Iron Absorption in Iron-Deficient Women, Who Received 65 mg Fe with an Indonesian Breakfast, Is Much Better from NaFe(III)EDTA than from Fe(II)SO₄, with an Acceptable Increase of Plasma NTBI. A Randomized Clinical Trial

Abstract

Plasma non-transferrin-bound iron (NTBI) is potentially harmful due to the generation of free radicals that cause tissue damage in vascular and other diseases. Studies in iron-replete and iron-deficient subjects, receiving a single oral test dose of Fe(II)SO₄ or NaFe(III)EDTA with water, revealed that FeSO₄ was well absorbed when compared with NaFeEDTA, while only the Fe(II) compound showed a remarkable increase of NTBI. As NaFeEDTA is successfully used for food fortification, a double-blind randomized cross-over trial was conducted in 11 healthy women with uncomplicated iron deficiency. All subjects received a placebo, 6.5 mg FeSO₄, 65 mg FeSO₄, 6.5 mg NaFeEDTA, and 65 mg NaFeEDTA with a traditional Indonesian breakfast in one-week intervals. Blood tests were carried out every 60 min for five hours. NTBI detection was performed using the fluorescein-labeled apotransferrin method. Plasma iron values were highly increased after 65 mg NaFeEDTA, twice as high as after FeSO₄. A similar pattern was seen for NTBI. After 6.5 mg of NaFeEDTA and FeSO₄, NTBI was hardly detectable. NaFeEDTA was highly effective for the treatment of iron deficiency if given with a meal, inhibiting the formation of nonabsorbable Fe-complexes, while NTBI did not exceed the range of normal values for iron-replete subjects.

Keywords: FeSO4; Indonesia; NaFeEDTA; developing countries; iron deficiency anemia; non-transferrin-bound iron (NTBI); nutrient iron; oral iron therapy.

Figure 1

Increase of serum iron (A) and serum NTBI (B) after 6.5 and 65 mg iron administered after a standard meal as Fe(II)SO₄ or as NaFe(III)EDTA.

Figure 2

Processing of absorbable iron by the duodenal mucosal cells. DMT1 = divalent metal transporter 1; DcytB = duodenal cytochrome B; HCP1 = hem carrier protein 1; HO1 = hem oxygenase-1; Cp = ceruloplasmin; Trf = transferrin.

Scheme 1

Iron supplement administration schedule and iron doses.

Scheme 2

Algorithm of the investigation.