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Iron Supplements for Anemia: Restoring Iron Levels and Vitality

Iron Supplements for Anemia: Restoring Iron Levels and Vitality

Introduction

Iron deficiency anaemia is a prevalent nutritional disorder affecting a significant portion of the global population, particularly women, children, and individuals with certain health conditions (Levi et al., 2016). Iron supplements for anemia are the primary treatment for this condition, aiming to replenish iron stores and stimulate erythropoiesis, the production of red blood cells (Brittenham, 2013). Iron is an essential mineral that plays a crucial role in the formation of haemoglobin, a protein in red blood cells that carries oxygen throughout the body. When iron levels are insufficient, the body struggles to produce enough healthy red blood cells, leading to anaemia and its associated symptoms, such as fatigue, weakness, and shortness of breath.

The importance of iron supplements in treating iron deficiency anaemia cannot be overstated. By restoring iron levels, these supplements enable the body to produce more red blood cells, thereby improving oxygen delivery to tissues and organs. This article will delve into the various types of iron supplements available, their dosage and administration, efficacy and safety, and special considerations for specific populations. We will also discuss the importance of monitoring and follow-up during iron supplementation to ensure optimal outcomes and patient well-being.

Types of Iron Supplements

Oral Iron Supplements

Oral iron supplements are the most common and readily available form of iron supplementation for treating iron deficiency anaemia. The most frequently used oral iron formulations include ferrous sulfate, ferrous gluconate, ferrous fumarate, and ferric citrate (Fishbane et al., 2017; Gasche et al., 2015). These supplements vary in their elemental iron content, which refers to the amount of iron available for absorption by the body.

Ferrous sulfate is the most widely used oral iron supplement due to its high elemental iron content and low cost (Brittenham, 2013). It is available in various forms, such as tablets, capsules, and liquid solutions. Ferrous gluconate and ferrous fumarate are also effective oral iron supplements, although they have slightly lower elemental iron content compared to ferrous sulfate (Brittenham, 2013).

Ferric citrate, a newer oral iron formulation, has been shown to be effective in treating iron deficiency anaemia in patients with chronic kidney disease (Fishbane et al., 2017). This formulation has the added benefit of acting as a phosphate binder, which is particularly useful in managing hyperphosphatemia in patients with chronic kidney disease (Fishbane et al., 2017).

In 2019, the U.S. Food and Drug Administration (FDA) approved a novel oral iron supplement called ferric maltol (Accrufer) for the treatment of iron deficiency anaemia in adults (Accrufer Prescribing Information, 2019). Ferric maltol has demonstrated efficacy in improving haemoglobin levels and replenishing iron stores in patients with inflammatory bowel disease (Gasche et al., 2015).

Intravenous (IV) Iron Supplements

Intravenous (IV) iron supplements are used when oral iron supplementation is ineffective, poorly tolerated, or contraindicated. IV iron is particularly beneficial for patients with chronic conditions, such as chronic kidney disease, inflammatory bowel disease, and heart failure, where iron deficiency anaemia is common and oral iron may not be sufficient (Onken et al., 2014; Ponikowski et al., 2015; Vadhan-Raj et al., 2014).

Several IV iron formulations are available, including ferric carboxymaltose (Injectafer), ferumoxytol (Feraheme), ferric derisomaltose (Monoferric), and iron sucrose (Venofer) (Wolf et al., 2021). These formulations differ in their dosing regimens, administration times, and safety profiles.

Ferric carboxymaltose and ferric derisomaltose are newer IV iron formulations that allow for higher doses of iron to be administered in a single session, reducing the number of infusions required (Wolf et al., 2021). Ferumoxytol is a unique IV iron formulation that can be administered as a rapid injection, making it a convenient option for patients who require quick iron repletion (Vadhan-Raj et al., 2014).

