A Review of Nutrients and Compounds, Which Promote or Inhibit Intestinal Iron Absorption: Making a Platform for Dietary Measures That Can Reduce Iron Uptake in Patients with Genetic Haemochromatosis

Abstract

Objective: To provide an overview of nutrients and compounds, which influence human intestinal iron absorption, thereby making a platform for elaboration of dietary recommendations that can reduce iron uptake in patients with genetic haemochromatosis.

Design: Review. Setting. A literature search in PubMed and Google Scholar of papers dealing with iron absorption.

Results: The most important promoters of iron absorption in foods are ascorbic acid, lactic acid (produced by fermentation), meat factors in animal meat, the presence of heme iron, and alcohol which stimulate iron uptake by inhibition of hepcidin expression. The most important inhibitors of iron uptake are phytic acid/phytates, polyphenols/tannins, proteins from soya beans, milk, eggs, and calcium. Oxalic acid/oxalate does not seem to influence iron uptake. Turmeric/curcumin may stimulate iron uptake through a decrease in hepcidin expression and inhibit uptake by complex formation with iron, but the net effect has not been clarified.

Conclusions: In haemochromatosis, iron absorption is enhanced due to a decreased expression of hepcidin. Dietary modifications that lower iron intake and decrease iron bioavailability may provide additional measures to reduce iron uptake from the foods. This could stimulate the patients' active cooperation in the treatment of their disorder and reduce the number of phlebotomies.

Figure 1

Mechanisms of intestinal iron absorption. Most iron is absorbed in the duodenum and proximal jejunum due to the acidic pH of the intestinal content. More, distally in the jejunum, pH becomes neutral or alkaline, and iron uptake declines. Nonheme food iron Fe³⁺ enters the nonheme iron pool and heme iron enters the heme iron pool. Fe³⁺ is reduced to Fe²⁺ by duodenal cytochrome B and subsequently enters the luminal side of the enterocyte by the iron importer DMT-1 pathway. Fe²⁺ is transferred to the basolateral side of the enterocyte, effluxed by the iron exporter ferroportin, and subsequently oxidized to Fe³⁺ by hephaestin and transferred to the carrier protein transferrin in the blood plasma. Part of the iron enters the intracellular ferritin iron pool and is lost by desquamation of the enterocyte into faeces. Hepcidin from the liver inactivates ferroportin, thereby inhibiting iron uptake. Heme iron is absorbed within the intact protoporphyrin ring by a separate pathway possibly involving a heme transporter and heme oxygenase. Figure adapted with permission from [27].