Lactoferrin -- related to Iron in the blood and Herpes outbreaks

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Lactoferrin -- related to Iron in the blood and Herpes outbreaks Empty Lactoferrin -- related to Iron in the blood and Herpes outbreaks

Post by Chromium6 on Sun Jan 05, 2020 6:21 am

Lactoferrin

Lactoferrin (LF), also known as lactotransferrin (LTF), is a multifunctional protein of the transferrin family. Lactoferrin is a globular glycoprotein with a molecular mass of about 80 kDa that is widely represented in various secretory fluids, such as milk, saliva, tears, and nasal secretions. Lactoferrin is also present in secondary granules of PMNs and is secreted by some acinar cells. Lactoferrin can be purified from milk or produced recombinantly. Human colostrum ("first milk") has the highest concentration, followed by human milk, then cow milk (150 mg/L).[5]

Molecular structure

Lactoferrin is one of the transferrin proteins that transfer iron to the cells and control the level of free iron in the blood and external secretions. It is present in the milk of humans and other mammals,[10] in the blood plasma and neutrophils and is one of the major proteins of virtually all exocrine secretions of mammals, such as saliva, bile, tears and pancreas.[15] Concentration of lactoferrin in the milk varies from 7 g/L in the colostrum to 1 g/L in mature milk.

X-ray diffraction reveals that lactoferrin is based on one polypeptide chain that contains about 700 amino acids and forms two homologous globular domains named N-and C-lobes. N-lobe corresponds to amino acid residues 1–333 and C-lobe to 345–692, and the ends of those domains are connected by a short α-helix.[16][17] Each lobe consists of two subdomains, N1, N2 and C1, C2, and contains one iron binding site and one glycosylation site. The degree of glycosylation of the protein may be different and therefore the molecular weight of lactoferrin varies between 76 and 80 kDa. The stability of lactoferrin has been associated with the high glycosylation degree.[18]

Lactoferrin belongs to the basic proteins, its isoelectric point is 8.7. It exists in two forms: iron-rich hololactoferrin and iron-free apolactoferrin. Their tertiary structures are different; apolactoferrin is characterized by "open" conformation of the N-lobe and the "closed" conformation of the C-lobe, and both lobes are closed in the hololactoferrin.[19]

Each lactoferrin molecule can reversibly bind two ions of iron, zinc, copper or other metals.[20] The binding sites are localized in each of the two protein globules. There, each ion is bonded with six ligands: four from the polypeptide chain (two tyrosine residues, one histidine residue and one aspartic acid residue) and two from carbonate or bicarbonate ions.

Lactoferrin forms reddish complex with iron; its affinity for iron is 300 times higher than that of transferrin.[21] The affinity increases in weakly acidic medium. This facilitates the transfer of iron from transferrin to lactoferrin during inflammations, when the pH of tissues decreases due to accumulation of lactic and other acids.[22] The saturated iron concentration in lactoferrin in human milk is estimated as 10 to 30% (100% corresponds to all lactoferrin molecules containing 2 iron atoms). It is demonstrated that lactoferrin is involved not only in the transport of iron, zinc and copper, but also in the regulation of their intake.[23] Presence of loose ions of zinc and copper does not affect the iron binding ability of lactoferrin, and might even increase it.

Polymeric forms

Both in blood plasma and in secretory fluids lactoferrin can exist in different polymeric forms ranging from monomers to tetramers. Lactoferrin tends to polymerize both in vitro and in vivo, especially at high concentrations.[22] Several authors found that the dominant form of lactoferrin in physiological conditions is a tetramer, with the monomer:tetramer ratio of 1:4 at the protein concentrations of 10−5 M.[24][25][26]

It is suggested that the oligomer state of lactoferrin is determined by its concentration and that polymerization of lactoferrin is strongly affected by the presence of Ca2+ ions. In particular, monomers were dominant at concentrations below 10−10−10−11 M in the presence of Ca2+, but they converted into tetramers at lactoferrin concentrations above 10−9−10−10 M.[24][27] Titer of lactoferrin in the blood corresponds to this particular "transition concentration" and thus lactoferrin in the blood should be presented both as a monomer and tetramer. Many functional properties of lactoferrin depend on its oligomeric state. In particular, monomeric, but not tetrameric lactoferrin can strongly bind to DNA.

