Factors affecting the absorption of iron from Fe(III)EDTA

Abstract

1. The modification of iron absorption from Fe(III)EDTA by agents known to promote or inhibit absorption was examined in 101 volunteer multiparous Indian women. Fe absorption from Fe(III)EDTA was compared with absorption of intrinsic food Fe in a further twenty-eight subjects. Finally the urinary excretion of radio-Fe after oral administration of59Fe(III)EDTA was studied in twenty-four subjects and evidence of intraluminal exchange of Fe was examined.2. Fe absorption from maize porridge fortified with Fe(III)EDTA was more than twice that from porridge fortified with FeSO4. 7H2O.3. Although bran decreased Fe absorption from FeSO4. 7H2O approximately 11-fold, it had no significant effect on Fe absorption from Fe(III)EDTA. Nevertheless tea, which is a more potent inhibitor of Fe absorption, decreased absorption from Fe(III)EDTA 7-fold.4. Fe absorption from Fe(III)EDTA given in water was only increased 40% by addition of 3 mol ascorbic acid/mol Fe but by 7-fold when the relative proportions were increased to 6:1. This enhancing effect was blunted when the Fe(III)EDTA was given with maize porridge. In these circumstances, an ascorbate:iron value of 3:1 (which doubles absorption from FeSO4. 7H2O) produced no significant increase in Fe absorption, while a value of 6:1 produced only a 2.5-fold increase.5. Fe absorption from Fe(III)EDTA was not altered by addition of maize porridge unless ascorbic acid was present.6. Less than 1% of59Fe administered as59Fe(III)EDTA was excreted in the urine and there was an inverse relationship between Fe absorption and the amounts excreted (r0.58,P> 0.05).7. Isotope exchange between55Fe(III)EDTA and59FeSO4. 7H2O was demonstrated by finding a similar relative value for the two isotopes in urine and erythrocytes when the two labelled compounds were given together orally. This finding was confirmed by in vitro studies, which showed enhanced59Fe solubilization from59FeSO4. 7H2O in maize porridge when unlabelled Fe(III)EDTA was added.8. Although Fe absorption from Fe(III)EDTA was marginally higher it appeared to form a common pool with intrinsic food iron in most studies. It is postulated that the mechanism whereby Fe(III)EDTA forms a common pool with intrinsic food Fe differs from that occurring with simple Fe salts. When Fe is present in the chelated form it remains in solution and is relatively well absorbed because it is protected from inhibitory ligands. Simple Fe salts, however, are not similarly protected and are absorbed as poorly as the intrinsic food Fe.9. It is concluded that Fe(III)EDTA may be a useful compound for food fortification of cereals because the Fe is well absorbed and utilized for haemoglobin synthesis. The substances in cereals which inhibit absorption of simple Fe salts do not appear to inhibit absorption of Fe from Fe(III)EDTA.

Ethylenediaminetetraacetic acid (EDTA) does not increase iron uptake or ferritin synthesis by Caco-2 cells

“…The high bioavailability of iron from NaFe-EDTA has been repeatedly reported, showing that iron absorption from this compound is at least 2 times higher than absorption from FeSO 4 , depending on the meal [2,9,10,16,31,32]. Iron uptake results from NaFe-EDTA by Caco-2 cells were unexpectedly low, since this model has been extensively validated regarding iron uptake.…”

“…It has been reported that the use of NaFe-EDTA does not represent any additional benefit over other iron compounds in meals of high bioavailability [1]. Iron absorption studies in humans [10], show that ascorbic acid enhanced iron absorption from a maize porridge when a 1:6 iron:ascorbic acid molar ratio was used. We found that a 1:2 iron:ascorbic acid molar ratio, significantly enhanced iron uptake by Caco-2 cells.…”

“…It has been described in humans that EDTA does not enter the enterocyte but it releases iron to apical border [10,18].…”

“…It has been reported that iron availability from NaFe-EDTA is high, its absorption is at least double than from other iron compounds such as ferrous sulfate [2,9,10], especially from diets high in phytates such as cereals [11,12]. At the same time it has been corroborated that increased iron absorption from EDTA, does not imply a significantly lower absorption of other elements such as zinc, calcium or copper [13][14][15].…”

“…Only a small fraction of EDTA is absorbed and excreted in the urine, while iron enters the non-heme iron pool to be absorbed [10,[17][18][19].…”