IV iron supplementation has been shown to be more effective than oral iron in rapidly increasing haemoglobin levels and replenishing iron stores in patients with iron deficiency anaemia (Onken et al., 2014; Ponikowski et al., 2015). However, IV iron also carries a higher risk of adverse reactions, such as infusion reactions and anaphylaxis, which requires close monitoring and management (Kalra & Bhandari, 2016).

Dosage and Administration

The recommended dietary allowance (RDA) for iron varies by age, sex, and pregnancy status (National Institutes of Health, 2021). For adult men and postmenopausal women, the RDA is 8 mg/day, while for premenopausal women, it is 18 mg/day (National Institutes of Health, 2021). Pregnant women require a higher iron intake, with an RDA of 27 mg/day (National Institutes of Health, 2021).

Oral iron supplements typically contain between 60 and 325 mg of elemental iron per dose (Moretti et al., 2015; Stoffel et al., 2017). However, lower doses of oral iron have been shown to be equally effective in treating iron deficiency anaemia while causing fewer gastrointestinal side effects (Moretti et al., 2015; Stoffel et al., 2017). A study by Moretti et al. (2015) found that a daily dose of 60 mg of elemental iron was as effective as higher doses in improving haemoglobin levels and iron stores in iron-depleted women.

Alternate-day dosing of oral iron supplements has been proposed as a strategy to improve iron absorption and reduce gastrointestinal side effects. Stoffel et al. (2020) demonstrated that alternate-day dosing of oral iron resulted in higher iron absorption compared to daily dosing in iron-deficient anaemic women. This finding suggests that alternate-day dosing may be a more efficient approach to oral iron supplementation.

IV iron dosing depends on the specific formulation used and the patient’s body weight and iron deficit. For example, ferric carboxymaltose can be administered as a single dose of up to 1,000 mg of iron, while iron sucrose requires multiple smaller doses of 200-300 mg of iron (Wolf et al., 2021). The dosing regimen for IV iron should be individualised based on the patient’s clinical condition and response to treatment.

Efficacy and Safety

Oral and IV iron supplements have been shown to be effective in treating iron deficiency anaemia, but their efficacy and safety profiles differ. A meta-analysis by Okam et al. (2016) compared the efficacy of oral and IV iron in treating iron deficiency anaemia and found that IV iron resulted in a more rapid and pronounced increase in haemoglobin levels compared to oral iron. However, the authors noted that the long-term efficacy of oral and IV iron was similar (Okam et al., 2016).

The CONFIRM-HF trial, a large randomised controlled study, demonstrated the efficacy and safety of long-term IV iron therapy with ferric carboxymaltose in patients with heart failure and iron deficiency (Ponikowski et al., 2015). The study showed that ferric carboxymaltose significantly improved functional capacity, quality of life, and reduced the risk of hospitalisation in these patients (Ponikowski et al., 2015).

While oral iron supplements are generally well-tolerated, they can cause gastrointestinal side effects, such as nausea, vomiting, diarrhoea, and constipation (Kalra & Bhandari, 2016). These side effects can lead to non-compliance and inadequate iron absorption. IV iron, on the other hand, bypasses the gastrointestinal tract and is associated with fewer gastrointestinal side effects (Kalra & Bhandari, 2016).

However, IV iron carries a risk of infusion reactions, which can range from mild symptoms, such as itching and flushing, to severe anaphylactic reactions (Kalra & Bhandari, 2016). The risk of infusion reactions varies among different IV iron formulations, with ferric derisomaltose and iron sucrose having a lower risk compared to ferric carboxymaltose and ferumoxytol (Wolf et al., 2021).

A study by Koutroubakis et al. (2010) evaluated the safety and efficacy of total-dose infusion of low molecular weight iron dextran for iron deficiency anaemia in patients with inflammatory bowel disease. The authors found that this approach was safe and effective in correcting anaemia and replenishing iron stores in these patients (Koutroubakis et al., 2010).

