Use of lactoferrin in iron deficiency anaemia in pregnancy

A key function of Lactoferrin is the ability to regulate iron in the body.  It belongs to the group of transferrins, and can pick up & distribute tri-valent iron.  In this way, it can offer a therapeutic approach to problems with iron metabolism. (See also Lactoferrin & iron deficiency disorders).
Iron deficiency anaemia (IDA) is an important topic worldwide, with particular importance in pregnancy. 41.8% of pregnant women worldwide are affected, both in developing and developed countries. In Europe, the figure is 25.1% [1].
This has consequences for the health of both mother and child. On one hand, women’s well-being is impaired by symptoms such as fatigue, shortness of breath, palpitations, headaches and irritability, and on the other hand, there is an increased risk of illness and mortality associated with pregnancy and childbirth.
IDA increases the risk of premature childbirth, delays in foetal development, low birth weight and perinatal death [2-4]. 
The current therapy is mainly based on the administration of iron supplements, since food sources do not provide adequate replenishment. However, this often causes gastrointestinal side effects due to the increased formation of free radicals. In about 30% of patients, this means that they cannot take the recommended dose [5,6].
A 2017 meta-analysis sought to determine how effective lactoferrin was in the treatment of iron deficiency anaemia in pregnancy, in a direct comparison to treatment with iron supplements [7].
Lactoferrin can reversibly bind iron and is able to export iron from the tissues to the blood.  It helps to regulate systemic iron homeostasis via modulation of ferroportin and hepcidin synthesis (see also problems of iron balance).
Ferroportin is a transmembrane protein that transports divalent iron (Fe2+) from within the cell to the extracellular space. It is inhibited when hepcidin binds to it [8].
Hepcidin, a cationic peptide hormone, is the main regulator of iron homeostasis.  Iron stores, and hypoxia can modulate its production. Hepcidin degrades the ferroportin transporter, meaning that high hepcidin levels lead to reduced iron export by ferroportin.  This leads to an iron overload in the cell. During inflammation, iron export is significantly impaired, because the release of pro-inflammatory messengers results in increased expression of hepcidin [8].
Three controlled randomised studies with a total of 600 female subjects were included in this 2017 meta-analysis. Haemoglobin was the primary outcome measure, with secondary blood parameters such as serum ferritin and iron, as well as the rate of gastrointestinal adverse effects.
The administration of lactoferrin (2x100mg/d [9-11], or 250mg/d [12]) was shown to be as effective in iron deficiency anaemia, when compared with iron supplementation (using iron sulphate), and with significantly less gastrointestinal side effects. As these side effects often lead to lack of compliance, the authors strongly recommend lactoferrin for the treatment of iron deficiency anaemia (IDA) in pregnancy.
Another later study on iron deficiency anaemia, focussed in particular on the influence of lactoferrin on ferroportin and hepcidin [8].  Lactoferrin can down-regulate the inflammatory agent interleukin 6 (IL-6) and thus improve ferroportin-mediated iron export from the cells into the blood.  
This was an intervention study, and included both pregnant and non-pregnant women with various forms of anaemia, including inflammation-related anaemia. Using lactoferrin, the IL-6 levels were lower compared to iron sulphate, and the iron level was significantly increased. Lactoferrin was particularly effective in the treatment of inflammation-related anaemia by lowering IL-6 and hepcidin.
The authors saw in their results a greater beneficial effect from the lactoferrin therapy compared to the standard therapy with iron sulphate, reaffirming the results of the metanalysis.
Commercial lactoferrin products have been investigated, and characterized in terms of their heterogeneity.  These differences influence their functional properties. Differentiating between these characteristics is essential when using lactoferrin as a therapy [13].
The quality is determined by how the lactoferrin protein is prepared.  Quality is defined by various parameters: purity (in terms of lactoferrin protein content); the degree of protein denaturing, its bioactivity, as well as purification from materials that can adhere to the lactoferrin.  Also relevant is the iron binding capacity and the degree of saturation that exists after the extraction/production.
On the subject of bioavailability, studies also investigate the delivery format, where a gastric juice-resistant encapsulation is a clear advantage.  With this, the lactoferrin is released intact, at some distance from stomach acid degradation, meaning that the uptake via the receptors in the small intestine can be maximized [14].
In summary, lactoferrin, using the appropriate quality and format, can offer promising potential and a solution in the treatment of iron deficiency anaemia, especially in pregnant women.