Kate Street

Iron deficiency remains the most common nutritional deficiency worldwide, affecting approximately one in four people.1 While oral iron supplementation is often the first-line approach to restore iron levels, successful treatment depends on more than simply prescribing a higher dose.2 The form of iron selected can have a significant impact on absorption, bioavailability, tolerability, and ultimately, patient outcomes.3In recent years, our understanding of iron supplementation has evolved. <a href="https://www.blackmoresinstitute.org/articles/iron-deficiency-hepcidin-translating-evidence-into-clinical-practice">While factors such as hepcidin regulation are increasingly recognised as important determinants of iron absorption</a>,2 clinicians are also paying closer attention to the characteristics of different iron formulations.3 For many patients, selecting a highly bioavailable and well-tolerated iron form may improve both adherence and the likelihood of successful repletion.3<h3>
Why bioavailability matters</h3>When comparing iron supplements, it is important to distinguish between the amount of elemental iron contained in a product and the amount that is actually absorbed and utilised by the body.2 A higher elemental iron dose does not necessarily translate to a better clinical outcome if absorption is limited or adverse effects reduce compliance.2Iron absorption is influenced by several factors, including dietary inhibitors,4 gastrointestinal health, gastric acid production, inflammation,5 and the form of iron itself.3 Poorly absorbed iron remains unavailable for utilisation by the body and may contribute to adverse gastrointestinal effects that can impact adherence and treatment success.6This is where iron form becomes clinically relevant. A preparation that supports efficient absorption at a lower dose may reduce the amount of unabsorbed iron in the gastrointestinal tract, which may in turn support better tolerability and adherence.7<h3>
Comparing common oral iron forms</h3><table><thead><tr><th>Iron form</th><th>Relative bioavailability</th><th>GI tolerability</th><th>Cost</th></tr></thead><tbody><tr><td>Ferrous sulfate/fumarate</td><td>Moderate to high8</td><td>Low8</td><td>Low3</td></tr><tr><td>Ferrous gluconate</td><td>Moderate9</td><td>Moderate9</td><td>Low3</td></tr><tr><td>Iron bisglycinate</td><td>High3,10</td><td>High3,10</td><td>Moderate3</td></tr><tr><td>Liposomal iron</td><td>High3,4</td><td>High3,4</td><td>High3,4</td></tr><tr><td>Ferric polysaccharide complexes (iron polymaltose, polydextrose)</td><td>Low to moderate11,12</td><td>Moderate to high11,12</td><td>Moderate to high3</td></tr><tr><td>Sucrosomial iron</td><td>High3</td><td>High3</td><td>High3</td></tr></tbody></table><h3>
Choosing the right form: Balancing efficacy and tolerability</h3>Ferrous sulfate has long been one of the most commonly prescribed oral iron supplements due to its affordability and established efficacy. However, its clinical usefulness may be limited in patients by gastrointestinal adverse effects, particularly at higher doses.6 These tolerability concerns are partly driven by the relatively low proportion of iron that is absorbed following supplementation.6 The remainder stays within the gastrointestinal tract, contributing to symptoms such as constipation, nausea, abdominal discomfort, and diarrhoea.6 These adverse effects are a common reason for poor adherence to oral iron therapy,6 limiting therapeutic outcomes.Beyond gastrointestinal symptoms, excess unabsorbed iron may contribute to oxidative stress through the generation of reactive oxygen species via the Fenton reaction.13 This process has been associated with intestinal inflammation, altered gut barrier function, and disruption of the gut microbiota.13 As a result, there is increasing interest in iron forms such as iron bisglycinate that support efficient absorption while minimising exposure of the gastrointestinal tract to unabsorbed iron.
<hr /><h3>Iron bisglycinate</h3>Iron bisglycinate is a chelated form of iron in which iron is bound to two glycine molecules as ligands. This structure enhances absorption and reduces interactions with common dietary inhibitors to absorption such as phytates.4 Research suggests iron bisglycinate has higher bioavailability than traditional iron salts, resulting in superior haemoglobin and ferritin concentrations.14 In addition, clinical studies have reported fewer gastrointestinal adverse effects compared with conventional oral iron salts.14<hr /><h3>Supporting optimal iron absorption</h3>Regardless of the form selected, several practical strategies may help maximise iron absorption and improve clinical outcomes:<ul><li>Take iron away from foods and beverages rich in calcium, phytates, tannins, and polyphenols where possible to minimise interference with absorption.3</li><li>Consider co-administration with vitamin C to enhance absorption.3</li><li>Address factors that may impair iron uptake, including low gastric acid production and certain medications. <a href="https://www.blackmoresinstitute.org/depletions">Refer to the Drug-Nutrient Depletion Guide for further information.</a>3,5</li><li>If appropriate, encourage dietary sources of both haem and non-haem iron as part of a comprehensive management plan to support iron repletion and reduce the risk of future deficiency.4</li><li>Consider alternate-day dosing where clinically appropriate, as higher-dose iron supplementation (≥60 mg/day) increases hepcidin concentrations and reduces subsequent iron absorption.12</li></ul><h3>
