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25-Hydroxyvitamin D concentrations do not affect the humoral or cellular immune response following SARS-CoV-2 mRNA vaccinations.
Lavell, AHA, Schramade, AE, Sikkens, JJ, van der Straten, K, van Dort, KA, Slim, MA, Appelman, B, van Vught, LA, Vlaar, APJ, Kootstra, NA, et al
Vaccine. 2024;(7):1478-1486
Abstract
BACKGROUND To improve effectiveness of vaccination against SARS-CoV-2, it is important to identify factors that influence the immune response induced by vaccination. Evidence for the role of vitamin D in immune response against SARS-CoV-2 is contradictory. It is therefore of interest whether 25-hydroxyvitamin D (25[OH]D) concentrations affect the humoral and/or cellular response following SARS-CoV-2 vaccination. METHODS In this prospective cohort study, blood samples were collected from 98 SARS-CoV-2 naive health care workers (HCW) receiving the first two doses of either BNT162b2 or mRNA-1273 in 2021. Wild-type spike (S) protein binding and neutralizing antibodies were determined approximately three weeks after the first dose and four to five weeks after the second dose. Antigen specific T-cells and functionality (proliferative response and interferon gamma [IFN-γ] release) were determined in 18 participants four weeks after the second dose of BNT162b2. We studied the association between 25(OH)D concentrations, which were determined prior to vaccination, and humoral and cellular immune responses following vaccination. RESULTS We found no association between 25(OH)D concentrations (median 55.9 nmol/L [IQR 40.5-69.8]) and binding or neutralizing antibody titers after complete vaccination (fold change of antibody titers per 10 nmol/L 25(OH)D increase: 0.98 [95% CI 0.93-1.04] and 1.03 [95% CI: 0.96-1.11], respectively), adjusted for age, sex and type of mRNA vaccine. Subsequently, continuous 25(OH)D concentrations were divided into commonly used clinical categories (<25 nmol/L [n = 6, 6%], 25-49 nmol/L [n = 33, 34%], 50-75 nmol/L [n = 37, 38%] and ≥75 nmol/L [n = 22, 22%]), but no association with the humoral immune response following vaccination was found. Also, 25(OH)D concentrations were not associated with the SARS-CoV-2 specific T cell response. CONCLUSION No association was found between 25(OH)D concentrations and the humoral or cellular immune response following mRNA vaccination against SARS-CoV-2. Based on our findings there is no rationale to advise vitamin D optimization preceding SARS-CoV-2 vaccination in HCW with moderate vitamin D status.
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Effects of Vitamin D on Respiratory Function and Immune Status for Patients with Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review and Meta-Analysis.
Yang, H, Sun, D, Wu, F, Xu, X, Liu, X, Wang, Z, Zhou, L
Computational and mathematical methods in medicine. 2022;:2910782
Abstract
BACKGROUND Many studies have demonstrated that vitamin D has clinical benefits when used to treat patients with chronic obstructive pulmonary disease (COPD). However, most of these studies have insufficient samples or inconsistent results. The aim of this meta-analysis was to evaluate the effects of vitamin D therapy in patients with COPD. METHODS We performed a comprehensive retrieval in the following electronic databases: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journals Database (VIP). Two trained reviewers identified relevant studies, extracted data information, and then assessed the methodical quality by the Cochrane risk of bias assessment tool, independently. Then, the meta-analyses were conducted by RevMan 5.4, binary variables were represented by risks ratio (RR), and continuous variables were represented by mean difference (MD) or standardized mean difference (SMD) to assess the efficacy of vitamin D therapy in patients with COPD. Then, publication bias assessment was conducted by funnel plot analysis. Finally, the quality of evidence was assessed by the GRADE system. RESULTS A total of 15 articles involving 1598 participants were included in this study. The overall results showed a statistical significance of vitamin D therapy in patients with COPD which can significantly improve forced expiratory volume in 1 second (FEV1) (MD: 5.69, 95% CI: 5.01-6.38,P < 0.00001,I2 = 51%) and FEV1/FVC (SMD:0.49, 95% CI: 0.39-0.60,P < 0.00001,I2 = 84%); and serum 25 (OH)D (SMD:1.21, 95% CI:1.07-1.34,P < 0.00001,I2 = 98%) also increase CD3+ Tcells (MD: 6.67, 95% CI: 5.34-8.00,P < 0.00001,I2 = 78%) and CD4+ T cells (MD: 6.00, 95% CI: 5.01-7.00,P < 0.00001,I2 = 65%); and T lymphocyte CD4+/CD8+ ratio (MD: 0.41, 95% CI: 0.20-0.61,P = 0.0001,I2 = 95%) obviously decrease CD8+ Tcells(SMD: -0.83, 95% CI: -1.05- -0.06,P < 0.00001,I2 = 82%), the times of acute exacerbation (RR: 0.40, 95% CI: 0.28-0.59,P < 0.00001,I2 = 0%), and COPD assessment test (CAT) score (MD: -3.77, 95% CI: -5.86 - -1.68,P = 0.0004,I2 = 79%). CONCLUSIONS Our analysis indicated that vitamin D used in patients with COPD could improve the lung function (FEV1 and FEV1/FVC), the serum 25(OH)D, CD3+ T cells, CD4 + T cells, and T lymphocyte CD4+/CD8+ ratio and reduce CD8+ T cells, acute exacerbation, and CAT scores.
