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1.
Vitamin D3 as Potential Treatment Adjuncts for COVID-19.
Malaguarnera, L
Nutrients. 2020;(11)
Abstract
Severe acute respiratory syndrome coronavirus type (SARS-CoV2, also known as COVID-19), which is the latest pandemic infectious disease, constitutes a serious risk to human health. SARS-CoV2 infection causes immune activation and systemic hyperinflammation which can lead to respiratory distress syndrome (ARDS). ARDS victims are characterized by a significant increase in IL-6 and IL-1. Macrophage activation, associated with the "cytokine storm", promotes the dysregulation of the innate immunity. So far, without vaccines or specific therapy, all efforts to design drugs or clinical trials are worthwhile. Vitamin D and its receptor vitamin D receptor (VDR) exert a critical role in infections due to their remarkable impact on both innate and adaptive immune responses and on the suppression of the inflammatory process. The protective properties of vitamin D supplementation have been supported by numerous observational studies and by meta-analysis of clinical trials for prevention of viral acute respiratory infection. In this review, we compare the mechanisms of the host immune response to SARS-CoV2 infection and the immunomodulatory actions that vitamin D exerts in order to consider the preventive effect of vitamin D supplementation on SARS-CoV2 viral infection.
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Efficiency of Vitamin D Supplementation in Healthy Adults is Associated with Body Mass Index and Baseline Serum 25-Hydroxyvitamin D Level.
Žmitek, K, Hribar, M, Hristov, H, Pravst, I
Nutrients. 2020;(5)
Abstract
Vitamin D (VitD) has a critical role in phosphorous-calcium metabolism as well as an important role in the immune system. In the human body, VitD is synthesized as cholecalciferol in the skin, but this process requires sunlight (UVB) radiation. Numerous reports showed high prevalence of VitD deficiency, particularly during the winter season, indicating the importance of VitD supplementation. Various factors can affect the absorption of VitD, including dosage and formulation. The primary study objective was to examine the efficiency of supplementation with three different formulations containing cholecalciferol in comparison with the control group. The secondary objective was to identify other factors affecting increase in serum 25-OH-VitD. A randomized controlled intervention study was conducted in Slovenia during wintertime (January- March) on 105 apparently healthy subjects (aged 18-65 years) with suboptimal VitD status (25-OH-VitD 30-50 nmol/L). Subjects were randomized into four groups: three treatment groups receiving (A) capsules with starch-adsorbed VitD, (B) oil-based Valens VitD oral spray, or (C) water-based Valens VitD oral spray and a control group (D) which did not receive supplemental VitD. Two months of supplementation with cholecalciferol (1000 IU; 25 µg daily) resulted in significant increase in serum 25-OH-VitD levels in comparison with control group (pooled Δc 32.8 nmol/L; 95% CI: 23.0, 42.5, p < 0.0001). While we did not observe any significant differences between the tested formulations, the efficiency of supplementation was associated with body mass index and baseline serum 25-OH-VitD level. Higher supplementation efficiency was observed in participants with normal body weight (BMI < 25) and in those with more pronounced VitD insufficiency. We also determined that tested dosage was not sufficient to achieve recommended 25-OH-VitD levels in all subjects.
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3.
Serum vitamin D level was not associated with severity of ventilator associated pneumonia.
Yaghoobi, MH, Taher, A, Seifrabie, MA, Sabahi, M, Rahimi-Bashar, F
Romanian journal of internal medicine = Revue roumaine de medecine interne. 2019;(1):55-60
Abstract
BACKGROUND AND OBJECTIVE Vitamin D deficiency is considered one of the most common nutritional deficiencies associated with weakened immune system and increased likelihood of sepsis. The current study was conducted to investigate the association between serum vitamin D level and the severity and prognosis of ventilator associated pneumonia (VAP) in inpatients in intensive care unit (ICU). METHODS Eighty-four consecutive patients with VAP were enrolled in this observational, prospective study conducted in the ICU of Besat Hospital, Hamadan. The patients were examined for serum 25-hydroxyvitamin D (vitD3) level and VAP severity and prognosis. Clinical pulmonary infection score was used for the diagnosis, and Sequential Organ Failure Assessment (SOFA) Score was used to determine the severity of VAP. RESULTS Low level serum vitD3 (under 30 ng/mL) was found in 66 (78.6%) patients. In this series of VAP patients, there were no significant differences in blood culture results, 14 and 28-day sepsis-associated mortality, mechanical ventilation duration, or SOFA Score on days 3, 7, and 14 between the low level and normal level vitD3 patients (p > 0.05). CONCLUSION Serum vitD3 level was not associated with mortality from VAP or complications due to sepsis in the inpatients in the ICU.
