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Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus.
McCarty, MF, DiNicolantonio, JJ
Progress in cardiovascular diseases. 2020;63(3):383-385
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This highly technical review paper summarises some known actions and mechanisms by which certain nutraceuticals can boost the type 1 interferon response, a specific immune response to viruses, including influenza and coronavirus. These include: Ferulate (ferulic acid) has been shown to stimulate type 1 interferon production, and enhanced survival in influenza A-infected mice. Sulforaphane (phytochemical found in cruciferous vegetables like broccoli) and lipoic acid have similar actions. Spirulina extract has been found to decrease mortality in influenza-infected mice. Clinical and preclinical evidence for the potential benefits of N-acetylcysteine (NAC), a precursor for the important antioxidant glutathione, and selenium are also discussed. A glucosamine-enriched diet increased survival of mice infected with influenza virus. The authors present a table with suggested dosages for the above nutrients, as well as yeast beta-glucans, zinc and elderberry extracts, for viral control, whilst calling for more research into these compounds.
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Impact of Vitamin D Supplementation on Influenza Vaccine Response and Immune Functions in Deficient Elderly Persons: A Randomized Placebo-Controlled Trial.
Goncalves-Mendes, N, Talvas, J, Dualé, C, Guttmann, A, Corbin, V, Marceau, G, Sapin, V, Brachet, P, Evrard, B, Laurichesse, H, et al
Frontiers in immunology. 2019;10:65
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This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in a sample of 38 deficient elderly persons, over 65-year olds, could improve influenza seroprotection and immune response. Vitamin D is known to both potentiate the innate immune response and inhibit the adaptive system, and so potentially modulate vaccination response. The participants were randomised into two arms: vitamin D supplementation group (D) and placebo group (P). The D group received 100,000 IU/15 days of cholecalciferol over a 3-month period after which both groups were given the influenza vaccine, and their blood was evaluated 28 days later. Several immune biomarkers were analysed including plasma cytokine profiles, phagocyte ROS production, and lymphocyte cells phenotyping to determine if Vitamin D enhanced immune response to the vaccination. No differences were found in serum ROS and antibody markers. However, Vitamin D supplementation did promote a higher TGFβ plasma level in response to influenza vaccination. Taken together, these results suggest that vitamin D supplementation is not an effective way to improve antibody response to influenza vaccine in deficient elderly people.
Abstract
Background: Immunosenescence contributes to reduced vaccine response in elderly persons, and is worsened by deficiencies in nutrients such as Vitamin (Vit-D). The immune system is a well-known target of Vit-D, which can both potentiate the innate immune response and inhibit the adaptive system, and so modulate vaccination response. Objective: This randomized placebo-controlled double-blind trial investigated whether Vit-D supplementation in deficient elderly persons could improve influenza seroprotection and immune response. Design: Deficient volunteers (Vit-D serum <30 ng/mL) were assigned (V1) to receive either 100,000 IU/15 days of cholecalciferol (D, n = 19), or a placebo (P, n = 19), over a 3 month period. Influenza vaccination was performed at the end of this period (V2), and the vaccine response was evaluated 28 days later (V3). At each visit, serum cathelicidin, immune response to vaccination, plasma cytokines, lymphocyte phenotyping, and phagocyte ROS production were assessed. Results: Levels of serum 25-(OH)D increased after supplementation (D group, V1 vs. V2: 20.7 ± 5.7 vs. 44.3 ± 8.6 ng/mL, p < 0.001). No difference was observed for serum cathelicidin levels, antibody titers, and ROS production in D vs. P groups at V3. Lower plasma levels of TNFα (p = 0.040) and IL-6 (p = 0.046), and higher ones for TFGβ (p = 0.0028) were observed at V3. The Th1/Th2 ratio was lower in the D group at V2 (D: 0.12 ± 0.05 vs. P: 0.18 ± 0.05, p = 0.039). Conclusions: Vit-D supplementation promotes a higher TGFβ plasma level in response to influenza vaccination without improving antibody production. This supplementation seems to direct the lymphocyte polarization toward a tolerogenic immune response. A deeper characterization of metabolic and molecular pathways of these observations will aid in the understanding of Vit-D's effects on cell-mediated immunity in aging. This clinical trial was registered at clinicaltrials.gov as NCT01893385.
