Lactoferrin:The Bioactive Peptide that Fights Disease

by Will Brink

As regular readers of the Life Extension magazine are aware, whey protein appears to function as a natural food against cancer, HIV, overtraining syndrome in athletes and a host of pathologies. In particular, whey's effects on glutathione levels and immunity are well documented in many animal studies with a growing number of human studies confirming the results with animals. Whey is one of two major proteins found in milk (the other being casein). When we talk about whey we are actually referring to a complex protein made up of many smaller protein subfractions (peptides), including beta-lactoglobulin, alpha-lactalbumin, immunoglobulins (IgGs), glycomacropeptides, bovine serum albumin (BSA), and minor peptides such as lactoperoxidases, lysozyme and lactoferrin. Each of the subfractions found in whey has its own unique biological properties. Up until quite recently, separating these subfractions on a large scale was either impossible or prohibitively expensive. Modern filtering technology has improved dramatically in the past few years allowing a handful of companies to separate some of the highly bioactive peptides from whey, such as lactoferrin. Many of these subfractions are only found in very minute amounts in cows milk, normally at less than 1%. For example, lactoferrin makes up approximately 0.5% - 1% or less of whey protein derived from cows milk (where as human mothers milk will contain up to 15% lactoferrin). Lactoferrin appears to be the subfraction of whey with documented anti-viral, anti-microbial, anti-cancer and immune modulating/enhancing effects. There is little doubt that lactoferrin could become the natural compound of choice in the treatment and prevention of a host of human ailments. To follow is a summary of what lactoferrin might have to offer.

Immunity

A minor fraction of whey, lactoferrin appears to have a wide variety of uses in biological systems and is considered a first line immune defense in the human body. Though a natural component of cows and human mothers milk, lactoferrin is found throughout the human body and occurs in all secretions that bathe mucous membranes such as saliva, tears, bronchial and nasal secretions, hepatic bile, pancreatic fluids, and is an essential factor in the immune response. Lactoferrin is concentrated in oral cavities where it will come in direct contact with pathogens (i.e. viruses, bacteria, etc.) and kills or greatly suppresses these pathogens through a variety of different mechanisms. Exactly how lactoferrin exerts all of its immune modulating or immune enhancing functions is not entirely clear, but it is known to enhance the immune response both directly and indirectly (passively) in response to a wide range of immune challenges. Specific receptors for lactoferrin are found on many key immune cells such as lymphocytes, monocytes and macrophages, and is known to be directly involved in the upregulation of natural killer (NK) cell activity. Most research points to lactoferrin as being more of an immune modulator rather than a simple immune stimulant.

Published studies that have examined the use of lactoferrin as a supplement and its effects on immunity have been quite promising. Research using various animals models (i.e., rats, sheep, pigs and cats, as well as others) has found the ingestion of lactoferrin to have direct protective effects on the regulation and modulation of the immune system.

For example, one study that examined the immune response to an endotoxin (lipopolysaccharide) known to cause severe septic shock found that feeding lactoferrin to mice dramatically reduced the lethality of this endotoxin while improving immune response parameters.(1) Another study with baby pigs found only 17% of the pigs died when fed lactoferrin and injected with the endotoxin escherichia coli as opposed to 74% of the pigs that died without the lactoferrin!(2) This could be a major finding, as septic shock is the most frequent cause of death for intensive care patients and the 13th leading cause of death in the United States. Two studies using healthy human volunteers found the ingestion of lactoferrin derived from cows milk had positive immunoregulatory effects that were specific to the individual. That is, depending on the initial profile of the immune system of each person, lactoferrin ingestion augmented the immune response, leading the researchers to conclude “. . .the data suggests that bovine (cows) lactoferrin may be applied in the clinic to improve the immune status of the patients.”(3) A similar human study using ten people who ingested lactoferrin concluded “these results suggest that lactoferrin administration may influence the primary activation of the host defense system.”(4)

Lactoferrin appears to be particularly important in the health and function of the intestinal tract and has been found to greatly reduce systemic and intestinal inflammation in such conditions as inflammatory bowel disease and others. Animals subjected to a variety of pathogens known to cause both systemic and intestinal inflammation and damage show much greater resistance and reduced inflammation when fed lactoferrin. The gastrointestinal tract must be viewed as an ecologic system in which a balance between both good and bad bacterial flora (micro flora) exists. An overgrowth of bad bacteria in the intestinal tract is known to cause a wide range of sever problems that cause a myriad of pro-inflammatory mediators to be released, causing disruptions throughout the entire body.

