Supplementation of L-glutamine enhanced mucosal immunity and improved hormonal status of combat-sport athletes.

BACKGROUND: Maintaining proper immune function and hormone status is important for athletes to avoid upper respiratory tract infection (URTI) and insufficient recovery, which is detrimental to sport performance and health. The aim of this study was to evaluate whether three-week supplementation of L-glutamine could benefit the mucosal immunity and hormonal status of combat-sport athletes as well as their rates of upper respiratory tract infection (URTI) and subjective feelings of well-being after intensive training. METHODS: Twenty-one combat-sport athletes from the National Taiwan University of Sport were recruited in this study. After intensive training, two groups of the participants were asked to consume powder form of 0.3 g/kg body weight of L-glutamine (GLU group) or maltodextrin (PLA group) with drinking water in a randomized design at the same time every day during 3 weeks. Saliva samples were collected to measure immunoglobulin A (IgA), nitric oxide (NO), testosterone (T) and cortisol (C) before and after three-week supplementation; moreover, Hooper's index questionnaires were completed for wellness assessment. The incidence and duration of URTI were recorded by using a health checklist throughout the entire study period. RESULTS: Supplementation of L-glutamine significantly enhanced the concentrations of IgA and NO in saliva; additionally, the incidence of URTI was significantly reduced. Regarding hormones, T concentration was significantly decreased in the PLA group, whereas C concentration was significantly increased, resulting in a significant decrease of T/C ratio. In contrast, the GLU group showed a significant increase of T/C ratio, while the mood scores of the Hooper's index questionnaire were higher in the PLA group. CONCLUSIONS: Three-week supplementation of L-glutamine after intensive training enhanced the mucosal immunity, improved hormonal status and reduced the rate of URTI of combat-sport athletes while feelings of well-being were also enhanced. Therefore, L-glutamine would be beneficial for the sports performance and recovery of athletes.

Effect of Daily Vitamin D Supplementation on Risk of Upper Respiratory Infection in Older Adults: A Randomized Controlled Trial.

BACKGROUND: Among individuals with vitamin D deficiency, daily vitamin D supplementation appears to lower risk of acute respiratory infection. However, recent trials, in different populations and using different regimens, have yielded null results. We investigated the effect of daily vitamin D supplementation (vs placebo) on risk of upper respiratory infection (URI) in older adults. METHODS: The VITamin D and OmegA-3 TriaL (VITAL) is a randomized, double-blind, placebo-controlled trial of supplemental vitamin D and/or omega-3 fatty acids in generally healthy men (age ≥50 years) and women (age ≥55 years). This prespecified analysis focuses on vitamin D3 (2000 IU/day) versus placebo in the 15 804 (61%) participants with baseline serum total 25-hydroxyvitamin D level. The primary outcome was self-report of a recent URI at 1-year follow-up. RESULTS: Participants had a mean age of 68 years and 51% were women; 76% were non-Hispanic White, 16% Black, and 8% other race/ethnicity. The mean 25-hydroxyvitamin D level at baseline was 31 (standard deviation, 10) ng/mL, with <12 ng/mL in 2.4%. The overall effect of vitamin D supplementation on recent URI was nonsignificant (odds ratio [OR], 0.96 [95% confidence interval {CI}, .86-1.06]). In the prespecified subgroup of primary interest (<12 ng/mL and denied taking concurrent vitamin D), which had only 255 participants, vitamin D supplementation was nonsignificant (OR, 0.60 [95% CI, .28-1.30]). Statistical power to assess effect modification in other subgroups was limited. CONCLUSIONS: In older adults not selected for vitamin D deficiency, supplemental vitamin D did not lower URI risk overall. Whether effects differ in subgroups requires further study. Clinical Trials Registration. NCT01169259.

Six Weeks of Supplementation with Bovine Colostrum Effectively Reduces URTIs Symptoms Frequency and Gravity for Up to 20 Weeks in Pre-School Children.

