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Effect of Lactoferrin Supplementation on Inflammation, Immune Function, and Prevention of Respiratory Tract Infections in Humans: A Systematic Review and Meta-analysis.
Berthon, BS, Williams, LM, Williams, EJ, Wood, LG
Advances in nutrition (Bethesda, Md.). 2022;13(5):1799-1819
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Human and bovine milk contains Lactoferrin, an iron-binding glycoprotein that may modulate immune function and has antimicrobial and antioxidant properties. In this systematic review and meta-analysis, 25 heterogeneous studies were included to evaluate the efficacy of lactoferrin supplementation on systemic inflammation, immune function, and respiratory tract infections in children and adults with various inflammatory conditions. Supplementation with Lactoferrin reduced only a few inflammatory markers, and beneficial effects were observed in less than half of the studies included. However, a beneficial effect was observed when the intervention was continued for at least three months, and dosages, such as 35 mg/d to 833 mg/d in infants, and 400 mg/d to 600 mg/d in adults, were also found to be beneficial. By modulating the immune system, lactoferrin supplementation reduces respiratory tract infections in children and infants. Based on the findings of this study, healthcare professionals may be able to understand the beneficial effects of Lactoferrin supplementation on immune modulation, inflammation reduction, and respiratory tract infections when supplemented as a combination with other supplements or as Lactoferrin alone. However, it is necessary to conduct further robust research to confirm the clinical effectiveness of Lactoferrin supplementation since the current research is limited in number and heterogeneous in nature.
Abstract
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.
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Micronutrients Deficiency, Supplementation and Novel Coronavirus Infections-A Systematic Review and Meta-Analysis.
Wang, MX, Gwee, SXW, Pang, J
Nutrients. 2021;13(5)
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Coronaviruses are a family of enveloped RNA viruses capable of infecting both humans and animals. A robust immune system has general protective effects against disease infection and severity. Micronutrients are shown to be fundamental in strengthening and maintaining immune function. The aim of this study was to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and its associated severity. This study is a systematic review and meta-analysis of 19 studies. Only literature on COVID-19 induced by SARS-CoV-2 were recovered from the systematic search. Results demonstrate significantly reduced odds of COVID-19 incidence, and ICU admissions or severe/critical disease onset in individuals without micronutrient deficiency. Authors conclude that integrating micronutrients into the prevention and therapeutic management of COVID-19 may complement nonpharmaceutical interventions to reduce the risk of transmission and disease severity in an unvaccinated population.
Abstract
BACKGROUND Micronutrients play roles in strengthening and maintaining immune function, but their supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. METHODS Systematic literature searches conducted in five electronic databases identified 751 unique studies, of which 33 studies (five supplementation studies, one supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. FINDINGS A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset when combined as a severity outcome (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures, namely mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. CONCLUSION The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.