When fed to adult animals and human infants, lactoferrin showed a dramatic increase in good micro flora—such as bifidus—and a decrease in bad bacteria, such as E. coli, streptococcus, clostridium and others. The result was desirable intestinal flora, which is known to be essential for optimal health, immunity and resistance to disease. An extensive review that examined the role of lactoferrin in inflammation and the health of the intestinal tract stated, “The possibility that lactoferrin limits the autodestructive inflammatory response presents a new alternative for the future management of systemic inflammation.”(5) Some research also suggests that lactoferrin is able to stimulate intestinal cell growth and may lead to better digestive functions, in addition to its ability to enhance the growth of “good” microflora in the intestine. There is little doubt that in addition to its immunomodulating effects, this natural peptide derived from whey has powerful pro-biotic properties.

How to Obtain Lactoferrin

Lactoferrin is a natural constituent of whey protein found in milk. High quality whey protein supplements contain about 0.5% lactoferrin. That means a 20 gram scoop of high quality whey protein isolate provides about 100mg of lactoferrin.

An adequate and cost effective dose of lactoferrin for the adjunctive treatment of disease is estimated to be 300 mg a day. There are dietary supplements that provide potent doses of lactoferrin extracted from whey. When using these supplements, it is important to use a form of lactoferrin called "apolactoferrin" that is depleted of iron. The apolactoferrin form has been shown in studies to provide the benefits of lactoferrin as an antioxidant, and studies show the "apo" form may have additional benefits over that of other forms of lactoferrin.

Anti-viral effects

Lactoferrin has been found to both directly and indirectly inhibit several viruses that cause disease in humans. It directly inhibits viruses by binding to viral receptor sites, thus preventing the virus from infecting healthy cells. For example, in vitro studies have found that lactoferrin strongly binds to the V3 loop of the gp120 receptor on HIV-1 and HIV-2, resulting in inhibition of virus-cell fusion and entry of the virus into cells.10 In addition, lactoferrin indirectly kills or inhibits viruses by augmenting the systemic immune response to a viral invasion. It’s interesting to note that there is a systemic deficiency of lactoferrin in people with HIV infection. One study that examined 22 asymptomatic and 45 symptomatic patients with HIV compared to 30 healthy controls found that “levels of plasma lactoferrin are decreased in HIV-1 infected patients in relation to the progression of the disease.”(6) Another study found that the lack of lactoferrin (and secretory Iga) found in the oral cavities of people with HIV correlated strongly with the frequent infections in those areas often seen with patients with AIDS.(11) Lactoferrin was also found to have “potent” anti-viral effects against the replication of both human HIV and cytomegalovirus (CMV) virus in several in vitro studies with no cytopathic effects on healthy cells.

In addition to HIV and CMV, additional studies have found that lactoferrin inhibits herpes simplex type 1 infection of healthy cells. The latter likely occurs by preventing viral attachment to healthy cells via the blocking of viral proteins and direct immune interactions with natural killer cells, lymphocytes and phagocytes.(7,8,9,10)

The importance of lactoferrin in viral infections warrants a great deal of further research and use by clinicians. There is little doubt that lactoferrin is a key molecule for the body and the immune system in the fight against viruses and other microbes, and could be an effective supplement for people with viral infections.

Anti-cancer effects

Perhaps one of the most promising uses for lactoferrin may be in its potential as a nontoxic adjuvant cancer treatment agent. Extensive in-vitro (test tube) and in-vivo research with animals has shown lactoferrin to be a powerful anti-cancer agent.

Two studies using healthy human volunteers found the ingestion of lactoferrin derived from cow's milk had positive immunoregulatory effects.