Bovine colostrum is considered to provide anti-infective protection. Here, we present the first randomized controlled trial (RCT) aimed at assessing the preventive use of colostrum against upper respiratory tract infections (URTIs) in healthy pre-school children. We analyzed 57 children-35 in the colostrum (COL-dried bovine colostrum) and 22 in the placebo (PBO-dried whey) group, who received these substances as follows: first 15 days 2 × 500 mg and then 30 days 1 × 500 mg. The reporting on the children's health status, specifically on the frequency and gravity of URTI symptoms and abdominal side effects, was performed via an online survey. The influence of colostrum on the frequency of days with URTI symptoms remained significant until the 20th week of observation and reached 31% of median reduction. The median reduction reached 37% when the gravity of symptoms was analyzed. When we grouped symptomatic days into episodes of second gravity level, the reduction in their frequency was even larger (50%) and lasted until the end of the trial (21 weeks). No significant side effects, especially abdominal, were reported during the trial. Colostrum supplementation in pre-school children is well tolerated, safe and provides protection from frequency of URTIs and their gravity.

Immunomodulatory Effects of Vitamin D in Respiratory Tract Infections and COVID-19 in Children.

Acute respiratory tract infections (ARTIs) are one of the main reasons that the pediatric population goes to the doctor. The connection between ARTI and vitamin D (VD) is currently debated by the medical community, and so far, there has been little agreement with regard to the ideal level of 25(OH)D concentration that would provide protection for the respiratory tract, or the effectiveness of its administration in the treatment of respiratory infections. The purpose of this literature review was to bring attention to the immunomodulatory and antiviral function of vitamin D and its relation to the respiratory system by examining the main ARTIs, including SARS-CoV-2. The latter has affected the pediatric population in different ways, from asymptomatic patients to severe forms with multisystem inflammatory syndrome in children (MIS-C). Although there are not much clinical data on the SARS-CoV-2 disease in the pediatric population worldwide, we tried to find out whether there is a connection between the severity of this disease, other ARTIs, and vitamin D supplementation. We also aimed to find out if 25OHD deficiency had an adverse effect on the evolution of the disease and the recovery period in the case of younger patients affected by COVID-19. For this literature review, the PICO framework was selected as the methodological approach. Our results demonstrated many methods by which this vitamin may lower the risk of ARTI with regard to the COVID-19 infection. Despite these significant advancements, more research is needed to support the idea that 25(OH)D concentration can influence the evolution of respiratory tract infections in children.

Beneficial Effects of Daily Consumption of Garlic and Onion Extract Concentrate on Infectious Respiratory Diseases in Elderly Resident Volunteers.

Aging is a biological process with high susceptibility to several infections. This risk increases in older patients in residential care facilities (RCF). Thus, there is a clear demand for developing preventive interventions with new therapeutic compounds that combine efficacy and safety. This could be the case of compounds derived from plants of the genus Allium spp. The purpose of this study was to evaluate the impact of a combination of a garlic and onion extract concentrate standardized in organosulfur compounds derived from propiin on the incidence of respiratory tract infections in elderly patients of RCF. Sixty-five volunteers were selected at random to receive a placebo or a single daily dose of the extract for thirty-six weeks. Different clinical visits were performed to evaluate the main respiratory diseases with an infectious origin, as well as the associated symptoms and their duration. The extract showed a clinical safety profile and significantly reduced the incidence of respiratory infections. Moreover, the treatment decreased the number and duration of the associated symptoms compared with the placebo group. For the first time, we demonstrated the protective effect of Alliaceae extract in respiratory infectious diseases in elderly healthy volunteers, which could be used prophylactically against the most common infectious respiratory diseases.

Supplementation of Vitamin D and Mental Health in Adults with Respiratory System Diseases: A Systematic Review of Randomized Controlled Trials.

Vitamin D is indicated to be beneficial for the prevention and treatment of both respiratory health and mental health problems, while mental health issues are a common consequence of diseases of the respiratory system. The aim of the presented systematic review was to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). The systematic review was conducted on the basis of the PubMed and Web of Science databases in agreement with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), while being registered within the database of the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020155779). A total of 8514 studies published before September 2021 were screened and 5 RCTs were included, which were assessed using the revised Cochrane risk-of-bias tool for randomized trials. Screening, inclusion, reporting, and assessment were conducted by two researchers independently. The studies focused on the assessment of patients with chronic obstructive pulmonary disease, but also increased susceptibility to respiratory tract infections, pulmonary tuberculosis, and bronchial asthma. The studies were conducted for various periods of time-from 2 months to a year-while the dose of vitamin D applied was also diverse-from 4000 IU applied daily, to 100,000 IU applied weekly, or monthly. The psychological measures applied within the studies allowed the assessment, mainly, of quality of life, but also well-being, and depression. For the majority of studies, some concerns regarding risk of bias were defined, resulting from the randomization process and selection of reported results; however, for one study, the risk was even defined as high. Within the included studies, three studies confirmed a beneficial effect of vitamin D (including those with a high risk of bias), but two studies did not confirm it. Taking into account the evidence gathered, in spite of a positive influence of vitamin D on mental health in individuals with increased susceptibility to respiratory tract infections and bronchial asthma, the conducted systematic review is not a strong confirmation of the beneficial effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases.

