The Power of Lactoferrin: A Comprehensive Guide for Enhancing Immune Function in Clinical Practice

Lactoferrin is celebrated for its impressive suite of qualities — immunomodulatory, antibacterial, and antiviral — making it a standout multifunctional protein. Predominantly present in mammalian milk, it has a pivotal role in bolstering the immune system.

This article sets out to explore the vast array of advantages lactoferrin presents for immune enhancement. We will discuss how lactoferrin works, from adjusting immune responses to fighting off microbial threats, and examine its practical application in clinical settings.

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Lactoferrin and Its Immune-Enhancing Properties

Lactoferrin is an iron-binding glycoprotein found in abundance in the whey protein of most mammalian milk with the highest concentrations in colostrum, the initial form of breastmilk produced after giving birth (20).

Lactoferrin can also be produced by human epithelial cells of various body organs and the fluids that they secrete. So, it is found extensively throughout the human body from organs such as the pancreas, gallbladder, lungs, and intestines to fluids such as saliva, tears, pancreatic secretions, and bile (17). Artificially, lactoferrin can be taken as a supplement in the form of bovine lactoferrin which is 70% homologous (having the same structure) to human lactoferrin (3).

Its presence in body fluids, especially those that interact with the external environment, such as saliva and nasal secretions, is likely due to lactoferrin’s important role in innate immunity (17).

The innate immune system is the body’s first line of defense, a non-specific reaction that involves repelling unwanted microorganisms by boosting natural barriers such as mucus production and releasing inflammatory signals to recruit immune cells that engulf and destroy pathogens before they can replicate within the body. Lactoferrin is also produced by neutrophils, a type of white blood cell vital to the innate immune response. In the presence of a pathogen, neutrophil granules release large amounts of lactoferrin to help fight off potential infection (22).

Antimicrobial Activity:

Lactoferrin is a part of the transferrin family, able to bind iron and help modulate iron levels in the body. Therefore it can reduce available iron levels for bacteria which prevents their proliferation and ability to cause an infection (3). It can also increase the permeability of gram-negative bacterial cell membranes to help kill bacteria. In viral infections, lactoferrin prevents viruses from entering cells where they could otherwise replicate and also prevents the ability of viruses to induce apoptosis (cell death) of human cells.

Lactoferrin has demonstrated anti-adhesive effects for certain viruses and bacteria in the upper respiratory and intestinal tract (17). In H. influenzae, lactoferrin inactivates adhesion peptides preventing the virus from adhering to respiratory mucosa. In the digestive tract, lactoferrin interferes with the ability of enterotoxigenic E.coli to adhere to human cells, where it can have a pathogenic action (17).

Lactoferrin’s antimicrobial activity is not just limited to viruses and bacteria. It also has demonstrated action against fungi, yeast, and parasites. Lactoferrin limits fungal growth through iron deprivation and is thought to also have direct actions on the surface of fungal cells (4).

In yeasts, lactoferrin has been shown to inhibit the growth of Candida albicans and prevent the formation of biofilms by disrupting their density and metabolic activity (17). Furthermore, its actions against parasites such as Plasmodium vivax, which causes malaria, and the protozoan Toxoplasma gondii suggest efficacy against parasitic infections (20).

Immunomodulation:

Lactoferrin has important immunomodulating effects on the body. It can reduce oxidative stress by binding to free iron particles that could otherwise create free radicals, thereby protecting organs and bodily tissues from inflammation-induced injury (22). Lactoferrin also modulates the production of inflammatory signaling proteins called cytokines in response to the presence or absence of a threat. In this way, it protects the body from excess inflammation by suppressing pro-inflammatory pathways when they are not needed and inducing these same pathways when a threat is present.

This action was demonstrated in a study where healthy participants were given 40mg of lactoferrin daily and had their blood tested against bacterial lipopolysaccharides to induce an inflammatory response. It was found that lactoferrin downregulated immune activity in participants with a strong response, whereas in participants with a reduced inflammatory response, it upregulated it (22).

