Submitted to: Journal of Agricultural and Food Chemistry
Publication Type: Peer reviewed journal
Publication Acceptance Date: 11/2/2004
Publication Date: 12/14/2004
Citation: Yeung, C.K., Glahn, R.P., Miller, D. 2004. Inhibition of iron uptake from iron salts and chelates by divalent metal cations in intestinal epithelial cells. Journal of Agricultural and Food Chemistry. Available: http://pubs.acs.org/journals/jafcau/. Interpretive Summary: Forms of iron used as food additives must be tested to determine if absorption of iron from the iron compound is adequately regulated by the human intestine. Improper regulation could result in iron-overload and be detrimental to health. This study compared iron uptake from radiolabeled ferrous sulfate, ferrous ascorbate, ferrous bis-glycinate, ferric chloride, ferric citrate and ferric EDTA using human intestinal cell cultures. The iron status of the cells were altered to produce iron-deficient and iron-overloaded cells and thereby mimic absorption from iron-deficient and iron-overloaded humans. In addition, studies were designed to test for the known inhibitory effect of cobalt and manganese on iron uptake from the above forms of iron. Iron uptake from all forms of iron was markedly inhibited in the presence of 100-fold molar excess of cobalt and manganese. Iron uptake from the novel forms of iron such as ferrous bis-glycinate and ferric EDTA appears to follow the same pathway as uptake from the common iron salts, thereby indicating that these forms meet this criteria for use as a food fortificant.
Technical Abstract: Iron uptake from radiolabeled ferrous sulfate, ferrous ascorbate, ferrous bis-glycinate, ferric chloride, ferric citrate and ferric EDTA by Caco-2 cells with different iron status, and in the presence of divalent metal cations, was compared. Supplemental iron, added to the cell culture medium at 20 umol/L 72 h prior to the uptake experiments, elevated the iron status of Caco-2 cells by increasing ferritin synthesis 100-fold, increasing HFE gene expression by 40%, and decreasing DMT-1 gene expression by 28%. In cells receiving supplemental iron, there were significant decreases in uptake from radiolabeled ferrous ascorbate and ferrous bis-glycinate, but not from ferric compounds, when compared to cells receiving no supplemental iron. Regardless of the iron status, ferrous ascorbate showed the highest percent uptake, followed by ferrous bis-glycinate, whereas uptake from all other forms of iron was significantly lower. Iron uptake from both salts and chelates was markedly inhibited in the presence of 100-fold molar excess of Co(II) and Mn(II) cations. The inhibition was more pronounced in ferrous iron uptake than ferric iron uptake, with ferrous ascorbate showing the greatest percent reduction (-90%). Our results suggest that ferrous iron is the predominant form of iron taken up by intestinal epithelial cells, and the DMT-1 pathway is the major pathway for iron uptake. Iron uptake from ferrous bis-glycinate and ferric EDTA appears to follow the same pathway as uptake from iron salts.