Special Populations

Pregnancy

Iron deficiency anaemia is common during pregnancy due to the increased iron demands of the growing fetus and placenta. Maternal iron deficiency anaemia is associated with adverse pregnancy outcomes, such as low birth weight, preterm delivery, and increased risk of maternal and neonatal mortality (Breymann et al., 2017).

The Centers for Disease Control and Prevention (CDC) recommends that all pregnant women receive a daily oral iron supplement of 30-60 mg of elemental iron to prevent iron deficiency anaemia (Breymann et al., 2017). For pregnant women diagnosed with iron deficiency anaemia, higher doses of oral iron or IV iron may be necessary to correct the anaemia and replenish iron stores (Breymann et al., 2017).

A study by Breymann et al. (2017) compared the efficacy and safety of IV ferric carboxymaltose with oral ferrous sulfate in pregnant women with iron deficiency anaemia. The authors found that ferric carboxymaltose was more effective than oral iron in improving haemoglobin levels and iron stores, with a better tolerability profile (Breymann et al., 2017).

Chronic Kidney Disease (CKD)

Iron deficiency is a common complication of chronic kidney disease (CKD) and contributes to the development of anaemia in this population. The prevalence of iron deficiency in CKD patients ranges from 24% to 85%, depending on the stage of CKD and the diagnostic criteria used (Fishbane et al., 2017).

Both oral and IV iron supplements are used to manage iron deficiency anaemia in CKD patients. However, the efficacy of oral iron may be limited in this population due to impaired iron absorption, increased hepcidin levels, and the presence of inflammation (Fishbane et al., 2017).

IV iron has been shown to be more effective than oral iron in treating iron deficiency anaemia in CKD patients (Kalra & Bhandari, 2016). A study by Fishbane et al. (2017) demonstrated that ferric citrate, an oral iron supplement, was effective in improving haemoglobin levels and iron stores in patients with non-dialysis-dependent CKD and iron deficiency anaemia.

Inflammatory Bowel Disease (IBD)

Iron deficiency anaemia is a common extraintestinal manifestation of inflammatory bowel disease (IBD), affecting up to 70% of patients with IBD (Gasche et al., 2015). The pathogenesis of iron deficiency anaemia in IBD is multifactorial and includes chronic blood loss, impaired iron absorption, and the presence of inflammation (Gasche et al., 2015).

IV iron is the preferred route of iron supplementation in IBD patients due to its better tolerance and efficacy compared to oral iron (Gasche et al., 2015; Koutroubakis et al., 2010). Oral iron may exacerbate gastrointestinal symptoms and increase inflammation in IBD patients (Gasche et al., 2015).

A phase-3 clinical trial program by Gasche et al. (2015) evaluated the efficacy and safety of ferric maltol in correcting iron deficiency anaemia in patients with IBD. The authors found that ferric maltol was effective in improving haemoglobin levels and iron stores, with a favourable safety profile (Gasche et al., 2015).

Monitoring and Follow-up

Monitoring response to iron supplementation is crucial to ensure the effectiveness of treatment and to detect any adverse reactions. Haemoglobin, ferritin, and transferrin saturation are the key parameters used to assess iron status and response to iron therapy (Okam et al., 2016; Ponikowski et al., 2015).

Haemoglobin levels should be monitored periodically during iron supplementation to evaluate the improvement in anaemia. Ferritin, a marker of iron stores, and transferrin saturation, an indicator of iron availability for erythropoiesis, should also be measured to assess the adequacy of iron supplementation (Okam et al., 2016; Ponikowski et al., 2015).

Treatment should be adjusted based on the patient’s response to iron supplementation. If the patient does not respond adequately to oral iron, a switch to IV iron may be necessary. Similarly, if the patient experiences adverse reactions to a particular iron formulation, an alternative formulation should be considered (Okam et al., 2016; Ponikowski et al., 2015).

