Ferrous bisglycinate is an iron amino acid chelate: One iron molecule is attached to two glycine molecules, forming two heterocyclic rings (Allen, 2002, EFSA NDA, 2006). Its structure partially prevents interactions with dietary inhibitors such as phytates and polyphenols and also protects the gastrointestinal surfaces from irritation by reducing the possibility of oxidation reactions (Layrisse et al., 2000, EFSA NDA, 2006). The chelation with glycine makes ferrous bisglycinate easily absorbable (Allen, 2002).
Ferrous bisglycinate is not only better absorbed than ferrous sulphate, but also well regulated by the control mechanisms of iron absorption (for explanation of regulatory mechanisms see here). It is well tolerated and less toxic compared to ferrous sulphate (Layrisse et al., 2000, Jeppsen & Borzelleca, 1999).
Due to its high bioavailability and efficacy at low doses, ferrous bisglycinate is particularly beneficial for the use in infants. As it could prevent iron over-dose but also ensure better tolerance of iron supplementation, especially in sensitive groups such as premature infants (Pineda & Ashmead, 2001, Bagna et al., 2018).
It is assumed that chelation with glycine partially protects the iron compound as it passes through the duodenum. Consequently, the iron can be absorbed not only in the duodenum but also in the jejunum (Pizarro et al., 2002, Layrisse et al., 2000).
The ferrous bisglycinate chelate is absorbed and added to the intestinal intraluminal pool of non-haem iron, hydrolysed into its iron and glycine molecules and metabolized subsequently (EFSA NDA, 2006, Allen, 2002). Humans, like all other mammals, have no controlled mechanism for the excretion of excess iron (for further information see here). Hence, the iron from ferrous bisglycinate is only excreted through blood loss, skin or epithelial cells desquamation (Wallace, 2016).
By chelating one iron molecule to two glycine molecules, the reactivity of the iron with dietary inhibitors is reduced, resulting in an enhanced bioavailability. In addition, the valence of the iron molecule is neutralised, thus protecting the gastrointestinal tract from irritations (EFSA NDA, 2006, WHO/ FAO, 2004b).
Supplementation with ferrous bisglycinate significantly increases ferritin and haemoglobin concentrations and efficiently replenishes iron stores. Even the application of low doses combined with short supplementation times (of 45 days) showed to be beneficial in the management of iron deficiency anaemia in children. The shortening of the required supplementation time (from 90 days to 45 days) is advantageous compared to other iron complexes, as it reduces the risk of treatment discontinuation (Name et al., 2018, Duque et al., 2014).
The positive effects seem to persist (for at least six months) even after the supplementation has ended. Clinical studies showed that the bisglycinate intervention was able to maintain elevated ferritin concentrations for up to six months after end of supplementation. No cases of discontinuation due to adverse effects were recorded in the study, indicating that bisglycinate is a safe and effective treatment option for iron deficiency and anaemia (Duque et al., 2014).
Due to its low acute toxicity, ferrous bisglycinate offers a safety margin that is 125 times higher than the maximum tolerable iron intake of 0.8 mg/kg bodyweight/day. In addition, no evidence of iron overload was found in iron-replete patients, so absorption is apparently physiologically regulated by the iron status of the body. EFSA and FAO/WHO therefore concluded that the use of ferrous bisglycinate does not raise any safety concerns (EFSA NDA, 2006, WHO/ FAO, 2004a). Safety assessments showed that fortification with 2 - 23 mg/day could be administered without adverse effects in children of 12 months and older, in adult men and women and also during pregnancy (EFSA NDA, 2006).
In extremely premature infants (≤ 32 weeks gestational age) ferrous bisglycinate was used in lower doses (about four times less) than ferrous sulphate and still exhibited a comparable erythropoietic response (Bagna et al., 2018). Similar results were obtained in term infants (6 to 36 months of age, 5 mg Fe/kg bodyweight/day for 28 days) where ferrous bisglycinate was absorbed 3.4 times better than ferrous sulphate. In these infants ferrous bisglycinate significantly increased haemoglobin and ferritin concentrations with a bioavailability of 90% (Pineda & Ashmead, 2001).
Iron bisglycinate, Iron sulphate
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