Lactoferrin seems to be capable of restoring suppressed immune functionality

uglevod

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Interesting research explaining why some CFS(and other chronic diseases) sufferers have their symptoms changed(to worse or better) with Lactoferrin.

In a few words: Lactoferrin is capable of upregulating suppressed immune system in the context of infection/toxins. Below it was used in the model of fungal infection(candida), but innate immunity reacts towards the whole set of acute(extracellular) pathogens more or less the same way(stimulation of TLR receptors -> pro inflammatory response -> pathogens clearance with phagocytosis):

Effect of orally administered bovine lactoferrin on the immune response in the oral candidiasis murine model
https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.05505-0

Therapeutic activity against oral candidiasis of orally administered bovine lactoferrin (LF), a multifunctional milk protein, was shown in a previous report using an immunosuppressed murine model. In the present study, the influence of orally administered LF on immune responses relevant to this therapeutic effect was examined. Because mice were immunosuppressed with prednisolone 1 day before and 3 days after the infection with Candida, the numbers of peripheral blood leukocytes (PBL) and cervical lymph node (CLN) cells were reduced. Lactoferrin feeding prevented the reduction in the numbers of peripheral blood leukocytes on day 1 and CLN cells on days 1, 5 and 6 in the Candida-infected mice. The number of CLN cells of individual mice on days 5 and 6 was inversely correlated with the Candida c.f.u. in the oral cavity. Increased production of IFN-γ and TNF-α by CLN cells stimulated with heat-killed Candida albicans on day 6 was observed in LF-treated mice compared with non-treated mice. Concanavalin A (ConA)-stimulated CLN cells from LF-treated mice also showed a significant increase in the production of IFN-γ and IL12 on day 5 and a tendency for increased production of IFN-γ and TNF-α on day 6. The levels of cytokine production by ConA-stimulated CLN cells on day 6 were inversely correlated with the Candida c.f.u. in the oral cavity. In conclusion, the alleviation of oral candidiasis by LF feeding in this model may correlate with the enhancement of the number of leukocytes and their cytokine responses in regional lymph nodes against Candida infection.

Oral candidiasis, caused by C. albicans, is most prevalent in infancy and old age and in individuals with immunosuppressive conditions. The clinical importance of oral candidiasis, which is not life-threatening but causes significant morbidity in patients, has increased recently (Hermann et al., 2001). Some drugs such as azole antifungal agents are used for chemotherapy of this fungal infection (Walsh et al., 2000), but long-term treatments sometimes lead to the appearance of drug-resistant Candida and side effects (Lopez-Ribot et al., 1999). Recently, we developed a new oral candidiasis model using immunosuppressed mice; the mice in this model have local symptoms characteristic of oral thrush (Takakura et al., 2003a). In an assessment of the potential of LF as a food component using this animal model, it was demonstrated that LF feeding improved oral candidiasis microbiologically and symptomatically (Takakura et al., 2003b). In that study, it was suggested that the effect of LF in this oral candidiasis model is not attributable simply to its direct antifungal activity. Therefore, the influence of orally administered LF on systemic or local immune responses relevant to its therapeutic effect in this model was examined in the present study.

On the other hand, there was no difference in the number of neutrophils in PBL between the two groups. This increase of lymphocytes in PBL by LF is in accord with the previous finding by Kuhara et al. (2000), that orally administered LF increased the number of cells in various lymphocyte subsets, including CD4+, CD8+ and asialoGM1+ cells, in the peripheral blood of tumour-bearing mice. CLNs are the most important lymph nodes in protection against oral infection (Elahi et al., 2000). The reduction in the number of CLN cells on day 1 was prevented by orally administered LF, as seen in PBL (Fig. 1d).