In addition to monitoring response to iron supplementation, it is essential to evaluate and address the underlying causes of iron deficiency anaemia. This may include investigating sources of blood loss, such as gastrointestinal bleeding or heavy menstrual bleeding, and assessing for malabsorption disorders (Ko et al., 2020).

The American Gastroenterological Association (AGA) recently published clinical practice guidelines on the gastrointestinal evaluation of iron deficiency anaemia (Ko et al., 2020). The guidelines recommend that adult patients with iron deficiency anaemia undergo upper and lower gastrointestinal endoscopy to evaluate for potential sources of blood loss and malabsorption (Ko et al., 2020).

Conclusion

Iron supplements play a vital role in treating iron deficiency anaemia, a prevalent nutritional disorder that affects a significant portion of the global population. By replenishing iron stores and stimulating erythropoiesis, these supplements enable the body to produce more healthy red blood cells, thereby improving oxygen delivery to tissues and organs. The various oral and intravenous iron formulations available offer healthcare professionals and patients a range of options to suit individual needs and preferences.

Tailoring the dosage, route of administration, and monitoring to the patient’s specific requirements and underlying conditions is essential for optimal outcomes. Factors such as age, sex, pregnancy status, and the presence of chronic diseases like chronic kidney disease and inflammatory bowel disease should be considered when selecting the most appropriate iron supplement and dosing regimen. Regular monitoring of haemoglobin, ferritin, and transferrin saturation levels is crucial to assess the response to treatment and make necessary adjustments.

Effective management of iron deficiency anaemia requires collaboration among healthcare professionals, including primary care physicians, haematologists, gastroenterologists, and obstetricians. A comprehensive approach that includes proper diagnosis, treatment, and follow-up is essential to ensure the best possible outcomes for patients. By addressing the underlying causes of iron deficiency, such as blood loss or malabsorption, and providing appropriate iron supplementation, healthcare professionals can help patients restore their iron levels, alleviate anaemia symptoms, and improve their overall quality of life.

Key Highlights and Actionable Tips

  • Iron supplementation is indicated for iron-deficient states secondary to conditions such as iron deficiency anemia, nutritional deficiency, malabsorption, chronic inflammatory state, blood loss, or an increased need for iron in the body.
  • Iron supplementation can be administered orally or intravenously. Oral iron supplements are associated with more gastrointestinal side effects compared to IV iron or placebo.
  • Patients with iron overload states such as hereditary hemochromatosis, hemosiderosis, or a history of hemolytic anemia should not receive iron supplementation.
  • Monitoring iron levels through labwork is crucial. Patients receiving oral iron should return for repeat bloodwork to monitor tolerability and effectiveness. Those receiving IV iron should have normal levels within six weeks of therapy.
  • Iron toxicity can manifest with cardiovascular, metabolic, central nervous, and hepatic instability and damage. Accidental iron ingestion in children under 6 has been a leading cause of fatal poisoning.

What are the common symptoms of iron deficiency?

Common symptoms of iron deficiency include fatigue, weakness, shortness of breath, pica (craving and chewing substances with no nutritional value), pagophagia (craving and chewing ice), tachycardia, altered mental status, hypothermia, and an increased risk of infection. These symptoms occur due to decreased production of hemoglobin and circulating erythrocytes in the body resulting from depleted iron stores.

Who is at higher risk of developing iron deficiency?

Certain populations are at a higher risk of developing iron deficiency:

  1. Women of childbearing age due to monthly menstrual blood loss and increased iron requirements during pregnancy.
  2. The elderly, who are more likely to have iron-poor diets and indolent gastrointestinal blood loss from gastritis or underlying malignancy.
  3. Patients with chronic kidney disease or on hemodialysis, as they often have iron deficiency and cannot stimulate their kidneys to produce erythropoietin, further exacerbating the anemia.
  4. People with malabsorptive states such as Whipple disease, small intestinal bacterial overgrowth (SIBO), celiac disease, and pernicious anemia, as they cannot effectively absorb the iron in their diets.