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4.
Comparison of the Association between Circulating Vitamin D3 Levels and Clinical Outcomes in Patients with Asthma and Chronic Obstructive Pulmonary Disease: A Prospective Observational Study.
Hirai, K, Shirai, T, Suzuki, Y, Shimomura, T, Itoh, K
Biological & pharmaceutical bulletin. 2019;(11):1861-1866
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Abstract
Vitamin D has an immune-modulating effect, related to the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD). However, few studies have focused on the difference between patients with asthma and COPD in the association of circulating vitamin D levels with clinical outcomes. We sought to investigate the associations of circulating vitamin D levels with health-related QOL (HR-QOL), severity, and exacerbations. Subjects included 152 asthma patients and 50 COPD patients. We measured plasma concentrations of 25-hydroxyvitamin D3 [25(OH)D3]. HR-QOL was assessed using the EuroQoL 5-Dimension (EQ-5D) and the 12-item Short Form Health Survey (SF-12) scales. Exacerbations were recorded during a one-year follow-up. Associations between plasma 25 (OH)D3 concentrations and outcome variables were evaluated using linear regression. Plasma concentrations of 25(OH)D3 were positively associated with the EQ-5D index value and the SF-12 physical component score in patients with asthma; however, such associations were not observed in patients with COPD. A significant association between severity and plasma concentrations of 25(OH)D3 was found only in patients with COPD. The hazard ratios (95% confidence interval) of plasma 25(OH)D3 concentrations (per 1 ng/mL decrease) for time to first exacerbation was 1.38 (1.10-1.75; p = 0.006) and 0.95 (0.87-1.03; p = 0.179) in patients with COPD and asthma, respectively. Lower concentrations of plasma 25(OH)D3 contributed to lower HR-QOL in patients with asthma, and were associated with severity and risk of future exacerbations in patients with COPD.
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5.
Nutrigenomics of Vitamin D.
Carlberg, C
Nutrients. 2019;(3)
Abstract
Nutrigenomics studies how environmental factors, such as food intake and lifestyle, influence the expression of the genome. Vitamin D₃ represents a master example of nutrigenomics, since via its metabolite 1α,25-dihydroxyvitamin D₃, which binds with high-affinity to the vitamin D receptor, the secosteroid directly affects the epigenome and transcriptome at thousands of loci within the human genome. Vitamin D is important for both cellular metabolism and immunity, as it controls calcium homeostasis and modulates the response of the innate and adaptive immune system. At sufficient UV-B exposure, humans can synthesize vitamin D₃ endogenously in their skin, but today's lifestyle often makes the molecule a true vitamin and micronutrient that needs to be taken up by diet or supplementation with pills. The individual's molecular response to vitamin D requires personalized supplementation with vitamin D₃, in order to obtain optimized clinical benefits in the prevention of osteoporosis, sarcopenia, autoimmune diseases, and possibly different types of cancer. The importance of endogenous synthesis of vitamin D₃ created an evolutionary pressure for reduced skin pigmentation, when, during the past 50,000 years, modern humans migrated from Africa towards Asia and Europe. This review will discuss different aspects of how vitamin D interacts with the human genome, focusing on nutritional epigenomics in context of immune responses. This should lead to a better understanding of the clinical benefits of vitamin D.
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Exploring the effect of vitamin D3 supplementation on the anti-EBV antibody response in relapsing-remitting multiple sclerosis.