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Vitamin D, Epstein-Barr virus, and endogenous retroviruses in multiple sclerosis - facts and hypotheses.
Brütting, C, Stangl, GI, Staege, MS
Journal of integrative neuroscience. 2021;(1):233-238
Abstract
The pathogenesis of multiple sclerosis (MS) remains poorly understood. Presumably, MS is caused by multiple environmental, epigenetic, and genetic factors. Among them, human endogenous retroviruses (HERVs), Epstein-Barr virus (EBV) and vitamin D have been suggested to play a role in the pathogenesis and course of MS. Because vitamin D can affect the immune system and infections, it can be hypothesized that there is a close interplay between vitamins, EBV and ERV in the pathogenesis of MS. Here, we summarize the important data on vitamin D, including polymorphisms in genes related to vitamin D metabolism, EBV and ERV, in the pathogenesis of MS and create hypotheses regarding their interactions. Data indicate that vitamin D has a strong impact on viral infections and interferes with EBV infection, while EBV is capable of activating silent ERVs. We believe that EBV could be the missing link between vitamin D and ERV in MS pathogenesis.
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Supplementation with vitamin D in the COVID-19 pandemic?
Hadizadeh, F
Nutrition reviews. 2021;(2):200-208
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Abstract
The coronavirus disease 2019 (COVID-19) pandemic was declared a public health emergency of international concern by the World Health Organization. COVID-19 has high transmissibility and could result in acute lung injury in a fraction of patients. By counterbalancing the activity of the renin-angiotensin system, angiotensin-converting enzyme 2, which is the fusion receptor of the virus, plays a protective role against the development of complications of this viral infection. Vitamin D can induce the expression of angiotensin-converting enzyme 2 and regulate the immune system through different mechanisms. Epidemiologic studies of the relationship between vitamin D and various respiratory infections were reviewed and, here, the postulated mechanisms and clinical data supporting the protective role of vitamin D against COVID-19-mediated complications are discussed.
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EFFECTS OF VITAMIN D SUPPLEMENTATION DURING PREGNANCY ON NEWBORNS AND INFANTS: AN INTEGRATIVE REVIEW.
Dutra, LV, Souza, FIS, Konstantyner, T
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo. 2021;:e2020087
Abstract
OBJECTIVE To identify the effects of vitamin D supplementation during pregnancy on newborns and infants. DATA SOURCES The present study is an integrative review of literature based on clinical trials published in journals indexed in the PubMed and Web of Science databases. Two searches were carried out, starting with the association (and) of the health term "vitamin D" with "pregnancy". In the search for information, selection criteria were established, and there was no language limitation and year of publication. DATA SYNTHESIS The final selection resulted in 44 clinical trials, most of which were randomized and double blind, which were carried out in outpatient clinics, referral hospitals and universities, mainly in Europe. The samples studied were predominantly of newborns. In these 44 trials, 23 types of different doses of vitamin D during pregnancy, with different doses, regimens and times of use, and 14 different outcomes were studied in newborns (NB) and infants. Of the 44 studies performed, 35 showed statistically significant beneficial effects of vitamin D supplementation during pregnancy on newborns and infants compared to control groups. CONCLUSIONS Vitamin D supplementation during pregnancy for at least three months before delivery has the potential of positively influencing calcium metabolism, physical growth and immune system development in newborns and infants. However, there is insufficient knowledge to define the optimal dose and to guarantee the absence of possible long-term adverse effects.
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Vitamin D and Allergy Susceptibility during Gestation and Early Life.
Briceno Noriega, D, Savelkoul, HFJ
Nutrients. 2021;(3)
Abstract
Worldwide, the prevalence of allergies in young children, but also vitamin D deficiency during pregnancy and in newborns is rising. Vitamin D modulates the development and activity of the immune system and a low vitamin D status during pregnancy and in early life might be associated with an increased risk to develop an allergy during early childhood. This review studies the effects of vitamin D during gestation and early life, on allergy susceptibility in infants. The bioactive form of vitamin D, 1,25(OH)2D, inhibits maturation and results in immature dendritic cells that cause a decreased differentiation of naive T cells into effector T cells. Nevertheless, the development of regulatory T cells and the production of interleukin-10 was increased. Consequently, a more tolerogenic immune response developed against antigens. Secondly, binding of 1,25(OH)2D to epithelial cells induces the expression of tight junction proteins resulting in enhanced epithelial barrier function. Thirdly, 1,25(OH)2D increased the expression of anti-microbial peptides by epithelial cells that also promoted the defense mechanism against pathogens, by preventing an invasive penetration of pathogens. Immune intervention by vitamin D supplementation can mitigate the disease burden from asthma and allergy. In conclusion, our review indicates that a sufficient vitamin D status during gestation and early life can lower the susceptibility to develop an allergy in infants although there remains a need for more causal evidence.
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Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc.