What should be done if a patient does not respond adequately to oral iron supplementation?

If a patient has an inadequate response to oral iron therapy, healthcare professionals should investigate the reasons behind it. Possible causes include non-compliance, reduced absorption, or gastrointestinal bleeding exceeding the amount of iron supplementation. In such cases, additional screening for other underlying etiologies should be performed, such as testing for H. pylori infection, autoimmune gastritis, and conducting a colonoscopy to screen for colorectal cancer.

How can the adverse effects of oral iron supplements be minimised?

Patients can decrease the adverse effects of oral iron supplements by taking them on an adjusted regimen, such as three times a week instead of daily or taking them with food. However, it is important to note that taking iron supplements with food may decrease absorption and be less convenient for the patient, potentially leading to non-compliance. Discussing these options with a healthcare professional can help determine the best approach for each individual.

What is the role of the interprofessional team in managing patients with iron deficiency?

Managing iron deficiency requires coordination among various healthcare professionals, including primary care providers, hematologists, gastroenterologists, and nephrologists, depending on the underlying cause of the anemia. The interprofessional team should ensure that patients are not assumed to have iron deficiency anemia based solely on a complete blood count (CBC) and receive unnecessary iron supplementation without a complete workup. If the patient does not improve with oral iron supplementation, the team should consider alternative routes of administration or investigate other underlying causes of the anemia. Effective care coordination and communication among the interprofessional team are essential for providing symptomatic relief and improving patient outcomes.

References

  1. Accrufer (ferric maltol) Prescribing Information. (2019). Shield Therapeutics UK Ltd. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212320Orig1s000lbl.pdf

  2. Breymann, C., Honegger, C., Hösli, I., & Surbek, D. (2017). Diagnosis and treatment of iron-deficiency anaemia in pregnancy and postpartum. Archives of Gynecology and Obstetrics, 296(6), 1229-1234. https://doi.org/10.1007/s00404-017-4526-2

  3. Brittenham, G. M. (2013). Disorders of Iron Metabolism: Iron Deficiency and Iron Overload. In R. Hoffman (Ed.), Hematology: Basic Principles and Practice (Sixth Edition, pp. 437-449). Elsevier Saunders.

  4. Fishbane, S., Block, G. A., Loram, L., Neylan, J., Pergola, P. E., Uhlig, K., & Chertow, G. M. (2017). Effects of Ferric Citrate in Patients with Nondialysis-Dependent CKD and Iron Deficiency Anemia. Journal of the American Society of Nephrology, 28(6), 1851-1858. https://doi.org/10.1681/ASN.2016101053

  5. Gasche, C., Ahmad, T., Tulassay, Z., Baumgart, D. C., Bokemeyer, B., Büning, C., Howaldt, S., Stallmach, A., & AEGIS Study Group. (2015). Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program. Inflammatory Bowel Diseases, 21(3), 579-588. https://doi.org/10.1097/MIB.0000000000000314

  6. Kalra, P. A., & Bhandari, S. (2016). Safety of intravenous iron use in chronic kidney disease. Current Opinion in Nephrology and Hypertension, 25(6), 529-535. https://doi.org/10.1097/MNH.0000000000000263

  7. Ko, C. W., Siddique, S. M., Patel, A., Harris, A., Sultan, S., Altayar, O., & Falck-Ytter, Y. (2020). AGA Clinical Practice Guidelines on the Gastrointestinal Evaluation of Iron Deficiency Anemia. Gastroenterology, 159(3), 1085-1094. https://doi.org/10.1053/j.gastro.2020.06.046

  8. Koutroubakis, I. E., Oustamanolakis, P., Karakoidas, C., Mantzaris, G. J., & Kouroumalis, E. A. (2010). Safety and efficacy of total-dose infusion of low molecular weight iron dextran for iron deficiency anemia in patients with inflammatory bowel disease. Digestive Diseases and Sciences, 55(8), 2327-2331. https://doi.org/10.1007/s10620-009-1022-y