Function

Lactoferrin belongs to the innate immune system. Apart from its main biological function, namely binding and transport of iron ions, lactoferrin also has antibacterial, antiviral, antiparasitic, catalytic, anti-cancer, and anti-allergic functions and properties.[28]


Antibacterial activity

Lactoferrin's primary role is to sequester free iron, and in doing so remove essential substrate required for bacterial growth.[37] Antibacterial action of lactoferrin is also explained by the presence of specific receptors on the cell surface of microorganisms. Lactoferrin binds to lipopolysaccharide of bacterial walls, and the oxidized iron part of the lactoferrin oxidizes bacteria via formation of peroxides. This affects the membrane permeability and results in the cell breakdown (lysis).[37]

Although lactoferrin also has other antibacterial mechanisms not related to iron, such as stimulation of phagocytosis,[38] the interaction with the outer bacterial membrane described above is the most dominant and most studied.[39] Lactoferrin not only disrupts the membrane, but even penetrates into the cell. Its binding to the bacteria wall is associated with the specific peptide lactoferricin, which is located at the N-lobe of lactoferrin and is produced by in vitro cleavage of lactoferrin with another protein, trypsin.[40][41] A mechanism of the antimicrobial action of lactoferrin has been reported as lactoferrin targets H+-ATPase and interferes with proton translocation in the cell membrane, resulting in a lethal effect in vitro.[42]

Lactoferrin prevents the attachment of H. pylori in the stomach, which in turn, aids in reducing digestive system disorders. Bovine lactoferrin has more activity against H. pylori than human lactoferrin.[43]

Antiviral activity

Lactoferrin in sufficient strength example;- 2 grams oral capsule daily acts, mostly in vivo, on a wide range of human and animal viruses based on DNA and RNA genomes,[44] including the herpes simplex virus 1 and 2,[45][46] cytomegalovirus,[47] HIV,[46][48] hepatitis C virus,[49][50] hantaviruses, rotaviruses, poliovirus type 1,[51] human respiratory syncytial virus, murine leukemia viruses[41] and Mayaro virus.[52]

The most studied mechanism of antiviral activity of lactoferrin is its diversion of virus particles from the target cells. Many viruses tend to bind to the lipoproteins of the cell membranes and then penetrate into the cell.[50] Lactoferrin binds to the same lipoproteins thereby repelling the virus particles. Iron-free apolactoferrin is more efficient in this function than hololactoferrin; and lactoferricin, which is responsible for antimicrobial properties of lactoferrin, shows almost no antiviral activity.[44]

Beside interacting with the cell membrane, lactoferrin also directly binds to viral particles, such as the hepatitis viruses.[50] This mechanism is also confirmed by the antiviral activity of lactoferrin against rotaviruses,[41] which act on different cell types.

Lactoferrin also suppresses virus replication after the virus penetrated into the cell.[41][48] Such an indirect antiviral effect is achieved by affecting natural killer cells, granulocytes and macrophages – cells, which play a crucial role in the early stages of viral infections, such as severe acute respiratory syndrome (SARS).[53]

Antifungal activity

Lactoferrin and lactoferricin inhibit in vitro growth of Trichophyton mentagrophytes, which are responsible for several skin diseases such as ringworm.[54] Lactoferrin also acts against the Candida albicans – a diploid fungus (a form of yeast) that causes opportunistic oral and genital infections in humans.[55][56] Fluconazole has long been used against Candida albicans, which resulted in emergence of strains resistant to this drug. However, a combination of lactoferrin with fluconazole can act against fluconazole-resistant strains of Candida albicans as well as other types of Candida: C. glabrata, C. krusei, C. parapsilosis and C. tropicalis.[55] Antifungal activity is observed for sequential incubation of Candida with lactoferrin and then with fluconazole, but not vice versa. The antifungal activity of lactoferricin exceeds that of lactoferrin. In particular, synthetic peptide 1–11 lactoferricin shows much greater activity against Candida albicans than native lactoferricin.[55]

Administration of lactoferrin through drinking water to mice with weakened immune systems and symptoms of aphthous ulcer reduced the number of Candida albicans strains in the mouth and the size of the damaged areas in the tongue.[57] Oral administration of lactoferrin to animals also reduced the number of pathogenic organisms in the tissues close to the gastrointestinal tract. Candida albicans could also be completely eradicated with a mixture containing lactoferrin, lysozyme and itraconazole in HIV-positive patients who were resistant to other antifungal drugs.[58] Such antifungal action when other drugs deem inefficient is characteristic of lactoferrin and is especially valuable for HIV-infected patients.[59] Contrary to the antiviral and antibacterial actions of lactoferrin, very little is known about the mechanism of its antifungal action. Lactoferrin seems to bind the plasma membrane of C. albicans inducing an apoptotic-like process.[56][60]

