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Lactoferrin, A Powerful Allay in Health and Disease

Lactoferrin (Lf) is a small molecule, as far as proteins go, with a bunch of glucose side chains, and is properly called a glycoprotein. Its structure is like a spring that coils onto itself which allows it to trap and hold minerals within its many folds. Lactoferrin is found abundantly in mothers’ milk, especially the first milk or colostrum that helps protect the newborn but is also present in other bodily fluids like tears, saliva, sweat, urine etc. signifying its importance as an important defence molecule.

Lactoferrin plays an important role in a wide range of diseases which briefly can be summarized in the following categories: as an antioxidant, anti-inflammatory, anticancer and as an antimicrobial with gut modifying microbiome properties. Let us discuss each of these categories.

Antioxidant:

Lactoferrin has this huge capacity to bind and trap different metal ions but particularly iron. Because of this unique feature, Lf helps maintain and balance levels of iron in the body. This is important because too little iron can cause anemia, which is reduced number of red blood cells and/or the oxygen carrying capacity of hemoglobin. Approximately 40% of pregnant women are anemic and approximately similar number of pre-school aged children. On the other hand, if the iron levels are too high then this can cause oxidative stress, where the body is put under pressure from within.  Iron exists in several different ionic forms like ferric or Fe3+, or ferrous Fe 2+. This occurs because electrons jump from one form to another, creating highly reactive cells called reactive oxygen species (ROS) which are quite harmful themselves, but also cause other cellular components like fats, proteins and DNA to become unstable and reactive, causing a cascade of damage much like the falling of dominos. By neutralizing electrons transfers, Lf disrupts the production of ROS and damage to the cells.

Mineral entrapment:

Due to the unique ability of lactoferrin to trap iron, Lf helps improve serum iron and hemoglobin levels by delivering iron to site where it is needed i.e., in the production of hemoglobin of the red blood cells. In several human studies, Lf has been shown to increase iron levels similar to iron supplements that physicians regularly prescribe like ferrous sulphate or gluconate during Iron deficiency anemia (IDA). Various studies have shown that Lf either shows similar or better benefits to iron supplementation purchased in pharmacies without the gastrointestinal side effects. In fact, a recent review confirms Lf as the drug of choice for IDA during pregnancy (Abu Hashim et-al, 2017).

Antimicrobial activity:

Lf has been shown to be active against a whole range of pathogenic or bad organisms including bacteria, viruses, fungi, and parasites.  Due to its unique aspect of entrapping iron, iron becomes less available to microorganisms and/or cancer cells both of which thrive on iron to grow. By withholding iron, pathogens and cancer cells are literally starved and less likely to grow and spread. Other mechanisms by which Lf fights off various pathogenic organisms include:

  • Lf binding directly with the microorganisms’ cell membrane by puncturing holes and weakening the membrane and causing it to leak and self-explode
  • Preventing adhesion of the microorganisms within the body especially in the gastrointestinal tract the major site of harbouring organisms
  • Preventing biofilm formation which is responsible for resistance against antibiotics.

Furthermore, several animal studies have shown that Lf reduces other bacteria like Helicobacter pylori, and fungi like Candida albicans infections.

Lf is also active against a range of viruses like Herpes simplex virus, Cytomegalovirus, Human hepatitis B and C viruses and possibly other viruses like SARS and HIV.

A recent randomized, prospective, intervention Italian study showed that Lf could counteract the coronavirus infection and inflammation by acting as natural barrier to both respiratory and intestinal tissues. The researchers found that Lf induced an early viral clearance and a fast-clinical symptoms recovery. The researchers concluded that Lf can be used as a safe and efficacious natural agent to prevent and treat COVID-19 infection.

