Effects of the pyrones, maltol and ethyl maltol, on iron absorption from the rat small intestine

Abstract

The pyrones, 3-hydroxy-2-methyl-4-pyrone (maltol) and 3-hydroxy-2-ethyl-4-pyrone (ethyl maltol) chelate iron with a high affinity and selectivity. The resulting 1:3 (metal-igand) complexes, being neutral, are able to partition readily across cell membranes and thus may facilitate iron transport across the intestinal wall. Absorption of radioactive iron (59Fe) in the presence of these pyrones was investigated in male rats 1, 2, 4 and 6 h after intraduodenal administration of a 7 μg dose and compared with that of 59Fe given as the sulphate, gluconate, fumarate or complexed to EDTA. Total body absorption and distribution were calculated from the 59Fe content of various tissue samples. With all the iron preparations used, blood levels of 59Fe were highest 1 h after injection whilst the 59Fe content at the major site of deposition, i.e. the bone marrow, increased up to 6 h. No 59Fe was found in the urine. Total body absorption of 59Fe was significantly higher from the pyrones than from the other four preparations. Over the dose range 0.7–700 μg, the proportion of 59Fe absorbed from both iron maltol and iron sulphate decreased with increasing dose. Enhanced 59Fe uptake from maltol was evident at 0.7–70 μg but not at 700 μg suggesting that use of these pyrones will not result in iron overload. Absorption of 59Fe given into the stomach was slower in onset but was sustained longer presumably via a steady delivery of iron to the duodenum from the gastric reservoir. The presence of excess maltol to maintain the integrity of the neutral 1:3 iron-maltol complex under a variety of physiological conditions did not appear critical in-vivo for effective iron absorption. There was no difference in 59Fe uptake between maltol, ethyl maltol or a mixture of ethyl maltol and maltol. 59Fe uptake was significantly enhanced in iron-deficient animals. Within 1 min of i.v. injection of iron complexed to maltol or ethyl maltol, 59Fe became associated with a plasma protein of molecular ratio similar to that of transferrin. With EDTA this process was much slower, i.e. up to 60 min. The half-life of 59Fe in the blood was similar whether administered as the maltol, ethyl maltol, sulphate or EDTA; at the 110 μg iron dose it was 133 ± 8 min and at 1 μg it was 74 ± 10 min in iron-replete animals and 44 ± 5 min in iron-deficient animals. The rate of absorption from the duodenum of 59Fe given as maltol, ethyl maltol or as iron sulphate increased with increasing dose but the shape of the absorption curve depended on the rate of movement of iron along the intestine. It is concluded that the pyrones, maltol and ethyl maltol, are able to enhance the initial stages of iron uptake from the intestinal lumen, possibly by holding the iron in a readily absorbable form, but do not influence subsequent iron distribution and so may provide safe and palatable alternatives to those iron preparations presently available for the treatment of iron deficiency.