Iron supplementation in women: impact of frequency on efficacy and tolerability

IRON METABOLISM AND DEFICIENCY

Iron deficiency is a common condition affecting an estimated 11.1% of UK women aged 15–49 years.¹ First-line treatment is generally oral (PO) supplementation, which is also known to cause gastrointestinal (GI) side effects in up to 70% of patients.²

Oral iron compounds contain iron in either ferrous or ferric forms.³ Ferrous iron (Fe2+) is readily absorbed in the duodenum whereas ferric iron (Fe3+) must be reduced to Fe2+ prior to absorption.^3–5 Ferrous salts are iron compounds that include the common preparations ferrous fumarate (C₄H₂FeO₄) (organic) and synthetic ferrous sulphate (FeO₄S) (inorganic). Ferrous salts have comparable bioavailability and side effect profiles but contain variable amounts of elemental iron.^3,5 Both preparations are effective iron supplements. After absorption, iron is transported into enterocyte cytoplasm by divalent metal transporter DMT1.^4,6 This is then stored as ferritin or exported into circulation by ferroportin, where it is bound by transferrin allowing for systemic transport.^4,6 Once iron has entered the blood stream there is no active excretion process and therefore iron absorption is carefully regulated.^4,6

Hepcidin is the main regulator of iron homeostasis^5,7 and high serum hepcidin (sHep) levels reduce bioavailability of PO iron.^6,7 Hepcidin binds to ferroportin receptors on cell surfaces, blocking their effect by endocytosis and degradation.^6–8 Decreased ferroportin function then leaves iron unabsorbed in the GI tract, which may cause inflammation and changes to the gut microbiome, resulting in common GI side effects such as nausea, constipation, diarrhoea, and epigastric pain.^{2,5 …}