The effects of orally administered lactoferrin in the prevention and management of viral infections: A systematic review

Abstract

It 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.

Efficacy of Vitamin D Supplements in Prevention of Acute Respiratory Infection: A Meta-Analysis for Randomized Controlled Trials

“…It has been reported that vitamin D modulates both the adaptive immune and innate immune systems from in vitro studies and animal studies. First, vitamin D could work as a direct and indirect regulator of T cells [7]. Vitamin D regulates T cells directly by inhibiting T cell proliferation, Interleukin-2 (IL-2) and Interferon-γ (INF-γ) transcription, and IL-17 secretion by helper T 17 cells.…”

“…Vaccination against influenza, pneumococcus, and tuberculosis is also being used for the primary prevention of ARIs. Additionally, although oral zinc, vitamin C supplements, vitamin D supplements, ginseng, and probiotics have been suggested to have a preventive effect on the development of ARIs in some studies, this remains inconclusive [5,6], whereas a meta-analysis of six randomized controlled trials (RCTs) reported that lactoferrin supplements, as one of the key immunomodulatory substances, had efficacy in reducing the risk of RTIs [7].…”

The Influence of Nutritional Supplementation for Iron Deficiency Anemia on Pregnancies Associated with SARS-CoV-2 Infection

“…They recommend increasing the amount of elemental iron to 60-120 mg/day in pregnancies associated with anemia [34]. Despite iron pills being the most common type of supplementation, recent studies debate the use of lactoferrin in treating anemia in pregnant women [35], with potential benefits in the context of preventing and managing COVID-19 [36]. The Network for the Advancement of Patient Blood Management, Hemostasis, and Thrombosis consensus statement also recommends daily oral iron supplementation with 30-60 mg/day in areas where there is a high prevalence of anemia during pregnancy and screening for iron deficiency in all pregnancies at risk of iron deficiency [37].…”

Lactoferrin: Cytokine Modulation and Application in Clinical Practice

“…They suggested that this treatment option might be considered in asymptomatic or paucisymptomatic patients to avoid the worsening of SARS-CoV2. The few studies that enrolled patients showed a shortening of the conversion of the rRT-PCR SARS-CoV2 RNA and lower IL-6 and D-Dimer levels, and a decrease of the length of symptoms has been highlighted [ 40 ]. It is important to mention that neither RCTs nor meta-analysis are currently available and further research is needed in order to better define the role of lf in the management of the current pandemic.…”