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The influence of prebiotic or probiotic supplementation on antibody titers after influenza vaccination: a systematic review and meta-analysis of randomized controlled trials.
Yeh, TL, Shih, PC, Liu, SJ, Lin, CH, Liu, JM, Lei, WT, Lin, CY
Drug design, development and therapy. 2018;12:217-230
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Influenza vaccination is widely used although concerns regarding its efficacy exist. Both prebiotics and probiotics have been shown to produce protective effects against influenza infection and may enhance the immune response to the vaccination, especially in the elderly. The aim of this systematic review and meta-analysis was to determine the effect of pre- and probiotics on immune response to the influenza vaccination. According to the existing literature, participants who took prebiotics or probiotics were found to have higher hemagglutination inhibition (HI) antibodies, meaning a reduced likelihood of the virus attaching to the host’s red blood cells. Based on these results, the authors conclude both pre- or probiotic supplementation may enhance immune response in three influenza strains. While these results are promising, larger controlled trials are warranted to confirm the effectiveness and establish best clinical practice for supplementation.
Abstract
BACKGROUND Influenza infection is a common disease with a huge disease burden. Influenza vaccination has been widely used, but concerns regarding vaccine efficacy exist, especially in the elderly. Probiotics are live microorganisms with immunomodulatory effects and may enhance the immune responses to influenza vaccination. METHODS We conducted a systematic review and meta-analysis to determine the influence of prebiotics/probiotics/synbiotics supplementation on vaccine responses to influenza vaccination. Studies were systematically identified from electronic databases up to July 2017. Information regarding study population, influenza vaccination, components of supplements, and immune responses were extracted and analyzed. Twelve studies, investigating a total of 688 participants, were included in this review. RESULTS Patients with prebiotics/probiotics supplements were found to have higher influenza hemagglutination inhibition antibody titers after vaccination (for A/H1N1, 42.89 vs 35.76, mean difference =7.14, 95% CI =2.73, 11.55, P=0.002; for A/H3N2, 105.4 vs 88.25, mean difference =17.19, 95% CI =3.39, 30.99, P=0.01; for B strain, 34.87 vs 30.73, mean difference =4.17, 95% CI =0.37, 7.96, P=0.03). CONCLUSION Supplementation with prebiotics or probiotics may enhance the influenza hemagglutination inhibition antibody titers in all A/H1N1, A/H3N2, and B strains (20%, 19.5%, and 13.6% increases, respectively). Concomitant prebiotics or probiotics supplementation with influenza vaccination may hold great promise for improving vaccine efficacy. However, high heterogeneity was observed and further studies are warranted.
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Effect of Probiotics and Prebiotics on Immune Response to Influenza Vaccination in Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Lei, WT, Shih, PC, Liu, SJ, Lin, CY, Yeh, TL
Nutrients. 2017;9(11)
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The influenza virus causes three to five million severe cases per year and currently the main way to minimise both morbidity and mortality is the influenza vaccine. Both prebiotics and probiotics have been shown to demonstrate protective effects against influenza infection. The aim of this systematic review and meta-analysis is to explore the effectiveness of probiotics and prebiotics on immune function in adults after an influenza vaccine. According to the existing literature, participants who took prebiotics or probiotics showed significant improvements in the immune response for three different strains of influenza vaccine. According to these results, the authors conclude that both pre- and pro- biotics can be used in adults prior to a seasonal influenza vaccine. Further large trials are required to both validate these findings as well as have a better understanding of the optimal dose and duration of supplementation.