Corrao, S, Mallaci Bocchio, R, Lo Monaco, M, Natoli, G, Cavezzi, A, Troiani, E, Argano, C
Nutrients. 2021;(4)
Abstract
More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.
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Vitamin D Receptor Gene Single Nucleotide Polymorphisms and Association With Vitamin D Levels and Endoscopic Disease Activity in Inflammatory Bowel Disease Patients: A Pilot Study.
Shirwaikar Thomas, A, Criss, ZK, Shroyer, NF, Abraham, BP
Inflammatory bowel diseases. 2021;(8):1263-1269
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Abstract
BACKGROUND Inflammatory bowel diseases (IBDs) comprise a heterogenous group of chronic gastrointestinal disorders that are multifactorial in etiology. Experimental in vitro and in vivo studies suggest that intestinal vitamin D receptor (VDR) signaling plays a role in modulating the immune response in IBD as a cause and/or a consequence of chronic inflammation. AIM: The aim of this study is to study the associations between vitamin D receptor gene single nucleotide polymorphisms(SNPs), vitamin D levels, and endoscopic disease activity in IBD. METHODS This is a cross-sectional analysis of IBD patients who underwent endoscopic evaluation at a tertiary care hospital. Demographic variables, IBD disease type and location, medical therapies, vitamin D levels, and endoscopic disease activity were collected. Colonic biopsies obtained were investigated for the presence of VDR SNPs: ApaI, TaqI, BsmI, FokI, and Tru9I. RESULTS Patients in endoscopic remission had higher vitamin D levels compared with those with inflammation found on endoscopy (P = <0.001). Patients with lower vitamin D levels were homozygous for Fok ancestral alleles (P = 0.0045). With regard to endoscopic disease activity, we found no differences in mutations of any of the VDR SNPs in our sample. CONCLUSIONS The association between the presence of the ancestral FokI and lower vitamin D levels suggests a multifactorial etiology for vitamin D deficiency in IBD. Higher vitamin D levels in those in endoscopic remission compared with lower levels in those with active inflammation suggests that the impact of VDR gene SNP on disease activity may be overcome with replacement therapy.
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COVID-19 and IL-6: Why vitamin D (probably) helps but tocilizumab might not.
Silberstein, M
European journal of pharmacology. 2021;:174031
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Interleukin 6 (IL-6), which is involved in the cytokine storm phenomenon, is a therapeutic target in COVID-19, but monoclonal receptor antibody therapeutic agents such as tocilizumab have demonstrated mixed results. Could Vitamin D, which modulates IL-6, be more effective than currently deployed IL-6 antagonists, including tocilizumab, thereby presenting a useful therapeutic option in COVID-19? A narrative review of published trials examining the effect of Vitamin D administration in COVID-19 patients was conducted, and the theoretical basis for the use of tocilizumab as an IL-6 antagonist was compared with the immunomodulatory effect of Vitamin D on IL-6 production. Four of the six included studies reported a positive effect of Vitamin D on outcomes. While tocilizumab non-selectively blocks both anti-inflammatory and pro-inflammatory actions of IL-6, Vitamin D lowers immune cell IL-6 production, potentially reducing pro-inflammatory effects, but does not specifically target IL-6 receptors, avoiding any deleterious effect on the anti-inflammatory actions of IL-6. Vitamin D may have advantages over tocilizumab as an IL-6 immunomodulator, and, given that it is safe if administered under clinical supervision, there is a strong rationale for its use.
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The Effects of Vitamin D Supplementation on Metabolic and Oxidative Stress Markers in Patients With Type 2 Diabetes: A 6-Month Follow Up Randomized Controlled Study.
Cojic, M, Kocic, R, Klisic, A, Kocic, G
Frontiers in endocrinology. 2021;:610893
Abstract
Vitamin D deficiency could play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) as it may alter several crucial processes in the development of diabetes and its complications, such as pancreatic insulin secretion, peripheral insulin resistance, persistence of systemic "sterile" inflammation and immune activation. Vitamin D may also have an antioxidant effect through the inhibition of free radicals generation. The reported study was designed with eligible consecutively recruited patients with T2DM on standard metformin therapy (n=130), randomized in 1:1 ratio, considered to have undergone Vitamin D supplementation according to the guidelines proposed by the Endocrine Society, or to have continued with metformin only. The potential benefit was monitored through the influence on glycemia level, glycated haemoglobin (HbA1c), insulin resistance index (calculated as homeostatic model assessment; HOMA-IR), Castelli Risk Index I and Tryglicerides/Thiobarbituric acid-reactive substances (TG/TBARS) Index in a 6-month follow up period. Our study indicates that oral daily doses of vitamin D improve HbA1c levels over the 3-month and 6-month period, followed by a significant decrease in advanced oxidation protein products levels over the 3-month period when higher vitamin D doses are given. The effect of vitamin D on HOMA-IR index, malondialdehyde levels and TG/TBARS index was not statistically significant. Further investigation should consider defining the doses of vitamin D in patients with T2DM which may attenuate the oxidative stress risk, the risk of metabolic syndrome and the risk of related cardiovascular events.