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1.
The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19.
Cerullo, G, Negro, M, Parimbelli, M, Pecoraro, M, Perna, S, Liguori, G, Rondanelli, M, Cena, H, D'Antona, G
Frontiers in immunology. 2020;:574029
Abstract
From Pauling's theories to the present, considerable understanding has been acquired of both the physiological role of vitamin C and of the impact of vitamin C supplementation on the health. Although it is well known that a balanced diet which satisfies the daily intake of vitamin C positively affects the immune system and reduces susceptibility to infections, available data do not support the theory that oral vitamin C supplements boost immunity. No current clinical recommendations support the possibility of significantly decreasing the risk of respiratory infections by using high-dose supplements of vitamin C in a well-nourished general population. Only in restricted subgroups (e.g., athletes or the military) and in subjects with a low plasma vitamin C concentration a supplementation may be justified. Furthermore, in categories at high risk of infection (i.e., the obese, diabetics, the elderly, etc.), a vitamin C supplementation can modulate inflammation, with potential positive effects on immune response to infections. The impact of an extra oral intake of vitamin C on the duration of a cold and the prevention or treatment of pneumonia is still questioned, while, based on critical illness studies, vitamin C infusion has recently been hypothesized as a treatment for COVID-19 hospitalized patients. In this review, we focused on the effects of vitamin C on immune function, summarizing the most relevant studies from the prevention and treatment of common respiratory diseases to the use of vitamin C in critical illness conditions, with the aim of clarifying its potential application during an acute SARS-CoV2 infection.
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2.
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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3.
Can Vitamins, as Epigenetic Modifiers, Enhance Immunity in COVID-19 Patients with Non-communicable Disease?
Singh, V
Current nutrition reports. 2020;(3):202-209
Abstract
PURPOSE OF REVIEW The highly infectious transmissible disease, the novel SARS-CoV-2, causing the coronavirus disease (COVID-19), has a median incubation time of 5 to 15 days. The symptoms vary from person to person and many are "hidden carriers." Few people experience immediate reaction and even death within 48 h of infection. However, many show mild to chronic symptoms and recover. Nevertheless, the death rate due to COVID-19 transmission is high especially among patients with non-communicable diseases. The purpose of this review is to provide evidence to consider vitamins as epigenetic modifiers to enhance immunity and reduce inflammatory response in COVID-19 patients with non-communicable diseases. RECENT FINDINGS Clinical evidence has suggested the risk of getting infected is high among individuals with non-communicable diseases such as cardiovascular disease, type-2 diabetes, cancer, acute respiratory distress syndrome, and renal disease, as well as the elderly with high mortality rate among the cohort. The impact is due to an already compromised immune system of patients. Every patient has a different response to COVID-19, which shows that the ability to combat the deadly virus varies individually. Thus, treatment can be personalized and adjusted to help protect and combat COVID-19 infections, especially in individuals with non-communicable diseases. Based on current published scientific and medical evidence, the suggestions made in this article for combination of vitamin therapy as epigenetic modifiers to control the unregulated inflammatory and cytokine marker expressions, further needs to be clinically proven. Future research and clinical trials can apply the suggestions given in this article to support metabolic activities in patients and enhance the immune response.
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4.
Inadequacy of Immune Health Nutrients: Intakes in US Adults, the 2005-2016 NHANES.
Reider, CA, Chung, RY, Devarshi, PP, Grant, RW, Hazels Mitmesser, S
Nutrients. 2020;(6)
Abstract
A well-functioning immune system is essential for human health and well-being. Micronutrients such as vitamins A, C, D, E, and zinc have several functions throughout the immune system, yet inadequate nutrient intakes are pervasive in the US population. A large body of research shows that nutrient inadequacies can impair immune function and weaken the immune response. Here, we present a new analysis of micronutrient usual intake estimates based on nationally representative data in 26,282 adults (>19 years) from the 2005-2016 National Health and Nutrition Examination Surveys (NHANES). Overall, the prevalence of inadequacy (% of population below estimated average requirement [EAR]) in four out of five key immune nutrients is substantial. Specifically, 45% of the U.S. population had a prevalence of inadequacy for vitamin A, 46% for vitamin C, 95% for vitamin D, 84% for vitamin E, and 15% for zinc. Dietary supplements can help address nutrient inadequacy for these immune-support nutrients, demonstrated by a lower prevalence of individuals below the EAR. Given the long-term presence and widening of nutrient gaps in the U.S.-specifically in critical nutrients that support immune health-public health measures should adopt guidelines to ensure an adequate intake of these micronutrients. Future research is needed to better understand the interactions and complexities of multiple nutrient shortfalls on immune health and assess and identify optimal levels of intake in at-risk populations.