Abstract
We conducted a meta-analysis to evaluate the effects of probiotics and prebiotics on the immune response to influenza vaccination in adults. We conducted a literature search of Pubmed, Embase, the Cochrane Library, the Cumulative Index to Nursing and Allied Health (CINAHL), Airiti Library, and PerioPath Index to Taiwan Periodical Literature in Taiwan. Databases were searched from inception to July 2017. We used the Cochrane Review risk of bias assessment tool to assess randomized controlled trial (RCT) quality. A total of 20 RCTs comprising 1979 adults were included in our systematic review. Nine RCTs including 623 participants had sufficient data to be pooled in a meta-analysis. Participants who took probiotics or prebiotics showed significant improvements in the H1N1 strain seroprotection rate (with an odds ratio (OR) of 1.83 and a 95% confidence interval (CI) of 1.19-2.82, p = 0.006, I² = 0%), the H3N2 strain seroprotection rate (OR = 2.85, 95% CI = 1.59-5.10, p < 0.001, I² = 0%), and the B strain seroconversion rate (OR = 2.11, 95% CI = 1.38-3.21, p < 0.001, I² = 0%). This meta-analysis suggested that probiotics and prebiotics are effective in elevating immunogenicity by influencing seroconversion and seroprotection rates in adults inoculated with influenza vaccines.
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Elderberry Supplementation Reduces Cold Duration and Symptoms in Air-Travellers: A Randomized, Double-Blind Placebo-Controlled Clinical Trial.
Tiralongo, E, Wee, SS, Lea, RA
Nutrients. 2016;8(4):182
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Long-haul air travel increases the occurrence of respiratory illnesses such as the common cold. Elderberries have anti-bacterial and anti-viral properties and previous studies have shown that an elderberry extract can reduce the duration and severity of cold and flu symptoms. This randomised controlled trial aimed to identify whether capsules containing a standardised elderberry extract are effective in preventing respiratory symptoms in travellers on long-haul flights. 325 healthy adults volunteered for the study. Participants were split into two groups: one group was given capsules each containing 300mg of Elderberry extract, and the other group was given placebo capsules. For both groups, participants were given 2 capsules a day for 10 days leading up to travelling, and 3 capsules a day during travel and for four to five days after reaching their destination. Participants completed health surveys 10 days and two days before travelling, and then again five days after. They also kept a daily diary of cold symptoms. Participants in both the placebo and elderberry group tended to experience an increase in respiratory symptoms after travelling. The elderberry group experienced less colds than the placebo group, although the difference was not statistically significant. Elderberry supplementation did however result in a reduction in symptoms, and shortened the cold duration by approximately two days compared to the placebo. The authors recommend that more clinical research with high quality elderberry preparations is carried out to better understand the health benefits of this traditional medicine.
Abstract
Intercontinental air travel can be stressful, especially for respiratory health. Elderberries have been used traditionally, and in some observational and clinical studies, as supportive agents against the common cold and influenza. This randomized, double-blind placebo-controlled clinical trial of 312 economy class passengers travelling from Australia to an overseas destination aimed to investigate if a standardised membrane filtered elderberry (Sambucus nigra L.) extract has beneficial effects on physical, especially respiratory, and mental health. Cold episodes, cold duration and symptoms were noted in a daily diary and assessed using the Jackson score. Participants also completed three surveys containing questions regarding upper respiratory symptoms (WURSS-21) and quality of life (SF-12) at baseline, just before travel and at 4-days after travel. Most cold episodes occurred in the placebo group (17 vs. 12), however the difference was not significant (p = 0.4). Placebo group participants had a significantly longer duration of cold episode days (117 vs. 57, p = 0.02) and the average symptom score over these days was also significantly higher (583 vs. 247, p = 0.05). These data suggest a significant reduction of cold duration and severity in air travelers. More research is warranted to confirm this effect and to evaluate elderberry's physical and mental health benefits.
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Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry.
