Role of Dietary Flavonoids in Iron Homeostasis

Abstract

Balancing systemic iron levels within narrow limits is critical for human health, as both iron deficiency and overload lead to serious disorders. There are no known physiologically controlled pathways to eliminate iron from the body and therefore iron homeostasis is maintained by modifying dietary iron absorption. Several dietary factors, such as flavonoids, are known to greatly affect iron absorption. Recent evidence suggests that flavonoids can affect iron status by regulating expression and activity of proteins involved the systemic regulation of iron metabolism and iron absorption. We provide an overview of the links between different dietary flavonoids and iron homeostasis together with the mechanism of flavonoids effect on iron metabolism. In addition, we also discuss the clinical relevance of state-of-the-art knowledge regarding therapeutic potential that flavonoids may have for conditions that are low in iron such as anaemia or iron overload diseases.

Keywords: flavonoids; iron absorption; iron homeostasis; non-haem iron.

Figure 1

Distribution of body iron. The adult human body has approximately 4 g of iron, with more than half (>2 g) incorporated in the haemoglobin of developing erythroid precursors (300 mg) and mature circulating erytrocytes (1800 mg). The remaining body iron is found in a transit pool in reticulo-endothelial macrophages (600 mg) or stored in hepatocytes (1000 mg). A smaller part is present in muscles within myoglobin (300 mg), while only a minor amount is present in plasma bound to transferrins (Tfs,3 mg) or incorporated in other proteins and enzymes that include iron in their structures. Approximately, 10–20 mg of iron is daily consumed by diet, from which only 1–2 mg is absorbed. The same amount is lost every day by blood loss of different etiology, shedding of the skin and sloughed enterocytes.

Figure 2

Mechanism of non-haem and haem iron absorption in duodenal cells. Non-haem iron from food is firstly reduced by the ferric reductase Dcytb yielding Fe²⁺, which afterwards enters the enterocytes via divalent metal transporter 1 (DMT1). On the other hand, haem is absorbed via haem carrier protein 1 (HCP1), subsequently broken down by HO-1, after which free Fe²⁺ from haem joins a common cell iron pool with iron from the non-haem source. If body iron stores are high, iron may be stored in the cell complexed with ferritin as Fe³⁺ and eventually lost when the cell is discarded from the intestinal villus tip. Otherwise, iron efflux into the circulation via the iron efflux transporter ferroportin (FPN), subsequently being re-oxidised through hephaestin (Heph) to enable loading into Tf, after which it is transferred to peripheral tissues that require iron.

Figure 3

Structure of Phytate.

Figure 4

Structure of some classes of flavonoids.

Figure 5

Structures of complexes between Fe³⁺ and quercetin.