Iron cannot be actively excreted by humans. Free iron can harm the body. Therefore, the body's iron status has to be strictly regulated to prevent damages (Wallace, 2016, Anderson & Frazer, 2017, Milman, 2012).
From the daily iron intake, only about 2 mg will be absorbed in adults. Iron is absorbed in the duodenum and proximal jejunum, where both haem and non-haem iron are absorbed via specific mechanisms (→) (Anderson & Frazer, 2017, Wallace, 2016).
Non-haem iron is not tightly sequestered and can easily be affected by other molecules and external factors: Low pH in the stomach and small organic acids keep the non-haem iron in the ferrous state (Fe2+) and thus soluble and increase its bioavailability. In contrast phytates, tannins and polyphenols bind to non-haem, reducing its absorption. To enter the bloodstream, the non-haem iron is transported across the apical brush-border by a specific transporter (DMT1, divalent metal transporter 1). This transporter uses only ferrous iron (Fe2+) as substrate. Therefore, all ferric iron (Fe3+) has to be reduced to the ferrous oxidation state (Fe2+) at the membrane before it binds to the transporter (Anderson & Frazer, 2017, Wallace, 2016, Yiannikourides & Latunde-Dada, 2019).
In contrast, haem iron is tightly bound within its protoporphyrin ring, making it less prone to the influence of external factors. It is absorbed more efficiently than non-haem iron, eventhough little is known definitely about the mechanisms. Presumably, haem iron binds to the brush-border of enterocytes and is endocytosed in its intact form before the iron is enzymatically released by the haem oxygenase in the endoplasmic reticulum (Anderson & Frazer, 2017).
Both haem and non-haem iron are either used immediately after entry into the enterocytes or exported via the carrierprotein ferroportin (FPN-1) and stored subsequently by storage proteins (Anderson & Frazer, 2017). In the body, iron is bound to proteins or other molecules to keep it soluble, limit its redox potential (likelihood of interaction with other molecules) and its availability to intestinal microorganisms. Approximately 60% of the body's iron is bound to haemoglobin, a reaction that takes place within the bone marrow, and subsequently circulates through the system. Another 30% is bound to storage proteins (ferritin and hemosiderin) and the remaining iron is bound to myoglobin, enzymes and transferrin (Friel et al., 2018, Yiannikourides & Latunde-Dada, 2019). Together, these form the iron pool.
The body's iron status must be strictly regulated as the human body has no controlled mechanism for excreting excess iron. Iron can only be discarded by blood loss, via sloughing of intestinal cells over the faeces and skin desquamation. Iron homeostasis is largely regulated by the liver via hepcidin. This hormone negatively regulates iron absorption by binding to ferroportin, the membrane export protein, thus blocking iron export from the endocytes into the blood stream (Wallace, 2016). The lack of a controlled excretion mechanism is the reason why iron toxicity can arise by over-fortification or over-supplementation. It has detrimental effects, like increased risk of infections, microbiome dysbiosis and increased oxidative stress (Domellöf, 2017, Friel et al., 2018). The risk of systemic iron overload is usually negligible with normal intestinal function and when iron is not supplemented. However, large intakes of iron could have a corrosive effect on the intestinal mucosa due to the production of free radicals, leading to bleading and loose stools or even organ damage (EFSA NDA, 2015, Milman, 2012).
Anderson GJ, Frazer DM. Current understanding of iron homeostasis. Am J Clin Nutr 2017; 106(Suppl 6):1559S-1566S. at: www.ncbi.nlm.nih.gov/pmc/articles/PMC5701707/
Domellöf M. Meeting the Iron Needs of Low and Very Low Birth Weight Infants. Annals of nutrition & metabolism 2017; 71 Suppl 3:16–23. at: pubmed.ncbi.nlm.nih.gov/29268255/
EFSA NDA. Scientific Opinion on Dietary Reference Values for iron [Panel on Dietetic Products, Nutrition and Allergies]. EFSA Journal 2015; 13(10):1–115. at: www.efsa.europa.eu/en/efsajournal/pub/4254
Friel J, Qasem W, Cai C. Iron and the Breastfed Infant. Antioxidants (Basel, Switzerland) 2018; 7(4):1–8. at: www.ncbi.nlm.nih.gov/pmc/articles/PMC5946120/
Milman N. Oral Iron Prophylaxis in Pregnancy: Not Too Little and Not Too Much! Journal of Pregnancy 2012:8. at: pubmed.ncbi.nlm.nih.gov/22888432
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