Image Map

guy mixing a shakeby: Benson Danneskjold

Lactoferrin is a minor protein found naturally in the milk of most mammals including humans and cows. It is part of the transferrin family, meaning that it has the ability to bind strongly with and transport iron. It was first isolated in the late 1930’s and remained a curiosity for some four decades when interest in producing a commercial infant formula (that provided the benefits of breast-feeding) led researchers to more closely examine the constituents of mammalian breast milk. The primary function of lactoferrin in milk is to assist the neonate in absorbing critical iron.

Beyond its iron transporting function, lactoferrin has some other interesting functions that may make it especially useful as a supplement for humans. To start with, lactoferrin is a potent anti-microbial agent. In addition to its presence in milk, lactoferrin shows up in relatively high concentrations in other areas of the human body that one might expect would be exposed to high levels of exogenous pathogens. Lactoferrin is found in human saliva, tears, nasal and vaginal secretions, bronchial mucus and gastro-intestinal tract.

Unlike many traditional antibiotic agents, lactoferrin appears to exert its effect in several different ways. Primarily, lactoferrin binds iron, making it unavailable for essential metabolic functions related to growth and reproduction/replication.1 In essence, one of the major mechanisms of action of lactoferrin on microbial growth is to starve these organisms. This is important because, as a somewhat indirect action, it is difficult for microbes to develop a resistance to this effect. Lactoferrin also appears to have more direct bactericidal effects beyond simple iron deprivation; perhaps also interfering with glucose uptake and metabolism.2 In the gut, when lactoferrin is exposed to digestive enzymes, it forms a peptide called lactoferricin which has a direct and substantial damaging effect on the structure of Gram-positive and negative bacteria, in addition to yeasts and fungi.3 Lactoferrin also appears able to interfere with the ability of non-living viruses to infect cells, and has been shown to be effective at reducing or preventing infection with Herpes Simplex and influenza.4,5 Exactly how lactoferrin exerts its antiviral effects has yet to be fully elucidated although it appears that it may be both through binding with specific sites on the viral body (thereby preventing entrance into host cells), and/or inducing programmed cell death shortly after infection has taken place.6,7

In addition to its iron-binding and direct anti-microbial effects, lactoferrin also appears to play a crucial role in the modulation of the host defense response to infection.8 Given orally to animals or humans, lactoferrin appears to stimulate a more aggressive immune response. Even at small oral doses (20mg), one study demonstrated an improved immune response versus placebo, leading researchers to conclude that oral lactoferrin “…could constitute an effective protective measure against post-surgical complications.”9 It is also interesting to note that taken orally, lactoferrin appears to be able, in some instances, to either partially or completely reverse the immune-suppressing effects of chemotherapeutic and anti-inflammatory drugs like cyclophosphamide and cortisteroids. 10,11 It may prove to be a useful adjuvant to mitigate the immunosuppressive effects of these drugs when that is not a desired effect of treatment.

Given its multi-pronged mechanism of action which includes both direct and indirect effects, lactoferrin would appear to be an important addition to man’s arsenal against infection. Although clearly effective on its own, it’s possible that lactoferrin could be combined with other antibiotic, antifungal and antiviral agents to increase their potency and effectiveness against a growing army of resistant bugs.

If the lactoferrin story ended here, we could be reasonably excited. A simple, easily produced agent that can inhibit microbial infections in small doses is, in and of itself, a pretty handy thing to have. What is really intriguing is that lactoferrin also appears to be a very potent anti-cancer agent as well.

Most current conventional chemotherapy agents in use for treating cancer are actually toxins that seek to take advantage of the higher metabolic rate of cancer cells compared to normal cells. Cancer cells take up these chemical toxins at a faster rate and are thus, in effect, poisoned more quickly and will hopefully be killed before the effects of the chemical toxin manifest too widely in normal tissue. Although much research has gone into finding agents that are only toxic to cancer cells, so far the treatment for most cancers relies on chemotherapeutic agents with non-specific toxicity.

Lactoferrin is a chemotherapy horse of a completely different color. Despite being virtually non-toxic and free from major side effects even in very large doses, numerous in vitro and in vivo animal studies have shown it to be a powerful anti-cancer agent both as a standalone and as a potentiator of the effectiveness of more conventional chemotherapy drugs.