Vitamin D supplementation and lower respiratory tract infection in infants: a nested case-control study.

PURPOSE: To assess the association between vitamin D (VD) supplementation and the risk of lower respiratory tract infection (LRTI) among infants. METHODS: This is a nested case-control study from an ongoing prospective birth cohort in Wuhan from 2013. Cases were subjects free of neonatal pneumonia but later developed LRTI during infancy, who were matched with five randomly selected controls by infant sex, birth year, and birth season. We included 190 cases and 950 controls in the final analysis. The primary outcome was the first LRTI incident and the exposure was VD supplementation from birth to the index endpoint. The association between VD supplementation and LRTI risk was assessed using the Cox proportional-hazards regression model. RESULTS: Infants taking supplements had a 59% relative reduction in the hazard ratio of LRTI (HR = 0.41; 95% CI 0.26, 0.64) compared to those not supplemented. There was a linear relationship between LRTI risk and VD supplementation within range of 0-603 IU/day: for each 100 IU per day increment in VD supplementation, infants experienced a 21% lower risk of developing LRTI (adjusted HR: 0.79; 95% CI 0.71, 0.89). The linear relationship was stably observed in the sensitivity analyses as well. CONCLUSIONS: VD supplementation was associated with the reduced risk of LRTI throughout infancy, and the optimal supplementation dose for infants may be beyond the current recommendation.

Tea consumption and risk of lower respiratory tract infections: a two-sample mendelian randomization study.

BACKGROUND: Observational studies have reported the association between tea consumption and the risk of lower respiratory tract infections (LRTIs). However, a consensus has yet to be reached, and whether the observed association is driven by confounding factors or reverse causality remains unclear. METHOD: A two-sample Mendelian randomization (MR) analysis was conducted to determine whether genetically predicted tea intake is causally associated with the risk of common LRTI subtypes. Genome-wide association study (GWAS) from UK Biobank was used to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea intake each day. The summary statistics for acute bronchitis, acute bronchiolitis, bronchiectasis, pneumonia, and influenza and pneumonia were derived from the FinnGen project. RESULTS: We found that genetically predicted an extra daily cup of tea intake was causally associated with the decreased risk of bronchiectasis [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.47-0.78, P < 0.001], pneumonia (OR = 0.90, 95% CI = 0.85-0.96, P = 0.002), influenza and pneumonia (OR = 0.91, 95% CI = 0.85-0.97, P = 0.002), but not with acute bronchitis (OR = 0.91, 95% CI = 0.82-1.01, P = 0.067) and acute bronchiolitis (OR = 0.79, 95% CI = 0.60-1.05, P = 0.100). Sensitivity analyses showed that no heterogeneity and pleiotropy could bias the results. CONCLUSIONS: Our findings provided new evidence that genetically predicted an extra daily cup of tea intake may causally associated with a decreased risk of bronchiectasis, pneumonia, and influenza and pneumonia.

Homeopathic medicinal products for preventing and treating acute respiratory tract infections in children.