Anticarcinogenic activity

The anticancer activity of bovine lactoferrin (bLF) has been demonstrated in experimental lung, bladder, tongue, colon, and liver carcinogeneses on rats, possibly by suppression of phase I enzymes, such as cytochrome P450 1A2 (CYP1A2).[61] Also, in another experiment done on hamsters, bovine lactoferrin decreased the incidence of oral cancer by 50%.[62] Currently, bLF is used as an ingredient in yogurt, chewing gums, infant formulas, and cosmetics.[62]

Cystic fibrosis

The human lung and saliva contain a wide range of antimicrobial compound including lactoperoxidase system, producing hypothiocyanite and lactoferrin, with hypothiocyanite missing in cystic fibrosis patients.[63] Lactoferrin, a component of innate immunity, prevents bacterial biofilm development.[64][65] The loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity is observed in patients with cystic fibrosis.[66] In cystic fibrosis, antibiotic susceptibility may be modified by lactoferrin[67] These findings demonstrate the important role of lactoferrin in human host defense and especially in lung.[68] Lactoferrin with hypothiocyanite has been granted orphan drug status by the EMEA[69] and the FDA.[70]
Necrotizing enterocolitis

A 2017 Cochrane review with low quality suggests that oral lactoferrin with or without probiotic decreases late onset of sepsis and necrotizing enterocolitis (stage II or III) in preterm infants with no adverse effects.[71]
In diagnosis

Lactoferrin levels in tear fluid have been shown to decrease in dry eye diseases such as Sjögren's syndrome.[72] A rapid, portable test utilizing microfluidic technology has been developed to enable measurement of lactoferrin levels in human tear fluid at the point-of-care with the aim of improving diagnosis of Sjögren's syndrome and other forms of dry eye disease.[73]

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Arch Virol. 1995;140(Cool:1469-72.
Lactoferrin inhibits herpes simplex virus type-1 (HSV-1) infection to mouse cornea.
Fujihara T1, Hayashi K.
Author information
Abstract

Lactoferrin inhibits bacterial growth in the conjunctival sac. However, its antiviral function particularly in ocular tissue has not been reported in the literature. We studied whether lactoferrin inhibits infection of herpes simplex virus type-1 (HSV-1) in vitro using Vero cell monolayer. We also tested the inhibitory effect of lactoferrin on HSV-1 infection in the mouse cornea. Lactoferrin prevented HSV-1 plaque formation. Administration of topical 1% lactoferrin prior to the virus inoculation suppressed infection on ocular tissue, however it did not inhibit propagation of the virus.

PMID:
7661698
DOI:
10.1007/bf01322673

https://www.ncbi.nlm.nih.gov/pubmed/7661698

---------


Lactoferrin, Alzheimer’s & Dementia

by Christian Santi / 21 Jul / In Uncategorized

Early diagnosis of mild cognitive impairment and Alzheimer’s disease based on salivary lactoferrin

The present publication has been prepared on the basis of the results obtained in the biomedical research project signed between the Geroa Diagnostics S.L. entity and the Hospital 12 de Octubre Biomedical Foundation under the title “search of new salivary biomarkers in Alzheimer’s disease and other neurodegenerative diseases: possible diagnostic application.” The research was carried out in accordance with the scientific-technical specifications provided by Geroa Diagnostics S.L. The results of this project belong to Geroa Diagnostics S.L., who holds the exclusive ownership of the intellectual property rights that protect them, with the exception of the ones inherent to the author/inventor. This publication has been executed with the prior authorization of the rights titleholder Geroa Diagnostics S.L.

Eva Carro, Fernando Bartolomé, Félix Bermejo-Pareja, Alberto Villarejo-Galende, José Antonio Molina, Pablo Ortiz, Miguel Calero, Alberto Rabano, José Luis Cantero, Gorka Orive
Abstract
Introduction

The Alzheimer’s disease (AD) process is likely initiated many years before clinical onset. Biomarkers of preclinical disease are critical for the development of disease-modifying or even preventative therapies. Current biomarkers for early disease, including cerebrospinal fluid tau and amyloid β (Aβ) levels, structural and functional magnetic resonance imaging, and the use of brain amyloid imaging, are limited because they are very invasive or expensive. Noninvasive biomarkers may be a more accessible alternative, but none can currently detect preclinical AD with the required sensitivity and specificity.
Methods