Multiple studies using both rats and mice exposed to a toxic chemical (azoxymethane) known to cause tumors throughout the gastrointestinal tract, administered concomitantly with lactoferrin, showed a large reduction in intestinal polyp development.(12,13) Just as important, there were no toxic effects to intestinal epithelial tissues. Another study found the addition of lactoferrin to cancer prone mice subjected to cancer causing chemicals reduced the number of tumors and suppressed angiogenesis (the production of new blood vessels), which tumors need to survive. This study also found lactoferrin “significantly inhibited” liver and lung metastasis of cancer cells in these animals.(14) In addition to what appears to be direct cancer inhibiting properties of lactoferrin, additional studies have found it increased natural killer (NK) cell toxicity to several cancer cell lines at low concentrations. This shows lactoferrin plays a systemic role in improving immune cell effectiveness to cancer cells, as well as a direct effect through mechanisms that are not fully clear at this time.

Yet another study found lactoferrin to be very effective at suppressing the growth of human pancreatic cancer cells. So much so the researchers concluded that lactoferrin “…might become one of the new drugs of choice for the adjuvant therapy against pancreatic cancer.”(15) Additional published studies have found both direct cancer suppressing activities of lactoferrin as well as systemic immune improvements in animals fed lactoferrin with chemical induced cancers. One study that examined lactoferrin’s effects on chemically induced colon cancer found that “no effects indicative of toxicity were noted [from the use of lactoferrin], but significant reductions in both incidence and number of adenocarcinomas (tumors) of the large intestine were observed in almost all treatments.”(12)

Anti-microbial effects

Probably lactoferrin’s best known role is as an iron binding protein. It’s referred to as hololactoferrin in its iron bound form and apolactoferrin in its iron depleted form. Studies have found it’s the apolactoferrin form that has the most powerful effects as an anti-microbial agent. Directly related to lactoferrin’s previously mentioned ability to suppress certain health degrading bacteria in the intestine, lactoferrin is a powerful anti-microbial that inhibits a wide range of pathogenic bacteria and other microbes. The mechanism appears to lie with lactoferrin’s ability to bind iron, as it is known to have an extremely high affinity for this metal. Many pathogenic bacteria need a supply of free iron to multiply—in the presence of lactoferrin, they are strongly inhibited or killed.

One study looked at lactoferrin as a “natural antibiotic” and found that lactoferrin both in-vitro and in-vivo strongly inhibited the toxic bacteria helicobacter pylori. They stated “It is concluded that bovine (cows) lactoferrin has significant antimicrobial activity against helicobacter species in-vitro and in-vivo.”(16) Another study using both in-vitro and in-vivo methods added lactoferrin to the drinking water of mice and subjected them to the toxic microbe staphylococcal. The study found that the mice getting the lactoferrin as 2% of calories reduced kidney infections by 40% to 60% and reduced bacterial counts 5- to 12-fold. They concluded “the results suggest a potential for the use of lactoferrin as natural anti-bacterial proteins for preventing bacterial infections.”(17) Interestingly, some studies have found lactoferrin from cows to be more effective than lactoferrin from humans for anti-bacterial properties(18) (though it’s well established that human mothers milk confers a great deal of protection to the newborn due to many factors, including a high lactoferrin content). Several studies have found lactoferrin to inhibit a wide range of gram positive and gram negative bacteria, yeasts and even certain intestinal parasites. Cholera, escherichia coli, shigella flexneri, staphylococcus epidermidis, pseudomonas aeruginosa, candida albicans and others have all been found to be strongly or partially inhibited in the presence of lactoferrin.(19,20) (It should be noted not every microbe that is pathogenic to humans is suppressed by lactoferrin).

Maybe most promising and interesting, there is research that points to lactoferrin being able to improve the efficiency of antibiotic treatments in the fight against pathogenic microbes. Considering the out of control use of antibiotics and the rise in antibiotic resistant strains of “bad bugs,” this is very good news. Would the combination of lactoferrin and antibiotics be the knockout punch to certain bacteria that are not being killed by antibiotic treatments alone? More research is needed, but the evidence is very compelling.