BACKGROUND: Acute respiratory tract infections (ARTIs) are common and may lead to complications. Most children experience between three and six ARTIs annually. Although most infections are self-limiting, symptoms can be distressing. Many treatments are used to control symptoms and shorten illness duration. Most treatments have minimal benefit and may lead to adverse events. Oral homeopathic medicinal products could play a role in childhood ARTI management if evidence for their effectiveness is established. This is an update of a review first published in 2018. OBJECTIVES: To assess the effectiveness and safety of oral homeopathic medicinal products compared with placebo or conventional therapy to prevent and treat ARTIs in children. SEARCH METHODS: We searched CENTRAL (2022, Issue 3), including the Cochrane Acute Respiratory Infections Specialised Register, MEDLINE (1946 to 16 March 2022), Embase (2010 to 16 March 2022), CINAHL (1981 to 16 March 2022), AMED (1985 to 16 March 2022), CAMbase (searched 16 March 2022), and British Homeopathic Library (searched 26 June 2013 - no longer operating). We also searched the WHO ICTRP and ClinicalTrials.gov (16 March 2022), checked references, and contacted study authors to identify additional studies. SELECTION CRITERIA: We included double-blind randomised controlled trials (RCTs) or double-blind cluster-RCTs comparing oral homeopathy medicinal products with identical placebo or self-selected conventional treatments to prevent or treat ARTIs in children aged 0 to 16 years. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: In this 2022 update, we identified three new RCTs involving 251 children, for a total of 11 included RCTs with 1813 children receiving oral homeopathic medicinal products or a control treatment (placebo or conventional treatment) for ARTIs. All studies focused on upper respiratory tract infections (URTIs), with only one study including some lower respiratory tract infections (LRTIs). Six treatment studies examined the effect on URTI recovery, and five studies investigated the effect on preventing URTIs after one to four months of treatment. Two treatment and three prevention studies involved homeopaths individualising treatment. The other studies used predetermined, non-individualised treatments. All studies involved highly diluted homeopathic medicinal products, with dilutions ranging from 1 x 10-4 to 1 x 10-200. We identified several limitations to the included studies, in particular methodological inconsistencies and high attrition rates, failure to conduct intention-to-treat analysis, selective reporting, and apparent protocol deviations. We assessed three studies as at high risk of bias in at least one domain, and many studies had additional domains with unclear risk of bias. Four studies received funding from homeopathy manufacturers; one study support from a non-government organisation; two studies government support; one study was co-sponsored by a university; and three studies did not report funding support. Methodological inconsistencies and significant clinical and statistical heterogeneity precluded robust quantitative meta-analysis. Only four outcomes were common to more than one study and could be combined for analysis. Odds ratios (OR) were generally small with wide confidence intervals (CI), and the contributing studies found conflicting effects, so there was little certainty that the efficacy of the intervention could be ascertained. All studies assessed as at low risk of bias showed no benefit from oral homeopathic medicinal products, whilst trials at unclear or high risk of bias reported beneficial effects. For the comparison of individualised homeopathy versus placebo or usual care for the prevention of ARTIs, two trials reported on disease severity; due to heterogeneity the data were not combined, but neither study demonstrated a clinically significant difference. We combined data from two trials for the outcome need for antibiotics (OR 0.79, 95% CI 0.35 to 1.76; low-certainty evidence). For the comparison of non-individualised homeopathy versus placebo or usual care for the prevention of ARTIs, only the outcome recurrence of ARTI was reported by more than one trial; data from three studies were combined for this outcome (OR 0.60, 95% CI 0.21 to 1.72; low-certainty evidence). For the comparison of both individualised and non-individualised homeopathy versus placebo or usual care for the treatment of ARTIs, two studies provided data on short-term cure (OR 1.31, 95% CI 0.09 to 19.54) and long-term cure (OR 1.01, 95% CI 0.10 to 9.96; very low-certainty evidence). The studies demonstrated an opposite direction of effect for both outcomes. Six studies reported on disease severity but were not combined as they used different scoring systems and scales. Three studies reported adverse events (OR 0.79, 95% CI 0.16 to 4.03; low-certainty evidence). AUTHORS' CONCLUSIONS: Pooling of five prevention and six treatment studies did not show any consistent benefit of homeopathic medicinal products compared to placebo on ARTI recurrence or cure rates in children. We assessed the certainty of the evidence as low to very low for the majority of outcomes. We found no evidence to support the efficacy of homeopathic medicinal products for ARTIs in children. Adverse events were poorly reported, and we could not draw conclusions regarding safety.

[Benefits of Green Tea: Clinical Evidence for Respiratory Tract Infections].