  9. Levi, M., Rosselli, M., Simonetti, M., Brignoli, O., Cancian, M., Masotti, A., Pegoraro, V., Cataldo, N., Heiman, F., Chelo, M., Cricelli, I., Cricelli, C., & Lapi, F. (2016). Epidemiology of iron deficiency anaemia in four European countries: a population-based study in primary care. European Journal of Haematology, 97(6), 583-593. https://doi.org/10.1111/ejh.12776

  10. Monoferric (ferric derisomaltose) Prescribing Information. (2020). Pharmacosmos A/S. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/208171s000lbl.pdf

  11. Moretti, D., Goede, J. S., Zeder, C., Jiskra, M., Chatzinakou, V., Tjalsma, H., Melse-Boonstra, A., Brittenham, G., Swinkels, D. W., & Zimmermann, M. B. (2015). Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood, 126(17), 1981-1989. https://doi.org/10.1182/blood-2015-05-642223

  12. National Institutes of Health. (2021). Iron: Fact Sheet for Health Professionals. Office of Dietary Supplements. https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/

  13. Okam, M. M., Koch, T. A., & Tran, M. H. (2016). Iron supplementation, response in iron-deficiency anemia: analysis of five trials. The American Journal of Medicine, 129(8), 991.e1-991.e8. https://doi.org/10.1016/j.amjmed.2016.03.045

  14. Onken, J. E., Bregman, D. B., Harrington, R. A., Morris, D., Buerkert, J., Hamerski, D., Iftikhar, H., Mangoo-Karim, R., Martin, E. R., Martinez, C. O., Qunibi, W., Saddler, N., Sika, M., & Swearingen, C. J. (2014). Ferric carboxymaltose in patients with iron-deficiency anemia and impaired renal function: the REPAIR-IDA trial. Nephrology, Dialysis, Transplantation, 29(4), 833-842. https://doi.org/10.1093/ndt/gft251

  15. Ponikowski, P., van Veldhuisen, D. J., Comin-Colet, J., Ertl, G., Komajda, M., Mareev, V., McDonagh, T., Parkhomenko, A., Tavazzi, L., Levesque, V., Mori, C., Roubert, B., Filippatos, G., Ruschitzka, F., Anker, S. D., & CONFIRM-HF Investigators. (2015). Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. European Heart Journal, 36(11), 657-668. https://doi.org/10.1093/eurheartj/ehu385

  16. Stoffel, N. U., Cercamondi, C. I., Brittenham, G., Zeder, C., Geurts-Moespot, A. J., Swinkels, D. W., Moretti, D., & Zimmermann, M. B. (2017). Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. The Lancet Haematology, 4(11), e524-e533. https://doi.org/10.1016/S2352-3026(17)30182-5

  17. Stoffel, N. U., Zeder, C., Brittenham, G. M., Moretti, D., & Zimmermann, M. B. (2020). Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica, 105(5), 1232-1239. https://doi.org/10.3324/haematol.2019.220830

  18. Vadhan-Raj, S., Strauss, W., Ford, D., Bernard, K., Boccia, R., Li, J., & Allen, L. F. (2014). Efficacy and safety of IV ferumoxytol for adults with iron deficiency anemia previously unresponsive to or unable to tolerate oral iron. American Journal of Hematology, 89(1), 7-12. https://doi.org/10.1002/ajh.23582

  19. Wolf, M., Auerbach, M., Kalra, P. A., Glaspy, J., Thomsen, L. L., & Bhandari, S. (2021). Safety of ferric derisomaltose and iron sucrose in patients with iron deficiency anemia: The FERWON-IDA/NEPHRO trials. American Journal of Hematology, 96(1), E11-E15. https://doi.org/10.1002/ajh.26035



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