Lactoferrin as an antioxidant

Finally, lactoferrin is an antioxidant that scavenges free iron, helping to prevent uncontrolled iron based free radical reactions, thus protecting certain cells from peroxidation. Though lactoferrin is both an iron scavenger and donor (depending on the cellular environment), it has been found to scavenge or donate iron at the appropriate times when the body is in need of the reaction. At normal physiological PH, lactoferrin binds iron tightly thus diminishing oxidative stress to tissues (from free radical production of iron). As would be expected, apolactoferrin, but not hololactoferrin, has been shown to prevent lipid peroxidation. However, there are times in fact when iron is needed as part of a controlled oxygen radical generating system by certain immune cells to kill microorganisms. Lactoferrin has been found to be an iron donor to this system under reduced PH conditions.

Several studies suggest lactoferrin reduces oxidative stress. Diseases such as cancer, heart diseases and AIDS are all closely related to oxidative stress either as a causative factor or as a factor in progression of the disease. One study that examined the role of whey proteins, multifermented whey proteins and lactoferrin in oxidative stress made the bold statement, “We can conclude that whey protein, lactoferrin and multifermented whey are good candidates as dietary inhibitors of oxidative stress and should be considered as potential medicinal foods in various pathologies as HIV infection and cancer.”(21) We couldn’t have said it better ourselves!

Conclusion

There is little doubt that lactoferrin is a major find and a potential breakthrough as a natural nontoxic treatment in an array of human ailments. Though a handful of companies are able to produce lactoferrin at this time, there is only one company producing the apolactoferrin (iron depleted) form in large quantity. Studies suggest that the superior form to supplement with is apolactoferrin.

William D. Brink is a well known medical, fitness and health writer for a variety of publications. He graduated from Harvard University with a degree in the natural sciences, and is a regular guest on national radio shows and a speaker at various conventions around the U.S.

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Further Reading

Arao S, Matsuura S, Nonomura M, Miki K, Kabasawa K, Nakanishi H. Measurement of urinary lactoferrin as a marker of urinary tract infection. J Clin Microbiol 1999 Mar;37(3):553-7.

Damiens E, Mazurier J, el Yazidi I, Masson M, Duthille I, Spik G, Boilly-Marer Y. Effects of human lactoferrin on NK cell cytotoxicity against haematopoietic and epithelial tumour cells. Biochim Biophys Acta 1998 Apr 24;1402(3):277-87.

Fillebeen C, Descamps L, Dehouck MP, Fenart L, Benaissa M, Spik G, Cecchelli R, Pierce A. Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier. J Biol Chem 1999 Mar 12;274(11):7011-7.

Hammerschmidt S, Bethe G, H Remane P, Chhatwal GS. Identification of pneumococcal surface protein A as a lactoferrin-binding protein of streptococcus pneumoniae. Infect Immun 1999 Apr;67(4):1683-7.

Manev V, Maneva A, Sirakov L. Effect of lactoferrin on the phagocytic activity of polymorpho-nuclear leucocytes isolated from blood of patients with autoimmune diseases and Staphylococcus aureus allergy. Adv Exp Med Biol 1998;443:321-30.

Marchetti M, Longhi C, Conte MP, Pisani S, Valenti P, Seganti L. Lactoferrin inhibits herpes simplex virus type 1 adsorption to Vero cells. Antiviral Res 1996 Mar;29(2-3):221-31.

Portelli J, Gordon A, May JT. Effect of compounds with antibacterial activities in human milk on respiratory syncytial virus and cytomegalovirus in vitro. J Med Microbiol 1998 Nov;47 (11):1015-8.

Roozendaal C, Horst G, Pogany K, van Milligen de Wit AW, Kleibeuker JH, Haagsma EB, Limburg PC, Kallenberg CG. Prevalence and clinical significance of anti-lactoferrin auto-antibodies in inflammatory bowel diseases and primary sclerosing cholangitis. Adv Exp Med Biol 1998;443:313-9.

Swart PJ, Kuipers ME, Smit C, Pauwels R, deBethune MP, de Clercq E, Meijer DK, Huisman JG. Antiviral effects of milk proteins: acylation results in polyanionic compounds with potent activity against human immunodeficiency virus types 1 and 2 in vitro. AIDS Res Hum Retroviruses 1996 Jun 10;12(9):769-75.

