Lactoferrin is a minor glycoprotein component of whey. It belongs to the iron transporter or transferrin family of glycoproteins. Lactoferrin is also found in exocrime secretions from mammals and is released from neutrophil granules during inflammation. The lactoferrin concentration in bovine (cows) milk is only 0.5% to 1.0% while human breast milk can contain as much as 15% lactoferrin.
Lactoferrin plays several important roles in human biology. First, Lactoferrin is believed to play a role in the uptake and absorption of iron through the intestinal mucosa. It may be the primary or sole source of iron for breast fed infants. Second, Lactoferrin appears to have antibacterial, antiviral, antifungal, anti-inflammatory, antioxidant and immunomodulatory activities.
How Lactoferrin Works
Receptors for lactoferrin are found in monocytes, lymphocytes, neutrophils, intestinal tissue and on certain bacteria. Lactoferrins ability to bind iron may account for some of its anti-bacterial activity. Iron is essential to support the growth of pathogenic bacteria. Lactoferrin may also inhibit the attachment of bacteria to the intestinal wall.
The possible antiviral activity of supplemental lactoferrin may be due to its inhibition of virus-cell fusion and viral entry into cells. It is believed that Lactoferrin may promote the growth and differentiation of T lymphocytes. Lactoferrin appears to bind uniquely to sites on the T4 (helper) and T8 (suppressor) lymphocytes. Lactoferrin also appears to play a role in the regulation of cytokines and lymphokines, such as tumor necrosis (TNF)-alpha and interleukin (IL)-6.
Lactoferrin's possible antioxidant activity may also contribute to its possible immunomodulatory activity. Antioxidants are getting increasing attention as possible therapeutic agents in infections and a variety of other diseases. Lactoferrin's ability to bind iron probably contributes to both its antioxidant properties and its antibacterial action. Free iron is a contributor in the generation of free radicals.
Lactoferrin Research Summary
Lactoferrin has exhibited significant activity against Escherichia coli, Proteus mirabilis, Staphyloccocus aureus, Candida albicans, HIV, herpes simplex type 1, hepatitis C, cytomegalovirus and other pathogens in vitro (in a lab dish) studies. Human studies, however, are almost entirely lacking.
Some individuals may have a hypersensitivity or allergy to lactoferrin. It is contraindicated for those individuals. It is generally recommended that pregnant women and nursing mothers avoid using lactoferrin because it has not been tested in these conditions.Some in vitro studies suggest that lactoferrin acts synergistically with antifungal agents, making them more potent.
Lactoferrin Dosage
Oral lactoferrin dosed at 40 mg daily has been used in a couple of clinical trials. Those who supplement with lactoferrin typically take 250 mg daily.
Lactoferrin has been the focus of attention in numerous investigations of the nutrition and host defense of term and preterm infants, but no physiological role for it has been established. Since the human lactoferrin gene has now been cloned, overexpression and large scale production are imminent. Thus, there is increased urgency for the characterization of lactoferrin function.
Three striking in vitro properties of lactoferrin may be of importance to its biological function: its ability to bind and release a wide variety of metal ions, especially ferric iron (Fe), its ability to bind cations, and its binding to a number of different types of cells. In milk, as in other secretions, lactoferrin is mostly iron-free, with a saturation level of about 8 to 10 percent.
In iron-free form it has pronounced bacteriostatic properties in vitro, probably dependent on its ability to bind adventitious iron extremely tightly, so depriving bacteria of iron essential for growth. The bacteriostatic properties of human milk are thought to derive largely from the high concentrations of lactoferrin present. In addition, sequestration of iron by lactoferrin inhibits iron-catalyzed free radical damage to cells. For these reasons, and because of its widespread occurrence in an frequent association with species such as lysozyme and immunoglobulins, lactoferrin is regarded as a component of the body's defense mechanisms. Lactoferrin is also a component of neutrophil secretory granules.
The lactoferrin molecules of different tissues and secretions appear to be identical in structure and function, and the cDNA sequence of leukocyte lactoferrin matches the amino acid sequence of milk lactoferrin. Lactoferrin is a member of the transferrin family of iron binding proteins, which includes serum transferrin, ovotransferrin, and the membrane-associated melanotransferrin. Lactoferrin also bears a striking relationship to a sulfate-binding protein of Salmonella typhimurium.
Lactoferrin has the capacity to bind reversibly two Fe ions concomitantly with two carbonate (C03=) or bicarbonate (HC03-) anions. Three features of metal binding by lactoferrin are particularly remarkable: the synergistic relationship between cation and anion binding, the extremely tight binding of iron, and the existence of mechanisms for the release of tightly-bound iron. Other metals can be substituted for iron in the two specific sites; those of similar size and charge (Ga, A1, Cr, Mn, Co) bind with affinities close to that of Fe, but even much larger cations such as lanthanides and some actinides (Th, Pu) can be accommodated.
Likewise, although CO3= is the anion of highest affinity, other anions with a carboxylate group, some quite bulky, can be substituted for it. The two lactoferrin structural cavities in which Fe and the anion are bound seem much larger than necessary for this function. To some this has suggested that lactoferrin may function to bind anionic toxins and xenobiotics. All the Mn in human milk is bound to lactoferrin, and lactoferrin has been suggested to have a role in Zn binding and heavy metal absorption. The physiological importance of transferrin in A1 binding and its proposed therapeutic use in detoxification may also apply to lactoferrin.
The ability of lactoferrin to bind to a variety of normal and leukemic blood cells has led to a suggestion that the lactoferrin released by neutrophilic leukocytes plays a role in modulating the immune and inflammatory responses. Lactoferrin promotes the aggregation of neutrophils and their adhesion to epithelial cells, and may be the agent that causes neutrophils to accumulate at inflammatory sites. Lactoferrin in its iron- saturated form is a highly active inhibitor of myelopoiesis, leading to the suggestion that lactoferrin might be useful in the treatment of leukemia.
Other observations that focus on the ability of lactoferrin to interact with cells include its activity as an essential growth factor for lymphocyte cell lines, its partial sequence homology with a group of lymphoma transforming proteins, its interference in the receptor-mediated uptake of chylomicron remnants into the liver, and the observation that some antibacterial activities of lactoferrin depend on actual contact with bacteria rather than simple sequestration of iron.
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sparkle7
Frequent Contributor (5K+ posts)
Member # 10397
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.
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