Wu, W, Li, R, Li, X, He, J, Jiang, S, Liu, S, Yang, J
Viruses. 2015;8(1)
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This mechanism study examines the role of quercetin at inhibiting influenza infection. Influenza A viruses (IAVs) are responsible for seasonal global pandemics and mortality, and genetic variations make it almost impossible to develop timely vaccines. Novel therapeutic strategies are anti-influenza agents are therefore of great interest. Two classes of anti-influenza drugs are widely used to inhibit viral entry and development, with varying side effects reported. Targeting viral entry and suppression of the infection at its early stage is an attractive therapeutic strategy. Quercetin is known to have anti-viral effects, alongside antioxidant, antibacterial and antiproliferation properties. Cells were infected with different influenza strains and exposed to quercetin, and the cytopathic effect and inhibition rates were measured at intervals. The results showed quercetin reduced transcription in influenza-virus-infected cells in a dose-dependent manner. This implies that quercetin’s mechanism of action may inhibit influenza in the early stage of viral attachment. Additional experiments found that quercetin directly targets the viral hemagglutinin protein particles rather than the host cells. The study concludes that quercetin possesses interesting anti-influenza activities which could be developed as a future therapeutic option for the therapy and prophylaxis of IAV infection.
Abstract
Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.
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Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: a randomized controlled trial.
Matsumoto, K, Yamada, H, Takuma, N, Niino, H, Sagesaka, YM
BMC complementary and alternative medicine. 2011;11:15
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Influenza infection is the main cause of acute respiratory illnesses worldwide with limited prevention and treatment options. Pre-clinical experiments have shown that green tea catechins can prevent influenza infection in vitro, but clinical evidence has not been conclusive. The aim of this randomised, double-blind study was to evaluate the clinical efficacy of two compounds from green tea, catechins and theanine, in preventing influenza infection. 196 participants completed the 5 months study. The incidence of clinically defined influenza infections was significantly lower in the catechin/theanine group than in the placebo group. The incidence of laboratory-confirmed influenza infection was also lower in the catechin/theanine group than in the placebo group, but this difference was not statistically significant. No serious adverse events were observed in either group. The occurrence of mild symptoms, such as bloating and constipation, did not significantly differ between the two groups. The authors concluded that the effectiveness of catechin/theanine in this trial might be underestimated due to methodological limitations and that larger scale randomised trials are needed to confirm the effectiveness of catechin/theanine to prevent laboratory-confirmed influenza infection.
Abstract
BACKGROUND Experimental studies have revealed that green tea catechins and theanine prevent influenza infection, while the clinical evidence has been inconclusive. This study was conducted to determine whether taking green tea catechins and theanine can clinically prevent influenza infection. METHODS DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled trial of 200 healthcare workers conducted for 5 months from November 9, 2009 to April 8, 2010 in three healthcare facilities for the elderly in Higashimurayama, Japan. INTERVENTIONS The catechin/theanine group received capsules including green tea catechins (378 mg/day) and theanine (210 mg/day). The control group received placebo. MAIN OUTCOME MEASURES The primary outcome was the incidence of clinically defined influenza infection. Secondary outcomes were (1) laboratory-confirmed influenza with viral antigen measured by immunochromatographic assay and (2) the time for which the patient was free from clinically defined influenza infection, i.e., the period between the start of intervention and the first diagnosis of influenza infection, based on clinically defined influenza infection. RESULTS Eligible healthcare workers (n = 197) were enrolled and randomly assigned to an intervention; 98 were allocated to receive catechin/theanine capsules and 99 to placebo. The incidence of clinically defined influenza infection was significantly lower in the catechin/theanine group (4 participants; 4.1%) compared with the placebo group (13 participants; 13.1%) (adjusted OR, 0.25; 95% CI, 0.07 to 0.76, P = 0.022). The incidence of laboratory-confirmed influenza infection was also lower in the catechin/theanine group (1 participant; 1.0%) than in the placebo group (5 participants; 5.1%), but this difference was not significant (adjusted OR, 0.17; 95% CI, 0.01 to 1.10; P = 0.112). The time for which the patient was free from clinically defined influenza infection was significantly different between the two groups (adjusted HR, 0.27; 95% CI, 0.09 to 0.84; P = 0.023). CONCLUSIONS Among healthcare workers for the elderly, taking green tea catechins and theanine may be effective prophylaxis for influenza infection. TRIAL REGISTRATION ClinicalTrials (NCT): NCT01008020.