Iron is the most abundant trace element in the human body. It occurs in two forms and two oxidation states, which differ in their bioavailability (Yiannikourides & Latunde-Dada, 2019, Friel et al., 2018). Human milk iron has a high bioavailabilty because of lactoferrin, although its total concentrations are low (Friel et al., 2018). The bioavailability of dietary iron is generally low yet can be influenced by other food components (Abbaspour et al., 2014).
Dietary iron is different from iron in human milk. It occurs in two oxidation states and two forms: one is non-haem iron, which is present in both oxidation states as ferric (Fe3+) and ferrous (Fe2+) iron. Non-haem iron mainly exists in the ferric state and is present in dark-green leafy vegetables, dairy products, in low amounts in red meat and is used in many food supplements. The other form is haem iron, which contains iron only in its ferrous (Fe2+) state. It is more easily absorbed by humans and is the predominant iron form in red meat (Wallace, 2016, WHO/ FAO, 2004, Yiannikourides & Latunde-Dada, 2019).
The iron concentration in human milk is independent from the mother's iron status and with 0.4 - 0.8 mg/l in colostrum and 0.2 ‑ 0.4 mg/l in mature milk rather low. Iron concentration in human milk cannot be increased by maternal supplementation nor diet. However, the bioavailability of iron in human milk is high: about 20% is absorbed easily whereas bioavailability in the general diet is approximately 10% (WHO, 2002, Lonnerdal et al., 2015, Yiannikourides & Latunde-Dada, 2019, Friel et al., 2018)
Responsible for the high bioavailability is the breast milk protein lactoferrin. This iron-binding protein is mostly resistant to gastric proteolysis and is absorbed via specific lactoferrin transporters present in the infant’s gut (WHO, 2002, Friel et al., 2018, Lonnerdal et al., 2015, Yiannikourides & Latunde-Dada, 2019). This makes absorption easier than haem or non-haem iron in the adult diet.
At birth, healthy, term born infants have high haemoglobin concentrations and iron stores, which contain around 25% of the body's total iron. This makes the infant well-equipped for the first six months of exclusive breastfeeding and nearly independent from dietary iron during the first months of life (Domellöf, 2017). In contrast, low birth weight infants (LBW, below 2500 g) often experience nutrient deficits or a short gestation that did not allow the build-up of iron stores. These infants – especially when born prematurely - have higher needs during their recovery growth phase. Hence, iron supplementation is recommended (→) to prevent iron deficiency (→) and long-term negative impacts like impaired neurodevelopment. A careful balance of iron intake is important: Excessive iron intake may lead to an increased risk of infections and changes in the gut microbiome. Such has been documented in LBW infants (Domellöf, 2017).
Unlike human milk, cow's milk contains almost no lactoferrin. Cow's milk iron is bound to casein, which decreases its bioavailability. During digestion of cow's milk, phosphopeptides are formed which further reduce iron absorption. High(er) concentrations of calcium in cow's milk also impact and decrease iron absorption, presumably by competing for similar non-specific mineral channels at the enterocytes apical membrane. Most infant formulas are based on cow´s milk, they are rich in calcium, and contain almost no lactoferrin. Hence, the iron in breast milk has a higher bioavailability compared to most infant formulas (Abbaspour et al., 2014, Lonnerdal et al., 2015, Hurrell & Egli, 2010).
As compensation for the less efficient iron uptake from cow's milk, iron concentrations in infant formula are set higher than those found in breast milk: In the EU, the range of iron concentrations for infant and follow-on formulas are set to 0.3 - 1.3 mg/ 100 kcal (EU/2016/127), for specialized medical products to 0.3 - 2.5 mg/ 100 kcal (EU/2016/128). The Codex Alimentarius defines a minimum above 0.45 mg/ 100 kcal (WHO/ FAO, 2016) and the needs of preterm infants – who have much higher needs than term born peers – have been defined in Europe and by international experts to span 1.8 - 2.7 mg/ 100 kcal (Koletzko et al., 2014, Agostoni et al., 2010) yet in the USA 1.3 - 3.6 mg/ 100 kcal (Kleinman & Greer, 2014).
The usual adult Western diet provides 15 - 20 mg of iron per day with around 90% in form of non-haem and 10% as haem iron (Yiannikourides & Latunde-Dada, 2019). Haem iron is part of haemoglobin and myoglobin in red meat, fish or poultry. It exhibits high bioavailibility varying between 13% and 35% and is nearly unaffected by dietary inhibitors. Non-haem iron intake occurs mostly through consumption of vegetables, fruit, cereals and legumes, but is less bioavailable (2 ‑ 20%) compared to haem iron (Abbaspour et al., 2014).
Despite its lower bioavailability, non-haem iron is the most common constituent of dietary iron for humans due to its high abundance (Abbaspour et al., 2014). Examples for iron contents in different food products are shown in the table 575-0.1-01.
The bioavailability of non-haem iron can be influenced by other components of the diet: Substances such as vitamin C (ascorbic acid) and citrate change (reduce) the oxidation state to ferrous (Fe2+) iron and thus increase iron absorption. These acids act as weak chelators and keep the iron soluble. In contrast, secondary plant metabolites such as phytate from foods that often simultaneously contain iron (e.g. soybeans, beans, lentils, oats and chickpeas) reduce the bioavailability of non-haem iron. Black and green tea reduces non-haem iron absorption because of its polyphenols (Abbaspour et al., 2014, Hurrell & Egli, 2010, Lesjak & K S Srai, 2019).
Haem iron on the other hand is not influenced by these inhibitors. Its absorption can be reduced by calcium, which potentially decreases the absorption of both non-haem and haem iron by competing for similar non-specific mineral channels (Abbaspour et al., 2014, Hurrell & Egli, 2010, Lesjak & K S Srai, 2019).
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