Abstract
SummaryIt has been demonstrated that lactoferrin (LF) plays a role in host defence, but evidence on its potential antiviral property from clinical studies is fragmented. Our systematic review aimed at identifying the effects of orally administered LF against virus infections. The systematic search was conducted on PubMed, Scopus, Web of Science, BioRxiv.org and ClinicalTrials.gov from database inception to 7th January 2021. Eligible articles investigated any virus family and provided data on the effects of orally administered LF of any origin in the prevention and/or management of confirmed viral infections in people of any age. A narrative synthesis of the results was performed. Quality was assessed with the Cochrane Risk‐Of‐Bias and ROBINS‐1 tools. A total of 27 records were included, nine of which were registered protocols. We found data on Flaviviridae (n = 10), Retroviridae (n = 3), Coronaviridae (n = 2), Reoviridae (n = 2) and Caliciviridae (n = 1). Most published trials were at high risk of bias. The findings were heterogeneous across and within viral families regarding virological, immunological and biological response, with no clear conclusion. Some weak but positive results were reported about decrease of symptom severity and duration, or reduction in viral loads. Despite high tolerability, the effects of LF as oral supplement are still inconsistent, both in preventing and managing viral infections. Small sample sizes, variety in recruitment and treatment protocols, and low study quality may have contributed to such heterogeneity. Better‐designed studies are needed to further investigate its potential benefits against viral infections, including SARS‐CoV‐2.
Highlights
The aim of our systematic review was to identify the effects of orally administered LF against viral infections, with a specific focus on those caused by coronaviruses, to provide a synthesis of the results and support clinicians in the evaluation of supplemental treatments for coronavirus disease (COVID)‐19
To reach adequate coverage of the clinical research conducted on the topic, two reviewers independently searched PubMed, Scopus and Web of Science from database inception to 7th January 2021 using the following terms: lactoferrin AND covid OR mers OR sars OR coronavirus OR virus OR hcov OR hku[1]
Four records were added to the previous 14 from the reference lists of relevant articles, and nine records retrieved from ClinicalTrials.gov met our inclusion criteria, for a total of 27 records included in the systematic review
Summary
Lactoferrin (LF) is a multifunctional glycoprotein, member of the transferrin family,[1] identified for the first time in 1939 in bovine milk and isolated in 1960 from human milk.[2,3] Several studies have demonstrated that it plays a role in host defence[4,5]; because of its structure, it is a component of the innate immune response and a potent immunomodulator.[6] Its ability to bind free iron ions[7] prevents the tissues from excessive inflammatory processes.[8] it is widely recognized for antioxidant activity[9,10] and antibacterial activity,[11] and Bezault et al presented convincing data about its anti‐ cancer activity in murine models of fibrosarcoma and melanoma.[12] In the 1980s, some authors documented for the first time that LF may affect the myelopoiesis of mice inoculated with a friend virus complex,[13] paving the way for other hypotheses about the role of LF in viral infections.[14]. The aim of our systematic review was to identify the effects of orally administered LF against viral infections, with a specific focus on those caused by coronaviruses, to provide a synthesis of the results and support clinicians in the evaluation of supplemental treatments for COVID‐19
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