Blackmores Institute

Iron deficiency is the most prevalent micronutrient deficiency worldwide,1 affecting nearly one-third of the population.2 It is also the most common cause of anaemia,3 with iron deficiency anaemia (IDA) affecting 30% of the population.4Through its roles in oxygen delivery, electron transport, and enzymatic activity, iron is essential for the functioning of all cells.5 Playing a key role in immune function,6 mood,7 thyroid function,8 energy production, and cardiovascular health,9 iron depletion can result in a range of pathophysiological effects, including increased cardiac disease risk, immune dysregulation, hair loss, and developmental delays.10<h3>
 Iron regulation and homeostasis</h3>Iron balance in the body is primarily regulated through dietary intake, intestinal absorption, and iron recycling.4 Central to this process is hepcidin, a liver-derived peptide hormone widely recognised as the master regulator of systemic iron homeostasis.11,12Hepcidin controls plasma iron levels by binding to and degrading ferroportin, an iron transporter located on intestinal cells and macrophages.13 This action reduces both the absorption of dietary iron and the release of stored iron into circulation.12 Importantly, iron absorption is inversely related to the body’s iron stores - when stores are high, hepcidin production increases to reduce absorption; when stores are low, hepcidin decreases to enhance iron uptake.13 However, hepcidin levels are also influenced by factors beyond iron status, such as inflammation,13 infection,14 intense physical activity,15 and psychological stress,16 with increases in these states contributing to reduced serum iron by decreasing iron absorption and utilisation. Interestingly, hepcidin appears to follow a diurnal rhythm, peaking during the day and declining at night.17<h3>
 How to recognise an iron deficiency</h3>Iron deficiency progresses from low iron stores to iron-deficiency anaemia.2 While iron deficiency refers to a decrease in the amount of iron stored in the body, anaemia refers to a drop in the number of red blood cells (RBCs) and/or the amount of haemoglobin within the RBCs.2 It typically takes several weeks after iron stores are depleted for the level of haemoglobin and production of RBCs to be affected and for anaemia to develop.2Prevalence of symptoms can vary depending on age, comorbidities, severity, and rate of development of iron deficiency.18 Individuals may be asymptomatic, or experience fatigue, irritability, depression, difficulty concentrating, restless legs syndrome, pica (cravings for specific substances such as liquorice, ice, dirt, or clay), shortness of breath, dizziness, and worsening heart failure.18<h3>
 Risk factors for iron deficiency</h3>Certain groups are at an increased risk of iron deficiency due to higher physiological demands, increased losses, or reduced intake and absorption (See Table 1). Recognising and addressing these factors is key to managing iron status effectively.<h4>Table 1. Identifying vulnerable populations and risk factors associated with iron deficiency</h4><table> <tr><th>Increased risk of iron deficiency</th><td> <ul><li>Women of reproductive age2</li><li>Elderly19</li><li>Vegans and vegetarians19</li><li>Athletes20</li></ul> </td></tr> <tr><th>Risk factors for iron deficiency that may impair iron absorption and metabolism</th><td> <ul><li>Gastrointestinal bleeding2</li><li>Menorrhagia2</li><li>Chronic inflammation12</li><li>Infections (e.g., Helicobacter pylori)19</li><li><a href="~/link.aspx?_id=BB4730406FA24296AF335F78312FB943&_z=z">Medications (e.g., antacids, proton pump inhibitors)</a>21</li></ul> </td></tr> </table><h3>