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5.
Immune Modulatory Effects of Vitamin D on Viral Infections.
Siddiqui, M, Manansala, JS, Abdulrahman, HA, Nasrallah, GK, Smatti, MK, Younes, N, Althani, AA, Yassine, HM
Nutrients. 2020;(9)
Abstract
Viral infections have been a cause of mortality for several centuries and continue to endanger the lives of many, specifically of the younger population. Vitamin D has long been recognized as a crucial element to the skeletal system in the human body. Recent evidence has indicated that vitamin D also plays an essential role in the immune response against viral infections and suggested that vitamin D deficiency increases susceptibility to viral infections as well as the risk of recurrent infections. For instance, low serum vitamin D levels were linked to increased occurrence of high burdens viral diseases such as hepatitis, influenza, Covid-19, and AIDS. As immune cells in infected patients are responsive to the ameliorative effects of vitamin D, the beneficial effects of supplementing vitamin D-deficient individuals with an infectious disease may extend beyond the impact on bone and calcium homeostasis. Even though numerous studies have highlighted the effect of vitamin D on the immune cells, vitamin D's antiviral mechanism has not been fully established. This paper reviews the recent mechanisms by which vitamin D regulates the immune system, both innate and adaptive systems, and reflects on the link between serum vitamin D levels and viral infections.
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6.
Clinical Significance of Analysis of Vitamin D Status in Various Diseases.
Kowalówka, M, Główka, AK, Karaźniewicz-Łada, M, Kosewski, G
Nutrients. 2020;(9)
Abstract
Vitamin D plays a role not only in the proper functioning of the skeletal system and the calcium-phosphate equilibrium, but also in the immune system, the cardiovascular system and the growth and division of cells. Although numerous studies have reported on the analysis of vitamin D status in various groups of patients, the clinical significance of measurements of vitamin D forms and metabolites remains ambiguous. This article reviews the reports analyzing the status of vitamin D in various chronic states. Particular attention is given to factors affecting measurement of vitamin D forms and metabolites. Relevant papers published during recent years were identified by an extensive PubMed search using appropriate keywords. Measurement of vitamin D status proved to be a useful tool in diagnosis and progression of metabolic syndrome, neurological disorders and cancer. High performance liquid chromatography coupled with tandem mass spectrometry has become the preferred method for analyzing the various forms and metabolites of vitamin D in biological fluids. Factors influencing vitamin D concentration, including socio-demographic and biochemical factors as well as the genetic polymorphism of the vitamin D receptor, along with vitamin D transporters and enzymes participating in vitamin D metabolism should be considered as potential confounders of the interpretation of plasma total 25(OH)D concentrations.
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7.
Antioxidant Activity with Increased Endogenous Levels of Vitamin C, E and A Following Dietary Supplementation with a Combination of Glutathione and Resveratrol Precursors.
