplementation with different doses of VitD on inflammation in relapsing-remitting MS (RRMS) patients. (2) Methods: The effect of 6-month supplementation with different doses of oral VitD (2000 IU/day) in a high-dose group (HD, n = 23) and a low-dose group (15,960 IU/month) (LD, n = 29) on selected markers of inflammation was assessed in 52 RRMS patients. (3) Results: Females constituted the majority of participants (63.46%). The median age [years] was 39.5 [34.5-49.8] and 47 [40.0-55.0] in the HD and LD groups, respectively. Significant differences were observed in age (p = 0.028), body weight (p = 0.014) and height (p = 0.001) between the study groups. Considering the BMI, statistically significant differences were not found (p = 0.496). The median 25(OH)D concentration [ng/mL] increased from 23.023 [15.578-25.76] in the HD group and 28.318 [20.644-32.232] in the LD group to 29.819 [24.937-38.064] and 30.837 [25.382-36.789], respectively (p < 0.01), and the increase was significantly higher in the HD group (p = 0.01). Hypovitaminosis D was found in most patients (71.2%) initially, and serum VitD levels were still <30.0 ng/mL in 46.2% of the participants at the follow-up. A significant increase in the levels of IL-4, IL-6, IL-17A, IL-22, IL-23 and TNF -α [pg/mL] and a decrease in IL-10 levels were reported during the study (p < 0.01). A significant positive correlation was observed between 25(OH)D serum levels and sCD40L (R = 0.33; p < 0.05) and TNF-α (R = 0.28; p < 0.05), and a significant negative correlation was reported between 25(OH)D and IL-23 (R = -0.32; p < 0.01) at the beginning of the study. (4) Conclusions: In RRMS patients, the doses of VitD were probably too low to induce beneficial effects on inflammation. Further studies are warranted to determine the effect of VitD supplementation on inflammatory markers in MS patients.
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Affiliation(s)
- Martyna Lis
- Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland (M.A.-S.)
| | - Natalia Niedziela
- Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland (M.A.-S.)
| | - Jowita Adamczyk-Zostawa
- Department of Ophthalmology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Krzysztof Wierzbicki
- Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland (M.A.-S.)
| | - Zenon Czuba
- Department of Microbiology and Immunology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Jolanta Zalejska-Fiolka
- Department of Biochemistry, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Wojciech Bartman
- Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland (M.A.-S.)
| | - Agata Świętek
- Silesia LabMed Research and Implementation Center, Medical University of Silesia in Katowice, 19 Jordana St., 41-808 Zabrze, Poland;
| | - Monika Adamczyk-Sowa
- Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland (M.A.-S.)
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Lis M, Niedziela N, Adamczyk-Zostawa J, Zalejska-Fiolka J, Błachut M, Szczygieł J, Świętek A, Adamczyk-Sowa M. Can Vitamin D Reduce Inflammation? The Influence of Supplementation on Selected Immunological Markers. Int J Mol Sci 2024; 25:7592. [PMID: 39062835 PMCID: PMC11277077 DOI: 10.3390/ijms25147592] [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: 05/20/2024] [Revised: 06/19/2024] [Accepted: 06/24/2024] [Indexed: 07/28/2024] Open
Abstract
There is increasing evidence that vitamin D (VitD) supplementation may reduce inflammation in individuals with multiple sclerosis (MS). The aim of this study was to evaluate the effect of different doses of VitD on selected markers of inflammation in patients with relapsing-remitting MS (RRMS). Participants were divided depending on the supplemented dose of VitD into a high-dose (2000 IU/d; HD) group and a low-dose (15,960 IU/month; LD) group (n = 23 and n = 29, respectively). The concentration of 25(OH)D and the levels of CXCL16, PTX3, ALCAM, IL-1RA, and OPG were measured initially and after six months of VitD supplementation in blood serum. A significant increase in the concentrations of CXCL16, PTX3, and OPG was observed during the study (p = 0.02, p = 0.01, and p < 0.01, respectively). Furthermore, a higher increase in PTX3 and OPG in the LD group was observed (p = 0.04 and p = 0.03, respectively). A significant positive correlation was observed between the 25(OH)D serum concentration and PTX3 (R = 0.28, p < 0.05) and OPG (R = 0.28, p < 0.05) only at the beginning of the study. In patients with RRMS, such doses of VitD might be too low to induce obvious beneficial effects on the pro-inflammatory and inflammatory balance.
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Affiliation(s)
- Martyna Lis
- Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (M.L.); (M.A.-S.)
| | - Natalia Niedziela
- Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (M.L.); (M.A.-S.)
| | - Jowita Adamczyk-Zostawa
- Department of Ophthalmology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Jolanta Zalejska-Fiolka
- Department of Biochemistry, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Michał Błachut
- Department of Psychiatry, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Jarosław Szczygieł
- Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (M.L.); (M.A.-S.)
| | - Agata Świętek
- Silesia LabMed Research and Implementation Center, Medical University of Silesia in Katowice, 19 Jordana St., 41-808 Zabrze, Poland;
| | - Monika Adamczyk-Sowa
- Department of Neurology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (M.L.); (M.A.-S.)
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Russo C, Santangelo R, Malaguarnera L, Valle MS. The "Sunshine Vitamin" and Its Antioxidant Benefits for Enhancing Muscle Function. Nutrients 2024; 16:2195. [PMID: 39064638 PMCID: PMC11279438 DOI: 10.3390/nu16142195] [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: 06/26/2024] [Revised: 07/08/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Pathological states marked by oxidative stress and systemic inflammation frequently compromise the functional capacity of muscular cells. This progressive decline in muscle mass and tone can significantly hamper the patient's motor abilities, impeding even the most basic physical tasks. Muscle dysfunction can lead to metabolic disorders and severe muscle wasting, which, in turn, can potentially progress to sarcopenia. The functionality of skeletal muscle is profoundly influenced by factors such as environmental, nutritional, physical, and genetic components. A well-balanced diet, rich in proteins and vitamins, alongside an active lifestyle, plays a crucial role in fortifying tissues and mitigating general weakness and pathological conditions. Vitamin D, exerting antioxidant effects, is essential for skeletal muscle. Epidemiological evidence underscores a global prevalence of vitamin D deficiency, which induces oxidative harm, mitochondrial dysfunction, reduced adenosine triphosphate production, and impaired muscle function. This review explores the intricate molecular mechanisms through which vitamin D modulates oxidative stress and its consequent effects on muscle function. The aim is to evaluate if vitamin D supplementation in conditions involving oxidative stress and inflammation could prevent decline and promote or maintain muscle function effectively.
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Affiliation(s)
- Cristina Russo
- Section of Pathology, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy;
| | - Rosa Santangelo
- Department of Medicine and Health Sciences, University of Catania, Via Santa Sofia, 97, 95124 Catania, Italy;
| | - Lucia Malaguarnera
- Section of Pathology, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy;
| | - Maria Stella Valle
- Section of Physiology, Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy;
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Sparaco M, Bonavita S. Vitamin D Supplementation: Effect on Cytokine Profile in Multiple Sclerosis. J Clin Med 2024; 13:835. [PMID: 38337529 PMCID: PMC10856360 DOI: 10.3390/jcm13030835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Revised: 01/26/2024] [Accepted: 01/27/2024] [Indexed: 02/12/2024] Open
Abstract
Vitamin D is known for its role in modulating calcium and phosphate homeostasis and is implicated both in bone mineralization and immune system regulation. The immune-modulatory role of vitamin D and its impact on multiple sclerosis (MS) courses are still debated. The aim of this review was to check the effect of vitamin D supplementation on cytokine profile regulation in people with MS. A significant increase in serum concentrations of interleukin (IL)-10 and Transforming growth factor (TGF)-β1 after vitamin D supplementation was demonstrated in most studies, with some of them reporting a reduction in disability scores after vitamin D supplementation and an inverse correlation between IL-10 levels and disability. The effect of vitamin D on the serum levels of IL-17 and IL-6 was controversial; different results across studies could be explained by a variability in the treatment duration, route, and frequency of administration, as well as the dosage of vitamin D supplementation, responses to vitamin D treatment and the serum levels reached with supplementation, including the methods used for cytokine analysis and the different cell types investigated, the MS phenotype, the disease phase (active vs. non-active) and duration, and concomitant treatment with disease-modifying therapies. Nevertheless, the significant increase in the serum concentrations of IL-10 and TGF-β1, demonstrated in most studies, suggests an anti-inflammatory effect of vitamin D supplementation.
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Affiliation(s)
| | - Simona Bonavita
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy;
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Chahardoli R, Robat-Jazi B, Azizi F, Amouzegar A, Khalili D, Zadeh-Vakili A, Mansouri F, Saboor-Yaraghi AA. Alterations in CD4 + T Cell Cytokines Profile in Female Patients with Hashimoto's Thyroiditis Following Vitamin D Supplementation: A Double-blind, Randomized Clinical Trial. Endocr Metab Immune Disord Drug Targets 2024; 24:1454-1463. [PMID: 38284726 DOI: 10.2174/0118715303273297231226153751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 10/06/2023] [Accepted: 10/27/2023] [Indexed: 01/30/2024]
Abstract
BACKGROUND Hashimoto's thyroiditis (HT) is an autoimmune disease characterized by the destruction of thyroid cells through immune processes involving T helper (Th)1 cytokines. This clinical trial investigates the impact of vitamin D supplementation on serum cytokine levels and gene expression in CD4+ T cells from HT patients, aiming to understand its effects on Th-1, Th-2, Th-17, and regulatory T (Treg) cell-associated factors. METHODS Female patients were randomly assigned in a double-blind design to either a vitamin D-supplemented group, which received cholecalciferol (1, 25(OH)2D3) at a dose of 50,000 IU, or the placebo group, which received a weekly placebo for a duration of three months. Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA), while genes' expression levels were measured using real-time PCR. RESULTS Serum 25-hydroxyvitamin D and levels exhibited a significant increase following vitamin D supplementation, in comparison to the placebo group. Additionally, the vitamin D supplementation resulted in a significant elevation of serum calcium (Ca) levels compared to baseline. In the vitamin D group, there was a significant decrease in both serum levels and expression of the interleukin (IL)-17 gene when compared to baseline, although no statistical difference was observed between the placebo and vitamin D groups. The gene expression of transforming growth factor-beta (TGFβ) was significantly increased in the vitamin D group compared to baseline, with no significant difference between the two study groups. Vitamin D treatment had no effect on serum levels of interferon-gamma (IFNϒ) and IL-4. While the gene expression of IL-4 in the vitamin D group did not exhibit a statistically significant increase, the level of GATA3 transcription factor increased significantly when compared to the placebo group. The expression of IFNϒ and transcription factors, T-bet, RORc, and forkhead box protein 3 (FOXP3) in genes did not show significant changes following vitamin D supplementation. CONCLUSION The findings suggest that vitamin D supplementation may hold potential benefits for autoimmune diseases, such as HT. However, further longitudinal clinical trials are necessary to gain a more comprehensive understanding of the specific effects of vitamin D on HT.
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Affiliation(s)
- Reza Chahardoli
- School of Advanced Technologies in Medicine, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | - Behrouz Robat-Jazi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Fereidoun Azizi
- Research Institute for Endocrine Science, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | - Atieh Amouzegar
- Research Institute for Endocrine Science, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | - Davood Khalili
- Research Institute for Endocrine Science, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Zadeh-Vakili
- Research Institute for Endocrine Science, Shaheed Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Mansouri
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Akbar Saboor-Yaraghi
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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Vo HVT, Nguyen YT, Kim N, Lee HJ. Vitamin A, D, E, and K as Matrix Metalloproteinase-2/9 Regulators That Affect Expression and Enzymatic Activity. Int J Mol Sci 2023; 24:17038. [PMID: 38069361 PMCID: PMC10707015 DOI: 10.3390/ijms242317038] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/25/2023] [Accepted: 11/29/2023] [Indexed: 12/18/2023] Open
Abstract
Fat-soluble vitamins (vitamin A, D, E, and K) assume a pivotal role in maintaining human homeostasis by virtue of their enzymatic functions. The daily inclusion of these vitamins is imperative to the upkeep of various physiological processes including vision, bone health, immunity, and protection against oxidative stress. Current research highlights fat-soluble vitamins as potential therapeutics for human diseases, especially cancer. Fat-soluble vitamins exert their therapeutic effects through multiple pathways, including regulation of matrix metalloproteinases' (MMPs) expression and enzymatic activity. As MMPs have been reported to be involved in the pathology of various diseases, such as cancers, cardiovascular diseases, and neurological disorders, regulating the expression and/or activity of MMPs could be considered as a potent therapeutic strategy. Here, we summarize the properties of fat-soluble vitamins and their potential as promising candidates capable of effectively modulating MMPs through multiple pathways to treat human diseases.