 A holistic approach to correcting an iron deficiency</h3>Correcting an iron deficiency requires a considered, individualised approach. Key recommendations include:<ul><li>Prioritise haem-iron rich sources: Found in a variety of animal foods including lean red meat, liver, poultry, and seafood, haem iron is more efficiently absorbed than non-haem forms.4</li><li>Combine non-haem iron with vitamin C: Found in a variety of plants such as legumes, fruit, and vegetables. Non-haem iron is less bioavailable, however absorption improves when paired with vitamin C.4</li><li>Avoid tannin-rich drinks with meals: Tea, coffee, and some herbal infusions contain tannins and polyphenols that hinder non-haem iron absorption.4</li><li>Test prior to supplementation: Pathology testing is recommended to confirm deficiency and guide treatment, as excess free iron can drive oxidative stress and tissue damage.22</li><li>Use alternate day dosing: Iron supplementation has been shown to induce an increase in serum hepcidin that persists for 24 hours. Therefore, it is recommended to dose iron supplements every other day to improve absorption by allowing hepcidin levels to drop between doses.23</li><li>Take supplements in the morning or evening: To align with the natural diurnal drop in hepcidin levels and support better absorption.23</li><li>Avoid taking iron immediately after exercise: Physical activity temporarily raises hepcidin, reducing iron absorption post-workout.15</li><li>Address gut health, infections, inflammation, and nutrient cofactors: Factors like dysbiosis,24 infections,19 chronic inflammation,19 and low vitamin A can impair iron absorption and utilisation.25</li></ul><h3>
 Conclusion</h3>Iron is an indispensable trace element, essential for numerous biological functions. Given iron’s critical role and the risks associated with both deficiency and overload, understanding the regulatory mechanisms of iron homeostasis is fundamental to optimising patient care. Through targeted nutritional strategies, appropriate pathology testing, and considered supplementation, healthcare practitioners can help support iron balance, enhancing overall health. <h3> References </h3><ol><li>Zhang GD, Johnstone D, Leahy MF, Olynyk JK. Updating the diagnosis and management of iron deficiency in the era of routine ferritin testing of blood donors by Australian Red Cross Lifeblood. The Medical Journal of Australia. 2024 Sep 3.</li><li>Elstrott B, Khan L, Olson S, Raghunathan V, DeLoughery T, Shatzel JJ. The role of iron repletion in adult iron deficiency anemia and other diseases. European Journal of Haematology. 2020 Dec 26;104(3). Available from: https://onlinelibrary.wiley.com/doi/full/10.1111/ejh.13345</li><li>World Health Organization. Anaemia. World Health Organization. 2025. Available from: https://www.who.int/news-room/fact-sheets/detail/anaemia</li><li>Kumar A, Sharma E, Marley A, Samaan MA, Brookes MJ. Iron deficiency anaemia: Pathophysiology, assessment, practical management. BMJ Open Gastroenterology. 2022 Jan 7;9(1):1–9. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8744124/</li><li>Georgieff MK. Iron Deficiency in Pregnancy. American Journal of Obstetrics and Gynecology. 2020 Mar;223(4):516–24.</li><li>Fady Moustarah, Daley SF. Dietary Iron. Nih.gov. StatPearls Publishing; 2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK540969</li><li>Berthou C, Iliou JP, Barba D. Iron, neuro‐bioavailability and depression. eJHaem. 2021 Dec 5;3(1):263–75.</li><li>Garofalo V, Condorelli RA, Cannarella R, Aversa A, Calogero AE, La Vignera S. Relationship between Iron Deficiency and Thyroid Function: A Systematic Review and Meta-Analysis. Nutrients. 2023 Nov 15;15(22):4790. Available from: https://pubmed.ncbi.nlm.nih.gov/38004184/</li><li>Sawicki KT, De Jesus A, Ardehali H. Iron Metabolism in Cardiovascular Disease: Physiology, Mechanisms, and Therapeutic Targets. Circulation Research. 2023 Feb 3;132(3):379–96.</li><li>Teh MR, Armitage AE, Drakesmith H. Why cells need iron: a compendium of iron utilisation. Trends in Endocrinology and Metabolism. 2024 May 1; Available from: https://www.sciencedirect.com/science/article/pii/S1043276024001097</li><li>Pagani A, Nai A, Silvestri L, Camaschella C. Hepcidin and Anemia: A Tight Relationship. Frontiers in Physiology. 