Rolf, L, Muris, AH, Mathias, A, Du Pasquier, R, Koneczny, I, Disanto, G, Kuhle, J, Ramagopalan, S, Damoiseaux, J, Smolders, J, et al
Multiple sclerosis (Houndmills, Basingstoke, England). 2018;(10):1280-1287
Abstract
BACKGROUND Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS). OBJECTIVES To investigate the effect of high-dose vitamin D3 supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels. METHODS This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks. Circulating levels of 25-hydroxyvitamin-D, and anti-EBNA-1, anti-EBV viral capsid antigen (VCA), and anti-cytomegalovirus (CMV) antibodies were measured. EBV load in leukocytes, EBV-specific cytotoxic T-cell responses, and anti-EBNA-1 antibody production in vitro were also explored. RESULTS The median antibody levels against EBNA-1, but not VCA and CMV, significantly reduced in the vitamin D3 group (526 (368-1683) to 455 (380-1148) U/mL) compared to the placebo group (432 (351-1280) to 429 (297-1290) U/mL; p = 0.023). EBV load and cytotoxic T-cell responses were unaffected. Anti-EBNA-1 antibody levels remained below detection limits in B-cell cultures. CONCLUSION High-dose vitamin D3 supplementation selectively reduces anti-EBNA-1 antibody levels in RRMS patients. Our exploratory studies do not implicate a promoted immune response against EBV as the underlying mechanism.
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Effect of Vitamin D Supplementation on Recurrent Wheezing in Black Infants Who Were Born Preterm: The D-Wheeze Randomized Clinical Trial.
Hibbs, AM, Ross, K, Kerns, LA, Wagner, C, Fuloria, M, Groh-Wargo, S, Zimmerman, T, Minich, N, Tatsuoka, C
JAMA. 2018;(20):2086-2094
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Abstract
IMPORTANCE Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. OBJECTIVE To assess the effectiveness of 2 vitamin D dosing strategies in preventing recurrent wheezing. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks' gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure. INTERVENTIONS Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group. MAIN OUTCOMES AND MEASURES Recurrent wheezing by 12 months' adjusted age was the primary outcome. RESULTS Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3%) completed the trial. Recurrent wheezing was experienced by 31.1% of infants in the sustained supplementation group and 41.8% of infants in the diet-limited supplementation group (difference, -10.7% [95% CI, -27.4% to -2.9%]; relative risk, 0.66 [95% CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9%) in the sustained group and 83 of 147 infants (56.5%) in the diet-limited group (difference, -1.6% [95% CI, -17.1% to 7.0%]). Lower respiratory infections were experienced by 33 of 153 infants (21.6%) in the sustained group and 37 of 147 infants (25.2%) in the diet-limited group (difference, -3.6% [95% CI, -16.4% to 4.4%]). CONCLUSIONS AND RELEVANCE Among black infants born preterm, sustained supplementation with vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months' adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of vitamin D supplementation on wheezing in children born preterm. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01601847.
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Vitamin D₃ Supplementation Reduces the Symptoms of Upper Respiratory Tract Infection during Winter Training in Vitamin D-Insufficient Taekwondo Athletes: A Randomized Controlled Trial.
Jung, HC, Seo, MW, Lee, S, Kim, SW, Song, JK
International journal of environmental research and public health. 2018;(9)
Abstract
Vitamin D insufficiency may be associated with increased risk of upper respiratory tract infection (URTI) in athletes. This study examined the effects of vitamin D₃ supplementation on salivary immune functions and symptoms of URTI in vitamin D-insufficient taekwondo athletes. Twenty-five male taekwondo athletes, aged 19⁻22 years with vitamin D insufficiency [serum 25-hydroxyvitamin-D concentrations (25(OH)D, 31.3 ± 1.39 nmol/L)], participated in this study. They were randomized to receive 5000 IU/day of vitamin D₃ (n = 13) or placebo capsule (n = 12) during 4 weeks of winter training. Blood samples were collected two times (pre- and post-tests) for analyzing serum 25(OH)D concentration while salivary samples were obtained three times (pre-, mid-, and post-tests) for secretory immunoglobulin A (SIgA) and lactoferrin analyses. The symptoms of URTI were reported daily during the intervention. Serum 25(OH)D concentration significantly increased by 255.6% in the vitamin D group, whereas in the placebo group it did not change (p < 0.001). While the significant increase in SIgA was observed in both groups (p < 0.001), elevated salivary lactoferrin level in response to winter training was found only in the placebo group (p = 0.011). The change in serum 25(OH)D concentration was negatively associated with total URTI symptoms (r = -0.435, p = 0.015). Vitamin D₃ supplementation may be effective in reducing the symptoms of URTI during winter training in vitamin D-insufficient taekwondo athletes.
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Vitamin D and immunomodulation in early rheumatoid arthritis: A randomized double-blind placebo-controlled study.
