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

Advances in nutrition (Bethesda, Md.). 2022;13(5):1799-1819

Plain language summary

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.

Lifestyle medicine

Fundamental Clinical Imbalances : Immune and inflammation
Patient Centred Factors : Mediators/Lactoferrin supplementation
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Not applicable
Bioactive Substances : Lactoferrin

Methodological quality

Jadad score : Not applicable
Allocation concealment : Not applicable

Metadata