Conclusion</h3>Effective iron repletion depends on more than dose alone. The form of iron selected can influence absorption, tolerability, adherence, and ultimately, treatment success. While ferrous sulfate remains a widely used option, more bioavailable forms such as iron bisglycinate may offer advantages for patients who experience intolerance or poor response to traditional iron salts. Combined with practical strategies to support absorption, informed formulation selection can help optimise iron repletion and patient outcomes.<h3>References</h3>1. Kolarš B, Mijatović Jovin V, Živanović N, Minaković I, Gvozdenović N, Dickov Kokeza I, et al. Iron deficiency and iron deficiency anemia: A comprehensive overview of established and emerging concepts. Pharmaceuticals (Basel). 2025;18(8):1104. doi:10.3390/ph180811042. Lo JO, Benson AE, Martens KL, Hedges MA, McMurry HS, DeLoughery T, et al. The role of oral iron in the treatment of adults with iron deficiency. Eur J Haematol. 2023;110(2):123–30. doi:10.1111/ejh.138923. Pantopoulos K. Oral iron supplementation: new formulations, old questions. Haematologica. 2024;109(9):2790–801. doi:10.3324/haematol.2024.2849674. Piskin E, Cianciosi D, Gulec S, Tomas M, Capanoglu E. Iron absorption: Factors, limitations, and improvement methods. ACS Omega. 2022;7(24):20441–56. doi:10.1021/acsomega.2c018335. Stein J, Connor S, Virgin G, Ong DEH, Pereyra L. Anemia and iron deficiency in gastrointestinal and liver conditions. World J Gastroenterol. 2016;22(35):7908–25. doi:10.3748/wjg.v22.i35.79086. McKay AK, Broome S, Tee N, Yim KL, Sim M, Peeling P, et al. Oral ferrous sulphate supplementation has greater efficacy, but lower tolerance than iron (III)-hydroxide polymaltose complexes in exercising women with low iron stores. Clin Nutr. 2026;58:106594. doi:10.1016/j.clnu.2026.1065947. Rout SR, Pradhan D, Haldar J, Rajwar TK, Dash P, Dash C, et al. Recent advances in the formulation strategy to improve iron bioavailability: A review. J Drug Deliv Sci Technol. 2024;95:105633. Available from: https://linkinghub.elsevier.com/retrieve/pii/S17732247240030228. Zhao X, Zhang X, Xu T, Luo J, Luo Y, An P. Comparative effects between oral lactoferrin and ferrous sulfate supplementation on iron-deficiency anemia: A comprehensive review and meta-analysis of clinical trials. Nutrients. 2022;14(3):543.9. Falahati V, Ghasemi A, Ghaffari K, Eghbali A, Khodabakhshi S, Almasi-Hashiani A, et al. Comparison of the effect of ferrous sulfate and ferrous gluconate on prophylaxis of iron deficiency in toddlers 6–24 months old: A randomized clinical trial. J Educ Health Promot. 2022;11(1):368.10. Hsu CY, Chen JC, Tsai YC, Chen TW. Low-dose ferrous bisglycinate chelate supplementation in chronic kidney disease and hemodialysis patients. J Chin Med Assoc. 2022;85(5):566–70.11. Name JJ, Vasconcelos AR, Valzachi Rocha Maluf MC. Iron bisglycinate chelate and polymaltose iron for the treatment of iron deficiency anemia: A pilot randomized trial. Curr Pediatr Rev. 2018;14(4):261–8.12. Stoffel NU, Von Siebenthal HK, Moretti D, Zimmermann MB. Oral iron supplementation in iron-deficient women: How much and how often? Mol Aspects Med. 2020;75:100865.13. Bloor SR, Schutte R, Hobson AR. Oral iron supplementation: Gastrointestinal side effects and the impact on the gut microbiota. Microbiol Res. 2021;12(2):491–502.14. Fischer JAJ, Cherian AM, Bone JN, Karakochuk CD. The effects of oral ferrous bisglycinate supplementation on hemoglobin and ferritin concentrations in adults and children: A systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2023;81(8):904–20. doi:10.1093/nutrit/nuac106

<h3>Key highlights
</h3><ul><li>Iron supplementation is not simply a question of dose. The amount absorbed and utilised is more clinically relevant than the amount contained in a product.</li><li>Poorly absorbed iron may remain in the intestinal lumen, where it can contribute to gastrointestinal discomfort, oxidative stress, and changes to the gut microbiota.</li><li>Ferrous sulfate remains widely used, despite tolerability concerns potentially limiting adherence in some patients.</li><li>Iron bisglycinate (ferrous bisglycinate) is a chelated iron form that may support absorption and reduce interactions with dietary inhibitors such as phytates.</li><li>Practical strategies such as considering dose timing, dietary inhibitors, vitamin C co-administration, and alternate-day dosing may help optimise iron absorption.</li></ul>

Key highlights

Recommended for you

Supporting urinary tract health

Spore-forming probiotics | Probiotics that go the distance

Psychoneuroimmunology | Connecting the mind, brain, gut, and immune system

Siberian ginseng for mental focus