The Immune-Boosting Power of Lactoferrin
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Mother’s milk — for the rest of us
The highest concentrations of lactoferrin are found in colostrum, the first form of milk produced by a mother’s mammary glands immediately after she gives birth. But don’t be fooled: lactoferrin supports the health and immune function of adults and babies alike.
Lactoferrin has a myriad of benefits, including the regulation of iron absorption, the modulation of immune responses, antimicrobial effects, anticancer activity, antioxidant function, and anti-inflammatory perks.
Fortunately, whether or not you received a drink of colostrum shortly after being born, the body still produces the protein on its various surfaces and in the immune cells throughout life. Lactoferrin may also be taken in the form of a supplement derived from bovine colostrum.
Let’s take a closer look at how lactoferrin can help us stay healthy through cold and flu season, and beyond:
One of lactoferrin’s many biological functions includes the regulation of iron absorption. By way of its role in iron transport, lactoferrin modulates the quantity of iron absorbed in the digestive tract, ensuring that our bodies get enough of the important mineral. In fact, lactoferrin has been shown to be an effective treatment for anemia in both pregnant and non-pregnant females, showing greater efficacy than standard treatment with ferrous sulfate (a form of iron commonly used in dietary supplements).[3,4]
Lactoferrin has been shown to be an effective treatment for anemia in both pregnant and non-pregnant females.
Lactoferrin doesn’t just increase iron levels, however: it can also decrease them, depending on what the body needs and where. Specifically, both human and bovine-derived lactoferrin have been shown to protect against intracellular iron overload (too much iron in the cells), a condition that increases our susceptibility to infections and that can lead to anemia of inflammation. Lactoferrin safeguards against these risks by moving the iron out of the overloaded cells and into the bloodstream. This has the effect of not only correcting anemia, but also of easing inflammation and fighting various infections. [1,5]
Digestive health and the first barrier of protection
Found not only in breast milk, but also in the fluids secreted within the digestive tract, lactoferrin is well understood to have antimicrobial effects.
By binding strongly to iron, lactoferrin deprives harmful microbes — like bacteria, fungi, and viruses — of the iron they need to grow. Lactoferrin may also prevent these “bad bugs” from forming biofilm, a slimy, sticky film produced by different microorganisms that “hides” them from our immune responders and improves their chances of survival in the human body. Lactoferrin thus undermines microbes’ abilities to attach to the gut lining, thereby reducing their risk of wreaking havoc.[6-8] Lactoferrin can also bind the endotoxin lipopolysaccharide (LPS) with high affinity.
Lactoferrin deprives harmful microbes — like bacteria, fungi, and viruses — of the iron they need to grow.
Lactoferrin consumption has been shown to help nursing infants fight infections and perform other immune-boosting functions, and to positively affect the microbiomes of pre-term babies. Thus, we find it, as well as colostrum, in some special formulas intended for infant care. Colostrum and lactoferrin supplementation in premature infants has even been shown to reduce the risk of necrotizing enterocolitis, a serious intestinal disease.[13,14]
Lactoferrin is well understood to enhance the innate immune system, our first line of defense against infections. The protein has in fact been described as “an important brick in the mucosal wall” for its role in protecting us from a myriad of undesirable microbes.[7,8]
Lactoferrin is a polyvalent immune regulator, meaning it protects us from microbial invasion through a number of different mechanisms.
In addition to lactoferrin’s role in supporting the innate immune system, the protein has also been shown to have indirect effects on acquired immunity. In other words: lactoferrin boosts the immune response in many ways, helping the body fight against various bacteria, fungi (including Candida), and viruses.[7,15]
Lactoferrin boosts the immune response in many ways, helping the body fight against various bacteria, fungi, and viruses.
In addition to its “antimicrobial-on-contact” properties, lactoferrin has further been shown to stimulate the growth of immune cells, regulate their activation, and guide their movement.