The enhancement by LF treatment of the number of PBL and CLN cells on day 1 was observed only in mice infected with Candida and also treated with PDS, and not in mice infected only, in mice treated with PDS only or in normal mice (Fig. 2a, b). Artym et al. (2003) demonstrated that the drop in the number of PBL and the strong reduction in the percentage of lymphocytes induced by cyclophosphamide, which is known to be a potent immunosuppressive drug, were prevented by orally administered LF in mice. In their study, LF decreased the number of PBL when administered to normal mice. Therefore, we can assume that oral LF may affect lymphocyte numbers in PBL and CLN cells in a manner dependent on the host's immune status.

Cytokine production by CLN cells stimulated with ConA or heat-killed C. albicans

After CLN cells were collected on day 5 or 6 and stimulated with ConA or heat-killed C. albicans, the levels of cytokines in the culture supernatants were measured. In this study, CLN cells were cultured for 4 days, because cytokine production was reduced by PDS treatment. On day 5, the level of IFN-γ and IL12 production by CLN cells stimulated with ConA was higher in LF-treated mice than in non-treated mice (Fig. 4). The level of production of IFN-γ by CLN cells stimulated with ConA was notably increased on day 6 compared with day 5, whereas that of IL12 was decreased. Augmentation of IFN-γ but not IL12 production by LF on day 6 was observed in CLN cells stimulated with Candida cells. Enhancement of TNF-α production by LF administration was also clearly seen on day 6 in CLN cells stimulated with Candida. IL2 production seemed somewhat higher in the LF group, but the difference between the two groups was not significant. Moreover, comparison of cytokine production by CLN cells and Candida c.f.u. in the oral cavity of individual mice on day 6 indicated that the levels of IFN-γ and TNF-α production after stimulation with ConA were inversely correlated with Candida c.f.u. (IFN-γ: r = −0.75, P = 0.02; TNF-α: r = −0.83, P = 0.01) and IL12 production by these cells was correlated with the number of C. albicans cells in the oral cavity (r = 0.70, P = 0.06).







It is well known that TNF-α and IFN-γ stimulate macrophages and neutrophils, which kill C. albicans directly (Tansho et al., 1994). Farah et al. (2002) demonstrated that TNF-α in oral tissue was an important mediator in the recovery from oropharyngeal candidiasis in mice. Their findings suggest that T lymphocyte infiltration into the oral tissue activates resident or accumulated macrophages and neutrophils by releasing TNF-α and inducing a phagocytic response against invading hyphal elements. CLN cells activated by LF feeding may migrate to the circulation, with some reaching the oral mucosa. Further examination is necessary of the influence of LF feeding on immunological events in the oral tissue using this model. In the past few years, several immunomodulatory effects of ingested LF in animals have been reported (Sekine et al., 1997; Wakabayashi et al., 2002). Very recently, we showed that LF feeding augmented macrophage activity at the local site where inactivated Candida was injected as a priming agent (Wakabayashi et al., 2003). These results support the possibility that LF feeding upregulates immune functions of effector cells and causes the early resolution of oral candidiasis in this model.

As shown by clinical observations and experimental data in animal models, impairment of cell-mediated immunity can enhance susceptibility to mucosal candidal infections (Fidel, 2002). Therefore, upregulation of cell-mediated immunity by LF feeding, as indicated by the enhancement of Th1-type cytokine production, may be beneficial for the treatment of oral candidiasis. Masci (2000) has already reported that a mouthwash containing LF and lysozyme was effective against oral candidiasis in an HIV patient. Our findings suggest that LF from cows’ milk can be used not only as a mouthwash but also as a dietary supplement with immunomodulatory action for antifungal treatment.
 
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I've never noticed negative effects from lactoferrin. And it does look great on paper. Everything from lowering tryptase to helping iron absorption to boosting immune response to viruses. But what I want to know is the safe dose range in humans. The bottle says 250 mg but i know lots of supplements say overly cautious doses.
 