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Affiliation(s)
- Ha Vy Thi Vo
- Department of Chemistry Education, Kongju National University, Gongju 32588, Republic of Korea;
| | - Yen Thi Nguyen
- Department of Chemistry, Kongju National University, Gongju 32588, Republic of Korea;
| | - Namdoo Kim
- Department of Chemistry, Kongju National University, Gongju 32588, Republic of Korea;
| | - Hyuck Jin Lee
- Department of Chemistry Education, Kongju National University, Gongju 32588, Republic of Korea;
- Kongju National University Institute of Science Education, Kongju National University, Gongju 32588, Republic of Korea
- Kongju National University’s Physical Fitness for Health Research Lab (KNUPFHR), Kongju National University, Gongju 32588, Republic of Korea
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Feki S, Naifar M, Dammak M, Majdoub S, Sakka S, Ben AY, Hachicha H, Mhiri C, Ayadi F, Masmoudi H. Vitamin D deficiency in relation with the systemic and central inflammation during multiple sclerosis. J Med Biochem 2023; 42:364-375. [PMID: 37814621 PMCID: PMC10560505 DOI: 10.5937/jomb0-37676] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 08/23/2022] [Indexed: 10/11/2023] Open
Abstract
Background During the last decade, vitamin D (VitD) has become a topic of interest in immune regulation, especially in multiple sclerosis (MS) disease. Amongst the wide range of effects reported for this vitamin on the immune system, a regulatory role on cytokines production has been described. Our aim is to analyze the status of VitD and its correlation with the circulating inflammation and the intrathecal humoral response during MS. Methods We analyzed samples of 318 individuals: 108 MS patients and 210 controls. Determination of 25-(OH) VitD3 level in serum was made using electrochemiluminescence method. Circulating inflammatory cytokines (IL-6, IL-8, IL-10, TNF-a, IL12p70 and IL-1b) were investigated using Cytometer Bead Array Technology. The central humoral response was characterized using CSF isofocusing test and IgG Index calculation. Results As expected, mean value of VitD was significantly lower in MS group (26 nmol/L) than in control group (34.75 nmol/L) (p=0.002), with a severe deficiency in 67% of MS patients. Mean value of VitD was significantly lower in MS female patients. Regarding cytokines, mean value of TNFa was significantly higher in MS patients with oligoclonal bands of IgG in the CSF. IL6 was positively correlated with IgG level in serum of MS patients. Conclusions Our results support the association of VitD deficiency with MS, especially in female patients of our region. However, the vitamin level seems to not correlate with inflammatory cytokines nor with disability. Interestingly, TNFa and IL6 levels were correlated with the intrathecal synthesis of IgG and the circulating IgG level, respectively.
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Affiliation(s)
- Sawsan Feki
- University of Sfax, Habib Bourguiba Hospital, Immunology Laboratory, Sfax, Tunisia
| | - Manel Naifar
- University of Sfax, Habib Bourguiba Hospital, Biochemistry Laboratory, Sfax, Tunisia
| | - Mariem Dammak
- University of Sfax, Habib Bourguiba Hospital, Neurology Department, Sfax, Tunisia
| | - Sabrina Majdoub
- University of Sfax, Habib Bourguiba Hospital, Immunology Laboratory, Sfax, Tunisia
| | - Salma Sakka
- University of Sfax, Habib Bourguiba Hospital, Neurology Department, Sfax, Tunisia
| | - Ali Yesmine Ben
- University of Sfax, Habib Bourguiba Hospital, Immunology Laboratory, Sfax, Tunisia
| | - Hend Hachicha
- University of Sfax, Habib Bourguiba Hospital, Immunology Laboratory, Sfax, Tunisia
| | - Chokri Mhiri
- University of Sfax, Habib Bourguiba Hospital, Neurology Department, Sfax, Tunisia
| | - Fatma Ayadi
- University of Sfax, Habib Bourguiba Hospital, Biochemistry Laboratory, Sfax, Tunisia
| | - Hatem Masmoudi
- University of Sfax, Habib Bourguiba Hospital, Immunology Laboratory, Sfax, Tunisia
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10
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Anwar MJ, Alenezi SK, Alhowail AH. Molecular insights into the pathogenic impact of vitamin D deficiency in neurological disorders. Biomed Pharmacother 2023; 162:114718. [PMID: 37084561 DOI: 10.1016/j.biopha.2023.114718] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 04/12/2023] [Accepted: 04/14/2023] [Indexed: 04/23/2023] Open
Abstract
Neurological disorders are the major cause of disability, leading to a decrease in quality of life by impairing cognitive, sensorimotor, and motor functioning. Several factors have been proposed in the pathogenesis of neurobehavioral changes, including nutritional, environmental, and genetic predisposition. Vitamin D (VD) is an environmental and nutritional factor that is widely distributed in the central nervous system's subcortical grey matter, neurons of the substantia nigra, hippocampus, thalamus, and hypothalamus. It is implicated in the regulation of several brain functions by preserving neuronal structures. It is a hormone rather than a nutritional vitamin that exerts a regulatory role in the pathophysiology of several neurological disorders, including Alzheimer's disease, Parkinson's disease, epilepsy, and multiple sclerosis. A growing body of epidemiological evidence suggests that VD is critical in neuronal development and shows neuroprotective effects by influencing the production and release of neurotrophins, antioxidants, immunomodulatory, regulation of intracellular calcium balance, and direct effect on the growth and differentiation of nerve cells. This review provides up-to-date and comprehensive information on vitamin D deficiency, risk factors, and clinical and preclinical evidence on its relationship with neurological disorders. Furthermore, this review provides mechanistic insight into the implications of vitamin D and its deficiency on the pathogenesis of neurological disorders. Thus, an understanding of the crucial role of vitamin D in the neurobiology of neurodegenerative disorders can assist in the better management of vitamin D-deficient individuals.
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Affiliation(s)
- Md Jamir Anwar
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Qassim, Unaizah 51911, Saudi Arabia
| | - Sattam Khulaif Alenezi
- Department of Pharmacology and Toxicology, Unaizah College of Pharmacy, Qassim University, Qassim, Unaizah 51911, Saudi Arabia.
| | - Ahmad Hamad Alhowail
- Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Qassim, Buraydah 51452, Saudi Arabia
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Muacevic A, Adler JR, Albeladi F, Tahiri AA, Kinani EM, Almohsen RA, Alamoudi NH, Alanazi AA, Alkhamshi SJ, Althomali NA, Alrubaiei SN, Altowairqi FK. An Overview of the History, Pathophysiology, and Pharmacological Interventions of Multiple Sclerosis. Cureus 2023; 15:e33242. [PMID: 36733554 PMCID: PMC9888604 DOI: 10.7759/cureus.33242] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/02/2023] [Indexed: 01/03/2023] Open
Abstract
Multiple sclerosis (MS) is an immune-inflammatory disease that attacks and damages myelinated axons in the central nervous system (CNS) and causes nontraumatic neurological impairment in young people. Historically, Lidwina of Schiedam documented the first MS case. After that, Augustus d'Este wrote for years about how his MS symptoms worsened. Age, sex, genetics, environment, smoking, injuries, and infections, including herpes simplex and rabies, are risk factors for MS. According to epidemiology, the average age of onset is between 20 and 40 years. MS is more prevalent in women and is common in Europe and America. As diagnostic methods and criteria change, people with MS may be discovered at earlier and earlier stages of the disease. MS therapy has advanced dramatically due to breakthroughs in our knowledge of the disease's etiology and progression. Therefore, the efficacy and risk of treatment medications increased exponentially. Management goals include reducing lesion activity and avoiding secondary progression. Current treatment approaches focus on managing acute episodes, relieving symptoms, and reducing biological activity. Disease-modifying drugs such as fingolimod, interferon-beta, natalizumab, and dimethyl fumarate are the most widely used treatments for MS. For proof of the efficacy and safety of these medications, investigations in the real world are necessary.
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12
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Bhatti GK, Singh HV, Sharma E, Sehrawat A, Mishra J, Navik U, Hemachandra Reddy P, Bhatti JS. Protective role of natural products and bioactive compounds in multiple sclerosis. TREATMENTS, NUTRACEUTICALS, SUPPLEMENTS, AND HERBAL MEDICINE IN NEUROLOGICAL DISORDERS 2023:453-482. [DOI: https:/doi.org/10.1016/b978-0-323-90052-2.00026-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
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13
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Galoppin M, Kari S, Soldati S, Pal A, Rival M, Engelhardt B, Astier A, Thouvenot E. Full spectrum of vitamin D immunomodulation in multiple sclerosis: mechanisms and therapeutic implications. Brain Commun 2022; 4:fcac171. [PMID: 35813882 PMCID: PMC9260308 DOI: 10.1093/braincomms/fcac171] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 05/03/2022] [Accepted: 06/28/2022] [Indexed: 11/17/2022] Open
Abstract
Vitamin D deficiency has been associated with the risk of multiple sclerosis, disease activity and progression. Results from in vitro experiments, animal models and analysis of human samples from randomized controlled trials provide comprehensive data illustrating the pleiotropic actions of Vitamin D on the immune system. They globally result in immunomodulation by decreasing differentiation of effector T and B cells while promoting regulatory subsets. Vitamin D also modulates innate immune cells such as macrophages, monocytes and dendritic cells, and acts at the level of the blood–brain barrier reducing immune cell trafficking. Vitamin D exerts additional activity within the central nervous system reducing microglial and astrocytic activation. The immunomodulatory role of Vitamin D detected in animal models of multiple sclerosis has suggested its potential therapeutic use for treating multiple sclerosis. In this review, we focus on recent published data describing the biological effects of Vitamin D in animal models of multiple sclerosis on immune cells, blood–brain barrier function, activation of glial cells and its potential neuroprotective effects. Based on the current knowledge, we also discuss optimization of therapeutic interventions with Vitamin D in patients with multiple sclerosis, as well as new technologies allowing in-depth analysis of immune cell regulations by vitamin D.
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Affiliation(s)
- Manon Galoppin
- IGF, University Montpellier, CNRS, INSERM , Montpellier , France
| | - Saniya Kari
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 – CNRS UMR5051 – Université Toulouse III , 31024 Toulouse cedex 3 , France
| | - Sasha Soldati
- Theodor Kocher Institute, University of Bern , Bern , Switzerland
| | - Arindam Pal
- Theodor Kocher Institute, University of Bern , Bern , Switzerland
| | - Manon Rival
- IGF, University Montpellier, CNRS, INSERM , Montpellier , France
- Department of Neurology, Nîmes University Hospital, University Montpellier , Nîmes , France
| | | | - Anne Astier
- Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291 – CNRS UMR5051 – Université Toulouse III , 31024 Toulouse cedex 3 , France
| | - Eric Thouvenot
- IGF, University Montpellier, CNRS, INSERM , Montpellier , France
- Department of Neurology, Nîmes University Hospital, University Montpellier , Nîmes , France
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14
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Zorzella-Pezavento SFG, Mimura LAN, Denadai MB, de Souza WDF, Fraga-Silva TFDC, Sartori A. Is there a window of opportunity for the therapeutic use of vitamin D in multiple sclerosis? Neural Regen Res 2022; 17:1945-1954. [PMID: 35142671 PMCID: PMC8848597 DOI: 10.4103/1673-5374.335139] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Multiple sclerosis is an autoimmune treatable but not curable disease. There are a multiplicity of medications for multiple sclerosis therapy, including a class entitled disease-modifying drugs that are mainly indicated to reduce the number and severity of disease relapses. Not all patients respond well to these therapies, and minor to severe adverse effects have been reported. Vitamin D, called sunshine vitamin, is being studied as a possible light at the end of the tunnel. In this review, we recapitulated the similar immunopathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis, the immunomodulatory and neuroprotective potential of vitamin D and the state-of-art concerning its supplementation to multiple sclerosis patients. Finally, based on our and other groups’ experimental findings, we analyzed the need to consider the relevance of the route and the different time-point administration aspects for a more rational indication of this vitamin to multiple sclerosis patients.
