Lactoferrin: a review

There are a wide variety of healthy peptides and proteins in milk, but lactoferrin may be the one to watch. One of the most beneficial and researched, it has applications in immune support, tissue repair and as a probiotic, to name a few. Find out how medicine is bringing attention to lactoferrin on this research review.

What is lactoferrin?

Lactoferrin is a multifunctional protein found in natural bodily secretions including pancreatic and digestive fluids, saliva, semen, uterine secretions and milk. Lactoferrin was first extracted from cow’s milk in 1939 and later from human breast milk in 1960, and since then has been the subject of over 3000 biomedical publications (1).

Lactoferrin’s main biological role is to bind free iron in the body. This is important in protecting tissues from oxidative damage, as iron generates the production of harmful reactive oxygen species (ROS). However, this is not lactoferrin’s only role within the body. Its iron-binding properties give it several secondary functions which are important in maintaining immune and gut health.

Applications of lactoferrin: nutraceutical and pharmacological 

Lactoferrin plays an important role in the early stages of life. Human colostrum (the first breast secretion following childbirth) contains high levels of lactoferrin and other immune molecules to assist in the development in the new-born’s immune system and gastrointestinal tract. However, lactoferrin is important throughout life and is now considered an ideal nutraceutical and pharmacological protein due to its relatively cheap production from cow’s milk, high tolerance following ingestion, and its broad bioprotective actions.

Biomedical research has shown promise for lactoferrin in several areas:

• Immune health. Lactoferrin is able to modify the immune response through a combination of activating or suppressing different immune components. For example, oral administration of lactoferrin has been shown to increase immunoglobulin secretion (2) and stimulate the proliferation of immune cells of mice with suppressed immune systems (3). This makes lactoferrin a potential addition to immunosuppressive drugs used in cancer therapy. On the other hand, lactoferrin can suppress the release of harmful inflammatory molecules such as tumour necrosis factor (TNF)-ɑ and interleukin (IL)-6 (4). Together, the “immune-modulating” effects of lactoferrin may pave the way to more effective treatments for a wide range of diseases.
• Supportive of cancer therapies. Free iron increases oxidative stress on DNA, which over time may lead to cancer. Research has shown that lactoferrin may be a preventative measure against tumour formation due to its iron-binding properties (5). Even more exciting is that lactoferrin may even enhance the effects of other cancer therapies (6).
• Tissue regeneration. Various studies have shown that lactoferrin has regenerative properties in a wide range of tissues, including bone. Maintaining bone strength is highly important in the elderly and postmenopausal women, who are particularly susceptible to the bone degenerative disease osteoporosis. Lactoferrin supplementation has been shown to stimulate the growth of bone cells, leading to improved bone density and strength (7). This could make lactoferrin a useful supplement in people susceptible to bone diseases such as osteoporosis. 

Antimicrobial and antiviral activities of lactoferrin.

The antimicrobial actions of lactoferrin are the most widely researched function of this powerful biomolecule. A huge range of microorganisms have proven susceptible to lactoferrin (8). This is because lactoferrin can kill harmful microorganisms in two ways:

• Preventing their growth. Many pathogenic microorganisms, especially those in the gut, need iron for growth. Lactoferrin binds free iron in the body, which means that microorganisms are unable to use it for themselves. This prevents their growth and eventually leads to death of the microorganisms.
• Acting as a bactericidal. Lactoferrin is able to bind to structural molecules in the cell walls of bacteria. This breaks the bacterial cell wall and kills the bacteria.

Lactoferrin does not just work against bacteria, as research has shown that lactoferrin is able to combat viruses as well. Lactoferrin has been shown to inhibit viral infections from the common cold and flu (9) to hepatitis C (10) and HIV (11).

Although lactoferrin appears to act against many microorganisms and viruses, lactoferrin is able to promote the growth of healthy gut bacteria. Many healthy gut bacteria have low iron requirements, so are not affected by lactoferrin’s iron-binding actions. Research has shown that orally administered lactoferrin has demonstrated a probiotic activity in both adults and infants, as it actually promotes the growth of beneficial gut bacteria (12). Having a large population of “good” gut bacteria is essential for preventing conditions like obesity, diabetes, heart disease, and gut inflammation.

Lactoferrin and gut barrier function: protection against leaky gut.

Inflammation of the gut lining can be caused by a wide range of factors, including prescription medicines, alcohol, caffeine and refined carbohydrates. Being exposed to these things on a regular basis can result in excessive inflammation, leading to leaky gut syndrome.

