Sandra Einerhand is the founder and head of nutrition consultancy Einerhand Science and Innovation. She gave a presentation at Fi Europe 2022 discussing lactoferrin as a potential intervention for treating Covid-19.
Covid-19 immune response offers potential targets for intervention
“Covid-19 has, to date, infected more than 622 million people worldwide,” said Einerhand.
While the lungs are the area of the body most susceptible to infection by the virus, about 18% of patients also suffer from gastrointestinal complaints. One in three patients goes on to have long-term symptoms and in one in five, the virus leads to more severe symptoms, resulting in hybrid inflammation.
After infection, the cells rapidly replicate in the lungs, causing an immune response leading to a cytokine storm; this, in turn, leads to multiorgan failure.
Older people are more susceptible to Covid-19, as they have a more imbalanced microbiota than younger people as well as low-grade inflammation. Einerhand pointed out that while vaccination is an important intervention, the vaccines currently available cannot offer total protection against infection.
Lactoferrin: A nutritional intervention that can enhance resilience?
What other approaches can be considered?
Einerhand highlighted milk lactoferrin as “a multifunctional iron-binding protein that is expressed in different areas in the body and is present in different bodily fluids”. Lactoferrin is present in breast milk but is also found in the saliva, nasal secretions, tears, bronchial secretions, and gastrointestinal fluids – all of which are expressed by organs that are especially affected by Covid-19.
Lactoferrin displays iron-binding, antiviral, anti-microbial, immune-supporting, microbiota-modulating, and intestinal barrier function activities – all of which have implications for lung and gut health.
“Furthermore, [lactoferrin] indirectly affects virus attack,” said Einerhand.
Covid-19 attacks haemoglobin in the blood, which is known for binding oxygen and iron, and for transporting oxygen to different organs. When the virus infects haemoglobin, oxygen and iron are released, thereby causing oxidative stress, which contributes to multiorgan failure.
By binding to iron, lactoferrin can sequester it; as iron is required for the virus to replicate in the lungs, this prevents replication of the virus.
In addition, through iron-binding, lactoferrin prevents oxidative stress and has an antioxidant effect, thus ameliorating Covid-19 symptoms.
Taken together, there is “some evidence that lactoferrin intake can protect the host from viral infections by preventing binding and entry of the virus, and of different variants” by sequestering the iron needed for viral replication, said Einerhand.
Lactoferrin displays two antiviral activities: by directly binding to the virus, or by binding to each receptor and thereby stopping the virus from binding to it.
By binding to its endogenous receptor, lactoferrin induces interferon alpha beta, in so doing inhibiting the replication of the virus.
Preclinical studies show that it affects the infection of different variants of the virus, including Delta and Omicron. These studies also demonstrate that lactoferrin works in combination with certain antiviral drugs.
“It is known that the oral cavity plays an important role in SARS-Cov-2 infection and transmission,” said Einerhand. “Lactoferrin is naturally present in the oral cavity, providing a microbial homeostasis.”
However, lactoferrin levels in the saliva decrease with age, leading to a dysbiosis in more senior people – explaining their heightened susceptibility to disease.
Einerhand highlighted studies showing that the protein can inhibit growth of gram-negative and gram-positive bacteria, as well as growth of fungi and protein. Lactoferrin is also very selective: it inhibits pathogen growth, whereas it doesn't inhibit the growth of beneficial bacteria.
Effects on intestinal permeability
Lactoferrin stimulates the synthesis of tight junction proteins, which are responsible for permeability and keeping cells tight to each other. An intervention study in humans showed that lactoferrin is able to reduce a drug-induced increase in intestinal permeability.
“In other words, lactoferrin supports mucosal or epithelial barrier function,” said Einerhand. “What does that mean in the context of Covid-19?”
There is a link between what happens in the gut and what happens in the lungs; lactoferrin given orally ends up in the gut, potentially modulating the microbiota, and thereby affecting the epithelial barrier functions, making it more difficult for pathogens to move to the lungs.
Several studies show that lactoferrin activates certain immune cells, “leading to an anti-inflammatory immune response and thereby suppressing the cytokines often increased in Covid-19, like IL-6 and TNF alpha”, explained Einerhand.
In a preclinical model, it has been shown to affect acute respiratory distress syndrome, or ARDS.
Of the four human intervention studies investigating the effects of lactoferrin intervention on Covid-19 published so far, three show that it induces faster recovery and offers symptom relief as a result. For instance, it dampens the effects on smell and taste and reduces cough and muscular pain.
In one study, immune biomarkers and iron biomarkers were also positively affected by lactoferrin, while another demonstrated lactoferrin to be more effective in older people.