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Affiliation(s)
| | - Luiza Ayumi Nishiyama Mimura
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - Marina Bonifácio Denadai
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | - William Danilo Fernandes de Souza
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
| | | | - Alexandrina Sartori
- Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu, São Paulo, Brazil
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15
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Janjusevic M, Gagno G, Fluca AL, Padoan L, Beltrami AP, Sinagra G, Moretti R, Aleksova A. The peculiar role of vitamin D in the pathophysiology of cardiovascular and neurodegenerative diseases. Life Sci 2022; 289:120193. [PMID: 34864062 DOI: 10.1016/j.lfs.2021.120193] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 11/24/2021] [Accepted: 11/29/2021] [Indexed: 02/07/2023]
Abstract
Vitamin D is a hormone with both genomic and non-genomic actions. It exerts its activity by binding vitamin D receptor (VDR), which belongs to the superfamily of nuclear receptors and ligand-activated transcription factors. Since VDR has been found in various tissues, it has been estimated that it regulates approximately 3% of the human genome. Several recent studies have shown pleiotropic effects of vitamin D in various processes such as cellular proliferation, differentiation, DNA repair and apoptosis and its involvement in different pathophysiological conditions as inflammation, diabetes mellitus, and anemia. It has been suggested that vitamin D could play an important role in neurodegenerative and cardiovascular disorders. Moderate to strong associations between lower serum vitamin D concentrations and stroke and cardiovascular events have been identified in different analytic approaches, even after controlling for traditional demographic and lifestyle covariates. The mechanisms behind the associations between vitamin D and cerebrovascular and cardiologic profiles have been widely examined both in animal and human studies. Optimization of vitamin D levels in human subjects may improve insulin sensitivity and beta-cell function and lower levels of inflammatory markers. Moreover, it has been demonstrated that altered gene expression of VDR and 1,25D3-membrane-associated rapid response steroid-binding (1,25D3-MARRS) receptor influences the role of vitamin D within neurons and allows them to be more prone to degeneration. This review summarizes the current understanding of the molecular mechanisms underlying vitamin D signaling and the consequences of vitamin D deficiency in neurodegenerative and cardiovascular disorders.
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Affiliation(s)
- Milijana Janjusevic
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy
| | - Giulia Gagno
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy
| | - Alessandra Lucia Fluca
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy
| | - Laura Padoan
- Cardiology and Cardiovascular Physiopathology, Azienda Ospedaliero-Universitaria S. Maria della Misericordia, 06156 Perugia, Italy
| | - Antonio Paolo Beltrami
- Clinical Pathology Department, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC) and Department of Medicine (DAME), University of Udine, 33100 Udine, Italy
| | - Gianfranco Sinagra
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy
| | - Rita Moretti
- Department of Internal Medicine and Neurology, Neurological Clinic, Complex Case Section, Trieste, Italy
| | - Aneta Aleksova
- Cardiothoracovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI) and Department of Medical Surgical and Health Science, University of Trieste, 34149 Trieste, Italy.
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16
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Amiri Z, Nosrati M, Sharifan P, Saffar Soflaei S, Darroudi S, Ghazizadeh H, Mohammadi Bajgiran M, Moafian F, Tayefi M, Hasanzade E, Rafiee M, Ferns GA, Esmaily H, Amini M, Ghayour-Mobarhan M. Factors determining the serum 25-hydroxyvitamin D response to vitamin D supplementation: Data mining approach. Biofactors 2021; 47:828-836. [PMID: 34273212 DOI: 10.1002/biof.1770] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 07/01/2021] [Indexed: 01/02/2023]
Abstract
Vitamin D supplementation has been shown to prevent vitamin D deficiency, but various factors can affect the response to supplementation. Data mining is a statistical method for pulling out information from large databases. We aimed to evaluate the factors influencing serum 25-hydroxyvitamin D levels in response to supplementation of vitamin D using a random forest (RF) model. Data were extracted from the survey of ultraviolet intake by nutritional approach study. Vitamin D levels were measured at baseline and at the end of study to evaluate the responsiveness. We examined the relationship between 76 potential influencing factors on vitamin D response using RF. We found several features that were highly correlated to the serum vitamin D response to supplementation by RF including anthropometric factors (body mass index [BMI], free fat mass [FFM], fat percentage, waist-to-hip ratio [WHR]), liver function tests (serum gamma-glutamyl transferase [GGT], total bilirubin, total protein), hematological parameters (mean corpuscular volume [MCV], mean corpuscular hemoglobin concentration [MCHC], hematocrit), and measurement of insulin sensitivity (homeostatic model assessment of insulin resistance). BMI, total bilirubin, FFM, and GGT were found to have a positive relationship and homeostatic model assessment for insulin resistance, MCV, MCHC, fat percentage, total protein, and WHR were found to have a negative correlation to vitamin D concentration in response to supplementation. The accuracy of RF in predicting the response was 93% compared to logistic regression, for which the accuracy was 40%, in the evaluation of the correlation of the components of the data set to serum vitamin D.
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Affiliation(s)
- Zahra Amiri
- Department of Pure Mathematics, Center of Excellence in Analysis on Algebraic Structures (CEAAS), Ferdowsi University of Mashhad, Mashhad, Iran
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mina Nosrati
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Payam Sharifan
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sara Saffar Soflaei
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Susan Darroudi
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamideh Ghazizadeh
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Mohammadi Bajgiran
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fahimeh Moafian
- Department of Pure Mathematics, Center of Excellence in Analysis on Algebraic Structures (CEAAS), Ferdowsi University of Mashhad, Mashhad, Iran
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Tayefi
- Norwegian Center for e-health Research, University hospital of North Norway, Tromsø, Norway
| | - Elahe Hasanzade
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahdi Rafiee
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gordon A Ferns
- Division of Medical Education, Brighton & Sussex Medical School, Brighton, UK
| | - Habibollah Esmaily
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
- Social Determinants of Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahnaz Amini
- Allergy Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Ghayour-Mobarhan
- International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran
- Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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17
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Chen YH, Cheadle CE, Rice LV, Pfeffer PE, Dimeloe S, Gupta A, Bush A, Gooptu B, Hawrylowicz CM. The Induction of Alpha-1 Antitrypsin by Vitamin D in Human T Cells Is TGF-β Dependent: A Proposed Anti-inflammatory Role in Airway Disease. Front Nutr 2021; 8:667203. [PMID: 34458299 PMCID: PMC8397538 DOI: 10.3389/fnut.2021.667203] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 07/09/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Vitamin D upregulates anti-inflammatory and antimicrobial pathways that promote respiratory health. Vitamin D synthesis is initiated following skin exposure to sunlight, however nutritional supplementation can be required to address deficiency, for example during the winter months or due to cultural constraints. We recently reported that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment induced alpha-1 antitrypsin (AAT) expression in CD4+, but not CD8+ T cells, with evidence supporting an immunoregulatory role. Research Question: To understand the relationship between vitamin D, lung AAT levels and T lymphocytes further we investigated whether TGF-β is required as a co-factor for 1,25(OH)2D3-induced upregulation of AAT by vitamin D in CD8+ T cells in vitro and correlated circulating vitamin D levels with lung AAT levels in vivo. Results: 1,25(OH)2D3 in combination with TGF-β1 increased AAT expression by CD8+ T cells, as well as VDR and RXRα gene expression, which may partly explain the requirement for TGF-β. CD4+ T cells may also require autocrine stimulation with TGF-β as a co-factor since 1,25(OH)2D3 was associated with increased TGF-β bioactivity and neutralisation of TGF-β partially abrogated 1,25(OH)2D3-induced SERPINA1 gene expression. Neither CD4+ nor CD8+ T cells responded to the circulating vitamin D precursor, 25-hydroxyvitamin D3 for induction of SERPINA1, suggesting that local generation of 1,25(OH)2D3 is required. Transcriptional gene profiling studies previously demonstrated that human bronchial epithelial cells rapidly increased TGF-β2 gene expression in response to 1,25(OH)2D3. Here, human epithelial cells responded to precursor 25(OH)D3 to increase bioactive TGF-β synthesis. CD8+ T cells responded comparably to TGF-β1 and TGF-β2 to increase 1,25(OH)2D3-induced AAT. However, CD8+ T cells from adults with AAT-deficiency, homozygous for the Z allele of SERPINA1, were unable to mount this response. AAT levels in the airways of children with asthma and controls correlated with circulating 25(OH)D3. Conclusions: Vitamin D increases AAT expression in human T cells and this response is impaired in T cells from individuals homozygous for the Z allele of SERPINA1 in a clinic population. Furthermore, a correlation between circulating vitamin D and airway AAT is reported. We propose that vitamin D-induced AAT contributes to local immunomodulation and airway health effects previously attributed to vitamin D.
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Affiliation(s)
- Yin-Huai Chen
- Peter Gorer Department of Immunobiology (Formerly Asthma, Allergy and Lung Biology), School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
| | - Charlotte E Cheadle
- Peter Gorer Department of Immunobiology (Formerly Asthma, Allergy and Lung Biology), School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.,Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom
| | - Louise V Rice
- Peter Gorer Department of Immunobiology (Formerly Asthma, Allergy and Lung Biology), School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.,Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom
| | - Paul E Pfeffer
- Peter Gorer Department of Immunobiology (Formerly Asthma, Allergy and Lung Biology), School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.,Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom
| | - Sarah Dimeloe
- Peter Gorer Department of Immunobiology (Formerly Asthma, Allergy and Lung Biology), School of Immunology and Microbial Sciences, King's College London, London, United Kingdom
| | - Atul Gupta
- Peter Gorer Department of Immunobiology (Formerly Asthma, Allergy and Lung Biology), School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.,National Heart and Lung Institute, Royal Brompton & Harefield National Health Service Foundation Trust, London, United Kingdom
| | - Andrew Bush
- Centre for Paediatrics and Child Health, National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom
| | - Bibek Gooptu
- Peter Gorer Department of Immunobiology (Formerly Asthma, Allergy and Lung Biology), School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.,National Institute for Health Research Leicester Biomedical Research Centre-Respiratory and Leicester Institute of Structural & Chemical Biology, University of Leicester, Leicester, United Kingdom.,London Alpha-1 Antitrypsin Deficiency Service, Royal Free Hospital, London, United Kingdom
| | - Catherine M Hawrylowicz
- Peter Gorer Department of Immunobiology (Formerly Asthma, Allergy and Lung Biology), School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.,Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, Guy's Hospital, King's College London, London, United Kingdom
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18
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Rolfes L, Pawlitzki M, Pfeuffer S, Huntemann N, Wiendl H, Ruck T, Meuth SG. Failed, Interrupted, or Inconclusive Trials on Immunomodulatory Treatment Strategies in Multiple Sclerosis: Update 2015-2020. BioDrugs 2021; 34:587-610. [PMID: 32785877 PMCID: PMC7519896 DOI: 10.1007/s40259-020-00435-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
In the past decades, multiple sclerosis (MS) treatment has experienced vast changes resulting from major advances in disease-modifying therapies (DMT). Looking at the overall number of studies, investigations with therapeutic advantages and encouraging results are exceeded by studies of promising compounds that failed due to either negative or inconclusive results or have been interrupted for other reasons. Importantly, these failed clinical trials are informative experiments that can help us to understand the pathophysiological mechanisms underlying MS. In several trials, concepts taken from experimental models were not translatable to humans, although they did not lack a well-considered pathophysiological rationale. The lessons learned from these discrepancies may benefit future studies and reduce the risks for patients. This review summarizes trials on MS since 2015 that have either failed or have been interrupted for various reasons. We identify potential causes of failure or inconclusiveness, looking at the path from basic animal experiments to clinical trials, and discuss the implications for our current view on MS pathogenesis, clinical practice, and future study designs. We focus on anti-inflammatory treatment strategies, without including studies on already approved and effective DMT. Clinical trials addressing neuroprotective and alternative treatment strategies are presented in a separate article.