Leaky gut syndrome makes the gut wall more permeable, so things that wouldn’t normally be able to leave the gut are able to “leak” into the bloodstream. In addition to this, inflammation can damage important molecules in the gut. This can lead to serious complications, including:

• Autoimmune conditions. When molecules enter the blood from the gut they are recognised as “foreign” by the immune system, since those molecules shouldn’t be there! This causes an immune response against molecules that aren’t actually foreign material, leading to autoimmunity.
• Nutrient deficiencies. Minerals and the molecules needed to transport them to cells are lost in the bloodstream in leaky gut syndrome. Different nutrient deficiencies can lead to many different health problems.
• Heart disease. Inflammation in the gut damages gut antibodies, allowing pathogens to enter the bloodstream. One type of bacteria, part of the gingivitis family, “eats” holes in arteries. These holes are patched up with cholesterol, which increases the risk of heart disease and stroke.

One proven treatment for leaky gut syndrome is colostrum. Colostrum is a natural substance found in early breast milk. This is because when babies are born, they too have a leaky gut. This is important to allow the mother to pass her immunoglobulins and other immunity molecules on to her child. After these have been passed on, colostrum closes the holes in the baby’s gut lining. But we can’t all drink breast milk to keep our gut lining intact! We can, however, supplement with lactoferrin.

Research has shown that lactoferrin is effective in stimulating the production of proteins that hold cells in the gut lining together (13). This, along with lactoferrin’s ability to promote the growth of healthy gut bacteria, makes it a brilliant supplement for those who suffer with problems in gut function.

Where to find lactoferrin.

Many lactoferrin supplements are obtained from cow’s milk. Whilst you could drink more milk to give your body a lactoferrin boost, you’d have to drink a lot of it!

Whilst there are lactoferrin supplements available, there are concerns about how effective these drugs are at reaching the stomach intact. This is because the pH of the gastrointestinal tract is very acidic and is able to break down drug linings very easily.

Undenatured, native whey is a great source of lactoferrin, as the absence of high heat or chemical filtration techniques used to manufacture the end product help preserve most of the lactoferrin content in whey - reaching in some cases up to 15 times the amount of lactoferrin found in isolates and hydrolisates.

References

1. Legrand, D. (2016). Overview of Lactoferrin as a Natural Immune Modulator. The Journal of Pediatrics, 173, S10–S15.
2. Sfeir, R. M., Dubarry, M., Boyaka, P. N., Rautureau, M., & Tomé, D. (2004). The Mode of Oral Bovine Lactoferrin Administration Influences Mucosal and Systemic Immune Responses in Mice. The Journal of Nutrition, 134(2), 403–409.
3. Artym, J., Zimecki, M., & Kruzel, M. L. (2003). Reconstitution of the cellular immune response by lactoferrin in cyclophosphamide-treated mice is correlated with renewal of T cell compartment. Immunobiology, 207(3), 197–205.
4. Machnicki, M., Zimecki, M., & Zagulski, T. (1993). Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6 in vivo. International Journal of Experimental Pathology, 74(5), 433–439.
5. Tsuda, H., Fukamachi, K., Xu, J., Sekine, K., Ohkubo, S., Takasuka, N., & Iigo, M. (2006). Prevention of carcinogenesis and cancer metastasis by bovine lactoferrin. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences, 82(7), 208–215.
6. Sun, X., Jiang, R., Przepiorski, A., Reddy, S., Palmano, K. P., & Krissansen, G. W. (2012). “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice. BMC Cancer, 12, 591.
7. Cornish, J., & Naot, D. (2010). Lactoferrin as an effector molecule in the skeleton. BioMetals, 23(3), 425–430.
8. Moreno-Expósito, L., Illescas-Montes, R., Melguizo-Rodríguez, L., Ruiz, C., Ramos-Torrecillas, J., & de Luna-Bertos, E. (2018). Multifunctional capacity and therapeutic potential of lactoferrin. Life Sciences, 195, 61–64.

9. Vitetta, L., Coulson, S., Beck, S. L., Gramotnev, H., Du, S., & Lewis, S. (2013). The clinical efficacy of a bovine lactoferrin/whey protein Ig-rich fraction (Lf/IgF) for the common cold: A double blind randomized study. Complementary Therapies in Medicine, 21(3), 164–171.
10. Ishii, K., Takamura, N., Shinohara, M., Wakui, N., Shin, H., Sumino, Y., … Yamauchi, K. (2003). Long-term follow-up of chronic hepatitis C patients treated with oral lactoferrin for 12 months. Hepatology Research, 25(3), 226–233.
11. Berkhout, B., van Wamel, J. L. B., Beljaars, L., Meijer, D. K. F., Visser, S., & Floris, R. (2002). Characterization of the anti-HIV effects of native lactoferrin and other milk proteins and protein-derived peptides. Antiviral Research, 55(2), 341–355.
12. Nguyen, D. N., Jiang, P., Stensballe, A., Bendixen, E., Sangild, P. T., & Chatterton, D. E. W. (2016). Bovine lactoferrin regulates cell survival, apoptosis and inflammation in intestinal epithelial cells and preterm pig intestine. Journal of Proteomics, 139, 95–102.
13. Kruzel, M. L., Zimecki, M., & Actor, J. K. (2017). Lactoferrin in a Context of Inflammation-Induced Pathology. Frontiers in Immunology, 8, 1438.