Biswas, P, Dellanoce, C, Vezzoli, A, Mrakic-Sposta, S, Malnati, M, Beretta, A, Accinni, R
Nutrients. 2020;(11)
Abstract
The effects of two different dietary supplements on the redox status of healthy human participants were evaluated. The first supplement (GluS, Glutathione Synthesis) contains the precursors for the endogenous synthesis of glutathione and the second (GluReS, Glutathione and Resveratrol Synthesis) contains in addition polydatin, a precursor of resveratrol. To assess the influence of GluS and GluReS on the redox status, ten thiol species and three vitamins were measured before (t0) and after 8 weeks (t1) of dietary supplementation. An inflammatory marker, neopterin, was also assessed at the same time points. Both supplements were highly effective in improving the redox status by significantly increasing the reduced-glutathione (GSH) content and other reduced thiol species while significantly decreasing the oxidized species. The positive outcome of the redox status was most significant in the GluRes treatment group which also experienced a significant reduction in neopterin levels. Of note, the endogenous levels of vitamins C, E and A were significantly increased in both treatment groups, with best results in the GluReS group. While both dietary supplements significantly contributed to recognized antioxidant and anti-inflammatory outcomes, the effects of GluReS, the combination of glutathione and resveratrol precursors, were more pronounced. Thus, dietary supplementation with GluReS may represent a valuable strategy for maintaining a competent immune status and a healthy lifespan.
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8.
Effect of 8-week of dietary micronutrient supplementation on gene expression in elite handball athletes.
Molina-López, J, Ricalde, MAQ, Hernández, BV, Planells, A, Otero, R, Planells, E
PloS one. 2020;(5):e0232237
Abstract
PURPOSE A study was made of the changes in gene expression in elite handball athletes, comparing gene modulation before, after and in the absence of an 8-week nutritional intervention with multivitamin/mineral supplements. METHODS Thirteen elite handball athletes (aged 22.9 ± 2.7 years) and 13 sedentary controls (aged 20.9 ± 2.8 years) were included. Three timepoints were established: T0 (baseline conditions); T8 (after 8 weeks of supplementation with a multivitamin/mineral complex); and T16 (after 8 weeks in the absence of supplementation). The expressions of a total 112 of genes were evaluated by RT-qPCR analysis with the QuantStudioTM 12K Flex Real-Time PCR System. RESULTS The analysis revealed different gene regulation profiles of genes implicated in cell communication, cell energy metabolism, inflammation and the immune system, oxidative stress and muscle function in athletes compared to sedentary controls under resting conditions (upregulated genes: effect size = large, ƞ2 = 1.011 to 1.398, p < 0.05; downregulated genes: effect size = large, ƞ2 = 0.846 and 1.070, p < 0.05, respectively). The nutritional intervention encouraged gene upregulation in elite athletes (p < 0.05). In a follow-up investigation, the IRAK1, CD81, ITGB1, ACADS PDHA2 and GPX1 genes were downregulated in athletes, with a moderate main effect for time-by-group interaction (ηP2 = 0.099 to 0.133; p < 0.05). Additionally, nutritional genes such as MTHFR and THTPA revealed a moderate effect over all the timepoints and group interaction in the study (ηP2 = 0.070 to 0.092; p < 0.05). CONCLUSIONS Elite handball athletes showed a different expression profile in reference to key genes implicated in several sports performance-related functions compared to the sedentary controls, in addition to modulation of gene expression after multivitamin/mineral supplementation.
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9.
Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging.
Sepe, V, Gregorini, M, Rampino, T, Esposito, P, Coppo, R, Galli, F, Libetta, C
BMC nephrology. 2019;(1):412
Abstract
BACKGROUND Inflammaging is a persistent, low-grade, sterile, nonresolving inflammatory state, associated with the senescence of the immune system. Such condition downregulates both innate and adaptive immune responses during chronic disorders as type II diabetes, cancer and hemodialysis, accounting for their susceptibility to infections, malignancy and resistance to vaccination. Aim of this study was to investigate hemodialysis inflammaging, by evaluating changes of several hemodialysis treatments on indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation. METHODS We conducted a randomized controlled observational crossover trial. Eighteen hemodialysis patients were treated with 3 different hemodialysis procedures respectively: 1) Low-flux bicarbonate hemodialysis, 