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Affiliation(s)
- Leoni Rolfes
- Department of Neurology With Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
| | - Marc Pawlitzki
- Department of Neurology With Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
| | - Steffen Pfeuffer
- Department of Neurology With Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
| | - Niklas Huntemann
- Department of Neurology With Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
| | - Heinz Wiendl
- Department of Neurology With Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
| | - Tobias Ruck
- Department of Neurology With Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
| | - Sven G Meuth
- Department of Neurology With Institute of Translational Neurology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany
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19
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Ghorbani Z, Rafiee P, Haghighi S, Razeghi Jahromi S, Djalali M, Moradi-Tabriz H, Mahmoudi M, Togha M. The effects of vitamin D3 supplementation on TGF-β and IL-17 serum levels in migraineurs: post hoc analysis of a randomized clinical trial. J Pharm Health Care Sci 2021; 7:9. [PMID: 33653409 PMCID: PMC7927391 DOI: 10.1186/s40780-021-00192-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 02/01/2021] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Although the exact mechanism involved in migraine pathogenesis remained uncertain, and different researches have been developed to address the role of neuroinflammation and immune dysfunction. Therefore, considering the immune protective functions of vitamin D3, we aimed to investigate the effects of daily administration of 2000 IU D3 supplements on serum status of immune markers in migraine patients. METHODS AND MATERIALS Eighty episodic migraineurs who randomly assigned into two equal groups to receive either vitamin D3 2000 IU/d or placebo for 12-week were enrolled in this placebo-controlled double-blind trial included. Serum concentrations of transforming growth factor-beta (TGF-β) and interleukin (IL)-17 were evaluated at baseline and after the trial via the ELISA method. RESULTS Applying ANCOVA adjusted for baseline levels and confounding variables, it was found that the serum level of TGF-β was significantly higher in vitamin D group (adjusted mean:1665.50 ng/L) than the placebo group (1361.90 ng/L) after the experiment (P-value = 0.012); on the other hand, vitamin D prevented the increment in IL-17 serum level in the intervention group after the trial (adjusted mean:37.84 ng/L) comparing to the controls (adjusted mean:70.09 ng/L; P-value = 0.039). The Pearson correlation analysis revealed a significant positive correlation between changes in serum 25-hydroxy-vitamin D (25(OH)D) and TGF-β (r = - 0.306, P-value = 0.008). In contrast, no significant correlations were noted between serum 25(OH) D and IL-17 changes throughout the study. CONCLUSION Based on the results of this study, it was revealed that 12-week vitamin D3 supplementation (2000 IU/day) could enhance the Th17/Treg related cytokines balance in episodic migraineurs. Although these findings are promising, it is needed to be extended. TRIAL REGISTRATION The trial is registered in the Iranian registry of clinical trials (IRCT) at 11 July 2018, with IRCT code: IRCT20151128025267N6 ( https://www.irct.ir/trial/31246 ).
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Affiliation(s)
- Zeinab Ghorbani
- Cardiovascular Diseases Research Center, Department of Cardiology, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Department of Community Medicine, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
- Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Pegah Rafiee
- Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
- Student Research Committee, Department and Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Samaneh Haghighi
- 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
| | - Soodeh Razeghi Jahromi
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, Shahid Beheshti 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
| | - Hedieh Moradi-Tabriz
- Department of Pathology, Sina University Hospital, Tehran 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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20
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Oyeyinka BO, Afolayan AJ. Potentials of Musa Species Fruits against Oxidative Stress-Induced and Diet-Linked Chronic Diseases: In Vitro and In Vivo Implications of Micronutritional Factors and Dietary Secondary Metabolite Compounds. Molecules 2020; 25:E5036. [PMID: 33142997 PMCID: PMC7663138 DOI: 10.3390/molecules25215036] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Revised: 09/10/2020] [Accepted: 09/23/2020] [Indexed: 12/12/2022] Open
Abstract
Nutritional quality and the well-being of the body system are directly linked aspects of human survival. From the unborn foetus to adulthood, the need for sustainable access to micronutrient-rich foods is pertinent and the global consumption of banana and plantain fruits, in effect, contributes to the alleviation of the scourge of malnutrition. This review is particularly aimed at evaluating the pharmacological dimensions through the biological mechanisms of Musa fruits in the body, which represent correlations with their constituent micronutrient factors and dietary polyphenolic constituents such as minerals, vitamin members, anthocyanins, lutein, α-,β- carotenes, neoxanthins and cryptoxanthins, epi- and gallo catechins, catecholamines, 3-carboxycoumarin, β-sitosterol, monoterpenoids, with series of analytical approaches for the various identified compounds being highlighted therein. Derivative value-products from the compartments (flesh and peel) of Musa fruits are equally highlighted, bringing forth the biomedicinal and nutritional relevance, including the potentials of Musa species in dietary diversification approaches.
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Affiliation(s)
| | - Anthony Jide Afolayan
- Medicinal Plants and Economic Development (MPED) Research Centre, Department of Botany, University of Fort Hare, Alice 5700, South Africa;
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21
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Parastouei K, Solaymani-Mohammadi F, Shiri-Shahsavar MR, Chahardoli R, Nasl-Khameneh AM, Zarandi MB, Ghotloo S, Saboor-Yaraghi AA. The effect of calcitriol and all-trans retinoic acid on T-bet, IFN-γ, GATA3 and IL-4 genes expression in experimental autoimmune encephalomyelitis. APMIS 2020; 128:583-592. [PMID: 32865844 DOI: 10.1111/apm.13073] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 08/12/2020] [Indexed: 01/07/2023]
Abstract
Multiple sclerosis (MS) is an immune-mediated inflammatory disease which affects the central nervous system (CNS). In the present study, the in vivo effects of ATRA, calcitriol, and their combinations on the expression of murine CD4+ T cell cytokines and their specific transcription factors in experimental autoimmune encephalomyelitis (EAE)-induced mice were explored. Thirty-two EAE induced inbred C57BL/6 female mice with an age ranged from 8 to 10 weeks were divided into four categories in a random manner. The first, second, and third groups received ATRA, calcitriol, ATRA+ calcitriol, respectively, and the fourth group received vehicle. The treatment started on the day prior to immunization and through the IP injections every other days for 21 days. The dosages of administration for calcitriol, ATRA, and calcitriol+ ATRA were 100 ng, 250 μg, and 50ng + 125 μg, respectively per mouse. An equal volume of excipient was administered for the vehicle group. T-bet, IFN-γ, GATA-3, and IL-4 genes expression were assessed in the splenocytes of EAE -induced mice. The expression of T-bet and IFN-γ genes in the splenocytes of ATRA, calcitriol and combination- treated mice were significantly reduced compared to vehicle group (p < 0.05). A significant decrease in T-bet expression was observed in the combination-treated group compared to the ATRA-treated group (p < 0.05). The expression of GATA3 and IL-4 genes was significantly increased in the ATRA-, calcitriol-, and combination-treated mice when compared with the control group (p < 0.05). Furthermore, the effect of calcitriol alone and in combination with ATRA was more considerable than that of ATRA alone. The nutraceutical approaches may be promising in the prevention and/or treatment of MS.
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Affiliation(s)
- Karim Parastouei
- Department of Cellular and Molecular Nutrition, Tehran University of Medical Sciences, Tehran, Iran
| | | | | | - Reza Chahardoli
- Department of Cellular and Molecular Nutrition, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mehdi Borhani Zarandi
- Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran
| | - Somayeh Ghotloo
- Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ali Akbar Saboor-Yaraghi
- Department of Cellular and Molecular Nutrition, Tehran University of Medical Sciences, Tehran, Iran.,Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
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22
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Yeh WZ, Gresle M, Jokubaitis V, Stankovich J, van der Walt A, Butzkueven H. Immunoregulatory effects and therapeutic potential of vitamin D in multiple sclerosis. Br J Pharmacol 2020; 177:4113-4133. [PMID: 32668009 DOI: 10.1111/bph.15201] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 07/04/2020] [Accepted: 07/07/2020] [Indexed: 12/19/2022] Open
Abstract
Initially recognised as an important factor for bone health, vitamin D is now known to have a range of effects on the immune system. Vitamin D deficiency is associated with an increased risk of multiple sclerosis (MS), a chronic immune-mediated demyelinating disease of the CNS. In this review, we explore the links between vitamin D deficiency, MS risk, and disease activity. We also discuss the known immune effects of vitamin D supplementation and the relevance of these observations to the immunopathology of MS. Finally, we review the existing evidence for vitamin D supplementation as an MS therapy, highlighting several recent clinical studies and trials.
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Affiliation(s)
- Wei Zhen Yeh
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Department of Neurology, Alfred Health, Melbourne, Victoria, Australia
| | - Melissa Gresle
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Department of Neurology, Alfred Health, Melbourne, Victoria, Australia
| | - Vilija Jokubaitis
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Department of Neurology, Alfred Health, Melbourne, Victoria, Australia
| | - Jim Stankovich
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | - Anneke van der Walt
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Department of Neurology, Alfred Health, Melbourne, Victoria, Australia
| | - Helmut Butzkueven
- Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Victoria, Australia.,Department of Neurology, Alfred Health, Melbourne, Victoria, Australia
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Miclea A, Bagnoud M, Chan A, Hoepner R. A Brief Review of the Effects of Vitamin D on Multiple Sclerosis. Front Immunol 2020; 11:781. [PMID: 32435244 PMCID: PMC7218089 DOI: 10.3389/fimmu.2020.00781] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Accepted: 04/06/2020] [Indexed: 12/15/2022] Open
Abstract
Multiple sclerosis (MS) is characterized as an autoimmune disease affecting the central nervous system. It is one of the most common neurological disorders in young adults. Over the past decades, increasing evidence suggested that hypovitaminosis D is a contributing factor to the risk of developing MS. From different risk factors contributing to the development of MS, vitamin D status is of particular interest since it is not only a modifiable risk factor but is also associated with MS disease activity. MS patients with lower serum vitamin D concentrations were shown to have higher disease activity. However, this finding does not demonstrate causality. In this regard, prospective vitamin D supplementation studies missed statistical significance in its primary endpoints but showed promising results in secondary outcome measures or post hoc analyses. An explanation for missed primary endpoints may be underpowered trials. Besides vitamin D supplementation as a potential add-on to long-term immunotherapeutic treatment, a recent laboratory study of our group pointed toward a beneficial effect of vitamin D to improve the efficacy of glucocorticoids in relapse therapy. In the following article, we will briefly review the effects of vitamin D on MS by outlining its effects on the immune and nervous system and by reviewing the association between vitamin D and MS risk as well as MS disease activity. We will also review the effects of vitamin D supplementation on MS risk and MS disease activity.