In a small Phase I trial, a patented form of oral lactoferrin given alone was able to either reduce the growth or actually shrink solid tumors when given to human patients in doses of 1.5-9g/day in a two week on/two week off schedule. No serious side effects were reported.12 In vitro studies of lactoferrin have also demonstrated its effectiveness in halting the growth and initiating cell death in human head and neck cancer lines; and the metabolic daughter, lactoferricin has been shown to induce apoptosis in human leukemia and carcinoma lines without effecting non-cancer cells.13

As if being a potent, natural antimicrobial and anticarcinogenic agent wasn’t good enough, lactoferrin also has demonstrated potent anti-inflammatory activity, especially in the human digestive tract. The ability of oral lactoferrin to modulate cytokine release and thereby modulate inflammatory response mean that it may be an important therapeutic agent in the treatment of systemic inflammatory diseases.14,15,16

In summary, lactoferrin appears to be a safe, non-toxic, inexpensive substance with broad therapeutic potential against some of the greatest human health threats. There is little doubt we will be seeing much more of this truly amazing milk protein in the future.

References

1. Kontoghiorghes GJ, Weinberg ED.
Iron: mammalian defense systems, mechanisms of disease, and chelation therapy approaches.
Blood Rev. 1995 Mar;9(1):33-45. Review.
PMID: 7795423

2. Arnold RR, Russell JE, Champion WJ, Brewer M, Gauthier JJ.
Bactericidal activity of human lactoferrin: differentiation from the stasis of iron deprivation.
Infect Immun. 1982 Mar;35(3):792-9.

3. Tomita M, Takase M, Bellamy W, Shimamura S.
A review: the active peptide of lactoferrin.
Acta Paediatr Jpn. 1994 Oct;36(5):585-91.

4. Jenssen H.
Anti herpes simplex virus activity of lactoferrin/lactoferricin — an example of antiviral activity of antimicrobial protein/peptide.
Cell Mol Life Sci. 2005 Dec;62(24):3002-13.

5. Shin K, Wakabayashi H, Yamauchi K, Teraguchi S, Tamura Y, Kurokawa M, Shiraki K.
Effects of orally administered bovine lactoferrin and lactoperoxidase on influenza virus infection in mice.
J Med Microbiol. 2005 Aug;54(Pt 8):717-23.

6. Weng TY, et al
Lactoferrin inhibits enterovirus 71 infection by binding to VP1 protein and host cells.
Antiviral Res. 2005 Jul;67(1):31-7.

7. Tinari A, Pietrantoni A, Ammendolia MG, Valenti P, Superti F.
Inhibitory activity of bovine lactoferrin against echovirus induced programmed cell death in vitro.
Int J Antimicrob Agents. 2005 May;25(5):433-8.

8. Yamauchi K, et al
Effects of orally administered bovine lactoferrin on the immune system of healthy volunteers.
Adv Exp Med Biol. 1998;443:261-5.

9.Zimecki M, et al
Lactoferrin regulates the immune responses in post-surgical patients.
Arch Immunol Ther Exp (Warsz). 2001;49(4):325-33.

10. Artym J, Zimecki M, Kruzel ML.
Reconstitution of the cellular immune response by lactoferrin in cyclophosphamide-treated mice is correlated with renewal of T cell compartment.
Immunobiology. 2003;207(3):197-205.

11. Takakura N, et al
Effect of orally administered bovine lactoferrin on the immune response in the oral candidiasis murine model.
J Med Microbiol. 2004 Jun;53(Pt 6):495-500.

12. Hayes TG, et al
Phase I trial of oral talactoferrin alfa in refractory solid tumors.
Invest New Drugs. 2005 Sep 20; [Epub ahead of print] PMID: 16193240

13. Xiao Y, et al
Lactoferrin down-regulates G1 cyclin-dependent kinases during growth arrest of head and neck cancer cells.
Clin Cancer Res. 2004 Dec 15;10(24):8683-6.
PMID: 15623653

14. Mader JS, Salsman J, Conrad DM, Hoskin DW.
Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines.
Mol Cancer Ther. 2005 Apr;4(4):612-24.
PMID: 15827335

15. Kruzel ML, Harari Y, Chen CY, Castro GA.
The gut. A key metabolic organ protected by lactoferrin during experimental systemic inflammation in mice.
Adv Exp Med Biol. 1998;443:167-73.

16. Baveye S, Elass E, Mazurier J, Spik G, Legrand D.
Lactoferrin: a multifunctional glycoprotein involved in the modulation of the inflammatory process.
Clin Chem Lab Med. 1999 Mar;37(3):281-6

×