Here, we show a novel, straight-forward, and noninvasive approach for assessment of early stages of cognitive decline. Salivary samples from cases of amnestic mild cognitive impairment (aMCI) and AD, and neurology controls were analyzed.
Results

We have discovered and validated a new single saliva biomarker, lactoferrin, which in our cross-sectional investigation perfectly discriminates clinically diagnosed aMCI and AD patients from a cognitively healthy control group. The accuracy for AD diagnosis shown by salivary lactoferrin was greater than that obtained from core cerebrospinal fluid (CSF) biomarkers, including total tau and CSF Aβ42. Furthermore, salivary lactoferrin can be used for population screening and for identifying those underdiagnosed subjects with very early stages of mild cognitive impairment and AD.
Conclusion

This biomarker may offer new insights in the early diagnostics for AD.

Read the full article: http://www.dadm.alzdem.com/article/S2352-8729(17)30024-6/fulltext

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Lactoferrin -- related to Iron in the blood and Herpes outbreaks Empty Re: Lactoferrin -- related to Iron in the blood and Herpes outbreaks

Post by Chromium6 on Sun Jan 05, 2020 6:28 am

8 Lactoferrin Health Benefits + Sources & Side Effects
Written by Aleksa Ristic, MS (Pharmacy) | Reviewed by Nattha Wannissorn, PhD | Last updated: December 15, 2019

(more at link: https://content.selfdecode.com/lactoferrin/ )

Lactoferrin is a naturally occurring protein found in milk and bodily fluids. It is a potent anti-microbial and modulator of the immune system. As a supplement, lactoferrin may improve iron status, skin health, immunity, and more. Read this post to learn the health benefits of lactoferrin, along with food sources & side effects.

What is Lactoferrin?

Lactoferrin (also known as lactotransferrin or LF) is a type of iron-binding glycoprotein that is mostly secreted from bodily fluids including milk, saliva, tears, vaginal fluids, semen, secretions from lungs and nose, bile, digestive juices, and urine [1].

It provides antibacterial and immune-supporting activity to human infants. LF is a component of the immune system responsible for defense at the mucosal level, due to its high antimicrobial activity.

Lactoferrin is crucial to the increase in immune functions for breastfed infants. It is also believed to be widely important to maintaining immune functions further in life past infancy.

Lactoferrin is also found in secondary neutrophil granules, blood, and amniotic fluid. It also binds to DNA and other molecules in milk like IgA, casein, albumin, etc. [2, 1].

It helps develop the gastrointestinal and immune system in newborns [3].

The iron-bound form of lactoferrin is called holo-lactoferrin, whereas the lactoferrin without iron is apo-lactoferrin.

Proponents:

Helps the immune system and prevents inflammation
Has anti-cancer properties
Supports iron absorption
Shields preterm infants
Anti-bacterial, anti-fungal, anti-viral
Promotes bone health

Marker of Inflammation and Infections

Lactoferrin kills bacteria and protects from infections. Therefore, natural lactoferrin levels in our bodies rise during times of infections and inflammation.

To combat bacterial infections, blood lactoferrin rapidly rises and iron levels drop during E. coli infection in the blood in mice [4].

Doctors test lactoferrin in the stool to detect inflammation in the intestines, especially to diagnose inflammatory bowel disease [5].

Fecal lactoferrin levels also naturally rise in the case of Clostridium difficile infections in humans [6].

Antioxidant Properties

Because iron can cause oxidative stress, lactoferrin can reduce oxidative stress by binding and removing iron, which prevents cell damage or cell death [7].

Lactoferrin supplementation can support the immune system as an antioxidant [8].

Roles in Immunity

There are lactoferrin receptors on many immune cells, so lactoferrin directly affects how these cells function [9, 10, 11].

Lactoferrin can exert changes on white blood cells, through increasing natural killer cell, neutrophils, and macrophage activities. This increases cytokine, and Nitric Oxide production as well as limit pathogen growth [12, 13, 14].

Lactoferrin also affects adaptive immune cells (T-cells and B-cells) [15].

In infants, lactoferrin is crucial to the development of their natural immune system function to prevent infection [16].

Anti-Inflammatory Effects

Although the direct mechanism has not been established yet, lactoferrin is a well-known anti-inflammatory component in humans [17].

Lactoferrin in the amniotic fluid is an important component to reducing fetal inflammation in pregnant women through reducing IL-6 levels and reducing infection causing the inflammation [18].

It has anti-inflammatory properties when interacting with the immune system against the Epstein-Barr virus, reducing inflammation by inhibiting the activation of TLR2 and TLR9 in the virus DNA [19].

