Fact-checking: Lactoferrin, Immunity & Coronavirus
03 May 2021
This is part 1 of our series that discusses the role of Lactoferrin in immunity.
Lactoferrin is a naturally occurring, iron-binding glycoprotein that is produced by the human body. It is a known part of the immune system and plays an important role in the first line of defence against microbial infections.
Lactoferrin derived from bovine milk has a very similar structure to the equivalent human protein. Dairy lactoferrin has received increased media & consumer attention lately due to certain groups making claims around it’s potential to address COVID-19.
As a nutrition company that prides itself in being grounded in solid science, we turned to a number of our scientists from across various disciplines, including immunology, microbiology and nutrition, to get their combined view on these claims.
Current research supports lactoferrin as an iron binding protein
Despite strong public and scientific interest in the role of lactoferrin against the SARS-CoV-2 Coronavirus, also known as COVID-19, there is currently no substantive clinical evidence to support claims regarding lactoferrin’s effectiveness specifically against the Corona virus.
There is currently no substantive clinical evidence to support claims regarding lactoferrin’s effectiveness specifically against the Corona virus.
Many clinical trials evolve from experimental laboratory results which do not involve human testing. Controlled laboratory conditions are obviously different from the complex physiological systems of the human body. So it is not unusual for laboratory research with positive results, to be found to have limited efficacy or even no efficacy, when repeated in human trials.
Some lactoferrin laboratory research which has attracted attention is based upon the iron-sequestering ability of lactoferrin. Iron is important for viral replication, so a lack of iron availability may negatively affect this.
Lactoferrin has also been shown to inhibit the binding of viral protein to ACE‐II receptors’ of human host cells, and hamper entry of the virus into human cells. However, whilst this might act as a first line of defence, a virus could still find other means to infiltrate human cells (e.g. binding to another type of receptor).
Also of interest, is the apparent ability of lactoferrin to modulate extreme inflammation, known as a cytokine storm.
- ACE‐II receptors: Enzyme proteins embedded on the surface of cells found in the lungs, arteries, heart, kidney, and intestines. This enzyme has been identified as an entry point for coronavirus to infect a cell.
- Apo-lactoferrin: A form of lactoferrin which has not yet bound ferric iron.
- Cytokine Storm: A situation where the immune system excessively produces inflammatory cytokines, which may lead to organ damage, and in some cases death.
- Liposomal: Describes something that is coated in a phospholipid bilayer, which encloses the object to form a ‘bubble’ and enable its transport across cell membranes. Liposomes are used to facilitate delivery of drugs or nutrients to cells.
Larger clinical trials needed to test claims on Lactoferrin treament in COVID-19 patients
To date, only one human clinicial trial has been conducted to evaluate the possible role of Lactoferrin treatment in COVID-19 patients. It was a small observational study using a combination of both oral and intranasal administration of liposomal apo-lactoferrin.
The study showed modest improvement in COVID-19 symptoms (joint pain and cough, but not fatigue) in patients that were asymptomatic or had less severe infections. The study also showed that lactoferrin induced earlier viral clearance in the population studied, which may be important as it could help decrease the risk of COVID-19 transmission and contagion.
However, there are key limitations to this clinical trial. It was a very small in size, and due to ethical reasons the study could not include a placebo group. The lack of placebo means, that this study could not evaluate the different disease evolution in lactoferrin treated and non-treated patients.
Key questions that are not yet understood include determining the dose required, the best form of lactoferrin to use, and the best route of administration.
It is important to note, the clinical trial standard required for human studies is clearly set out in guidelines for randomized, double-blind, placebo-controlled trials. These are the gold standard clinical studies required to generate results that have high confidence.
Regulators around the world tend to set a high threshold for claims that a product can treat or cure a disease. This means that for regulators to approve a claim that lactoferrin treats or cures COVID-19, they would likely require evidence from multiple large clinical trials relevant to the local population.
The population to be studied would have to be clearly defined, because clinical findings in one subset of the population (e.g. elderly) will not necessary translate to another part of the population (e.g. infants).
- Placebo Controlled: Research that includes a group of participants who are given a ‘substitute’ treatment that appears to be like the treatment under investigation but is actually not a treatment at all (e.g. a sugar pill). Placebos are used to create a benchmark for comparison against the treatment being investigated and help to minimise cognitive bias
- Randomized Trial: Research where the participants are randomly sorted into treatment and placebo groups. This is done to prevent selection bias e.g. where patients who are likely to have a positive outcome are sorted into the treatment group to increase the chance of a result in favour of the treatment being studied.
- Double-blind Trial: A trial where neither the researcher of the participant knows who is receiving the treatment and the placebo, until the trial is over. This is done to minimise cognitive bias.
Lactoferrin has the potential to support general immunity
Most of the evidence being cited in support of lactoferrin’s ability to deal with COVID-19, is based on bench top laboratory research, so does not necessarily reflect how lactoferrin impacts the immune response against COVID in the body.
The one human clinical that has assessed lactoferrin as a COVID-19 treatment, has major limitations. Further work needs to be done to truly understand how lactoferrin can be applied in varying COVID-19 cases.
Whilst it is understandable that consumers want to proactively seek solutions for themselves, it is important that people do not resort to unproven COVID-19 treatments.
Although the recent vaccines provide hope for reducing the risk of contraction or severity of infections, NZMP strongly reiterates the advice of many governments & health organisations that there is currently no concrete scientific evidence to suggest that there is any treatment that is guaranteed to specifically prevent or cure COVID-19.
However, as science is a field that is always evolving, we will continue to monitor this space to ensure we can provide our customers with the most up-to-date and accurate information, interpreted by multi-disciplinary science team.