# Lactoferrin Production: A Systematic Review of the Latest Analytical Methods
## 1 Introduction
### The Effects of Bovine Lactoferrin on the Human Body  
Lf plays a key role in iron transport and has antiviral, antibacterial, antioxidant, and anti-inflammatory properties [16; 17; 18]. It is commonly used to treat iron deficiency anaemia (IDA). Oral bovine Lf supplementation improves haemoglobin concentrations as effectively as standard iron supplementation [19; 20; 21; 22; 23; 24], and Lf supplementation of children with IDA is better than iron supplements alone [25; 26; 27; 28]. It also has fewer side effects than iron supplements (such as constipation), thus making it a safer solution for children, especially those with different comorbidities [29; 30]. \begin{table}
\begin{tabular}{l l l} \hline \hline
**Product** & **Lf Concentration** & **Reference** \\ \hline Human colostrum & 7 mg/mL & [11] \\ Human mature milk & 2 mg/mL & [11] \\ Bovine colostrum & 1.5 mg/mL & [10] \\ Bovine mature milk & 0.2 mg/mL & [10] \\ Goat colostrum & 0.39 mg/mL & [12] \\ Goat mature milk & 0.06 mg/mL & [12] \\ Camel milk & 0.229 \(\pm\) 0.135 mg/mL & [13] \\ Buffalo milk & 0.332 \(\pm\) 0.165 mg/mL & [14] \\ Infant formula (cow’s milk-based) & 0.1 mg/mL & [15] \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Average lactoferrin concentration in milk products. Figure 1: The visualisation of lactoferrin structure [8]. Pregnant women are also at higher risk of IDA, but Lf is a safe and effective product to use in this group, increasing the positive effect of ferrous sulphate supplementation and reducing gastrointestinal side effects [31]. It has a similarly positive outcome when used alone and increased haemoglobin levels better than ferrous sulphate [21]. Lf is a safe alternative for high-risk patients; for example, it can be used as a less invasive treatment in patients with cancer, where standard anaemia treatment consists of intravenous iron [32]. Additionally, it reduces hepcidin levels, which rise during the inflammatory response, as hepcidin is an inflammatory mediator. Therefore, it is an effective alternative for patients undergoing regular haemodialysis--a procedure, which, if carried out regularly, increases the inflammatory response [33]. During an infection, iron absorption is restricted due to inflammation to decrease iron availability for pathogens, thus disabling certain metabolic pathways [34]. Besides strong iron absorption properties, Lf also exerts antiviral effects, possibly due to its ability to retain iron in an acidic environment, specific for infection and inflammation. It binds to negatively charged viral fragments and receptors, resulting in viral inhibition [35]. Lf reduces the frequency of common cold events, shortens the duration of infectious diseases, and significantly reduces lower respiratory tract events in infants [36; 37; 38; 39]. There is some evidence of its ability to lower the risk of bacterial and fungal sepsis in preterm infants [38; 40; 41]. Inconsistent findings report Lf's effectiveness in treating chronic hepatitis C virus (HCV). Some studies show a significant increase in virological response in Lf monotherapy, as well as combined with standard HCV therapy [42]. It is an effective treatment for hepatitis B virus (HBV) [43; 44]. Similar outcomes were reported on Lf activity against human papillomavirus (HPV) as it inhibits the binding of HPV to the cell surface [45; 46]. Recently, Lf nanoparticles have been applied in human immunodeficiency virus (HIV) therapy. Lf can be used as a drug carrier, thereby improving its bioavailability. It can also prevent HIV nuclear translocation and abrogate extracellular entry [47; 48; 49; 50]. Studies conducted on participants infected with SARS-CoV-2 and treated with Lf show promising effects. It resulted in a shorter time to test negative and faster clinical recovery since it reduced SARS-CoV-2 seroconversion in patients with mild to moderate symptoms [51; 52; 53]. Lf possesses antibacterial properties due to its ability to sequester iron from the environment, making it inaccessible to pathogens.