Crux

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But what I want to know is the safe dose range in humans. The bottle says 250 mg but i know lots of supplements say overly cautious doses.
I've seen in some papers that massive doses were used on neonates ;

https://pubmed.ncbi.nlm.nih.gov/32846100/
Bovine lactoferrin at doses up to 300 mg·kg-1·day-1 is safe in preterm infants.

I'll say that with prolonged intake of lactoferrin, there may be some inflammation. I've been taking it orally and intranasally for a month now, and I'm experiencing some inflammation. I'm going to pulse dose it now. Was as high 1000 mg. daily for a short time. Intranasally, 15 or so pumps a day.
 
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I've seen in some papers that massive doses were used on neonates ;

https://pubmed.ncbi.nlm.nih.gov/32846100/
Bovine lactoferrin at doses up to 300 mg·kg-1·day-1 is safe in preterm infants.

I'll say that with prolonged intake of lactoferrin, there may be some inflammation. I've been taking it orally and intranasally for a month now, and I'm experiencing some inflammation. I'm going to pulse dose it now. Was as high 1000 mg. daily for a short time. Intranasally, 15 or so pumps a day.
How do you do a safe intranasal use
 

Crux

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How do you do a safe intranasal use
There are a couple of products available on line. A nasal spray. Liposomal.

Sesderma Lactyferrin defense. makes one, so does TDC apolactoferrin.

They are sent from Europe to US, so it's not as easy as Amazon, but the companies are reputable.

If you tag me in the ' Adventures in Lactoferrin' thread, it may be simpler since I posted over there so much.
 
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I've seen in some papers that massive doses were used on neonates ;

https://pubmed.ncbi.nlm.nih.gov/32846100/
Bovine lactoferrin at doses up to 300 mg·kg-1·day-1 is safe in preterm infants.

I'll say that with prolonged intake of lactoferrin, there may be some inflammation. I've been taking it orally and intranasally for a month now, and I'm experiencing some inflammation. I'm going to pulse dose it now. Was as high 1000 mg. daily for a short time. Intranasally, 15 or so pumps a day.
@rpapen77 do you see this???
 

godlovesatrier

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I tried 750mg 250mg 3x a day and that did appear to get rid of some UTI like symptoms, which I think might be prostitis - this only occurs when my immune system is depressed from a virus or a particular type of vaccine. But it could also be endothelial inflammation brought on by these events, essentially a worsening of "ME" in this case would mean endothelial cells becoming inflamed. Making it feel like a UTI - might also allow bacteria to proliferate.

Anyway what I found with the dosing was that it just gave me diarrhea, or if not that I was going to the toilet 5 times a day - which just seems a bit excessive! But I can see how it would be quite useful.

At any rate I might try it again, as I do think it helps. Might also help with intestinal wall permeability maybe?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337092/

The intestinal epithelial barrier plays a key protective role in the gut lumen. Bovine lactoferrin (bLF) has been reported to improve the intestinal epithelial barrier function, but its impact on tight junction (TJ) proteins has been rarely described.
Conclusion
In conclusion, the present data indicate that bLF increases the expression of TJ proteins, and protects the intestinal epithelial barrier function. bLF initially exerted a marked effect on intestinal epithelial cell growth and then on cell differentiation. Meanwhile, bLF enhanced the integrity of the intestinal epithelial barrier by increasing TEER values, decreasing Papp values, and up-regulating TJ protein expression at both protein and mRNA level.
 

nerd

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There are a couple of products available on line. A nasal spray. Liposomal.
Where is liposomal LF available?

I'm asking because bioavailability is the key issue of its limited efficacy and the main reason for some researchers' denial of efficacy.

I know that a study looked at liposomal LF for COVID-19, which makes sense because LF can disrupt viral adhesion to cells and also normalize abnormal cytokine levels due to its universal mimicry of many cytokines.