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Affiliation(s)
- Andrei Miclea
- Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland
| | - Maud Bagnoud
- Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland
| | - Andrew Chan
- Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland
| | - Robert Hoepner
- Department of Neurology, University Hospital Bern and University of Bern, Bern, Switzerland
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24
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Häusler D, Torke S, Weber MS. High-Dose Vitamin D-Mediated Hypercalcemia as a Potential Risk Factor in Central Nervous System Demyelinating Disease. Front Immunol 2020; 11:301. [PMID: 32161591 PMCID: PMC7053380 DOI: 10.3389/fimmu.2020.00301] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2019] [Accepted: 02/06/2020] [Indexed: 12/28/2022] Open
Abstract
The exact cause of multiple sclerosis (MS) is unknown; however, it is considered to be an inflammatory disease of the central nervous system (CNS) triggered by a combination of both environmental and genetic factors. Vitamin D deficiency is also discussed as a possible disease-promoting factor in MS, as low vitamin D status is associated with increased formation of CNS lesions, elevated number of relapses and accelerated disease progression. However, it remains unclear whether this association is causal and related and most importantly, whether vitamin D supplementation in MS is of direct therapeutic benefit. Recently, we could show that in a murine model of MS, administration of a moderate vitamin D dose was of clinical benefit, while excessive vitamin D supplementation had a negative effect on disease severity. Of note, disease exacerbation was associated with high-dose vitamin D caused secondary hypercalcemia. Mechanistically dissecting this outcome, we found that hypercalcemia independent of vitamin D similarly triggered activation of disease-perpetuating T cells. These findings caution that vitamin D should be supplemented in a controlled and moderate manner in patients with MS and concomitantly highlight calcium as a novel potential MS risk factor by itself. In this review, we will summarize the current evidence from animal and clinical studies aiming to assess whether vitamin D may be of benefit in patients with MS. Furthermore, we will discuss any possible secondary effects of vitamin D with a particular focus on the role of calcium on immune cells and in the pathogenesis of CNS demyelinating disease.
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Affiliation(s)
- Darius Häusler
- Department of Neuropathology, Institute of Neuropathology, University Medical Center, Göttingen, Germany
| | - Sebastian Torke
- Department of Neuropathology, Institute of Neuropathology, University Medical Center, Göttingen, Germany
| | - Martin S Weber
- Department of Neuropathology, Institute of Neuropathology, University Medical Center, Göttingen, Germany.,Department of Neurology, University Medical Center, Göttingen, Germany
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25
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Paricalcitol improves experimental autoimmune encephalomyelitis (EAE) by suppressing inflammation via NF-κB signaling. Biomed Pharmacother 2020; 125:109528. [PMID: 32106388 DOI: 10.1016/j.biopha.2019.109528] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2019] [Revised: 10/01/2019] [Accepted: 10/01/2019] [Indexed: 12/25/2022] Open
Abstract
Multiple sclerosis (MS) is known as an autoimmune disease in the central nervous system (CNS) characterized by motor deficits, pain, fatigue, cognitive impairment, and sensory and visual dysfunction. MS is considered to be resulted from significant inflammatory response. Paricalcitol (Pari) is a vitamin D2 analogue, which has been indicated to show anti-inflammatory activities in kidney and heart diseases. In the present study, if Pari could ameliorate the experimental autoimmune encephalomyelitis (EAE) was investigated. Here, the C57BL/6 mice were immunized using myelin oligodendrocyte glycoprotein 35-55 (MOG35-55). Subsequently, Pari was intraperitoneally injected into the mice. As for in vitro analysis, RAW264.7 and Jurkat cells were incubated with Pari together with corresponding stimulus. The results indicated that Pari administration reduced the paralytic severity, neuropathology and apoptosis in MOG-treated mice compared to the MOG single group. Pari also exhibited a significantly inhibitory effect on immune cell infiltration, glial cell activation, expression of pro-inflammatory factors and the activation of nuclear factor κB (NF-κB). The expression of pro-inflammatory regulators and the translocation of NF-κB from cytoplasm into nuclear in RAW264.7 and Jurkat cells under specific stimulation was clearly down-regulated by Pari incubation. Furthermore, we found that suppressing NF-κB with its inhibitor combined with Pari could further reduce the expression of pro-inflammatory factors and associated proteins. These data illustrated that Pari could diminish MOG-triggered EAE, as well as macrophages and T cells activation through blocking NF-κB activation. Collectively, Pari might have therapeutic effects in mouse models with MS.
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26
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Mohammed EM. Environmental Influencers, MicroRNA, and Multiple Sclerosis. J Cent Nerv Syst Dis 2020; 12:1179573519894955. [PMID: 32009827 PMCID: PMC6971968 DOI: 10.1177/1179573519894955] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Accepted: 11/25/2019] [Indexed: 02/06/2023] Open
Abstract
Multiple sclerosis (MS) is a complex neurological disorder characterized by an aberrant immune system that affects patients' quality of life. Several environmental factors have previously been proposed to associate with MS pathophysiology, including vitamin D deficiency, Epstein-Barr virus (EBV) infection, and cigarette smoking. These factors may influence cellular molecularity, interfering with cellular proliferation, differentiation, and apoptosis. This review argues that small noncoding RNA named microRNA (miRNA) influences these factors' mode of action. Dysregulation in the miRNAs network may deeply impact cellular hemostasis, thereby possibly resulting in MS pathogenicity. This article represents a literature review and an author's theory of how environmental factors may induce dysregulations in the miRNAs network, which could ultimately affect MS pathogenicity.
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27
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Vitamin D and Demyelinating Diseases: Neuromyelitis Optica (NMO) and Multiple Sclerosis (MS). Autoimmune Dis 2020; 2020:8718736. [PMID: 32373353 PMCID: PMC7187724 DOI: 10.1155/2020/8718736] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2019] [Accepted: 11/30/2019] [Indexed: 12/18/2022] Open
Abstract
Vitamin D deficiency is prevalent in all ages regardless of climate or geographical location and evidence is emerging that the incidence of autoimmune diseases is increasing worldwide. Women make up a large proportion of autoimmune disease diagnoses, underscoring the importance of fully elucidating the complex synergistic relationships between estrogens and vitamin D. Vitamin D receptor-activating drugs appear to enhance remyelination in patients diagnosed with multiple sclerosis (MS) and other demyelinating diseases such as neuromyelitis optica (NMO). This review is intended to update health practitioners about the potential role of vitamin D deficiency demyelination and to motivate future research on dietary recommendations for vitamin D in preventing and treating demyel1nating diseases.
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28
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Circulating cytokine concentrations are not altered by supplemental vitamin D in knee osteoarthritis: A pilot study. JOURNAL OF NUTRITION & INTERMEDIARY METABOLISM 2019. [DOI: 10.1016/j.jnim.2019.100103] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Dietary Supplements on Controlling Multiple Sclerosis Symptoms and Relapses: Current Clinical Evidence and Future Perspectives. MEDICINES 2019; 6:medicines6030095. [PMID: 31547410 PMCID: PMC6789617 DOI: 10.3390/medicines6030095] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/12/2019] [Revised: 09/09/2019] [Accepted: 09/10/2019] [Indexed: 12/13/2022]
Abstract
Background: Multiple sclerosis (MS) constitutes a chronic progressive demyelinating disease which negatively affects the central nervous system. MS symptoms detrimentally affect the quality of life, as well as the life expectancy of MS patients. In this aspect, the present study aims to critically summarize and evaluate the currently available clinical studies focusing on the potential beneficial effects of dietary supplements on controlling MS symptomatology and relapse. Methods: PubMed database was comprehensively searched, using relative keywords to identify clinical trials that investigated the beneficial effects of dietary supplementation against MS symptomatology and progression. 40 clinical trials were found, which were divided into categories. Results: Nutritional status of MS patients, as well as supplementation have been suggested as potential factors affecting progression. Several substantial studies have documented a systematically high prevalence of vitamin A, B12 and D3 deficiency amongst MS patients. At present, clinical data have suggested that most of the dietary supplements under study may exert antioxidant and anti-inflammatory properties, improving depression symptomatology and quality of life overall. However, malnutrition risk in MS patients has not been adequately explored in order for more precise conclusions to be drawn. The supplements that may have a positive effect on MS are vitamins, fatty acids, antioxidants, phytochemicals and melatonin. Conclusions: Several dietary supplements may decrease inflammation and fatigue, also increasing also autoimmunity tolerance in MS patients, and thus improving quality of life and life expectancy. Currently, there is no effective clinical indication for applying dietary supplementation as complementary treatment against MS symptomatology.
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30
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Häusler D, Weber MS. Vitamin D Supplementation in Central Nervous System Demyelinating Disease-Enough Is Enough. Int J Mol Sci 2019; 20:E218. [PMID: 30626090 PMCID: PMC6337288 DOI: 10.3390/ijms20010218] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2018] [Revised: 12/24/2018] [Accepted: 12/24/2018] [Indexed: 01/30/2023] Open
Abstract
The exact cause of multiple sclerosis (MS) remains elusive. Various factors, however, have been identified that increase an individual's risk of developing this central nervous system (CNS) demyelinating disease and are associated with an acceleration in disease severity. Besides genetic determinants, environmental factors are now established that influence MS, which is of enormous interest, as some of these contributing factors are relatively easy to change. In this regard, a low vitamin D status is associated with an elevated relapse frequency and worsened disease course in patients with MS. The most important question, however, is whether this association is causal or related. That supplementing vitamin D in MS is of direct therapeutic benefit, is still a matter of debate. In this manuscript, we first review the potentially immune modulating mechanisms of vitamin D, followed by a summary of current and ongoing clinical trials intended to assess whether vitamin D supplementation positively influences the outcome of MS. Furthermore, we provide emerging evidence that excessive vitamin D treatment via the T cell-stimulating effect of secondary hypercalcemia, could have negative effects in CNS demyelinating disease. This jointly merges into the balancing concept of a therapeutic window of vitamin D in MS.
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Affiliation(s)
- Darius Häusler
- Institute of Neuropathology, University Medical Center, 37099 Göttingen, Germany.
| | - Martin S Weber
- Institute of Neuropathology, University Medical Center, 37099 Göttingen, Germany.
- Department of Neurology, University Medical Center, 37099 Göttingen, Germany.
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31
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Rolf L, Smolders J, van den Ouweland J, Hupperts R, Damoiseaux J. Correlation of different cellular assays to analyze T cell-related cytokine profiles in vitamin D 3-supplemented patients with multiple sclerosis. Mol Immunol 2018; 105:198-204. [PMID: 30550982 DOI: 10.1016/j.molimm.2018.12.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2018] [Revised: 10/31/2018] [Accepted: 12/04/2018] [Indexed: 01/13/2023]
Abstract
Different laboratory approaches have been exploited to analyze an effect of vitamin D3 supplements on T cell cytokine profiles in multiple sclerosis, with poorly reproducible results. We assessed the correlation between intra-cellular flowcytometry analysis of CD4 T cell-enriched CD3+CD8- lymphocytes after PMA/ionomycin stimulation directly ex-vivo or after 72 h pre-stimulation with anti-CD3, and cytokine levels excreted in culture supernatants. Pre-stimulation with anti-CD3 resulted in higher proportions of cells positive for IFN-γ, IL-17 A, IL-4, IL-10 and GM-CSF (all P < 0.001), but not TNF-α. Positive correlation between approaches was highly variable, but most eminent for IFN- γ and IL-4 (R = 0.608-0.612 and R = 0.677-0.777, resp., all P < 0.001). No effect of 16-weeks vitamin D3 supplements on any outcome was found except for a decreased TNF-α concentration in culture supernatants. Choice of immune-assay is, apparently, a relevant confounder for the reproducibility of individual studies.
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Affiliation(s)
- Linda Rolf
- Academic MS Center Limburg, Zuyderland Medical Center, Sittard, the Netherlands; School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Joost Smolders
- Academic MS Center Limburg, Zuyderland Medical Center, Sittard, the Netherlands; Department of Neurology, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
| | - Jody van den Ouweland
- Laboratory for Clinical Chemistry, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands
| | - Raymond Hupperts
- School for Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, the Netherlands
| | - Jan Damoiseaux
- Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands.
