Lactoferrin for Prevention and Treatment of Anemia and Inflammation in Pregnant Women: A Comprehensive Review

Jolanta Artym, Michał Zimecki, Marian L Kruzel, Jolanta Artym, Michał Zimecki, Marian L Kruzel

Abstract

Pregnancy is a physiological state that demands higher level of nutrients, including vitamins and minerals, for the growth and maintenance of the fetus. Iron deficiency is a part of most common diet deficiencies in pregnancy and has high clinical significance leading to the development of syderopenic anemia and its consequences for mother and child, such as higher risk of perinatal death, susceptibility to infection, intra-uteral growth inhibition, prematurity and low birth weight. Hence, iron supplementation is recommended for pregnant women; however dietary intake of iron from most commercially available formulas is often insufficient due to iron-poor bioavailability, or have undesired side-effects in the gastrointestinal tract, resulting in a discouraging and distrustful attitude to such treatment. The results of numerous studies indicate that diet supplementation with lactoferrin (LTF), an iron-binding protein, may be advantageous in prophylaxis and treatment of iron deficiency anemia. LTF, administered orally, normalizes iron homeostasis, not only by facilitating iron absorption, but also by inhibiting inflammatory processes responsible for anemia of chronic diseases, characterized by a functional iron deficit for physiological processes. LTF also protects against infections and inflammatory complications, caused by diagnostic surgical interventions in pregnant women. Beneficial, multidirectional actions of LTF during pregnancy encompass, in addition, inhibition of oxidative stress, normalization of intestine and genital tract microbiota and carbohydrate-lipid metabolism, protection of intestine barrier function, promotion of wound healing, as well as hypotensive, analgesic and antistress actions. Bovine lactoferrin (BLTF) is readily available on the nutritional market and generally recognized as safe (GRAS) for use in human diet.

Keywords: anemia of inflammation; iron deficiency; iron deficiency anemia; lactoferrin; pregnancy.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Turnover of iron in the human body. Given values indicate amounts of absorbed, used, stored and expelled iron.
Figure 2
Figure 2
Processes of iron absorption in small intestine enterocytes and release from hepatic/spleen macrophages. For uptake of non heme Fe3+ ions, their reduction to Fe2+ is essential, involving Dcytb. Fe2+ ions are transported into cells by means of DMT-1 transporter and here may be stored in a form of ferritin (after prior oxidation) or released into circulation by FPN transporter (after prior oxidation by membrane hephaestin or serum Cp). In circulation, Fe3+ ions bind to TF that transports them to all tissues; in the left upper corner (in the circle) a possible participation of LTF in the process of iron absorption is presented. Iron from waste, recycled erythrocytes, is accumulated in hepatic/splenic macrophages (reticuloendothelial system) as ferritin or, as necessary, released from cells by means of FPN, bound to TF and transported into tissues. In both cases, hepatic hepcidin (induced among other by proinflammatory cytokines) inhibits activity of FPN and iron release into circulation. LTF inhibits expression of proinflammatory cytokines and in this way inhibits expression of hepcidin, ensuring activity of FPN and iron absorption and its release from body resources (in the middle of figure, in the circle). Cp–ceruloplasmin, Dcytb–duodenal cytochrome b, DMT-1–divalent metal transporter 1, Fe–iron ions, FPN–ferroportin, HCP-1–heme carrier protein 1, IL–interleukin, LTF–lactoferrin, RBC–red blood cells, TF–transferrin.
Figure 3
Figure 3
Dangerous consequences of coexisting iron deficiency anemia (IDA) and anemia of inflammation (AI) during pregnancy. Inadequate delivery of iron from diet is responsible for “true” deficit (IDA), which is aggravated by simultaneous inflammation responsible for “functional” deficiency (AI). IDA and AI are dangerous to mother and her offspring. Fe—iron ions, IL—interleukin, IFN—interferon.
Figure 4
Figure 4
Immune response in normal pregnancy. Pregnancy may be divided into three immunologically different phases: the first trimester with inflammatory processes conditioned by proinflammatory cytokines and chemokines (IL-6, IL-8, MCP-1, RANTES, G-CSF), the second trimester with silencing of inflammatory reactions thanks to anti-inflammatory cytokines (IL-4, IL-10, IL-13) and the third trimester with the inflammation intensified again due to the activity of proinflammatory factors conditioning the proper course of delivery and childbirth.
Figure 5
Figure 5
Lactoferrin (BLTF) isolated from bovine milk.

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