Antibacterial Properties

Lactoferrin helps stop the activity of bacteria. Most bacteria need iron to function, and lactoferrin can stop bacteria from taking up iron in the human body [1].

In addition to this, it can block bacteria’s carbohydrate metabolism, destabilize their cell walls, or interact with lysozymes in milk to stop bacteria [1].

Roles in Fetal/Infant Development

Infants require lactoferrin to develop and adapt to the intestinal system. It is responsible for differentiating small intestinal epithelial cells, affecting small intestinal mass, length, and enzyme expression [20].

In human fetuses, lactoferrin serves as a bone growth regulator in the early phases of human bone development [21].

Lactoferrin promotes cartilaginous tissue growth at various stages of fetal development by stimulating immature osteocytes and osteoblasts [22].

In human fetuses, LF promotes iron absorption and development of the brush border, allowing for healthy growth and gut development before birth [23].

High levels of LF in the fetus prevent infection and ruptures of fetal membranes while increasing the ease of labor [24].
Health Benefits of Lactoferrin Supplementation

Possibly Effective:

1) Iron Deficiency in Pregnancy

Lactoferrin helps increase iron absorption in the intestine. It is also responsible for the delivery of iron to cells.

According to a meta-analysis of four clinical trials and 600 pregnant women, “oral bovine lactoferrin is just as good as ferrous sulfate in improving hematological parameters with fewer gastrointestinal side effects.” Lactoferrin showed better effects on hemoglobin levels in pregnant women with moderate anemia [25].

2) Premature Delivery Risks

Many preterm babies suffer from necrotizing enterocolitis when bacteria can destroy the intestinal walls and cause the intestinal cells to die [26].

Preliminary reports suggested that human and bovine lactotransferrin can kill bacteria in the intestines and help stop necrotizing enterocolitis. A study of 743 preterm infants confirmed these findings [26, 27].

Lactoferrin is naturally found in breast milk in high amounts, which is another reason why breastfeeding is essential for infant development [28].

Additionally, lactoferrin (oral and intravaginal) stopped the shortening of the cervical length, reduced uterine contractions, and prevented vaginal infections in two clinical trials [29, 30].

3) Skin Health

36 young adults were given milk with lactoferrin and their skin condition improved. They had less acne and skin inflammation compared to the placebo group [31].

22 psoriasis patients also benefited from topical application. The redness and size of their skin lesions improved after applying 10% or 20% LF cream (equally effective) [32].

In 55 diabetic patients, topical applications of recombinant lactoferrin improved the healing of foot ulcers with no side effects [33].

4) Hepatitis C

In a preliminary study of 11 patients with chronic hepatitis C (CHC), an 8‐week treatment of bovine lactoferrin (1.8 or 3.6 g/day) significantly reduced serum alanine transaminase (ALT) and the viral RNA in patients with milder forms of infection [34].

The same group of researchers then conducted a placebo-controlled trial of 63 CHC patients. They found that bovine lactoferrin (600 mg/day) produce a Th1-cytokine dominant environment (IL-4 and IFN-gamma), which supports the IFN therapy for hepatitis C [35].

Two additional studies of 310 CHC patients confirmed that lactoferrin may increase the effectiveness of standard treatment, but doesn’t have therapeutic properties on its own [36, 37].
Insufficient Evidence:

No valid clinical evidence supports the use of lactoferrin for any of the conditions in this section. Below is a summary of up-to-date animal studies, cell-based research, or low-quality clinical trials which should spark further investigation. However, you shouldn’t interpret them as supportive of any health benefit.

5) Cancer Treatment Support

Lactoferrin supports the immune system by activating microbe- and cancer-fighting cells such as natural killer (NK) cells and T lymphocytes. Researchers have developed human recombinant lactoferrin, talactoferrin, that showed promising results as a drug candidate [38].

In a study of 110 patients with advanced or metastatic lung cancer, talactoferrin significantly improved the effectiveness of standard treatment (carboplatin + paclitaxel) [39].

Talactoferrin significantly improved survival in a trial of 100 patients with chemotherapy-resistant lung cancer. However, it didn’t show significant benefits for the same condition in a much larger study of 742 patients [40, 41].

Ten lung cancer patients undergoing chemotherapy had increased immune system response after taking lactoferrin post-treatment [42].

In rats, supplementation of bovine lactoferrin interacted with phase 1 enzymes to reduce the carcinogenic effects of lung, bladder, tongue, colon, and liver cancer. It also had the ability to restore white and red blood cell count after chemotherapy (43, 44).