2019 Oct 9;10. Available from: https://www.frontiersin.org/articles/10.3389/fphys.2019.01294/full</li><li>Chambers K, Ashraf MA, Sharma S. Physiology, Hepcidin. Nih.gov. StatPearls Publishing; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK538257</li><li>Kesharwani P, Dash D, Koiri RK. Deciphering the role of hepcidin in iron metabolism and anemia management. Journal of Trace Elements in Medicine and Biology. 2025 Jan 8;127591. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0946672X25000045</li><li>Nemeth E, Ganz T. Hepcidin and Iron in Health and Disease. Annual Review of Medicine. 2023 Jan 27;74(1):261–77.</li><li>Larsuphrom P, Latunde-Dada GO. Association of Serum Hepcidin Levels with Aerobic and Resistance Exercise: A Systematic Review. Nutrients. 2021 Jan 27;13(2):393.</li><li>Reid BM, Georgieff M. The Interaction between Psychological Stress and Iron Status on Early-Life Neurodevelopmental Outcomes. Nutrients. 2023 Aug 30 [cited 2023 Dec 13];15(17):3798–8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10490173/</li><li>Attwell C, McKay A, Sim M, Dugan C, Nicholas J, Hopper L, et al. Timing is everything, but does it really matter? Impact of 8-weeks morning versus evening iron supplementation in ballet and contemporary dancers. European Journal of Sport Science. 2023 Jul 10;23(12):2275–82.</li><li>Auerbach M, DeLoughery TG, Tirnauer JS. Iron Deficiency in Adults. JAMA. 2025 Mar 30.</li><li>Khan MI, Shah J, Ullah M, Rasheed H, Khan S, Yousaf MS, et al. Prevalence of Iron Deficiency Among Patients With Helicobacter pylori Infection at a Tertiary Care Hospital. Cureus. 2024 Aug 30;</li><li>Nebl J, Schuchardt JP, Ströhle A, Wasserfurth P, Haufe S, Eigendorf J, et al. Micronutrient Status of Recreational Runners with Vegetarian or Non-Vegetarian Dietary Patterns. Nutrients. 2019 May 22;11(5):1146. Available from: https://www.mdpi.com/2072-6643/11/5/1146</li><li>Blackmores Institute. Complementary Medicines Interactions Guide - Iron. 2025 [cited 2025 May 5]. Available from: https://www.blackmoresinstitute.org/interactions/iron</li><li>Ru Q, Li Y, Chen L, Wu Y, Min J, Wang F. Iron homeostasis and ferroptosis in human diseases: mechanisms and therapeutic prospects. Signal Transduction and Targeted Therapy. 2024 Oct 14;9(1). Available from: https://pubmed.ncbi.nlm.nih.gov/39396974/</li><li>Stoffel NU, Zeder C, Brittenham GM, Moretti D, Zimmermann MB. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2019 Aug 14;105(5):1232–9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193469/</li><li>Coll E, Cigarran S, Portolés J, Cases A. Gut Dysbiosis and Its Role in the Anemia of Chronic Kidney Disease. Toxins. 2024 Nov 17;16(11):495.</li><li>Mejia LA, Erdman JW. Impact of Vitamin A Deficiency on Iron Metabolism and Anemia: A Historical Perspective and Research Advances. Nutrition Reviews. 2024 Dec 12; Available from: https://doi.org/10.1093/nutrit/nuae183</li></ol>

<h3>Key highlights:</h3><ul><li>Iron deficiency is the most common micronutrient deficiency worldwide.</li><li>Hepcidin is the master hormone regulating iron — when it rises, iron absorption drops, and when it falls, absorption improves.</li><li>Hepcidin levels increase with inflammation, infection, stress, and intense exercise, reducing iron absorption and utilisation. It also appears to follow a daily rhythm, peaking during the day and dropping at night.</li><li>Common symptoms of iron deficiency include fatigue, low mood, brain fog, restless legs, cravings for specific substances like ice or dirt, shortness of breath, and dizziness.</li><li>Always check iron levels with a pathology test before supplementing. If needed, take supplements in the morning or evening on alternate days for better absorption.</li><li>Boost dietary iron intake and address gut health, inflammation, and infections to help restore healthy iron levels.</li></ul>Read on to learn how to confidently recommend iron supplementation in practice.

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