Yoo YC, Watanabe S, Watanabe R, Hata K, Shimazaki K, Azuma I. Bovine lactoferrin and Lactoferricin inhibit tumor metastasis in mice. Adv Exp Med Biol 1998;443:285-91.
References

1. Zhang GH, Mann DM, Tsai CM. Neutralization of endotoxin in vitro and in vivo by a human lactoferrin-derived peptide. Infect Immun 1999 Mar;67(3):1353-8.

2. Lee WJ, Farmer JL, Hilty M, Kim YB. The Protective Effects of Lactoferrin Feeding against Endotoxin Lethal Shock in Germfree Piglets. Infect Immun Apr. 1999: Vol 66 No 4, 1421-1426.

3. Zimecki M, Wlaszczyk A, Cheneau P, Brunel AS, Mazurier J, Spik G, Kubler A. Immunoregulatory effects of a nutritional preparation containing bovine lactoferrin taken orally by healthy individuals. Arch Immunol Ther Exp (Warsz) 1998;46(4):231-40.

4. Yamauchi K, Wakabayashi H, Hashimoto S, Teraguchi S, Hayasawa H, Tomita M. Effects of orally administered bovine lactoferrin on the immune system of healthy volunteers. Adv Exp Med Biol 1998;443:261-5.

5. 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.

6. Defer MC, Dugas B, Picard O, Damais C. Impairment of circulating lactoferrin in HIV-1 infection. Cell Mol Biol (Noisy-le-grand) 1995 May;41(3):417-21.

7. Puddu P, Borghi P, Gessani S, Valenti P, Belardelli F, Seganti L. Antiviral effect of bovine lactoferrin saturated with metal ions on early steps of human immunodeficiency virus type 1 infection. Int J Biochem Cell Biol 1998 Sep;30(9):1055-62.

8. Superti F, Ammendolia MG, Valenti P, Seganti L. Antirotaviral activity of milk proteins: lactoferrin prevents rotavirus infection in the enterocyte-like cell line HT-29. Med Microbiol Immunol (Berl) 1997 Oct;186(2-3):83-91.

9. Harmsen MC, Swart PJ, de Bethune MP, Pauwels R, De Clercq E, The TH, Meijer DK. Antiviral effects of plasma and milk proteins: lactoferrin shows potent activity against both human immunodeficiency virus and human cytomegalovirus replication in vitro. J Infect Dis 1995 Aug;172(2):380-8.

10. Swart PJ, Kuipers EM, Smit C, Van Der Strate BW, Harmsen MC, Meijer DK. Lactoferrin. Antiviral activity of lactoferrin. Adv Exp Med Biol 1998;443:205-13.

11. Muller F, Holberg-Petersen M, Rollag H, Degre M, Brandtzaeg P, Froland SS. Nonspecific oral immunity in individuals with HIV infection. J Acquir Immune Defic Syndr 1992;5(1):46-51.

12. Tsuda H, Sekine K, Nakamura J, Ushida Y, Kuhara T, Takasuka N, Kim DJ, Asamoto M, Baba-Toriyama H, Moore MA, Nishino H, Kakizoe T. Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats. Adv Exp Med Biol 1998;443:273-84.

13. Ushida Y, Sekine K, Kuhara T, Takasuka N, Iigo M, Tsuda H. Inhibitory effects of bovine lactoferrin on intestinal polyposis in the Apc(Min) mouse. Cancer Lett 1998 Dec 25;134(2):141-5.

14. Yoo YC, Watanabe S, Watanabe R, Hata K, Shimazaki K, Azuma I. Bovine lactoferrin and lactoferricin, a peptide derived from bovine lactoferrin, inhibit tumor metastasis in mice. Jpn J Cancer Res 1997 Feb;88(2):184-90.

15. Sakamoto N. Antitumor effect of human lactoferrin against newly established human pancreatic cancer cell line SPA. Gan To Kagaku Ryoho 1998 Aug;25(10):1557-63.

16. Dial EJ, Hall LR, Serna H, Romero JJ, Fox JG, Lichtenberger LM. Antibiotic properties of bovine lactoferrin on Helicobacter pylori. Dig Dis Sci 1998 Dec;43(12):2750-6.