Green tea components, such as catechins have been reported to provide several benefits including anti-oxidative, anti-viral/bacterial, and anti-inflammatory effects in vitro and in vivo. Catechins effectively inhibited the adsorption and replication of the influenza virus. Additionally, green tea contains theanine and vitamin C, which enhance the immunity against viral/bacterial infections. Based on these, green tea is hypothesized to have potential benefits in the prevention of influenza and other respiratory tract infections in the clinical setting. However, its specific effects in patients remain unclear. To determine the clinical significance of green tea in the prevention of respiratory tract infections, we conducted an observational study and eight interventional studies. Based on the results of three studies, consuming or gargling green tea or its components significantly aided in the prevention of influenza. Meanwhile, one study showed that green tea successfully prevented common colds. Catechin inhalation was also reported to decrease the bacterial load of methicillin-resistant Staphylococcus aureus in the sputum. Although the anti-viral/anti-bacterial effects of green tea components have been demonstrated in experimental studies, the clinical evidence remains limited. Further studies are required to confirm the clinical efficacy of green tea and its components in preventing respiratory tract infections.

Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT).

OBJECTIVE: To determine the effect of population level implementation of a test-and-treat approach to correction of suboptimal vitamin D status (25-hydroxyvitamin D (25(OH)D) <75 nmol/L) on risk of all cause acute respiratory tract infection and covid 19. DESIGN: Phase 3 open label randomised controlled trial. SETTING: United Kingdom. PARTICIPANTS: 6200 people aged ≥16 years who were not taking vitamin D supplements at baseline. INTERVENTIONS: Offer of a postal finger prick test of blood 25(OH)D concentration with provision of a six month supply of lower dose vitamin D (800 IU/day, n=1550) or higher dose vitamin D (3200 IU/day, n=1550) to those with blood 25(OH)D concentration <75 nmol/L, compared with no offer of testing or supplementation (n=3100). Follow-up was for six months. MAIN OUTCOME MEASURES: The primary outcome was the proportion of participants with at least one swab test or doctor confirmed acute respiratory tract infection of any cause. A secondary outcome was the proportion of participants with swab test confirmed covid-19. Logistic regression was used to calculate odds ratios and associated 95% confidence intervals. The primary analysis was conducted by intention to treat. RESULTS: Of 3100 participants offered a vitamin D test, 2958 (95.4%) accepted and 2674 (86.3%) had 25(OH)D concentrations <75 nmol/L and received vitamin D supplements (n=1328 lower dose, n=1346 higher dose). Compared with 136/2949 (4.6%) participants in the no offer group, at least one acute respiratory tract infection of any cause occurred in 87/1515 (5.7%) in the lower dose group (odds ratio 1.26, 95% confidence interval 0.96 to 1.66) and 76/1515 (5.0%) in the higher dose group (1.09, 0.82 to 1.46). Compared with 78/2949 (2.6%) participants in the no offer group, 55/1515 (3.6%) developed covid-19 in the lower dose group (1.39, 0.98 to 1.97) and 45/1515 (3.0%) in the higher dose group (1.13, 0.78 to 1.63). CONCLUSIONS: Among people aged 16 years and older with a high baseline prevalence of suboptimal vitamin D status, implementation of a population level test-and-treat approach to vitamin D supplementation was not associated with a reduction in risk of all cause acute respiratory tract infection or covid-19. TRIAL REGISTRATION: ClinicalTrials.gov NCT04579640.

Red propolis supplementation does not decrease acute respiratory events in stunted preschool children: A paired nonrandomized clinical trial.

BACKGROUND & AIMS: This study aimed to evaluate the efficacy of "red propolis" supplementation in the frequency of acute respiratory infections incidence in stunted preschool children. We hypothesized that the "red" propolis supplementation is effective in the reduce frequency of acute respiratory complications in stunted children. METHODS: This is a non-randomized, pair-matched clinical trial with 70 children, ranging from 1 to 5 years old, followed for 1 year, which were paired into two groups according to age, sex, and stunting classification. The children were in the day hospital regimen of CREN and received 5 meals/day and an additional 8 ml of honey or honey with "red propolis" in a 3% dilution. The children had access to nutritional, psychological, dental, and physician care. Respiratory complications were recorded in a pre-existing protocol of the institution by the same pediatrician, who was blind for the children's allocation. Anthropometric measurements and biochemical tests such as hemogram, IGF-1, and immunoglobulin E, G, M were conducted. RESULTS: The most prevalent symptoms were coughing, runny nose, nasal congestion and wheezing. The use of "red propolis" did not decrease the frequency of infections between the control and propolis groups, respectively (2 [1-7] vs 3 [1-7], p = 0.10), which was within the estimated by the Pan American Health Organization. There were no differences between groups in anthropometric and biochemical parameters. CONCLUSION: Supplementation with "red propolis" did not reduce the number of infections in stunted children over 1 year. Possibly, the dilution percentage (3%) may have been insufficient to allow effective action. The protocol of published in the Brazilian Registry of Clinical Trials (http://www.ensaiosclinicos.gov.br/rg/RBR-4n7j6h).

