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

Abstract

Lactoferrin (Lf) is a glycoprotein present in human and bovine milk with anti-microbial 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 which 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 in adults) were included, of which 8/13 studies (61%) in adults reported a decrease in at least one systemic inflammatory biomarker. Immune function improved in 6/8 studies (75%) in adults, with changes in immune cell populations in 2/6 studies (33%), and changes in immune cell activity in 2/5 studies (40%). RTI outcomes reduced in 6/10 studies (60%) (n=5 in adults, n=5 in children), with decreased incidence in 3/9 (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 (SMD): -0.09; 95% CI: -0.82, 0.65], or natural killer (NK) cell cytotoxicity [MD: 4.84%; 95% CI: -3.93, 13.60%]. RTI incidence was reduced in infants and children [odds ratio (OR): 0.78; 95% CI: 0.61, 0.98] but not adults [OR: 1.00; 95% CI: 0.76, 1.32]. Clinical studies on Lf supplementation are limited, though findings show 200mg/day Lf reduces systemic inflammation, while formulas containing 35-833mg/day Lf 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. PROSPERO registration number: CRD42021232186

Bovine lactoferrin for the prevention of COVID-19 infection in health care personnel: a double-blinded randomized clinical trial (LF-COVID)

“…The dose of 600 mg/day of lactoferrin was chosen based on previous studies that used between 400 and 600 mg/day of bLF for prevention of respiratory infections (Oda et al 2020 ; Vitetta et al 2013 ). Doses of bLF between 200 mg/day to 1.5 g/day have been previously used without describing any severe side-effect (Berthon et al 2022 ). The LF chewable tablets were of 250 mg and composed of 100 mg of bLF and other ingredients (reduced maltose, dietary fiber—indigestible dextrin, maltodextrin and rapeseed hydrogenated oil) (Online Appendix 1).…”

Preventing Respiratory Viral Diseases with Antimicrobial Peptide Master Regulators in the Lung Airway Habitat

“…Conclusively, lactoferrin has potential antiviral and immunomodulatory properties to protect against respiratory viral infection and is suggested to be used as a nutraceutical [ 58 ]. Interestingly, lactoferrin confirmed to have protective effects and reduced respiratory tract infections in controlled randomized clinical trials via modulation of inflammation and immune response [ 59 , 60 ].…”

Research Advances of Lactoferrin in Electrostatic Spinning, Nano Self-Assembly, and Immune and Gut Microbiota Regulation

“…LF also raises IgA antibody levels in the blood and lowers inflammatory indicators. 105,106 The specific mechanism by which LF repairs the tissue barrier in colitis to reduce inflammation is that it regulates the expression of tissue barrier defense-related proteins and tight junction proteins, as well as downregulates the expression of inflammatory factors such as IL-1β, IL-6, and TNF-α and increases the expression levels of anti-inflammatory factors such as IL-10 and TGF-β. 100 ■ OTHER APPLICATIONS LF can be active in the Maillard reaction, protein interactions, and so on through covalent or noncovalent interaction with functional groups in the structure.…”

“…The interaction of LF with inflammatory or anti-inflammatory factors via the gut microbiota is shown in Figure . LF also raises IgA antibody levels in the blood and lowers inflammatory indicators. , The specific mechanism by which LF repairs the tissue barrier in colitis to reduce inflammation is that it regulates the expression of tissue barrier defense-related proteins and tight junction proteins, as well as downregulates the expression of inflammatory factors such as IL-1β, IL-6, and TNF-α and increases the expression levels of anti-inflammatory factors such as IL-10 and TGF-β …”