17. Bhimani RS, Vendrov Y, Furmanski P. Influence of lactoferrin feeding and injection against systemic staphylococcal infections in mice. J Appl Microbiol 1999 Jan;86(1):135-44.

18. Vorland LH, Ulvatne H, Andersen J, Haukland H, Rekdal O, Svendsen JS, Gutteberg TJ. Lactoferricin of bovine origin is more active than lactoferricins of human, murine and caprine origin. Scand J Infect Dis 1998;30(5):513-7.

19. Percival M. Intestinal Health. Clin. Nutri. Insights. 1997, Vol 5. No 5, 1-6.

20. Kuwata H, Yip TT, Tomita M, Hutchens TW. Direct evidence of the generation in human stomach of an antimicrobial peptide domain (lactoferricin) from ingested lactoferrin. Biochim Biophys Acta 1998 Dec 8;1429(1):129-41.

21. Stella V, Postaire E. Evaluation of the antiradical protector effect of multifermented milk serum with reiterated dosage in rats. C R Seances Soc Biol Fil 1995;189(6):1191-7.

Lactoferrin 300 mg

Lactoferrin Update

by Will Brink

Readers of Life Extension magazine expect the latest research on natural non-toxic supplements that prevent disease and improve health. A lactoferrin update is therefore in order. Lactoferrin has captured the interest of many researchers as a natural compound with a wide variety of uses. What follows is a summary of previously published information on the research and effects of lactoferrin followed by some of the more up-to-date studies.

Lactoferrin appears to be a subfraction of whey with the best documented anti-viral, anti-microbial, anti-cancer and immune modulating/enhancing effects.When we talk about whey we are actually referring to a complex protein made up of many smaller protein subfractions (peptides). Many of these subfractions are only found in very minute amounts in cows’ milk, normally at less than 1%. For example, lactoferrin makes up only 0.5% to 1% or less of whey protein derived from cows’ milk. Mothers’ milk, on the other hand, will contain up to 15% lactoferrin.

Immunity

Lactoferrin is found throughout the human body and occurs in all secretions that bathe mucous membranes such as saliva, tears, bronchial and nasal secretions, hepatic bile, pancreatic fluids, and is an essential factor in the immune response. Lactoferrin is concentrated in oral cavities where it will come in direct contact with pathogens (i.e. viruses, bacteria, etc.) and kills or greatly suppresses these pathogens through a variety of different mechanisms. In fact, there are specific receptors for lactoferrin found on many key immune cells, such as lymphocytes, monocytes and macrophages, and is known to be directly involved in the upregulation of natural killer (NK) cell activity. One study with baby pigs found that only 17% of the pigs died when fed lactoferrin and injected with a toxin (escherichia coli) as opposed to 74% of the pigs that died without the lactoferrin!

Gastrointestinal function

Lactoferrin appears to be particularly important in the health and function of the intestinal tract. It has been found to greatly reduce systemic and intestinal inflammation in such conditions as inflammatory bowel disease, among others. Animals subjected to a variety of pathogens known to cause both systemic and intestinal inflammation and damage show much greater resistance and reduced inflammation when fed lactoferrin.

Antiviral effects

Lactoferrin has been found to both directly and indirectly inhibit several viruses that cause disease in humans. For example, in vitro (test tube) studies have found that lactoferrin strongly inhibits HIV (the virus thought to cause AIDS). The exact clinical relevance of this information has yet to be elucidated, but lactoferrin may be an exceptionally effective, nontoxic compound in the fight against viruses that cause death and ill health in humans.

Anti-cancer effects

Perhaps one of the most promising uses for lactoferrin may be in its potential as a non-toxic, anti-cancer agent. Extensive in-vitro and in-vivo research with animals has shown lactoferrin to be a powerful anti-cancer agent. Multiple studies using both rats and mice exposed to a toxic chemical (azoxymethane) known to cause tumors throughout the gastro intestinal tract, administered concomitantly with lactoferrin, showed a large reduction in intestinal polyp development throughout the intestinal tract. One study found lactoferrin to be very effective at suppressing the growth of human pancreatic cancer cells. So much so the researchers concluded that lactoferrin “…might become one of the new drugs of choice for the adjuvant therapy against pancreatic cancer.”