[Non-antibiotic Prophylaxis of Infections]. / Nicht-antibiotische Prophylaxe von Infekten.

Non-antibiotic Prophylaxis of Infections Abstract. The increasing resistance to antibiotics makes the search for non-antibiotic alternatives for the treatment and prevention of - above all - respiratory and urinary tract infections crucial. Potential non-antibiotic approaches include phytopharmaceuticals (Echinacea purpurea, Pelargonium sidoides, cranberry extract), zinc, immunostimulants (OM-85 BV, OM-89), and behavior modifications. Some of these approaches are promising options; however, a high level of evidence is required before specific recommendations for their use can be made.

Effect of Catechins on Upper Respiratory Tract Infections in Winter: A Randomized, Placebo-Controlled, Double-Blinded Trial.

Tea catechins are plant-derived compounds that improve immune functions. Previous randomized control trials have demonstrated the efficacy of primarily epi-type catechins against upper respiratory tract infections (URTIs). Green tea can be consumed in several ways, including popular bottled beverages. These beverages, however, require sterilization during manufacturing, which results in catechin isomerization. We conducted a randomized, double-blinded, placebo-controlled trial involving healthy Japanese participants to evaluate whether catechin consumption via bottled beverages has an alleviating effect on the duration and severity of URTIs in winter. The catechin group (490 mg catechin, 0.14%, containing 59% epi-type catechin, n = 55) showed reduced durations of running nose, nasal congestion, and headache, compared with the placebo group (0 mg catechin, n = 54; p = 0.013, 0.018, and <0.001, respectively). Furthermore, when considering physical symptoms, the duration of nasopharyngeal symptoms improved significantly in the catechin group (p < 0.001) compared with that in the control group. The daily consumption of catechin thus reduced the duration and severity of URTIs in healthy men and women. Humans are regularly exposed to several potential infectious threats, and the oral administration of heat-epimerized tea catechins might help prevent and reduce the severity of URTIs.

Effect of Lactoferrin Supplementation on Inflammation, Immune Function, and Prevention of Respiratory Tract Infections in Humans: A Systematic Review and Meta-analysis.

Lactoferrin (Lf) is a glycoprotein present in human and bovine milk with antimicrobial and immune-modulating properties. This review aimed to examine the evidence for the effect of Lf supplementation on inflammation, immune function, and respiratory tract infections (RTIs) in humans. Online databases were searched up to December 2020 to identify relevant, English-language articles that examined the effect of Lf supplementation in human subjects of all ages, on either inflammation, immune cell populations or activity, or the incidence, duration, or severity of respiratory illness or RTIs. Twenty-five studies (n = 20 studies in adults) were included, of which 8 of 13 studies (61%) in adults reported a decrease in at least 1 systemic inflammatory biomarker. Immune function improved in 6 of 8 studies (75%) in adults, with changes in immune cell populations in 2 of 6 studies (33%), and changes in immune cell activity in 2 of 5 studies (40%). RTI outcomes were reduced in 6 of 10 studies (60%) (n = 5 in adults, n = 5 in children), with decreased incidence in 3 of 9 studies (33%), and either decreased frequency (2/4, 50%) or duration (3/6, 50%) in 50% of studies. In adults, Lf reduced IL-6 [mean difference (MD): -24.9 pg/mL; 95% CI: -41.64, -8.08 pg/mL], but not C-reactive protein (CRP) [standardized mean difference: -0.09; 95% CI: -0.82, 0.65], or NK cell cytotoxicity [MD: 4.84%; 95% CI: -3.93, 13.60%]. RTI incidence was reduced in infants and children (OR: 0.78; 95% CI: 0.61, 0.98) but not in adults (OR: 1.00; 95% CI: 0.76, 1.32). Clinical studies on Lf supplementation are limited, although findings show 200 mg Lf/d reduces systemic inflammation, while formulas containing 35-833 mg Lf/d may reduce RTI incidence in infants and children, suggesting improved immune function. Future research is required to determine optimal supplementation strategies and populations most likely to benefit from Lf supplementation. This trial was registered at PROSPERO (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232186) as CRD42021232186.