Buondonno, I, Rovera, G, Sassi, F, Rigoni, MM, Lomater, C, Parisi, S, Pellerito, R, Isaia, GC, D'Amelio, P
PloS one. 2017;(6):e0178463
Abstract
The aim of this study was to evaluate differences in T helper cell sub-types and osteoclast (OCs) precursors in peripheral blood between patients affected by early rheumatoid arthritis (eRA) and healthy controls. The effect of administration of cholecalcipherol on clinical and laboratory parameters was subsequently evaluated, by a parallel, randomized double blind, placebo controlled trial. Thirty nine eRA patients and 31 age-matched controls were enrolled and compared for levels of 25OH vitamin D, T helper cell sub-types, OCs precursors including both classical and non-classical and pro-inflammatory cytokines at baseline. Eligible patients were female ≥18 years of age with a diagnosis of RA, as defined by the American College of Rheumatology 2010 criteria for <6 months prior to inclusion in the study. Patients with auto-immune or inflammatory diseases other than RA were excluded. Patients treated with glucocorticoids (GCs), disease modifying activity drugs and biologic agents within the past 6 months were also excluded. In the second phase of the study, eRA patients were randomly assigned to standard treatment with methotrexate (MTX) and GCs with (21) or without (18) cholecalcipherol (300,000 IU) and followed for 3 months; the randomization was done by computer generated tables to allocate treatments. Three patients didn't come back to the follow up visit for personal reasons. None of the patients experienced adverse events. The main outcome measures were T cells phenotypes, OCs precursors and inflammatory cytokines. Secondary outcome measure were clinical parameters. In eRA, 25OH vitamin D levels were significantly lower. CD4+/IFNγ+,CD4+/IL4+, CD4+/IL17A+ and CD4+IL17A+IFNγ+, cells were increased in eRA as well as non-classical OCs precursors, whereas T regulatory cells were not altered. TNFα, TGFβ1, RANKL, IL-23 and IL-6 were increased in eRA. Non-classical OCs, IL-23 and IL-6 correlated with disease severity and activity. Standard treatment with MTX and GC ameliorated clinical symptoms and reduced IL-23, whereas it did not affect CD4+ cells sub-sets nor OCs precursors. After 3 months, the combined use of cholecalcipherol significantly ameliorated the effect of treatment on global health. In eRA, a significant imbalance in T CD4+ sub-types accompanied by increased levels of non-classical OCs precursors and pro-inflammatory cytokines was observed. A single dose of cholecalcipherol (300,000 IU) combined with standard treatment significantly ameliorates patients general health.
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10.
Cholecalciferol decreases inflammation and improves vitamin D regulatory enzymes in lymphocytes in the uremic environment: A randomized controlled pilot trial.
Carvalho, JTG, Schneider, M, Cuppari, L, Grabulosa, CC, T Aoike, D, Q Redublo, BM, C Batista, M, Cendoroglo, M, Maria Moyses, R, Dalboni, MA
PloS one. 2017;(6):e0179540
Abstract
It has been reported that vitamin D regulates the immune system. However, whether vitamin D repletion modulates inflammatory responses in lymphocytes from dialysis patients is unclear. In the clinical trial, thirty-two (32) dialysis patients with 25 vitamin D ≤ 20ng/mL were randomized to receive either supplementation of cholecalciferol 100,000 UI/week/3 months (16 patients) or placebo (16 patients). In the in vitro study, B and T lymphocytes from 12 healthy volunteers (HV) were incubated with or without uremic serum in the presence or absence of 25 or 1,25 vitamin D. We evaluated the intracellular expression of IL-6, IFN-γ TLR7, TLR9, VDR, CYP27b1 and CYP24a1 by flow cytometry. We observed a reduction in the expression of TLR7, TLR9, INF-γ and CYP24a1 and an increase in VDR and CYP27b1 expression in patients which were supplemented with cholecalciferol, whereas no differences were found in the placebo group. Uremic serum increased the intracellular expression of IL-6, IFN-γ, TLR7, TLR9, VDR, CYP27b1 and CYP24a1. Treatment with 25 or 1,25 vitamin D decreased IL-6 and TLR9. CYP24a1 silencing plus treatment with 25 and/or 1,25 vitamin D had an additional reduction effect on IL-6, IFN-γ, TLR7 and TLR9 expression. This is the first study showing that cholecalciferol repletion has an anti-inflammatory effect and improves vitamin D intracellular regulatory enzymes on lymphocytes from dialysis patients.