Antimicrobial effects

Probably lactoferrin’s best known role is as an iron binding protein. It’s referred to as hololactoferrin in its iron bound form and apolactoferrin in its iron depleted form. Studies have found that it is the apolactoferrin form that has the most powerful effects as an antimicrobial agent.

Lactoferrin is a powerful antimicrobial able to inhibit a wide range of pathogenic bacteria and other microbes. The mechanism appears to lie with lactoferrin’s ability to bind iron, as it’s known to have an extremely high affinity for this metal. Many pathogenic bacteria need a supply of free iron to multiply and in the presence of lactoferrin are strongly inhibited or killed. One study added lactoferrin to the drinking water of mice and subjected them to the toxic microbe called staphylococcal. The study found that the mice getting the lactoferrin as 2% of calories reduced kidney infections by 40% to 60%, and reduced bacterial counts 5-to-12 fold. They concluded, “The results suggest a potential for the use of lactoferrin as natural anti-bacterial proteins for preventing bacterial infections.”

Lactoferrin as an antioxidant

Finally, lactoferrin is an antioxidant that scavenges free iron helping to prevent uncontrolled iron based free radical reactions, thus protecting certain cells from peroxidation. Though lactoferrin is both an iron scavenger and donor (depending on the cellular environment), it has been found to scavenge or donate iron at the appropriate times when the body is in need of the reaction. At normal physiological PH, lactoferrin binds iron tightly thus diminishing oxidative stress to tissues (from free radical production of iron). Apolactoferrin, but not hololactoferrin, has been shown to prevent lipid peroxidation. One study that examined the role of whey proteins, multi-fermented whey proteins and lactoferrin in oxidative stress made the bold statement, “We can conclude that whey protein, lactoferrin and multi-fermented whey are good candidates as dietary inhibitors of oxidative stress and should be considered as potential medicinal foods in various pathologies as HIV infection and cancer.”

New research: antiviral, antibacterial, antifungal

Previous studies have found lactoferrin to be a powerful inhibitor of a wide range of viruses. Recently, lactoferrin was tested against the deadly hantavirus and was directly compared to the anti-viral drug ribavirin.1 The study found that lactoferrin treated and pretreated cells greatly suppressed hantavirus. Perhaps even more intriguing, it was found that a powerful synergism existed when lactoferrin was combined with ribavirin. The researchers concluded, “These results indicate that lactoferrin has anti-hantaviral activity in vitro and inhibition of virus adsorption to cells, which play an important role in revealing the anti-hantaviral activity of lactorferrin. This paper reports for the first time the anti-hantaviral effect of lactoferrin.”

As mentioned above, lactoferrin has been found to be a powerful anti-microbial agent that suppresses bacteria. Scientists wanted to see if feeding animals either human derived lactoferrin, bovine derived lactoferrin or peptides derived from lactoferrin might be effective against urinary tract infections caused by the bacteria escherichia coli (e coli).(2)

Urinary tract infections, or UTIs, are a common infection in humans, especially in women. Human lactorferrin, bovine lactoferrin and the peptides were given orally to female mice 30 minutes after the instillation of escherichia coli bacteria into the urinary bladder. The study found that the amount of bacteria in the kidneys and bladder of mice was significantly reduced 24 hours later by the lactoferrin treatments, compared to the findings for the control group. Interestingly, only the human lactoferrin showed a strong anti-inflammatory effect, which contradicts other research. Previous studies have found that both BLF and HLF have strong anti-inflammatory properties, the BLF being the more powerful anti-bacterial agent. Lactoferrin may be effective as a combination therapy in the treatment of UTIs for women, but more research is warranted.

A clinical study was conducted to evaluate the effectiveness of lactoferrin in the treatment of tinea pedis.(3) Tinea pedis is a fungal infection often referred to as “athletes foot” but can be found in other areas of the body. A dose of either 600 mg or 2000 mg of lactoferrin or a placebo was orally administered daily for eight weeks to 37 adults who were judged to have mild or moderate tinea pedis. A mycological cure was not seen in any of the subjects. However, there were statistically significant improvements found in dermatological symptoms (itching, redness, etc) in the active groups receiving lactoferrin, leading researchers to conclude, “The potential usefulness of lactoferrin as a functional food material for treating tinea pedis was seen for the first time in this study.”