Research has clearly shown that lactoferrin’s antiviral activity applies to both enveloped viruses (like influenza) and naked viruses (like adenovirus and poliovirus).[8,17 Lactoferrin has also been shown to enhance antibody protection against influenza in newborn mice.
Pro-inflammatory effects, when needed
Inflammation can actually be a good thing in the fight against infections: by causing the small blood vessels of the body to become “leakier,” inflammation helps the cells of the immune system to pass out of the vessels and into the site of infection. Lactoferrin has been shown to promote this important, healthy response.[7,9]
A study of piglets found that supplementing with lactoferrin supported this pro-inflammatory response in the presence of bacterial infection, while enhancing an anti-inflammatory response in the absence of infection. Similar to iron, lactoferrin helped balance out the good and the bad of the inflammatory response.
As part of the body’s pro-inflammatory response to an infection, immune cells known as polymorphonuclear leukocytes (or PMNs) release lactoferrin and various other small particles.[20,21] Once unleashed from the PMNs, lactoferrin exerts direct antimicrobial properties at the site of infection. It also regulates the immune system’s response to the infection, strengthening the body’s fight against the disease and reducing the risk of septic shock.
Anti-inflammatory and antioxidant effects
Lactoferrin is no one-trick pony, however: the protein may also fight inflammation, if that’s what’s called for.
Lactoferrin has proven itself to be a powerful ally in the treatment of common inflammatory diseases, including allergies in the skin and lungs[22,23] – thanks again to its strong affinity for iron.
Inflamed tissues tend to accumulate iron; this iron then triggers the production of hydroxyl radicals (the most harmful type of free radical). These hydroxyl radicals set off a cascade of oxidative stress and damage, thus causing further damage to the body. This is part of why inflammation can be harmful if left unchecked.
By binding to free iron, however, lactoferrin aids in detoxification and spares the body this secondary harm. In other words, lactoferrin is both anti-inflammatory and antioxidant.
Lactoferrin is both anti-inflammatory and antioxidant.
It is perhaps for this reason that increased lactoferrin has been observed in the brains of people with neurodegenerative diseases (conditions like ALS and Alzheimer’s, Parkinson’s, and Huntington’s diseases). Iron deposits cause oxidative stress and the death of neurons (brain cells) in these ailments. Part of the body’s response may be to shunt more lactoferrin through the blood-brain barrier to protect the brain.[7,25,26]
From “first milk” to the front lines
Of all the proteins Nature could have offered us as our first meal beyond the womb, we are lucky that lactoferrin was a winner.
While lactoferrin is found in highest concentrations in colostrum, it is also synthesized in the mouth and intestinal lining, and is found in our tears, saliva, nasal secretions, and bile. Lactoferrin is produced in our white blood cells as well.
Lactoferrin, in other words, bathes us from birth throughout life, helping us stay healthy along the way.
ReferencesClick here to see References
- Hao L, et al. Lactoferrin: major physiological functions and applications. Curr Protein Pept Sci. 2018;20(2):139-44.
- Telang S. Lactoferrin: a critical player in neonatal host defense. Nutrients. 2018;10(9).
- Hughes V. Recombinant Lactoferrin [Internet]. Annapolis (MD): Lactation Education Resources; 2016 [cited 2020 Oct 30]. Available from: https://www.lactationtraining.com/easyblog/entry/recombinant-lactoferrin
- Sherman MP, et al. Lactoferrin and necrotizing enterocolitis. Curr Opin Pediatr. 2014;26(2):146-50.
- Donovan SM. The role of lactoferrin in gastrointestinal and immune development and function: a preclinical perspective. J Pediatr. 2016;173:S16-28.
- Bartick MC, et al. Suboptimal breastfeeding in the United States: maternal and pediatric health outcomes and costs. Matern Child Nutr. 2017;13(1):e12366.
- Binns C, et al. The long-term public health benefits of breastfeeding. Asia-Pacific J Public Heal. 2016;28(1):7-14.
- Gertosio C, et al. Breastfeeding and its gamut of benefits. Minerva Pediatr. 2016;68(3):201-12.