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Hodge R, Mandle HB, Ray S, Tandon S, Peterson M, Henry A, Jahan FA, Bostick RM, Baron JA, Barry EL, Yacoub R, Rutherford RE, Seabrook ME, Fedirko V. Effects of Supplemental Calcium and Vitamin D on Expression of Toll-Like Receptors and Phospho-IKKα/β in the Normal Rectal Mucosa of Colorectal Adenoma Patients. Cancer Prev Res (Phila) 2018; 11:707-716. [PMID: 30209117 PMCID: PMC6214739 DOI: 10.1158/1940-6207.capr-18-0123] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2018] [Revised: 07/19/2018] [Accepted: 08/28/2018] [Indexed: 02/06/2023]
Abstract
Chronic inflammation in the colorectum, a significant contributor to colorectal carcinogenesis, can be triggered by the activation of proinflammatory signaling pathways such as those initiated by Toll-like receptors (TLR) and nuclear factor κB (NF-κB). Although experimental evidence supports calcium and vitamin D potentially modifying these proinflammatory pathways in the colorectum, human data in these regards are scarce. We investigated supplemental calcium (1,200 mg daily) and/or vitamin D3 (1,000 IU daily) effects on inflammatory signaling pathway-related biomarkers in a subset of 105 participants from a colorectal adenoma recurrence chemoprevention clinical trial. We assessed expression of TLR4 and TLR5, which recognize the bacterial components lipopolysaccharides and flagellin, respectively, and phospho-IKKα/β (pIKKα/β), a biomarker of inflammation, in the normal-appearing rectal crypt epithelium and stroma using standardized, automated immunohistochemistry and quantitative image analysis. Following 1 year of treatment, TLR4, TLR5, and pIKKα/β expression in the rectal mucosa did not statistically significantly change with vitamin D or calcium supplementation, taken alone or in combination. Several baseline participant characteristics, including body mass index, history of sessile serrated adenomas, high red/processed meat intake, and high levels of rectal epithelial cell proliferation (as measured by MIB-1/Ki-67), were associated with higher baseline expression of TLRs or pIKKα/β. Our findings suggest that vitamin D and calcium may have no substantial effect on the investigated biomarkers. However, several modifiable lifestyle factors may be associated with TLRs and pIKKα/β expression in the normal rectal mucosa, supporting their future investigation as potentially treatable, preneoplastic risk factors for colorectal neoplasms. Cancer Prev Res; 11(11); 707-16. ©2018 AACR.
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Affiliation(s)
- Rebecca Hodge
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Hannah B Mandle
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Stephen Ray
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Sonia Tandon
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Meaghan Peterson
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Abigail Henry
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Ferdous A Jahan
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Roberd M Bostick
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
- Winship Cancer Institute, Emory University, Atlanta, Georgia
| | - John A Baron
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
- Department of Medicine, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
- University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Elizabeth L Barry
- Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire
| | - Rami Yacoub
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Robin E Rutherford
- Division of Digestive Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia
| | | | - Veronika Fedirko
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia.
- Winship Cancer Institute, Emory University, Atlanta, Georgia
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Reginald McDaniel H, LaGanke C, Bloom L, Goldberg S, Lages LC, Lantigua LA, Atlas SE, Woolger JM, Lewis JE. The Effect of a Polysaccharide-Based Multinutrient Dietary Supplementation Regimen on Infections and Immune Functioning in Multiple Sclerosis. J Diet Suppl 2018; 17:184-199. [PMID: 30285512 DOI: 10.1080/19390211.2018.1495675] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Multiple sclerosis (MS) is a progressive neurodegenerative disease associated with increased infection rates, chronic inflammation, and premature death. Optimization of nutritional status via dietary supplementation may improve immune function in people suffering from MS and lead to decreased rates of infection. Fifteen individuals with a diagnosis of relapsing-remitting MS for an average of 12.4 years (SD =7.4; R = 2, 25) were enrolled in a one-year open-label clinical trial. Participants consumed a broad-spectrum dietary supplement regimen containing polysaccharides, phytochemicals, antioxidants, vitamins, and minerals three times per day. The occurrence of infections and a panel of cytokines, growth factors, and T- and B-cell subsets were assessed at baseline and 12 months. Seven female and 8 male participants with an average age of 51.3 years (SD =7.2; R = 38, 65) completed the study. At the end of the intervention, participants had fewer total infections (M = 7.9, SD =8.1 at baseline and M = 2.5, SD =4.3 at 12-month follow-up). At 12 months, IL-2, TNF-α, EGF, and CD95 + CD34+ significantly increased, while IL-1β significantly decreased. No major adverse effects were reported; only mild gastrointestinal intolerance was reported in four cases. A decreased occurrence of infection was observed in MS patients treated with 12 months of a polysaccharide-based multinutrient dietary supplement. Significant changes were also noted in several key biomarkers that would be physiologically favorable to the MS population. Thus, the results of this study suggest an immunomodulatory effect of the dietary supplement regimen studied.
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Affiliation(s)
| | | | - Laura Bloom
- Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | | | - Lucas C Lages
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Laura A Lantigua
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Steven E Atlas
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Judi M Woolger
- Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - John E Lewis
- Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA
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Jagannath VA, Filippini G, Di Pietrantonj C, Asokan GV, Robak EW, Whamond L, Robinson SA. Vitamin D for the management of multiple sclerosis. Cochrane Database Syst Rev 2018; 9:CD008422. [PMID: 30246874 PMCID: PMC6513642 DOI: 10.1002/14651858.cd008422.pub3] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
BACKGROUND This review is an update of a previously published review, "Vitamin D for the management of multiple sclerosis" (published in the Cochrane Library; 2010, Issue 12). Multiple sclerosis (MS) is characterised by inflammation, demyelination, axonal or neuronal loss, and astrocytic gliosis in the central nervous system (CNS), which can result in varying levels of disability. Some studies have provided evidence showing an association of MS with low levels of vitamin D and benefit derived from its supplementation. OBJECTIVES To evaluate the benefit and safety of vitamin D supplementation for reducing disease activity in people with MS. SEARCH METHODS We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Specialized Register up to 2 October 2017 through contact with the Information Specialist with search terms relevant to this review. We included references identified from comprehensive electronic database searches and from handsearches of relevant journals and abstract books from conferences. SELECTION CRITERIA We included randomised controlled trials (RCTs) and quasi-RCTs that compared vitamin D versus placebo, routine care, or low doses of vitamin D in patients with MS. Vitamin D was administered as monotherapy or in combination with calcium. Concomitant interventions were allowed if they were used equally in all trial intervention groups. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed the methodological quality of studies, while another review author sorted any disagreements. We expressed treatment effects as mean differences (MDs) for continuous outcomes (Expanded Disability Status Scale and number of magnetic resonance imaging (MRI) gadolinium-enhancing T1 lesions), as standardised MDs for health-related quality of life, as rate differences for annualised relapse rates, and as risk differences (RDs) for serious adverse events and minor adverse events, together with 95% confidence intervals (CIs). MAIN RESULTS We identified 12 RCTs enrolling 933 participants with MS; 464 were randomised to the vitamin D group, and 469 to the comparator group. Eleven trials tested vitamin D₃, and one trial tested vitamin D₂. Vitamin D₃ had no effect on the annualised relapse rate at 52 weeks' follow-up (rate difference -0.05, 95% CI -0.17 to 0.07; I² = 38%; five trials; 417 participants; very low-quality evidence according to the GRADE instrument); on the Expanded Disability Status Scale at 52 weeks' follow-up (MD -0.25, 95% CI -0.61 to 0.10; I² = 35%; five trials; 221 participants; very low-quality evidence according to GRADE); and on MRI gadolinium-enhancing T1 lesions at 52 weeks' follow-up (MD 0.02, 95% CI -0.45 to 0.48; I² = 12%; two trials; 256 participants; very low-quality evidence according to GRADE). Vitamin D₃ did not increase the risk of serious adverse effects within a range of 26 to 52 weeks' follow-up (RD 0.01, 95% CI -0.03 to 0.04; I² = 35%; eight trials; 621 participants; low-quality evidence according to GRADE) or minor adverse effects within a range of 26 to 96 weeks' follow-up (RD 0.02, 95% CI -0.02 to 0.06; I² = 20%; eight trials; 701 participants; low-quality evidence according to GRADE). Three studies reported health-related quality of life (HRQOL) using different HRQOL scales. One study reported that vitamin D improved ratings on the psychological and social components of the HRQOL scale but had no effects on the physical components. The other two studies found no effect of vitamin D on HRQOL. Two studies reported fatigue using different scales. One study (158 participants) reported that vitamin D₃ reduced fatigue compared with placebo at 26 weeks' follow-up. The other study (71 participants) found no effect on fatigue at 96 weeks' follow-up. Seven studies reported on cytokine levels, four on T-lymphocyte proliferation, and one on matrix metalloproteinase levels, with no consistent pattern of change in these immunological outcomes. The randomised trials included in this review provided no data on time to first treated relapse, number of participants requiring hospitalisation owing to progression of the disease, proportion of participants who remained relapse-free, cognitive function, or psychological symptoms. AUTHORS' CONCLUSIONS To date, very low-quality evidence suggests no benefit of vitamin D for patient-important outcomes among people with MS. Vitamin D appears to have no effect on recurrence of relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), and MRI lesions. Effects on health-related quality of life and fatigue are unclear. Vitamin D₃ at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Seven ongoing studies will likely provide further evidence that can be included in a future update of this review.
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Affiliation(s)
- Vanitha A Jagannath
- Department of Paediatrics, American Mission Hospital, Manama, Manama, Bahrain, PO Box 1
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Abstract
Vitamin D exerts several immunological functions in addition to its homeostatic functions on calcium and bone metabolism. Current data show that relative vitamin D deficiency (< 75 nmol/l 25-hydroxyvitamin D) as well as acquired seasonal vitamin D deficiency (< 50 nmol/l) are frequent in Germany. As confirmed by our own data, UV exposure plays a major role for maintenance of vitamin D status, e.g., in patients with UV-triggered diseases, vitamin D deficiency is more frequent, even throughout the year. The beneficial impact of vitamin D on immune functions is highlighted by epidemiologic, genetic, and experimental evidence. In the past years, numerous publications have presented associations between vitamin D deficiency, on the one hand, and severity and prevalence of allergic asthma in children and adults, on the other hand.
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Moretti R, Morelli ME, Caruso P. Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact. Int J Mol Sci 2018; 19:2245. [PMID: 30065237 PMCID: PMC6121649 DOI: 10.3390/ijms19082245] [Citation(s) in RCA: 92] [Impact Index Per Article: 13.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 07/25/2018] [Accepted: 07/26/2018] [Indexed: 12/22/2022] Open
Abstract
It is widely known that vitamin D receptors have been found in neurons and glial cells, and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. Vitamin D helps the regulation of neurotrophin, neural differentiation, and maturation, through the control operation of growing factors synthesis (i.e., neural growth factor [NGF] and glial cell line-derived growth factor (GDNF), the trafficking of the septohippocampal pathway, and the control of the synthesis process of different neuromodulators (such as acetylcholine [Ach], dopamine [DA], and gamma-aminobutyric [GABA]). Based on these assumptions, we have written this review to summarize the potential role of vitamin D in neurological pathologies. This work could be titanic and the results might have been very fuzzy and even incoherent had we not conjectured to taper our first intentions and devoted our interests towards three mainstreams, demyelinating pathologies, vascular syndromes, and neurodegeneration. As a result of the lack of useful therapeutic options, apart from the disease-modifying strategies, the role of different risk factors should be investigated in neurology, as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long-term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.