Gut Health and Immunity:

Lactoferrin can promote healthy gut function via its immunomodulatory actions as well as its ability to enhance mucosal barriers. It stimulates the growth and activity of intestinal epithelial cells, increasing nutrient absorption while also protecting the cells against pathogens and the damaging effects of food allergens (20). Its actions on iron sequestration promote the growth of beneficial bacteria such as Lactobacillus sp. and Bifidobacterium sp. that have low iron needs (23).

In this way, lactoferrin is considered a prebiotic, promoting the growth of healthy probiotic strains (20).

Lactoferrin helps prevent gastrointestinal infections due to its antibacterial, antiviral, fungicidal, and anti-parasitic actions. It has shown the ability to inhibit biofilm formation by gut pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa (20). Clinical Applications of Lactoferrin

Clinical Applications of Lactoferrin

Lactoferrin can helpful in the following conditions:

Infectious Diseases:

With its ability to fight off infections caused by viruses, bacteria, fungi, yeast, and parasites, lactoferrin can play an important role as an adjunctive therapeutic in the presence of certain infectious diseases such as influenza A viruses and HSV (17). Its immunomodulating functions in the gut make it a viable adjunct in the treatment of gastrointestinal infections, especially when biofilms are a concern (23).

Its ability to reduce oxidative stress may help prevent an overstimulated inflammatory response, such as seen in COVID-19, and in managing chronic infections.

Chronic Inflammation and Autoimmune Conditions:

Lactoferrin’s ability to assess and control appropriate inflammatory responses makes it a potentially powerful therapeutic in the treatment of chronic inflammatory and autoimmune conditions. Evidence suggests that it may play an adjunctive role in inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease by helping to mitigate inflammation in the digestive tract (23).

A small clinical study showed improvements in multiple sclerosis symptoms in participants given oral lactoferrin with concomitant reductions in pro-inflammatory cytokines (22).

Pediatric Health:

The positive effects of lactoferrin on pediatric health start as early as in the womb. Lactoferrin helps promote healthy tissue and bone development, iron absorption, and protection against infectious diseases. Indeed, lactoferrin is one of the key components responsible for the positive immunoprotective effects of breast milk.

Even bovine-derived lactoferrin has been shown to reduce fungal infections, incidences of diarrhea, respiratory infections, and risk for sepsis in infants and young children (20). In infants at high risk for anemia, a study found that oral supplementation with bovine lactoferrin for 3 months improved iron status.

Incorporating Lactoferrin into Clinical Practice

Here are helpful tips for recommending lactoferrin in practice:

Dosage and Administration:

Lactoferrin taken supplementally is often in the form of bovine lactoferrin. Lactoferrin dosing varies widely across studies, with an average range of 100-400mg per day for most conditions across all age ranges. For chronic conditions, dosing duration often extends to 6 months or more, especially in the treatment of chronic inflammatory and autoimmune diseases (22).

When lactoferrin is administered orally, much of it is degraded in the stomach by gastric juices, decreasing its therapeutic potential. Therefore, lactoferrin in high amounts in multiple doses per day is recommended (23).

Additionally, liposomal delivery forms are advantageous in that they have greater potential to resist gastric degradation and, therefore, improve lactoferrin delivery into the small intestine and general circulation (3).

Safety and Contraindications:

Bovine lactoferrin is considered safe by the Food and Drug Administration (FDA) when taken orally at appropriate doses (less than 7000mg per day). Multiple studies indicate few side effects with lactoferrin administration, implying safety even in young children.

As bovine lactoferrin is derived from proteins in cow’s milk, it is contraindicated in patients with milk protein allergies. Bovine lactoferrin does not contain milk sugar, however, and so is safe to use in patients with lactose intolerance (20).

Monitoring and Evaluation:

Despite the safety of lactoferrin supplementation, it is important to work with a healthcare provider to ensure efficacy and appropriate implementation. Symptoms should be monitored to determine whether dosage adjustments are needed and to determine treatment duration. For patients using lactoferrin to improve gut health, GI testing may be appropriate to assess positive changes in microbiome populations and inflammatory markers.