ZINC SURVIVAL IN THE GASTRIC JUNGLE

Regardless of the source, the first stage of trace mineral absorption is the exposure to the acidic environment of the stomach, where gastric juices and low pH promote the solubilization of trace minerals. In the stomach, most trace minerals dissociate from ligands to which they are bound, allowing the resulting free metallic ions to enter the small intestine.

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Nowadays, some of the trace minerals are being chelated to improve their bioavailability and minimize antagonistic interactions with phytase, calcium, or other dietary components. This process helps them resist degradation in the stomach's acidic conditions, thereby sustaining mineral homeostasis. Some advocates of chelation assert that these chelated trace minerals utilize active transport pathways supported by amino acid and peptide transporters across enterocytes, thereby optimizing mineral absorption and tissue deposition but these claims are not well supported scientifically.

According to recent European Food Safety Authority (EFSA) opinions, studies have shown that Zn deposition in animal tissues from chelates of glycine, methionine, or amino acids hydrate have demonstrated no significant differences when compared to that of inorganic Zn.

Additionally, previous studies using radioisotope labeling have shown varying ratios of Zn to Carbon and Sulfate isotopes from Zn-methionine at the gut barrier and within enterocytes. These studies have also revealed distinct time kinetics of absorption of these labeled Zn ions compared to Carbon and Sulfate ions in enterocytes. These results would suggest that the mineral and organic portions would follow different absorption pathways and that Zinc provided by Zinc chelate are dissociated and absorbed separately.

Other studies applying X-ray spectroscopy determined identical Zn-speciation within intestinal cells of broilers provided further evidence that entry routes for Zn into the organism are all similar whatever is the dietary Zn sources (Sui et al., 2011 and Liu et al., 2014).

Recent research in pigs and poultry has illustrated that chelating agent alone significantly reduces phytate antagonism with Zn when compared to Zn sulfate. This suggests that the occasional superiority of chelates under high phytate conditions is mainly attributable to a reduction of chemical interactions between zinc and phytate rather than an hypothetical new pathway of absorption (Windisch et al., 2002 and Boerboom, 2021). In the absence of phytic acid in the diet, the superiority of chelated Zn as opposed to Zn sulfate is significantly diminished, causing even numerically lower true absorption rates due to a small intestinal solubility of the chelates.

CHELATED MINERALS STABILITY UNDER DIFFERENT pH CONDITIONS

The stability of chelates can be severely affected by pH. A simulation (Figure 2) represents a model of the copper-glycinate complex behavior in water at varying pH levels. Initially, before any interaction with water, copper is entirely bound to glycine in a stable complex. However, when the pH is lowered to 3, approximately 80% of copper becomes free ions (Cu2+), indicating reduced stability of the complex. On the contrary, at high pH levels, both the complex and precipitated forms equally make up 50% of copper, with no free ions present, suggesting a less reactive complex. The figure also shows that at pH 5.25, only 70% of the chelate is available, highlighting its decreased proportion as the pH decreases. This emphasizes the partial dissociation of chelates in acidic stomach conditions and potential chelate reformation or formation of another complex with organic molecules present in the higher pH environment of the small intestine.

In considering the absorption mechanisms, the supporters of chelates claim that their product is not using the standard zinc or copper transporters but are absorbed  via amino acid or peptide transporters. Taking Zn as an example, the main transporter responsible for the active absorption of Zinc into the enterocytes is called ZIP4 (Zrt/Irt-like Protein 4). As part of the homeostasis mechanism, ZIP4 expression tends to be downregulated if there is a sufficient or oversupply of Zn to prevent excessive Zn absorption. When there is an excess of free Zn ions in the cytosol of the enterocyte, ZnT1 is activated as a response to maintain Zn balance. ZnT1 works by transporting Zn across the basolateral membrane of the enterocyte, directing it toward the circulation and preventing an accumulation of Zn within the cell. If chelated Zn would indeed be absorbed intact, it poses a risk of toxicity. A chelator with such strength that even the metal transporters at the apical gut mucosa (which are strong chelators themselves) cannot extract its metal would fail to dissociate within the enterocyte cytoplasm, leading to uncontrolled accumulation. But, all available data to date suggests that Zn from both chelated and inorganic sources is luckily subject to homeostatic regulation, which strongly suggests that both deliver free ionic Zn into enterocytes.

In the animal nutrition industry, various chelated Zn sources claimed superior bioavailability over inorganic. However, it is crucial to highlight that EFSA's opinions have not definitively concluded on this matter.

In conclusions, it seems that the differences of bioavailabity demonstrated in-vivo between the various sources of minerals are more determined by the dissociation kinetics rather than specific absorption pathways. Regardless of the source, all forms of trace minerals face instability at low pH, including chelates, as at least some of them are partially dissociated and then re-chelated at a higher pH environment. Bioavailability studies performed in the past decades without phytase should be reevaluated today with the addition of phytase to taken into consideration the effect of its interactions with minerals.

Among trace mineral forms, sources with slow dissolution kinetics along the acidic segment of the GIT must be considered, as they provide a constant flow of free ions for absorption while limiting exposure to interactions with phytase.