Bovine lactotransferrin decreases breast cancer cell viability and cell growth, and increased cell death in a couple of cell-based studies [45, 46].

Larger, well-designed clinical trials should investigate the anticancer effects of lactoferrin. At this point, it can’t be recommended for cancer treatment or prevention.

6) Weight Loss

Obese Japanese men and women (n=26) were given lactoferrin tablets (300 mg) for eight weeks. The treatment reduced their fat mass, body weight (-1.5 kg), BMI, and hip circumference (-2.6 cm) [47].

Lactoferrin appears to control fat accumulation in humans. There is also some evidence that iron deficiency might contribute to obesity, but more studies need to be done [48].

Further research is needed to confirm the benefits of lactoferrin for weight control. Caloric restriction and regular exercise remain the best approach that no supplements can replace.

7) Digestive Support

In a study of 32 Japanese women, LF suppressed the growth of E. coli and Salmonella while promoting the growth of beneficial Bifidobacteria. As a result, the treatment significantly improved digestion and relieved constipation [49].

Cool Bone Health

In 38 postmenopausal women, RNAse-enriched lactoferrin supplementation significantly improved their bone health and stimulated bone formation. More research is needed to make definite conclusions [50].
Animal and Cellular Research (Lacking Evidence)

No clinical evidence supports the use of lactoferrin for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit.

Bacterial Infections

In animals with bacterial LPS toxicity, injecting them with lactoferrin reduces many symptoms of toxicity, and reduce risks of death from LPS toxicity by five-fold [51, 52].

Lactoferrin and lysozyme prevented the spread of Streptococcus pneumoniae to sterile cells in a cell-based study [53].

In mice infected with Listeria monocytogenes, treatment with lactoferrin boosted the immune function and decreased the overall level of invading bacteria [54].

In test tubes, human lactoferrin taken alongside iron supplementation was successful in fighting Actinobacillus pleuropneumoniae infection by inhibiting the growth and spread of the bacteria [55].

Viral Infections

In human cell cultures, lactoferrin can prevent viruses from entering human cells by blocking cellular receptors or directly binding to the viruses [56].

The bovine lactoferrin was more efficient than the human version in stopping the herpes virus in human cell culture. However, both types were able to stop the virus from entering the cells [56].

Lactoferrin was also effective in stopping the effects of HIV by blocking the entry process in vitro [56].

In human cells, lactoferrin also inhibited hepatitis B, HPV, rotavirus, HSV, and influenza by using similar mechanisms [56].

Other Infections

Fungi

Both bovine (cow) and human lactoferrin stopped the growth of fungi in human cell cultures [57].
Parasites

In cows infected with a parasite, lactoferrin supplementation increases the immune system response to the parasite, helping to expel it from the body [58].

Allergies and Asthma

Lactoferrin helped reduce airway inflammation in a mouse asthma model [59].

In test tubes, it blocked histamine release from colon mast cells [60].

Brain Development

In a study on piglets, lactoferrin helped improve cognition and brain development. They learned how to complete learning tasks more efficiently [61].

Lactoferrin Side Effects

Lactoferrin is safe and well-tolerated; high doses (>1,100 mg a day) might cause some abdominal pain, diarrhea, or constipation [62].

In some human subjects, injections of 5 mg of LF may increase liver enzymes. Further studies will be needed to test the safety of LF injections in humans [63].

Lactoferrin Sources and Digestion
Raw vs Pasteurized Milk

Lactoferrin is heat stable and may survive pasteurization, but not high-pressure treatment [64].

5 studies have shown that there is no significant reduction in lactoferrin levels in pasteurized milk compared to raw milk, except for one study using UV-C pasteurization found that lactoferrin is significantly decreased after pasteurization [65].

In milk and colostrum, lactoferrin is at the concentration of 7g/L [66].

Digestion and Absorption

About 60 – 80% of ingested lactoferrin from cow’s milk survives stomach digestion in humans depending on whether it is bound to iron [67].

Some lactoferrin is digested by stomach enzymes like pepsin. This digestion results in smaller proteins or peptides which have stronger antimicrobial activities than the protein itself.

Lactoferrin and its peptides are absorbed either just through intestinal cells or through the Intelectin 1 receptor. It gets incorporated into the lymphatic system before entering the systemic circulation. It can also be transported into the gut immune system [68].

Once lactoferrin enters systemic circulation, it is cleared rapidly by the liver [69].

https://content.selfdecode.com/lactoferrin/

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