2) Low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers, and 3) Hemodialfitration. The control group consisted of 14 hospital staff healthy volunteers. Blood samples were collected from all 18 hemodialysis patients just after the long interdialytic interval, at the end of each hemodialysis treatment period. RESULTS Hemodialysis kynurenine and kynurenine/L - tryptophan blood ratio levels were significantly higher, when compared to the control group, indicating an increased indoleamine 2,3-dioxygenase-1 activity in hemodialysis patients. At the end of the low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers period, L - tryptophan serum levels remained unchanged vs both low-flux bicarbonate hemodialysis and hemodialfitration. Kynurenine levels instead decreased, resulting in a significant reduction of kynurenine/L - tryptophan blood ratio and indoleamine 2,3-dioxygenase-1 activity, when matched to both low-flux bicarbonate hemodialysis and HDF respectively. Serum nitric oxide control group levels, were significantly lower when compared to all hemodialysis patient groups. Interestingly, low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers nitric oxide serum levels from venous line blood samples taken 60 min after starting the hemodialysis session were significantly lower vs serum taken simultaneously from the arterial blood line. CONCLUSIONS The treatment with more biocompatible hemodialysis procedure as low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers, reduced indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation when compared to both low-flux bicarbonate hemodialysis and hemodialfitration. These data suggest that low-flux bicarbonate hemodialysis with vitamin E - loaded dialyzers lowering hemodialysis inflammaging, could be associated to changes of proinflammatory signalling a regulated molecular level. TRIAL REGISTRATION NCT Number: NCT02981992; Other Study ID Numbers: 20100014090. First submitted: November 26, 2016. First posted: December 5, 2016. Last Update Posted: December 5, 2016.
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10.
Association of Rare Predicted Loss-of-Function Variants in Cellular Pathways with Sub-Phenotypes in Age-Related Macular Degeneration.
Pietraszkiewicz, A, van Asten, F, Kwong, A, Ratnapriya, R, Abecasis, G, Swaroop, A, Chew, EY
Ophthalmology. 2018;(3):398-406
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Abstract
PURPOSE To investigate the association of rare predicted loss-of-function (pLoF) variants within age-related macular degeneration (AMD) risk loci and AMD sub-phenotypes. DESIGN Case-control study. PARTICIPANTS Participants of AREDS, AREDS2, and Michigan Genomics Initiative. METHODS Whole genome sequencing data were analyzed for rare pLoF variants (frequency <0.1%) in the regions of previously identified 52 independent risk variants known to be associated with AMD. Frequency of the rare pLoF variants in cases with intermediate or advanced AMD was compared with controls. Variants were assigned to the complement, extracellular matrix (ECM), lipid, cell survival, immune system, metabolism, or unknown/other pathway. Associations of rare pLoF variant pathways with AMD sub-phenotypes were analyzed using logistic and linear regression, and Cox proportional hazards models. MAIN OUTCOME MEASURES Differences in rare pLoF variant pathway burden and association of rare pLoF variant pathways with sub-phenotypes within the population with AMD were evaluated. RESULTS Rare pLoF variants were found in 298 of 1689 cases (17.6%) and 237 of 1518 controls (15.6%) (odds ratio [OR], 1.11; 95% confidence interval [CI], 0.91-1.36; P = 0.310). An enrichment of rare pLoF variants in the complement pathway in cases versus controls (OR, 2.94; 95% CI, 1.49-5.79; P = 0.002) was observed. Within cases, associations between all rare pLoF variants and choroidal neovascularization (CNV) (OR, 1.34; 95% CI, 1.04-1.73; P = 0.023), calcified drusen (OR, 1.33; 95% CI, 1.04-1.72; P = 0.025), higher scores on the AREDS Extended AMD Severity Scale (Standardized Coefficient Beta (β)=0.346 [0.086-0.605], P = 0.009), and progression to advanced disease (hazard ratio, 1.25; 95% CI, 1.01-1.55; P = 0.042) were observed. At the pathway level, there were associations between the complement pathway and geographic atrophy (GA) (OR, 2.17; 95% CI, 1.12-4.24; P = 0.023), the complement pathway and calcified drusen (OR, 3.75; 95% CI, 1.79-7.86; P < 0.001), and the ECM pathway and more severe levels in the AREDS Extended AMD Severity Scale (β = 0.62; 95% CI, 0.04-1.20; P = 0.035). CONCLUSIONS Rare pLoF variants are associated with disease progression. Variants in the complement pathway modify the clinical course of AMD and increase the risk of developing specific sub-phenotypes.