How do different iron forms compare?

Oral iron replacement therapy is typically the first-line treatment for IDA. Iron is available in different forms (e.g., tablets, liquid) and compounds (e.g., ferrous sulfate, ferrous fumarate, ferrous bisglycinate, etc.), each of which provides different amounts of elemental iron.^[1]

Here are some of the most common forms of iron found in supplements:

Formulations containing ferrous iron (Fe²⁺) are more bioavailable, but they are also more likely to cause side effects. In contrast, ferric iron (Fe³⁺) preparations are usually better-tolerated but not as effective.^[2]

Ferrous bisglycinate is another popular iron form found in supplements, wherein iron is chelated to two glycine molecules. Ferrous bisglycinate is marketed as more bioavailable than the other iron salts, and as having fewer gastrointestinal side effects. Furthermore, due to its stable chemical structure, ferrous bisglycinate is less affected by common iron absorption inhibitors (e.g., phytates found in cereals). However, although results from a meta-analysis showed that while iron bisglycinate was more effective than other iron salts in increasing hemoglobin levels in pregnant women, in children its effectiveness was comparable to other iron preparations.^[3]

Heme iron polypeptide (HIP) is another form of iron. It is commonly produced from swine or bovine blood using enzymatic hydrolysis, in which heme iron is bound to peptides derived from the digested hemoglobin.^[4] This form of iron has increased in popularity due to claims that it has enhanced bioavailability and fewer gastrointestinal side effects than other iron compounds. One study showed that when compared to ferrous fumarate, HIP taken with meals significantly increased iron absorption, but was not associated with side effects.^[5] However, larger studies should be conducted to compare its efficacy and safety to other iron preparations.

When iron is administered intravenously, IV ferric carboxymaltose and IV iron sucrose appear to be the most effective forms at increasing hemoglobin and ferritin levels within a period of four weeks.^[6]

Finally, one in vitro study compared modified-release iron supplements to immediate-release formulations and found that the slow-release tablets did not completely dissolve even after 24 hours, and iron uptake was considerably lower compared to regular tablets.^[7] Although modified-release iron preparations may be better tolerated, with fewer side effects, they may not be as effective. These findings need further clarification through in vivo clinical studies.