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Effect of micronutrient supplements on influenza and other respiratory tract infections among adults: a systematic review and meta-analysis.
Abioye, AI, Bromage, S, Fawzi, W
BMJ global health. 2021;(1)
Abstract
Acute respiratory tract infections (ARIs) are a leading cause of ill-health and death globally. Individual or multiple micronutrients have been shown to modulate immune function and affect the risk and severity of a number of infectious diseases. We systematically reviewed the evidence on the impact of micronutrient supplements to reduce the occurrence of ARIs and shorten the duration of ARI symptoms among adults. Random effects meta-analyses were conducted to estimate the pooled effects of vitamin D, vitamin C, zinc and multiple micronutrient supplementation (MMS) on the occurrence of ARIs and the duration of ARI symptoms. Vitamin D supplementation reduced the risk of ARI (risk ratio (RR)=0.97; 95% CI 0.94 to 1.00; p=0.028) and shortened the duration of symptoms (per cent difference: -6% (95% CI -9% to -2%; p=0.003)). The RR of vitamin D to prevent ARI was farther from the null when diagnosis was based on clinical diagnosis or laboratory testing, compared with self-report and when the loading dose was <60 000 IU. Vitamin C supplementation reduced the risk of ARIs (RR=0.96; 95% CI 0.93 to 0.99; p=0.01) and shortened the duration of symptoms (per cent difference: -9% (95% CI -16% to -2%; p=0.014)). The effect of vitamin C on preventing ARI was stronger among men and in middle-income countries, compared with women and high-income countries, respectively. Zinc supplementation did not reduce the risk of ARIs but shortened the duration of symptoms substantially (per cent difference: -47% (95% CI -73% to -21%; p=0.0004)). Our synthesis of global evidence from randomised controlled trials indicates that micronutrient supplements including zinc, vitamins C and D, and multiple micronutrient supplements may be modestly effective in preventing ARIs and improving their clinical course. Further research is warranted to better understand the effectiveness that individual or multiple micronutrients have on SARS-CoV-2 infection and treatment outcomes.
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The association between vitamin D status and infectious diseases of the respiratory system in infancy and childhood.
Zisi, D, Challa, A, Makis, A
Hormones (Athens, Greece). 2019;(4):353-363
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PURPOSE Respiratory tract infections (RTIs) are a major cause of illness worldwide and the most common cause of hospitalization for pneumonia and bronchiolitis. These two diseases are the leading causes of morbidity and mortality among children under 5 years of age. Vitamin D is believed to have immunomodulatory effects on the innate and adaptive immune systems by modulating the expression of antimicrobial peptides, like cathelicidin, in response to both viral and bacterial stimuli. The aim of this review is to summarize the more recently published data with regard to potential associations of 25-hydroxyvitamin D [25(OH)D] with infectious respiratory tract diseases of childhood and the possible health benefits from vitamin D supplementation. METHODS The literature search was conducted by using the PubMed, Scopus, and Google Scholar databases, with the following keywords: vitamin D, respiratory tract infection, tuberculosis, influenza, infancy, and childhood. RESULTS Several studies have identified links between inadequate 25(OH)D concentrations and the development of upper or lower respiratory tract infections in infants and young children. Some of them also suggest that intervention with vitamin D supplements could decrease both child morbidity and mortality from such causes. CONCLUSIONS Most studies agree in that decreased vitamin D concentrations are prevalent among most infants and children with RTIs. Also, normal to high-serum 25(OH)D appears to have some beneficial influence on the incidence and severity of some, but not all, types of these infections. However, studies with vitamin D supplementation revealed conflicting results as to whether supplementation may be of benefit, and at what doses.
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Recommendations to maintain immune health in athletes.
Walsh, NP
European journal of sport science. 2018;(6):820-831
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Numerous studies over the last 35 years report an increase in upper respiratory infection (URI) symptoms in athletes during periods of heavy training and competition. Challenges athletes face such as heavy exercise and life stress influence immune function via activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system and the resulting immunoregulatory hormones. Both innate and acquired immunity are often reported to decrease transiently in the hours after heavy exertion, typically 15-70%: prolonged heavy training sessions in particular have been shown to decrease immune function; potentially providing an 'open window' for opportunistic infections. Whether the observed changes in immunity with acute strenuous exercise or periods of heavy training account for the increased susceptibility to URI symptoms remains contentious. Nevertheless, there is little doubt that URI symptoms hinder athletic training and competition; underpinning the need to identify the prominent risk factors and appropriate countermeasures. Recent studies have identified prominent risk factors, including: intensified training in the winter; long-haul travel; low energy availability; high levels of psychological stress and anxiety; and depression. Given the shared pathways and effector limbs for the body's response to physical and psychological challenges, it is logical that psychological strain influences immunity and illness incidence in athletes under heavy training; indeed, stress and anxiety have recently been shown to modify the immune response to exercise. This mini-review provides new insights and evidence-based recommendations for coping with the various challenges that athletes encounter on immune health, including: heavy exercise; life stress; sleep disruption; environmental extremes and nutritional deficits.