Additional studies of interest

- A study published in the Dec. 2000 issue of the Journal of Cell Biochem (15;79(4):583-593) found that lactoferrin is involved in the upregulation of CD4 lymphocytes, which are essential to the body’s disease fighting abilities. It’s well known that lactoferrin is directly connected to the host immune response, and this study may be another piece of the puzzle relating to the lactoferrin-immune-system connection.

- A recent study (Early Hum Dev 2000 Aug 1;59(2):95-105) called “Lactoferrin is responsible for the fungistatic effect of human milk” found that lactoferrin is the primary peptide in milk that suppresses the growth of dangerous fungi. Human milk has recognized anti-microbial effects and it has been repeatedly shown that breast-fed infants have fewer and less severe infections than formula-fed infants. While most studies have focused on anti-bacterial and anti-viral activities, few have focused on the anti-fungal effect of human milk. Dermal and other infections caused by fungi are common in infants with low bodyweight. In vitro, this study found milk to have a potent inhibitory effect on fungal growth. They concluded: “Most, if not all of this effect was caused by lactoferrin via its iron-binding capacity…” Interestingly, they state “…In contrast, other human milk proteins with known or suggested anti-microbial effects rather increased fungal growth.”

- One study called “Lactoferrin and anti-lactoferrin antibodies: Effects of iron loading of lactoferrin on albumin extravasation in different tissues in rats” (Erga KS, Peen E, Tenstad O, Reed RK) found that iron depleted, but not iron saturated, lactoferrin may protect lung tissue during the release of reactive oxygen species. In vivo, only iron-free lactoferrin reduced inflammatory hyperpermeability in the lung tissue of mice and rats. Although interesting, additional research is needed to confirm lactoferrin’s protective role in lungs that have been damaged during hyper inflammatory periods.

- One interesting study used the level of lactoferrin in nasal secretions as a diagnostic tool for diagnosing the common cold from the more serious sinusitis (infection of the sinuses). As mentioned before, lactoferrin is found in all secretions that bathe mucus membranes and is a first line defense against viruses and other pathogens. It comes as no surprise that higher amounts of lactoferrin would be found in the nasal secretions of people with serious sinus infections. The study found nasal lactoferrin helps distinguish sinusitis from common colds. The study was called “Lactoferrin and eosinophilic cationic protein in nasal secretions of patients with experimental rhinovirus colds, natural colds, and presumed acute community-acquired bacterial sinusitis” (J Med Microbiol 2000 Aug;49(8):
719-23).

Conclusion

Science is examining lactoferrin in search for potential treatment and diagnostic tools in a wide range of human ailments. It is expected that further research will come to light regarding this bioactive peptide.

Will Brink is a well known medical, fitness and health writer for a variety of publications. He is most noted for his articles and work with whey proteins and essential fatty acids in athletics and the treatment and prevention of various diseases.

References

1. Murphy ME, Kariwa H, Mizutani T, Yoshimatsu K, Arikawa J, Takashima I. In vitro antiviral activity of lactoferrin and ribavirin upon hantavirus. Arch Virol 2000;145(8):1571-82.

2. Haversen LA, Engberg I, Baltzer L, Dolphin G, Hanson LA, Mattsby-Baltzer I. Human lactoferrin and peptides derived from a surface-exposed helical region reduce experimental escherichia coli urinary tract infection in mice. Infect Immun 2000 Oct;68(10):5816-23.

3. Yamauchi K, Hiruma M, Yamazaki N, Wakabayashi H, Kuwata H, Teraguchi S, Hayasawa H, Suegara N, Yamaguchi H Oral administration of bovine lactoferrin for treatment of tinea pedis. A placebo-controlled, double-blind study. Mycoses 2000;43(5):197-202.

Lactoferrin 300 mg

These statements have not been evaluated by the FDA. These products are not intended to diagnose, treat, cure, or prevent any disease