Decreasing risk of sepsis, especially in the neonates

Lf is present in large concentrations in mother’s milk especially the first milk (colostrum). Babies born pre-term are at risk of infections because their immune system hasn’t fully developed. One such condition is called necrotizing enterocolitis (NEC) which not only causes damage to the gastrointestinal tract, but as a result causes inflammation and sepsis. Lactoferrin has been shown to dramatically reduce such an incidence. Part of this benefit may also be due to Lf acting as a pre-biotic or food for the good bacteria so they can be nourished and flourish while competing against the bad or pathogenic bacteria.

AOR has been instrumental in one such study in Montreal University, and an ongoing multi-centre study in five different hospitals in Canada.

Anti-inflammatory action

Several studies have indicated that Lf acts as an immune modulator by both helping the immune system to mature fully especially in the newborn, infants and children but also in the immune compromised population e.g., HIV, transplant patients taking immunosuppressive drugs like cyclosporin, and in seniors who have weakened immune system. Lf supresses the common inflammatory mediators like NF-kB and acting at the nuclear levels by turning off the various pro-inflammatory genes.

Other effects

Lf has been looked at the following:

  • Reducing obesity
  • Bone health
  • Dry eyes
  • Skin health, especially dermatitis

Conclusion

Lf has been studied for a long time and has been shown to be a natural immune enhancer acting in a unique manner of denying pathogens and cancer cells the vital iron they need as food. Lf is also an excellent supplement for gut health; promoting growth of beneficial bacteria like Akkermansia at the expense of pathogenic bacteria. Finally, Lf is a safe ingredient widely used in infant formulas but also supplementation against NEC.

References:

Supreti F “Lactoferrin from Bovine Milk: A protective role for life” Nutrients 2020, 12: 2562-2587

Wang B et-al, “Lactoferrin: Structure, function, denaturation and digestion”. Crit Rev. Food Sci. 2019, 59: 580-596

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

Sharma D et-al, “Role of lactoferrin in neonatal care: A systemic review” J Matern. Fetal neonatal Med, 2017, 30: 1920-1932

Orisi, N, “The antimicrobial activity of lactoferrin” Biometals, 2004, 17: 189-196

Giansanti, F et-al, “Lactoferrin from Milk: Nutraceutical and Pharmacological properties” 2016, 9: 61-69

Fernandes KE et-al, “The antifungal activity of lactoferrin and its derived peptides: Mechanisms of action and synergy with drugs against fungal pathogens” Front Microbiol, 2017, 8: 2-11

Campione E, et-al “Lactoferrin as Protective Natural Barrier of Respiratory and Intestinal Mucosa against Coronavirus Infection and Inflammation”. Int J Mol Sci. 2020 Jul 11;21(14):4903. doi: 10.3390/ijms21144903. PMID: 32664543; PMCID: PMC7402319. https://pubmed.ncbi.nlm.nih.gov/32664543/

Campione, E, et al, “Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: randomized clinical trial, in vitro and in silico preliminary evidence” bioRxiv 2020.08.11.244996; doi: https://doi.org/10.1101/2020.08.11.244996 https://www.biorxiv.org/content/10.1101/2020.08.11.244996v3

 

Asztalos E et-al, “Lactoferrin infant feeding trial Canada (LIFT): protocol for a randomized trail of adding lactoferrin to feeds of very-low-birth-weight preterm infants” BMC Pediatrics 2020, 20: 40

Grzywacz K et-al, “Bovine lactoferrin supplementation does not disrupt microbiota development in preterm infants receiving probiotics”, j Pediatric Gastro. Nutrition, 2020, 7:216-222

Muscedere J et-al, “Prevention of nosocomial infections in critically ill patients with lactoferrin: A randomised double-blind, placebo-controlled study”. Critical Care Medicine, 2018;46:1450-1456

Dr. Traj Nibber, PhD

About The Author

Dr. Traj Nibber is the Director of AOR, he has a degree in Pharmacy, a Masters in Toxicology and a PhD in Pathology. Dr. Nibber founded AOR to clear the misdirection prevalent in the nutraceutical world, and provide people with highly effective, research backed products.

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