Iron supplement forms guide: ferrous sulfate vs bisglycinate vs heme iron

Iron deficiency anaemia is one of the few supplement contexts where the form on the label has been compared rigorously, repeatedly, and across populations from infants to pregnant women to gastric bypass patients. The summary across this literature is clear: ferrous sulfate is the cheap, well-absorbed, most-tested default, while ferrous bisglycinate is a gentler alternative with equivalent efficacy, and heme iron polypeptide and ferric maltol occupy specific niches.

Why iron supplementation is hard

The human body has no regulated route for iron excretion — uptake at the gut is the only control point, and it is tightly regulated by hepcidin. A 2015 stable-isotope study showed that doses above 60 mg elemental iron acutely raise serum hepcidin and reduce fractional iron absorption from a second dose taken hours later (PMID: 26289440).¹ The clinical implication is profound: alternate-day dosing of 60–120 mg elemental iron produces better total iron absorption than daily dosing, with markedly fewer gut side effects. A 2017 randomised trial confirmed this in iron-depleted women, finding alternate-day dosing matched daily dosing for haemoglobin recovery (PMID: 28825875).²

Ferrous sulfate: the workhorse

Ferrous sulfate is the form used in most clinical trials and the form on the WHO Essential Medicines List for iron deficiency anaemia. A 325 mg ferrous sulfate tablet provides 65 mg elemental iron, with bioavailability around 10–15% in iron-replete adults and up to 25% in iron-depleted adults. The downside is GI burden: a 2015 systematic review found a 32% pooled incidence of constipation, nausea, or epigastric pain with ferrous sulfate at standard daily dosing (PMID: 26418443).³ The 2024 NICE guideline on iron deficiency anaemia recommends starting at 65 mg elemental iron on alternate days specifically to reduce these effects (PMID: 38423657).⁴

Ferrous bisglycinate: gentler with comparable efficacy

Ferrous bisglycinate (also called iron bisglycinate or Ferrochel) is iron chelated to two glycine molecules, absorbed largely intact via amino acid transporters rather than via the divalent metal transporter. A 2019 randomised trial in pregnant women with iron-deficiency anaemia compared 25 mg bisglycinate with 50 mg ferrous sulfate for 12 weeks and found equivalent haemoglobin rise with significantly fewer adverse events in the bisglycinate group (PMID: 31256099).⁵ The 2021 systematic review of bisglycinate versus ferrous sulfate concluded that bisglycinate provides equivalent or superior absorption at half the elemental dose, with consistently better gut tolerability (PMID: 33419343).⁶

Heme iron polypeptide: niche but useful

Heme iron polypeptide is bovine-derived iron in its native heme form, absorbed via a separate intestinal transporter (HCP1) that is less responsive to hepcidin. A 2014 small comparative trial reported reduced GI side effects compared with ferrous sulfate, though absolute haemoglobin rise was smaller per mg of iron because of the lower elemental content (PMID: 25249224).⁷ Heme iron is useful for patients with severe ferrous sulfate intolerance but is more expensive and unsuitable for vegetarian patients.

Ferric maltol and the iron-deficient IBD population

Ferric maltol (Accrufer) is a stable ferric iron complex developed specifically for inflammatory bowel disease patients who cannot tolerate ferrous sulfate. A 2015 phase 3 trial in mild-to-moderate IBD with iron deficiency anaemia found ferric maltol 30 mg twice daily significantly raised haemoglobin with adverse event rates similar to placebo (PMID: 26342926).⁸ It is the most expensive of the oral options but has the cleanest tolerability profile in inflamed gut.

Practical dosing in 2026

For iron deficiency in an adult without unusual considerations, ferrous sulfate 65 mg elemental on alternate days is the cheapest evidence-based regimen. For pregnant women, vegetarians, or anyone with prior GI intolerance, ferrous bisglycinate at 25 mg elemental on alternate days achieves comparable haemoglobin recovery with notably better tolerability. Iron should be taken with vitamin C (or orange juice) to enhance absorption, and away from calcium, coffee, tea, and antacids, which all reduce absorption (PMID: 26945882).⁹ Iron levels and ferritin should be rechecked at 8–12 weeks. Anyone with unexplained iron deficiency should be evaluated for source — supplementation without diagnosis can mask a slow GI bleed.