ADVERTORIAL
The influence of lactoferrin on iron homeostasis
By Laura Dwyer | BHSc ( Naturopathy )
Anaemia is a global public health concern , predominately afflicting adolescent girls , women of reproductive age , pregnant women , and children . 1 While ID and IDA are leading causes of years lived with disabilities worldwide , they are one of the most preventable and treatable conditions . 2 Oral iron supplementation such as ferrous sulphate , ferrous fumarate or iron polymaltose are frequently prescribed to replete body iron stores ; however , high doses are required , which causes numerous undesirable effects . 3 Unabsorbed iron from high supplemental doses promotes gastrointestinal upset by increasing oxidative stress , subclinical inflammation and gut microbiome alterations . 4 , 5 Therefore , novel clinical treatment options that are safe and effective are essential in managing iron deficiency disorders .
Lactoferrin , an iron-binding protein , participates in regulating free iron levels in the body and has been observed to possess antimicrobial , antiviral , immunomodulating and antioxidant activity . 6 Abundantly expressed in human breast milk , lactoferrin is produced by circulating neutrophils during infection and inflammation and is functionally and structurally similar to transferrin . 7 Research indicates lactoferrin is an essential regulator of iron homeostasis as it increases iron absorption , reduces inflammation and sequesters iron during infection .
Lactoferrin increases iron absorption
Lactoferrin plays a significant role in iron uptake by the intestinal mucosa .
Almost all iron in human breast milk is bound to lactoferrin , which suggests a strong involvement in iron absorption in the underdeveloped gastrointestinal tract ( GIT ) of newborns . Lactoferrin can directly supply iron to intestinal epithelial cells through a unique lactoferrin-binding receptor . 8 Expression of this receptor is found abundantly along the small intestine , with high amounts observed in the duodenum , jejunum and ileum .
Lactoferrin modulates inflammatory cytokines
It is well established that systemic iron homeostasis is influenced by inflammation and infection . Inflammatory cytokines such as interleukin-6 ( IL-6 ) induce the production of hepcidin , a circulating peptide hormone produced by hepatocytes . Dysregulation of hepcidin by inflammation has been recognised as a mechanism of action for the development of iron disorders . 9 Lactoferrin has been shown to significantly reduce IL-6 concentrations in pregnant women suffering from ID / IDA , thus restoring iron homeostasis .
Lactoferrin sequesters iron during infection
Lactoferrin is produced endogenously by neutrophils during infection as a measure to reduce available iron . Chronic infection in the GIT by pathogens including Helicobacter pylori and parasites can significantly contribute to ID by reducing available iron for absorption . 10 Lactoferrin may sequester iron in the GIT and carry it across the intestinal mucosa , making it available for the body ' s own iron pool . 11
Clinical Evidence
Multiple studies have demonstrated lactoferrin to have the same or greater efficacy than oral iron forms in improving haemoglobin , total serum iron and serum ferritin values with fewer gastrointestinal side effects amongst iron-deficient pregnant women , 12-17 and
18 , 19 children .
In cancer patients with functional iron deficiency , lactoferrin increased haemoglobin and reduced high ferritin levels and inflammatory markers compared to intravenous iron , suggesting lactoferrin normalises iron levels by improving iron mobilisation in acute or chronic inflammation . 20 Lastly , lactoferrin alongside oral iron supplementation , prevented a drop in ferritin , serum iron and red blood cell count compared to iron alone in female long-distance runners . 21
Summary
As clinical presentations and complications differ according to the type of anaemia and its level of severity , attention must be paid to effective and safe interventions . Owing to its influence on systemic iron homeostasis , emerging evidence supports the use of lactoferrin to improve iron status in various population groups .
* References available on request
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Disclaimer : The views and opinions expressed in these advertorials are those of the authors and do not necessarily reflect the opinions of ATMS or its Directors .
174 | vol28 | no3 | JATMS