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Upper Respiratory Symptoms, Gut Health and Mucosal Immunity in Athletes.
Colbey, C, Cox, AJ, Pyne, DB, Zhang, P, Cripps, AW, West, NP
Sports medicine (Auckland, N.Z.). 2018;(Suppl 1):65-77
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Upper respiratory symptoms remain the most common illness in athletes. Upper respiratory symptoms during heavy training and competition may impair performance. Preventing illness is the primary reason for the use of supplements, such as probiotics and prebiotics, for maintaining or promoting gut health and immune function. While exercise-induced perturbations in the immune system may increase susceptibility to illness and infection, growing evidence indicates that upper respiratory symptoms are related to a breakdown in the homeostatic regulation of the mucosal immune system of the airways. Balancing protection of the respiratory tract with normal physiological functioning requires dynamic orchestration between a wide array of immune parameters. The intestinal microbiota regulates extra-intestinal immunity via the common mucosal immune system and new evidence implicates the microbiota of the nose, mouth and respiratory tract in upper respiratory symptoms. Omics' approaches now facilitate comprehensive profiling at the molecular and proteomic levels to reveal new pathways and molecules of immune regulation. New targets may provide for personalised nutritional and training interventions to maintain athlete health.
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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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Cationic pullulan nanogel as a safe and effective nasal vaccine delivery system for respiratory infectious diseases.
Nakahashi-Ouchida, R, Yuki, Y, Kiyono, H
Human vaccines & immunotherapeutics. 2018;(9):2189-2193
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The mucosal surfaces of the respiratory and gastrointestinal tracts are continuously exposed to countless beneficial and pathologic antigens. These mucosal surfaces are thus equipped with an immune system that is unique from those elsewhere in the body; this unique system provides the first line of immune surveillance and defense against pathogen invasion. The sophisticated immune induction machinery in the aero-digestive tract involves mucosa-associated lymphoid tissues, including nasopharyngeal- and gut-associated lymphoid tissues, for the generation of antigen-specific humoral and cellular immune responses. Consequently, nasal or oral immunization with an appropriate vaccine delivery vehicle prompts the induction of protective immunity in both the mucosal and systemic compartments, leading to a double layer of protection against pathogens. To harness the benefits of mucosal vaccines, various mucosal antigen delivery vehicles are under development, and a cationic cholesteryl-group-bearing pullulan nanogel (cCHP nanogel) has emerged as a potent nasal vaccine delivery system for the induction of protective immunity against respiratory infections.
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Salivary immunity and lower respiratory tract infections in non-elite marathon runners.
Cantó, E, Roca, E, Perea, L, Rodrigo-Troyano, A, Suarez-Cuartin, G, Giner, J, Feliu, A, Soria, JM, Nescolarde, L, Vidal, S, et al
PloS one. 2018;(11):e0206059
Abstract
RATIONALE Respiratory infections are common after strenuous exercise, when salivary immunity may be altered. We aim to investigate changes in salivary immunity after a marathon and its relationship with lower respiratory tract infections (LRTI) in healthy non-elite marathon runners. METHODS Forty seven healthy marathon runners (28 males and 19 females) who completed the 42.195 km of the 2016 Barcelona marathon were studied. Saliva and blood samples were collected the day before the marathon and two days after the end of the race. Salivary IgA, antimicrobial proteins (lactoferrin, lysozyme) and chemokines (Groα, Groβ, MCP-1) were determined using ELISA kits in saliva supernatant. Blood biochemistry and haemogram were analyzed in all participants. The presence of LRTI was considered in those runners who reported infectious lower respiratory tract symptoms during a minimum of 3 consecutive days in the 2 weeks after the race. RESULTS Eight participants (17%) presented a LRTI during the 2 weeks of follow-up. Higher lysozyme levels were detected after the race in runners with LRTI when compared with those without infection. A decrease in salivary lysozyme, Groα and Groβ levels after the race were observed in those runners who did not develop a LRTI when compared to basal levels. Salivary Groα levels correlated with basophil blood counts, and salivary lysozyme levels correlated with leukocyte blood counts. CONCLUSIONS LRTI are common after a marathon race in non-elite healthy runners. Changes in salivary antimicrobial proteins and chemokines are related to the presence of LRTI and correlate with systemic defense cells, which suggest an important role of salivary immunity in the development of LRTI in non-elite marathon runners.