- Siqueiros-Cendón T, et al. Immunomodulatory effects of lactoferrin. Acta Pharmacol Sin. 2014;35(5):557-66.
- Abu Hashim H, et al. Lactoferrin or ferrous salts for iron deficiency anemia in pregnancy: a meta-analysis of randomized trials. Eur J Obstet Gynecol Reprod Biol. 2017;219:45-52.
- Lepanto MS, et al. Efficacy of lactoferrin oral administration in the treatment of anemia and anemia of inflammation in pregnant and non-pregnant women: an interventional study. Front Immunol. 2018 Sep 21;9:2123.
- Rosa L, et al. Lactoferrin: a natural glycoprotein involved in iron and inflammatory homeostasis. Int J Mol Sci. 2017;18(9):1985.
- Ward PP, Conneely OM. Lactoferrin: role in iron homeostasis and host defense against microbial infection. BioMetals. 2004;17(3):203-8.
- Legrand D, et al. Lactoferrin: A modulator of immune and inflammatory responses. Cell Mol Life Sci. 2005;62(22):2549-59.
- Berlutti F, et al. Antiviral properties of lactoferrin-a natural immunity molecule. Molecules. 2011;16(8):6992-7012.
- Baveye S, et al. Lactoferrin: a multifunctional glycoprotein involved in the modulation of the inflammatory process. Clin Chem Lab Med. 1999;37(3):281-6.
- Sherman MP, et al. Randomized control trial of human recombinant lactoferrin: a substudy reveals effects on the fecal microbiome of very low birth weight infants. J Pediatr. 2016;173:S37-42.
- Johnston WH, et al. Growth and tolerance of formula with lactoferrin in infants through one year of age: double-blind, randomized, controlled trial. BMC Pediatr. 2015 Nov 7;15:173.
- Viejo-Díaz M, et al. Different anti-Candida activities of two human lactoferrin-derived peptides, Lfpep and kaliocin-1. Antimicrob Agents Chemother. 2005;49(7):2583-8.
- Legrand D. Overview of lactoferrin as a natural immune modulator. J Pediatr. 2016;173:S10-5.
- Seganti L, et al. Antiviral activity of lactoferrin towards naked viruses. BioMetals. 2004;17(3):295-9.
- Sherman MP, et al. Lactoferrin acts as an adjuvant during influenza vaccination of neonatal mice. Biochem Biophys Res Commun. 2015;467(4):766-70.
- Gifford JL, et al. Lactoferricin: a lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties. Cell Mol Life Sci. 2005;62(22):2588-98.
- Bian Z, et al. Regulation of the inflammatory response: enhancing neutrophil infiltration under chronic inflammatory conditions. J Immunol. 2012;188(2):844-53.
- Masson PL, et al. Lactoferrin, an iron-binding protein in neutrophilic leukocytes. J Exp Med. 1969;130(3):643-58.
- Elrod KC, et al. Lactoferrin, a potent tryptase inhibitor, abolishes late-phase airway responses in allergic sheep. Am J Respir Crit Care Med. 1997;156:375-81.
- Griffiths CEM, et al. Exogenous topical lactoferrin inhibits allergen-induced Langerhans cell migration and cutaneous inflammation in humans. Br J Dermatol. 2001;144(4):715-25.
- Britigan BE, et al. Uptake of lactoferrin by mononuclear phagocytes inhibits their ability to form hydroxyl radical and protects them from membrane autoperoxidation. J Immunol. 1991;147(12):4271-7.
- Fillebeen C, et al. Lactoferrin is synthesized by activated microglia in the human substantia nigra and its synthesis by the human microglial CHME cell line is upregulated by tumor necrosis factor α or 1-methyl-4-phenylpyridinium treatment. Mol Brain Res. 2001;96(1-2):103-13.
- Fillebeen C, et al. Tumor necrosis factor-α increases lactoferrin transcytosis through the blood-brain barrier. J Neurochem. 1999;73(6):2491-500.
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Dr. Erica Zelfand
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