Efficacy of Vitamin D Supplements in Prevention of Acute Respiratory Infection: A Meta-Analysis for Randomized Controlled Trials.

BACKGROUND: Previous systematic reviews and meta-analyses of randomized controlled trials (RCTs) have reported inconsistent results regarding the efficacy of vitamin D supplements in the prevention of acute respiratory infections (ARIs). METHODS: We investigated these efficacy results by using a meta-analysis of RCTs. We searched PubMed, EMBASE, and the Cochrane Library in June 2021. RESULTS: Out of 390 trials searched from the database, a total of 30 RCTs involving 30,263 participants were included in the final analysis. In the meta-analysis of all the trials, vitamin D supplementation showed no significant effect in the prevention of ARIs (relative risk (RR) 0.96, 95% confidence interval (CI) 0.91-1.01, I2 = 59.0%, n = 30). In the subgroup meta-analysis, vitamin D supplementation was effective in daily supplementation (RR 0.83, 95% CI, 0.73-0.95, I2 = 69.1%, n = 15) and short-term supplementation (RR 0.83, 95% CI, 0.71-0.97, I2 = 66.8%, n = 13). However, such beneficial effects disappeared in the subgroup meta-analysis of high-quality studies (RR 0.89, 95% CI, 0.78-1.02, I2 = 67.0%, n = 10 assessed by the Jadad scale; RR 0.87, 95% CI, 0.66-1.15, I2 = 51.0%, n = 4 assessed by the Cochrane's risk of bias tool). Additionally, publication bias was observed. CONCLUSIONS: The current meta-analysis found that vitamin D supplementation has no clinical effect in the prevention of ARIs.

Current opinion on the role of vitamin D supplementation in respiratory infections and asthma/COPD exacerbations: A need to establish publication guidelines for overcoming the unpublished data.

BACKGROUND & AIMS: The role of prophylactic vitamin D supplementation in prevention and treatment of respiratory infections and other related pathologies has been extensively explored with conflicting results. The aim of this systematic review and meta-analysis was to evaluate the prophylactic and therapeutic effects of vitamin D administration on respiratory infections. METHODS: A systematic search was performed and randomized controlled trials (RCTs) of vitamin D supplementation and a total of 65 RCTs involving 50,554 participants were included. RESULTS: The overall incidence of respiratory infections in terms of count data (OR: 0.87; 95%CI [0.80-0.95]; p = 0.0028; I2 = 43%) and event rate (IRR: 0.81; 95%CI [0.70-0.95]; p = 0.010; I2 = 79%) was significantly reduced in the intervention group. However, no effect of vitamin D on duration or upper respiratory tract infection severity was observed following the overall analysis. Subgroup analyses revealed more details regarding the protective effect of particular dose ranges, administration frequencies and trial durations on different disease types. CONCLUSIONS: Despite between-study heterogeneity was high for most outcomes and publication bias may have led to an effect size overestimation of incidence count data, vitamin D supplementation could be beneficial in improving resistance to overall respiratory infections, particularly when administered on a daily basis.

Whether Immunostimulants Are Effective in Susceptible Children Suffering From Recurrent Respiratory Tract Infections: A Modeling Analysis Based on Literature Aggregate Data.

Immunostimulants are gradually being used in the prevention and treatment of recurrent respiratory tract infections in susceptible children, but their drug effects have not been quantified. The purpose of this study was to confirm the efficacy of immunostimulants in the prevention and treatment of recurrent respiratory tract infections in susceptible children. A model-based meta-analysis was used to describe the time course of placebo and immunostimulants in the prevention of respiratory tract infections in children. The cumulative number of respiratory tract infections was used as an indicator of efficacy. A meta-analysis was used to analyze the incidence of drug-related adverse events. Fourteen articles with 2400 pediatric subjects were finally included in the analysis. The results showed that the cumulative number of respiratory tract infections increased linearly with time, with the incidence of respiratory tract infections in the placebo group being 0.65 (95% confidence interval [CI], 0.55-0.75) per month. OM-85 BV and pidotimod reduced the incidence of respiratory tract infections by 0.21 (95%CI, 0.16-0.26) and 0.19 (95%CI, 0.17-0.21) compared to placebo per month, respectively. Pidotimod and OM-85 BV can effectively reduce the incidence of respiratory tract infections in susceptible children, with no significant increase in the incidence of drug-related adverse events when compared with placebo (risk ratio values were 1.07 [95%CI, 0.66-1.71] and 1.31 [95%CI, 0.54-3.19], respectively). This study provides quantitative support for the application of immunostimulants for the prevention of recurrent respiratory tract infections in children.