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Affiliation(s)
- Rita Moretti
- Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
| | - Maria Elisa Morelli
- Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
| | - Paola Caruso
- Neurology Clinic, Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
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Zheng C, He L, Liu L, Zhu J, Jin T. The efficacy of vitamin D in multiple sclerosis: A meta-analysis. Mult Scler Relat Disord 2018; 23:56-61. [PMID: 29778041 DOI: 10.1016/j.msard.2018.05.008] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 05/08/2018] [Accepted: 05/11/2018] [Indexed: 12/26/2022]
Abstract
BACKGROUND Multiple sclerosis (MS) is a chronic inflammatory demyelination disorder in the central nervous system (CNS) leading to a high level of neurological disability. The pathogenesis of MS remains largely unknown, which explains the lack of significant efficacy of therapy in MS. Vitamin D deficiency is widely considered to be an environmental risk factor for MS. Many studies investigating the therapeutic effects of vitamin D on MS have been applied. The objective of this systematic review and meta-analysis was to evaluate the effectiveness of vitamin D in MS patients. METHODS To obtain a more comprehensive estimate of the efficacy of vitamin D on MS patients, we conducted a meta-analysis to determine the role of vitamin D in MS. The PubMed, EMBASE and Cochrane databases were searched in October 2017. Randomized, double-blind, placebo-controlled clinical trials recorded within the three main databases were considered. The analysis was conducted for two specific outcomes: Expanded Disability Status Scale (EDSS) score and annual relapse rate (ARR). RESULTS Vitamin D3 as add-on treatment had no significant therapeutic effect on MS according to EDSS score (mean difference -0.01 [95% CI -0.34 to 0.33]). The ARR was higher in the vitamin D group than in the placebo group (mean difference 0.05 [95% CI 0.01 to 0.1]). CONCLUSION Our findings suggest that vitamin D appeared to have no therapeutic effect on EDSS score or ARR in the patients with MS.
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Affiliation(s)
- Chao Zheng
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Xinmin Street 71, Changchun 130021, China
| | - Liang He
- Department of Urinary Surgery, The First Hospital of Jilin University, Changchun, China
| | - Lingling Liu
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Xinmin Street 71, Changchun 130021, China
| | - Jie Zhu
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Xinmin Street 71, Changchun 130021, China; Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | - Tao Jin
- Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Xinmin Street 71, Changchun 130021, China.
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Lu M, Taylor BV, Körner H. Genomic Effects of the Vitamin D Receptor: Potentially the Link between Vitamin D, Immune Cells, and Multiple Sclerosis. Front Immunol 2018; 9:477. [PMID: 29593729 PMCID: PMC5857605 DOI: 10.3389/fimmu.2018.00477] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Accepted: 02/22/2018] [Indexed: 12/12/2022] Open
Abstract
Vitamin D has a plethora of functions that are important for the maintenance of general health and in particular, the functional integrity of the immune system, such as promoting an anti-inflammatory cytokine profile and reducing the Treg/Th17 ratio. Multiple sclerosis (MS) is a chronic, inflammatory, and neurodegenerative central nervous system (CNS) disorder of probable autoimmune origin. MS is characterized by recurring or progressive demyelination and degeneration of the CNS due in part to a misguided immune response to as yet undefined (CNS) antigens, potentially including myelin basic protein and proteolipid protein. MS has also been shown to be associated significantly with environmental factors such as the lack of vitamin D. The role of vitamin D in the pathogenesis and progression of MS is complex. Recent genetic studies have shown that various common MS-associated risk-single-nucleotide polymorphisms (SNPs) are located within or in the vicinity of genes associated with the complex metabolism of vitamin D. The functional aspects of these genetic associations may be explained either by a direct SNP-associated loss- or gain-of-function in a vitamin D-associated gene or due to a change in the regulation of gene expression in certain immune cell types. The development of new genetic tools using next-generation sequencing: e.g., chromatin immunoprecipitation sequencing (ChIP-seq) and the accompanying rapid progress of epigenomics has made it possible to recognize that the association between vitamin D and MS could be based on the extensive and characteristic genomic binding of the vitamin D receptor (VDR). Therefore, it is important to analyze comprehensively the spatiotemporal VDR binding patterns that have been identified using ChIP-seq in multiple immune cell types to reveal an integral profile of genomic VDR interaction. In summary, the aim of this review is to connect genomic effects vitamin D has on immune cells with MS and thus, to contribute to a better understanding of the influence of vitamin D on the etiology and the pathogenesis of this complex autoimmune disease.
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Affiliation(s)
- Ming Lu
- Menzies Institute for Medical Research Tasmania, Hobart, TAS, Australia
| | - Bruce V. Taylor
- Menzies Institute for Medical Research Tasmania, Hobart, TAS, Australia
| | - Heinrich Körner
- Menzies Institute for Medical Research Tasmania, Hobart, TAS, Australia
- Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Engineering Technology Research Center of Anti-inflammatory and Immunodrugs in Anhui Province, Hefei, China
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Gubatan J, Mitsuhashi S, Longhi MS, Zenlea T, Rosenberg L, Robson S, Moss AC. Higher serum vitamin D levels are associated with protective serum cytokine profiles in patients with ulcerative colitis. Cytokine 2018; 103:38-45. [PMID: 29324259 DOI: 10.1016/j.cyto.2017.12.023] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 12/18/2017] [Accepted: 12/20/2017] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Vitamin D has immune modulating effects on cytokines. Serum vitamin D levels are associated with the risk of relapse in patients with ulcerative colitis (UC), through unknown mechanisms. We tested the hypothesis that this beneficial role of vitamin D on UC is mediated through anti-inflammatory serum cytokine profiles. METHODS Serum samples from a prospective cohort of seventy UC patients in clinical remission were collected and baseline histological and endoscopic scores were recorded at enrollment. Clinical relapse events were recorded over the 12-month follow-up period. Serum vitamin D and cytokines levels (IL-6, IL-8, IL-17A, TNF-α, IFN-γ, IL-4, IL-10) were quantified using ELISA. Linear regression was used to determine correlation between vitamin D and cytokine profiles. Logistic regression models were used to determine the association between serum cytokine profiles and baseline histologic mucosal healing and clinical relapse. RESULTS Higher serum vitamin D levels positively correlated with higher ratios of IL-4 + IL-10/IL-17A + TNF-α (r = 0.37, P < .01), and IL-4 + IL-10/IL-6 + TNF-α (r = 0.32, P < .01). In multivariate analysis, IL-4 + IL-10/IL-17A + TNF-α ratios at baseline were associated with the presence of histologic mucosal healing (O.R. 1.29, 95% CI 1.02-1.62, P = .03). A higher ratio of serum IL-4 + IL-10 to IL-6 + TNF-α was associated with a reduced risk of clinical relapse (O.R. 0.72, 95% CI 0.58-0.89, P = .003), and longer time to relapse (p = .03), over the 12-month follow-up period. This ratio during remission had an AUC of 0.7 in predicting later clinical relapse. CONCLUSIONS Vitamin D is associated with anti-inflammatory serum cytokine profiles. Anti-inflammatory cytokine patterns may mediate the protective effects of higher serum vitamin D levels in patients with ulcerative colitis.
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Affiliation(s)
- John Gubatan
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
| | - Shuji Mitsuhashi
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Maria Serena Longhi
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Talia Zenlea
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Laura Rosenberg
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Simon Robson
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
| | - Alan C Moss
- Department of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
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Wang C, Zeng Z, Wang B, Guo S. Lower 25-Hydroxyvitamin D Is Associated with Higher Relapse Risk in Patients with Relapsing-Remitting Multiple Sclerosis. J Nutr Health Aging 2018; 22:38-43. [PMID: 29300420 DOI: 10.1007/s12603-017-0894-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
OBJECTIVES To investigate the association between serum circulating 25-hydroxyvitamin D [25(OH) D] concentrations and exacerbation risk in Chinese patients with relapsing-remitting multiple sclerosis (RR-MS). METHODS From January 2014 to December 2014, consecutive RR-MS patients admitted to the Department of Neurology of our hospital were identified. Blood samples for 25(OH) D measurements were taken at admission. All included patients visited the outpatient clinic of our hospital 1 year after admission. The influence of serum 25[OH] D levels on exacerbation was performed by binary logistic regression analysis. RESULTS In this study, 109 patients finished the follow-up. Median follow-up time was 1 year (range 1.0-1.1). Twenty-one out of the 109 was at risk period for infection. A total of 32 patients experienced a total of 76 exacerbations during the study. In the follow-up, a total of 32 patients experienced exacerbations. Thus, the exacerbation rate was 29.4% (95%CI: 20.8%-37.9%). Exacerbation rates were found to decrease with increasing levels of serum 25-OH-D concentrations. For the quartiles category, the risk of an exacerbation was significantly increased in the group with first quartile compared to the group with fourth. Rate ratios for the first, second and third group were 4.2, 3.3 and 2.0, respectively (p for trend =0.011) when compared with the fourth group. Simultaneous evaluation of quartile categories of levels of serum 25(OH) D and infections showed that both factors were related to the exacerbation rate. CONCLUSION The data demonstrates that lower vitamin D status is a sign of more active disease in patients with RR-MS and suggests a beneficial effect of vitamin D on disease course in MS.
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Affiliation(s)
- C Wang
- Shougang Guo, NO.324, Jingwu Road, Huaiyin district, Jinan, 250021, China, ; Tel: +86 13220585081; Fax: +86-0531-80936542
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Koduah P, Paul F, Dörr JM. Vitamin D in the prevention, prediction and treatment of neurodegenerative and neuroinflammatory diseases. EPMA J 2017; 8:313-325. [PMID: 29209434 PMCID: PMC5700019 DOI: 10.1007/s13167-017-0120-8] [Citation(s) in RCA: 91] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2017] [Accepted: 10/18/2017] [Indexed: 12/14/2022]
Abstract
Vitamin D research has gained increased attention in recent times due to its roles beyond bone health and calcium homeostasis, such as immunomodulation. In some parts of the brain and on immune cells, vitamin D hydroxylating enzymes and its receptors are located. Epidemiological evidence demonstrates that deficiency of Vitamin D is relevant for disease risk and course in multiple sclerosis (MS) and presumably also in neuromyelitis optica spectrum disorders (NMOSD), Parkinson's disease (PD), and Alzheimer's disease (AD). Although the exact mechanism underlying vitamin D effects in these diseases remains widely unexplored, human and animal studies continue to provide some hints. While the majority of vitamin D researchers so far speculate that vitamin D may be involved in disease pathogenesis, others could not show any association although none have reported that sufficient vitamin D worsens disease progression. The studies presented in this review suggest that whether vitamin D may have beneficial effects in disease course or not, may be dependent on factors such as ethnicity, gender, diet, vitamin D receptor (VDR) polymorphisms and sunlight exposure. We here review the possible role of vitamin D in the pathogenesis and disease course of MS, NMOSD, PD, and AD and potential therapeutic effects of vitamin D supplementation which may be relevant for predictive, preventive, and personalized medicine. We suggest areas to consider in vitamin D research for future studies and recommend the need to supplement patients with low vitamin D levels below 30 ng/ml to at least reach sufficient levels.
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Affiliation(s)
- Priscilla Koduah
- Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt- Universitäts zu Berlin, and Berlin Institute of Health, Neurocure Cluster of Excellence, Berlin, Germany
| | - Friedemann Paul
- Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt- Universität zu Berlin, and Berlin Institute of Health, Neurocure Cluster of Excellence and Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité – Universitätsmedizin Berlin, Berlin, Germany
| | - Jan-Markus Dörr
- Charité – Universitätsmedizin, corporate member of Freie Universität Berlin, Humboldt- Universitäts zu Berlin, and Berlin Institute of Health, Neurocure Cluster of Excellence, and Multiple Sclerosis Center Hennigsdorf, Oberhavel Clinics, Berlin, Germany
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Vitamin D and Neurological Diseases: An Endocrine View. Int J Mol Sci 2017; 18:ijms18112482. [PMID: 29160835 PMCID: PMC5713448 DOI: 10.3390/ijms18112482] [Citation(s) in RCA: 88] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Revised: 11/18/2017] [Accepted: 11/20/2017] [Indexed: 02/07/2023] Open
Abstract
Vitamin D system comprises hormone precursors, active metabolites, carriers, enzymes, and receptors involved in genomic and non-genomic effects. In addition to classical bone-related effects, this system has also been shown to activate multiple molecular mediators and elicit many physiological functions. In vitro and in vivo studies have, in fact, increasingly focused on the "non-calcemic" actions of vitamin D, which are associated with the maintenance of glucose homeostasis, cardiovascular morbidity, autoimmunity, inflammation, and cancer. In parallel, growing evidence has recognized that a multimodal association links vitamin D system to brain development, functions and diseases. With vitamin D deficiency reaching epidemic proportions worldwide, there is now concern that optimal levels of vitamin D in the bloodstream are also necessary to preserve the neurological development and protect the adult brain. The aim of this review is to highlight the relationship between vitamin D and neurological diseases.
