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Can lactoferrin help?

I first came across lactoferrin while I was researching the iron blog, and I’ve been keen to increase my understanding of it since. Lactoferrin is a natural compound found in milk, tears and sweat, and is well known for increasing iron absorption and for its antimicrobial properties. It has powerful antiviral, antibacterial and antifungal activity [1] as well as being anti-cancer and anti-oxidant, and promoting good metabolism by lowering triglycerides and visceral fat [2]. Lactoferrin also has anti-inflammatory effects [1] and is now being tested as an anti-fibrotic agent in animal models [3].


The anti-inflammatory effects alone make lactoferrin a potential therapeutic option for arthrofibrosis, and if it also has anti-fibrotic effects this would be very interesting. However, research indicates that lactoferrin promotes myofibroblast formation and wound healing after injury [4], and if this effect continued for too long lactoferrin might actually promote fibrosis. Countering this concern, a number of studies have concluded that lactoferrin is anti-fibrotic, at least in animals [3,5], even when fibrosis is already present before lactoferrin treatment [3]. And Chen et. al [6]. found that lactoferrin reversed many of the effects of heart fibrosis in aging mice, reducing myofibroblast activation, collagen synthesis, tissue stiffness and inflammation.


A number of studies have concluded that lactoferrin is anti-fibrotic, at least in animals, even when fibrosis is already present.

However, lactoferrin has not been tested for treating arthrofibrosis, and there are problems interpreting the results of animal studies, including the different physiology of rodents and the much higher doses of the therapeutic agent compared to human dosing. In addition, some people with autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus (SLE) have natural antibodies to lactoferrin, which causes an increase in inflammation and altered immune function. It was also recently reported that almost half of people with endometriosis, which is a fibrotic disorder, also have anti-lactoferrin antibodies [7]. It’s not clear if lactoferrin supplementation would be therapeutic for people who have antibodies to it.


Although the jury is still out on the anti-fibrotic potential of lactoferrin supplements in humans, research suggests that it may be useful. And given the well-established anti-inflammatory and anti-microbial effects, lactoferrin supplements may be worth a try, particularly for people taking immune-suppressing medications that leave them more vulnerable to infection. Enteric-coated lactoferrin probably has better bioavailability compared to regular lactoferrin, since it is not degraded by stomach enzymes [1].


Lactoferrin supplements may be worth a try

However, please consult your doctor before starting lactoferrin supplements. Although it is considered safe with few side-effects and good tolerance [4] people with milk allergies may have an allergic reaction, and those with gut problems may find that it causes discomfort. In addition, it may interfere with your medications.


For further reading on supplements and arthrofibrosis, please have a look at the page Prescription Free.


References
  1. Kell, D. B., Heyden, E. L. & Pretorius, E. The Biology of Lactoferrin, an Iron-Binding Protein That Can Help Defend Against Viruses and Bacteria. Front Immunol 11, 1221, doi:10.3389/fimmu.2020.01221 (2020).

  2. Aoyama, Y. et al. Lactoferrin Prevents Hepatic Injury and Fibrosis via the Inhibition of NF-kappaB Signaling in a Rat Non-Alcoholic Steatohepatitis Model. Nutrients 14, doi:10.3390/nu14010042 (2021).

  3. Al-Najjar, A. H., Ayob, A. R. & Awad, A. S. Role of Lactoferrin in Treatment of Bile Duct Ligation-Induced Hepatic Fibrosis in Rats: Impact on Inflammation and TGF-β1/Smad2/α SMA Signaling Pathway. Journal of Clinical and Experimental Hepatology, doi:10.1016/j.jceh.2022.12.014 (2022).

  4. Moreno-Exposito, L. et al. Multifunctional capacity and therapeutic potential of lactoferrin. Life Sci 195, 61-64, doi:10.1016/j.lfs.2018.01.002 (2018).

  5. Hsu, Y. H. et al. Lactoferrin Contributes a Renoprotective Effect in Acute Kidney Injury and Early Renal Fibrosis. Pharmaceutics 12, doi:10.3390/pharmaceutics12050434 (2020).

  6. Chen, R. et al. Lactoferrin ameliorates myocardial fibrosis by inhibiting inflammatory response via the AMPK/NF-κB pathway in aged mice. Journal of Functional Foods 93, 105106, doi:10.1016/j.jff.2022.105106 (2022).

  7. Mori-Yamanaka, K. et al. Exploratory Study of Serum Lactoferrin and Anti-Lactoferrin Antibody Concentrations in Patients with Endometriosis. Tohoku J Exp Med 259, 135-142, doi:10.1620/tjem.2022.J106 (2023).



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