The Effects of Prebiotics, Synbiotics, and Short-Chain Fatty Acids on Respiratory Tract Infections and Immune Function: A Systematic Review and Meta-Analysis.

Prebiotics, synbiotics, and SCFAs have been shown to decrease systemic inflammation and play a protective role in chronic respiratory conditions. However, their effects on infection and immune function are unclear. The objective of this systematic review was to summarize the current evidence for prebiotic, synbiotic, and SCFA supplementation on respiratory tract infections (RTIs) and immune function. The protocol for this systematic review was registered with PROSPERO (National Institute for Health Research, University of York, UK), accessed online at https://www.crd.york.ac.uk/prospero (CRD42019118786). Relevant English-language articles up to May 2021 were identified via online databases: MEDLINE, EMBASE, CINAHL, and Cochrane Library. Included studies (n = 58) examined the effect of prebiotics, synbiotics, or SCFA, delivered orally, on the incidence, severity, or duration of RTIs and/or markers of immune function (e.g., peripheral blood immunophenotyping, NK cell activity). The majority of studies were randomized controlled trials reporting on RTIs in infants and children. The meta-analysis indicated that the numbers of subjects with ≥1 RTI were reduced with prebiotic (OR, 0.73; 95% CI: 0.62-0.86; P = 0.0002; n = 17) and synbiotic (OR, 0.75; 95% CI: 0.65-0.87; P = 0.0001; n = 9) supplementation compared to placebo. Further, NK cell activity was increased with synbiotic (standardized mean difference, 0.74; 95% CI: 0.42-1.06; P < 0.0001, n = 3) supplementation. This review provides evidence that prebiotic, specifically oligosaccharide, supplementation may play a protective role in RTIs in infants and children. There is less evidence for this effect in adults. Supplementation with prebiotic and synbiotic treatment may alter immune function by increasing NK cell activity, though effects on immunophenotype were less clear.

Nutrient supplementation for prevention of viral respiratory tract infections in healthy subjects: A systematic review and meta-analysis.

It remains uncertain as to whether nutrient supplementation for the general population considered healthy could be useful in the prevention of RTIs, such as COVID-19. In this systematic review and meta-analysis, the evidence was evaluated for primary prevention of any viral respiratory tract infection (RTI) such as SARS-CoV-2, through supplementation of nutrients with a recognized role in immune function: multiple micronutrients, vitamin A, folic acid, vitamin B12, C, D, E, beta-carotene, zinc, iron and long-chain polyunsaturated fatty acids. The search produced 15,163 records of which 93 papers (based on 115 studies) met the inclusion criteria, resulting in 199,055 subjects (191,636 children and 7,419 adults) from 37 countries. Sixty-three studies were included in the meta-analyses, which was performed for children and adults separately. By stratifying the meta-analysis by world regions, only studies performed in Asia showed a significant but heterogeneous protective effect of zinc supplementation on RTIs (RR 0.86, 95% CI 0.7-0.96, I2  = 79.1%, p = .000). Vitamin D supplementation in adults significantly decreased the incidence of RTI (RR 0.89, 95% CI 0.79-0.99, p = .272), particularly in North America (RR 0.82 95% CI 0.68-0.97), but not in Europe or Oceania. Supplementation of nutrients in the general population has either no or at most a very limited effect on prevention of RTIs. Zinc supplementation appears protective for children in Asia, whilst vitamin D may protect adults in the USA and Canada. In 10/115 (8.7%) studies post-hoc analyses based on stratification for nutritional status was performed. In only one study zinc supplementation was found to be more effective in children with low zinc serum as compared to children with normal zinc serum levels.