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Vitamin D modulation of innate immune responses to respiratory viral infections.
Zdrenghea, MT, Makrinioti, H, Bagacean, C, Bush, A, Johnston, SL, Stanciu, LA
Reviews in medical virology. 2017;(1)
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Vitamin D, in addition to its classical functions in bone homeostasis, has a modulatory and regulatory role in multiple processes, including host defense, inflammation, immunity, and epithelial repair. Patients with respiratory disease are frequently deficient in vitamin D, implying that supplementation might provide significant benefit to these patients. Respiratory viral infections are common and are the main trigger of acute exacerbations and hospitalization in children and adults with asthma and other airways diseases. Respiratory monocytes/macrophages and epithelial cells constitutively express the vitamin D receptor. Vitamin D, acting through this receptor, may be important in protection against respiratory infections. Whether the in vitro findings can be translated into a substantial in vivo benefit still remains uncertain. Here we review the in vitro data on the role of vitamin D in antiviral innate immunity, the data concerning the deficient levels of vitamin D in lung diseases, and the in vivo role of supplementation as protection against respiratory viral infections in healthy individuals and in patients with chronic respiratory diseases. Finally, we suggest ways of improving the effectiveness of vitamin D as an adjuvant in the prevention and treatment of acute respiratory infections.
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Impact of vitamin D on infectious disease.
Kearns, MD, Alvarez, JA, Seidel, N, Tangpricha, V
The American journal of the medical sciences. 2015;(3):245-62
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BACKGROUND Observational studies have linked vitamin D status and infectious disease. This association is supported by the presence of the vitamin D receptor and CYP27B1 in immune cells. This review aims to consolidate data from clinical trials that used vitamin D for the treatment or prevention of infectious disease. METHODS The authors searched the term "(vitamin D OR ergocalciferol OR cholecalciferol OR vitamin D2 OR vitamin D3 OR calcitriol) AND (infection OR tuberculosis OR sepsis OR pneumonia)" with limits preset to manuscripts published in English and with human subjects. They identified controlled trials that measured infectious outcomes (eg, incidence and severity of disease, time to disease resolution or recurrence, measures of clinical improvement, mortality). Studies that used analog, topical or micronutrient formulations of vitamin D, assessed only vitamin D status or lacked a comparison group were excluded. The references from eligible manuscripts and from 2 recent reviews were scanned for additional manuscripts. RESULTS One thousand two hundred eighty-four manuscripts were identified with our search terms, with 60 papers still eligible after review of the title and abstract. Full review of these papers, their references and 2 related reviews yielded 38 manuscripts. CONCLUSIONS Although some prospective studies show positive results regarding vitamin D on infectious disease, several robust studies are negative. Factors such as high variability between studies, the difference in individual responsiveness to vitamin D and study designs that do not primarily investigate infectious outcomes may mask the effects of vitamin D on infections.
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Vitamin D supplementation to patients with frequent respiratory tract infections: a post hoc analysis of a randomized and placebo-controlled trial.
Bergman, P, Norlin, AC, Hansen, S, Björkhem-Bergman, L
BMC research notes. 2015;:391
Abstract
BACKGROUND Vitamin D is considered to be important for a healthy immune system. The aim of this study was to test the hypothesis that vitamin D supplementation reduces number of respiratory tract infections (RTIs) and prolong the time to the first RTI in adult patients with frequent RTIs. METHODS We performed a post hoc analysis of a randomized, placebo-controlled and double-blinded study, where adult patients with a high burden of RTIs were randomized to placebo or vitamin D (4000 IE/day for 1 year, n = 124 in the per protocol cohort presented here). RESULTS Vitamin D supplementation increased the probability to stay free of RTI during the study year (RR 0.64, 95% CI 0.43-0.94). Further, the total number of RTIs was also reduced in the vitamin D-group (86 RTIs) versus placebo (120 RTIs; p = 0.05). Finally, the time to the first RTI was significantly extended in the vitamin D-group (HR 1.68, 95% CI 1.03-2.68, p = 0.0376). CONCLUSION Vitamin D supplementation was found to significantly increase the probability of staying infection free during the study period. This finding further supports the notion that vitamin D-status should be monitored in adult patients with frequent RTIs and suggests that selected patients with vitamin D deficiency are supplemented. This could be a safe and cheap way to reduce RTIs and improve health in this vulnerable patient population. The original trial was registered at http://www.clinicaltrials.gov (NCT01131858).