I've considered producing my own liposomes from it but I have no experience with it and don't have the tools to evaluate its quality.
 

dave11

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"Bovine lactoferrin is sold in bulk powder form, capsules (typically 250–300 mg), liposomal syrups (32 mg/10 ml) or as a liposomal lactoferrin nebulizer [95,123,142]. The majority of bovine lactoferrin taken orally can be considered to survive gastric transit (62% for the apo form and 79% for the more stable iron-bound form [143]) and thereafter enter the intestine from where it is absorbed into the circulation, but liposomalization or encapsulation has been shown to enhance availability and effect [144,145]. It is also important to note that digestion with enzymes in the GI tract (pepsin, trypsin or chymotrypsin) yields lactoferrin fragments that are still able to bind iron [146], and that fragments of lactoferrin have antimicrobial activity [39], which may be stronger than that of the intact protein [59,60]. Peptides of lactoferrin are considered promising antivirals, but isolation costs and stability pose challenges to reach the clinical phase [42], thus, at present the whole intact protein or food products/supplements with high content of lactoferrin are more accessible."
https://www.futuremedicine.com/doi/10.2217/fvl-2020-0170
 

nerd

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The majority of bovine lactoferrin taken orally can be considered to survive gastric transit (62% for the apo form and 79% for the more stable iron-bound form [143]) and thereafter enter the intestine from where it is absorbed into the circulation, but liposomalization or encapsulation has been shown to enhance availability and effect [144,145]
One might say that this was cherry-picked by the authors. Gastric survival doesn't directly translate to the bioavailability of where it is needed. Do you need it in the liver or in the lymph system? This makes the research sort of limited. Also, the mice received higher equivalents of what a human would normally take, as far as I can tell.
 

junkcrap50

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Where is liposomal LF available?

I'm asking because bioavailability is the key issue of its limited efficacy and the main reason for some researchers' denial of efficacy.

I know that a study looked at liposomal LF for COVID-19, which makes sense because LF can disrupt viral adhesion to cells and also normalize abnormal cytokine levels due to its universal mimicry of many cytokines.

I've considered producing my own liposomes from it but I have no experience with it and don't have the tools to evaluate its quality.
Sesderma brand "Lactyferrin" is the only liposomal lactoferrin I could find. Some of the other liposomal lactoferrin I found was actually liposomal colostrum (which is more easily found), which isn't really same thing. I don't know how liposomal colostrum would work or if it'd be an equal substitute.
 

dave11

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The commonly available form of lactoferrin in the USA is neither liposomal or enteric coated.

The Jarrow brand apolactoferrin product says on its label that digestion of lactoferrin by gastric pepsin liberates the immune-supporting peptide lactoferricin B.

This article, "Lactoferricin: a lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties", seems relevant, but the full article is behind a paywall:

"Abstract The peptide lactoferricin (Lfcin) can be released from the multifunctional protein lactoferrin (LF) through proteolysis by pepsin under acidic conditions, a reaction that occurs naturally in the stomach. Lfcin encompasses a large portion of the functional domain of the intact protein, and in many cases it not only retains the activities of LF but is more active. Lfcin possesses strong antimicrobial and weak antiviral activities, and it also has potent antitumor and immunological properties. This review covers the current state of research in this field, focusing on the many beneficial activities of this peptide. Throughout we will discuss the breadth of Lfcin activity as well as the mechanism of action. Many recent studies have drawn attention to the fact that the main site of action for the peptide may be intracellular. In addition the results of structural and dynamic studies of Lfcin are presented, and the relationship between structure and activity is explored."
https://pubmed.ncbi.nlm.nih.gov/16261252/
 

nerd

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Sesderma brand "Lactyferrin" is the only liposomal lactoferrin I could find.
Awesome, thanks for answering. I thought there wasn't any brand.

Lactoferricin: a lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties"
Interesting... Most of the research either looked at iron-saturated or at apo. There are multiple mechanisms of action, extracellular and intracellular - at least for SARS viruses. I'd say it's a bit overstated because that's where the faith in its in vivo efficacy comes from; from its normal form.