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van den Hoogen WJ, Laman JD, 't Hart BA. Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota. Front Immunol 2017; 8:1081. [PMID: 28928747 PMCID: PMC5591889 DOI: 10.3389/fimmu.2017.01081] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 08/21/2017] [Indexed: 12/11/2022] Open
Abstract
Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research.
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Affiliation(s)
| | - Jon D Laman
- Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Bert A 't Hart
- Department of Neuroscience, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.,Department of Immunobiology, Biomedical Primate Research Center, Rijswijk, Netherlands
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Iridoy Zulet M, Pulido Fontes L, Ayuso Blanco T, Lacruz Bescos F, Mendioroz Iriarte M. Epigenetic changes in neurology: DNA methylation in multiple sclerosis. NEUROLOGÍA (ENGLISH EDITION) 2017. [DOI: 10.1016/j.nrleng.2015.03.020] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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Chirumbolo S, Bjørklund G, Sboarina A, Vella A. The Role of Vitamin D in the Immune System as a Pro-survival Molecule. Clin Ther 2017; 39:894-916. [PMID: 28438353 DOI: 10.1016/j.clinthera.2017.03.021] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Revised: 03/30/2017] [Accepted: 03/31/2017] [Indexed: 02/07/2023]
Abstract
PURPOSE Vitamin D is a fascinating and attractive molecule that has gained particular attention in medicine in recent years. Its immunomodulatory and anti-inflammatory potential might resemble the activity of many nature-derived molecules (eg, flavonoids), but its role in biology was selected during a long evolutionary pathway to dampen the damaging effect of cell stress response and of the immune reaction. In this sense, this molecule can be considered an ancient hormone that serves, in its primary role, as a pro-survival agent. The goal of this review was to elucidate this topic. METHODS The article reviews current literature on the field, focusing on issues regarding the role of vitamin D in immunity. FINDINGS Vitamin D participates in the survival machinery used by the cell, and in particular it plays a major role in synchronizing calcium oscillatory signaling to allow cell autophagy or apoptosis during a stress response. IMPLICATIONS Vitamin D should be better highlighted in its molecular action and vitamin D receptor genomics to conceive a more suited therapeutic supplementation protocol in clinics.
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Affiliation(s)
- Salvatore Chirumbolo
- Department of Neurological and Movement Sciences, University of Verona, Verona, Italy.
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine, Mo i Rana, Norway
| | - Andrea Sboarina
- Department of Surgery, Dentistry, Gynaecology and Paediatrics, University of Verona, Verona, Italy
| | - Antonio Vella
- Department of Medicine-University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
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Milovanović OZ. Vitamin D Deficiency and its Importance - A Global Problem of Today, Realistic or Not? SERBIAN JOURNAL OF EXPERIMENTAL AND CLINICAL RESEARCH 2017. [DOI: 10.1515/sjecr-2016-0045] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Abstract
Vitamin D, also known as the “sun vitamin” in the literature, has been examined for many years and still arouses researchers’ interest due to the pleiotropic effects achieved in the human body. Because of the influence on mineral homeostasis, the initially observed effects of vitamin D on the prevention and treatment of rickets, have now been extended to a large number of diseases with different aetiologies such as cardiovascular, autoimmune, endocrine, infectious, neurological, malignant and other diseases. Due to the large number of experimental studies in animals and humans, we have exact information about the role of vitamin D in many of these conditions. Reaching an adequate level of 25(OH)D in the human body is a basic requirement for the realization of these effects; 25(OH)D is a metabolic product that reflects the vitamin D status but that does not have any biological activity. The biological activities of vitamin D can occur only after the formation of a second metabolic product, 1,25(OH)2D, in the kidneys. The three main sources of acquiring vitamin D are through food, skin and supplementation. Food is not a rich source of vitamin D; it is clear that the most important influences to achieve an optimal vitamin D status in the human body are vitamin D synthesis at the skin and adequate supplementation intake. An alarming fact is that vitamin D deficiency is detected in an increasing number of people from one day to another in the general world population and that this condition has pandemic dimensions. Introducing the beneficial effects and sources of vitamin D to the general population and to medical experts with adequate supplementation regime can decrease the number of people who are vitamin D deficient.
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Luque-Córdoba D, Luque de Castro MD. Metabolomics: A potential way to know the role of vitamin D on multiple sclerosis. J Pharm Biomed Anal 2016; 136:22-31. [PMID: 28063332 DOI: 10.1016/j.jpba.2016.12.023] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2016] [Revised: 12/15/2016] [Accepted: 12/16/2016] [Indexed: 02/07/2023]
Abstract
The literature about the influence of vitamin D on multiple sclerosis (MS) is very controversial, possibly as a result of the way through which the research on the subject has been conducted. The studies developed so far have been focused exclusively on gene expression: the effect of a given vitamin D metabolite on target receptors. The influence of the vitamin D status (either natural or after supplementation) on MS has been studied by measurement of the 25 monohydroxylated metabolite (also known as circulating form), despite the 1,25 dihydroxylated metabolite is considered the active form. In the light of the multiple metabolic pathways in which both forms of vitamin D (D2 and D3) are involved, monitoring of the metabolites is crucial to know the activity of the target enzymes as a function of both the state of the MS patient and the clinical treatment applied. The study of metabolomics aspects is here proposed to clarify the present controversy. In "omics" terms, our proposal is to take profit from up-stream information-thus is, from metabolomics to genomics-with a potential subsequent step to systems biology, if required.
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Affiliation(s)
- Diego Luque-Córdoba
- Department of Analytical Chemistry, Annex Marie Curie Building, Campus of Rabanales, University of Córdoba, Córdoba, Spain; University of Córdoba Agroalimentary Excellence Campus, ceiA3, Spain; Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofía University Hospital, University of Córdoba, E-14005 Córdoba, Spain
| | - María D Luque de Castro
- Department of Analytical Chemistry, Annex Marie Curie Building, Campus of Rabanales, University of Córdoba, Córdoba, Spain; University of Córdoba Agroalimentary Excellence Campus, ceiA3, Spain; Maimónides Institute of Biomedical Research (IMIBIC), Reina Sofía University Hospital, University of Córdoba, E-14005 Córdoba, Spain.
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Pimentel SP, Casarin RC, Ribeiro FV, Cirano FR, Rovaris K, Haiter Neto F, Casati MZ. Impact of micronutrients supplementation on bone repair around implants: microCT and counter-torque analysis in rats. J Appl Oral Sci 2016; 24:45-51. [PMID: 27008256 PMCID: PMC4775009 DOI: 10.1590/1678-775720150293] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 11/12/2015] [Indexed: 01/04/2023] Open
Abstract
UNLABELLED The use of natural substances and micronutritional approaches has been suggested as a therapeutic alternative to benefit the bone healing associated with no side effects. Nevertheless, the influence of micronutritional interventions with therapeutic proprieties on the bone repair has yet to be intensely evaluated, and no evidence is available exploring the impact of micronutrient supplementation on the peri-implant bone healing. OBJECTIVE This study investigated the effect of micronutrients supplementation on the bone repair around implants. MATERIAL AND METHODS One screw-shaped titanium implant was inserted in each tibia of each rat, which were assigned to: daily administration, for 30 d, of the placebo solution (Placebo group-n:18) or micronutrients supplementation (Micronutrients group-n:18), based on calcium, magnesium, zinc, and vitamin D3 intake. After, the animals were sacrificed. One of the implants was removed by applying a counter-torque force to evaluate the force to rupture the bone-implant interface. The other implant was evaluated by microcomputed tomography (CT) examination to determine the bone-to-implant contact (BIC) and the bone volume (BV/TV). RESULTS No statistically significant differences were observed between the groups for both counter-torque values and microCT parameters (p>0.05). CONCLUSION Within the limits of this study, micronutrients supplementation did not provide additional benefits to the bone healing around dental implants.
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Affiliation(s)
| | | | | | | | - Karla Rovaris
- Departamento de Radiologia, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, Piracicaba, SP, Brasil
| | - Francisco Haiter Neto
- Departamento de Radiologia, Faculdade de Odontologia de Piracicaba, Universidade Estadual de Campinas, Piracicaba, SP, Brasil
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Immune regulatory effects of high dose vitamin D 3 supplementation in a randomized controlled trial in relapsing remitting multiple sclerosis patients receiving IFNβ; the SOLARIUM study. J Neuroimmunol 2016; 300:47-56. [PMID: 27806875 DOI: 10.1016/j.jneuroim.2016.09.018] [Citation(s) in RCA: 64] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 09/26/2016] [Accepted: 09/30/2016] [Indexed: 11/20/2022]
Abstract
Multiple sclerosis (MS) is characterized by a disturbed immune homeostasis and low serum vitamin D levels are associated with an increased disease activity. While vitamin D has been hypothesized to promote the maintenance of immune homeostasis, vitamin D supplementation could be of benefit to patients with MS. The SOLAR study investigated the effects of high dose vitamin D3 supplementation on clinical outcomes in a randomized controlled trial. Here we present the immune regulatory effects, investigated in the SOLARIUM sub-study. Thirty Dutch relapsing remitting (RR) MS patients treated with IFNβ-1a received high dose vitamin D3 supplementation and 23 patients received placebo during a period of 48weeks. Lymphocytes were phenotypically characterized by flow cytometry and in vitro cytokine secretion was assessed in the presence or absence of 1,25(OH)2D3 using Luminex technology. Changes in immune regulatory parameters were determined within subjects as well as between treatment groups. The proportion of cells in the immune regulatory cell compartment (nTreg, iTreg and Breg) was not altered upon high dose vitamin D3 supplementation. Proportions of T helper subsets were not affected by vitamin D3, except for the proportion of IL4+ Th cells, which decreased in the placebo but not in the vitamin D3 group. T cell cytokine secretion increased, most pronounced for IL5 and latency activated protein of TGFβ, in the placebo group but not in the vitamin D3 group. Lymphocytes remained equally reactive to in vitro 1,25(OH)2D3. In conclusion, high dose vitamin D3 supplementation did not result in a relative increase in lymphocytes with a regulatory phenotype. However, this study supports the hypothesis that vitamin D contributes to the maintenance of immune homeostasis by preventing further disturbance of the T cell compartment early in the disease course of MS.
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Simmons RD, Ponsonby AL, van der Mei IAF, Sheridan P. What affects your MS? Responses to an anonymous, Internet-based epidemiological survey. Mult Scler 2016; 10:202-11. [PMID: 15124768 DOI: 10.1191/1352458504ms1006oa] [Citation(s) in RCA: 58] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Evolving information techno logy has raised the possibility of new methods of data collection in multiple sclerosis (MS) research. A n anonymous, self-report, Internet-based survey was developed, which asked people with MS their opinion on how various extrinsic factors affected their condition. From September 2001 to July 2002, a total of 2529 people completed the questionnaire. The demographic and clinical profiles of the anonymous respondents indicated that most were likely to have MS. C ommon factors reported as beneficial were cannabis, cold baths, meditation and dietar y factors. C ommon adverse factors reported were high stress, exposure to high temperatures and viral infections. There was an increasing report of high temperatures as being adverse with increasing respondent age (test for trend, P B-0.001). The adverse report of high temperatures correlated significantly with the report of strong sunlight apparently making MS worse (r =0.35, P B-0.0001). In A ustralia, high temperatur es were more likely to be reported as adverse in warmer, lower latitude regions. The association between strong sunlight as adverse and age or region did not persist after adjustment for high temperatures. Thus, this apparent adverse factor appeared to relate to solar heat, not solar light. People with MS may risk vitamin D deficiency because of sun avoidance due to heat-related fatigue or intolerance. This is of clinical significance not only for bone health but because vitamin D may have beneficial immunomodulatory properties. The present study provides new information from people with MS on factors that may influence symptoms or clinical course. This information will now be used in the design of formal epidemiological cohort studies.
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