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Efficacy and Tolerability of Oral Iron Protein Succinylate in the Treatment of Iron Deficiency Anemia in Adults with Gastrointestinal Diseases

Iron deficiency anemia (IDA) is commonly associated with several pathological gastrointestinal (GI) conditions in adults, being induced through different mechanisms, such as chronic bleeding, chronic inflammation, malabsorption, autoimmune re-actions, or, quite frequently, as a combination of different mechanisms. All patients must be treated with iron supplementation with the aim of restoring normal hemoglobin levels and iron status. Oral iron compounds are the first line treatment options for ID clinical conditions, according to International Guidelines, as they have proven to be efficacious, safe, and relatively inexpensive. However, ferric salts are scarcely absorbed, and ferrous compounds present a poor GI tolerability. Iron-protein succinylate (IPS), an iron complex that keeps ferric iron bonded to the protein content of a succinylated casein shell at acid pH values, has been shown to release gradually iron into the intestinal lumen, protecting the gastrointestinal mucosa from eventual damage, an ensuring an optimal intestinal iron absorption. This review focuses on IPS in the treatment of IDA associated to a variety of GI medical conditions in adults. Results from diverse studies including IDA due to acute and chronic GI conditions, as well as IDA associated to gastric surgery, confirm a consistent improvement in hematologic parameters and clinical symptoms, and an optimal tolerability profile.

Iron Deficiency, Iron Deficiency Anemia, Iron Protein Succinylate, Gastrointestinal Diseases

Luis Izquierdo. (2021). Efficacy and Tolerability of Oral Iron Protein Succinylate in the Treatment of Iron Deficiency Anemia in Adults with Gastrointestinal Diseases. International Journal of Gastroenterology, 5(2), 40-47.

Copyright © 2021 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License ( which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. Balarajan Y, Ramakrishnan U, Ozaltin E et al. Anaemia in low-income and mid-dle-income countries. Lancet 2011; 378: 2123-2135.
2. Johnson-Wimbley TD, Graham DY. Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol 2011; 4: 177-184.
3. De Franceschi L, Iolascon A, Taher A, Cappellini MD. Clinical management of iron deficiency anemia in adults: Systemic review on advances in diagnosis and treatment. Eur J Intern Med 2017; 42: 16-23.
4. Goddard AF, James MW, McIntyre AS et al. Guidelines for the management of iron deficiency anaemia. Gut 2011; 60: 1309-1316.
5. Camaschella C. Iron-Deficiency Anemia. N Engl J Med 2015; 373: 485-486.
6. Kassebaum NJ, Jasrasaria R, Naghavi M et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood 2014; 123: 615-624.
7. Auerbach M, Adamson JW. How we diagnose and treat iron deficiency anemia. Am J Hematol 2016; 91: 31-38.
8. Stein J, Connor S, Virgin G et al. Anemia and iron deficiency in gastrointestinal and liver conditions. World J Gastroenterol 2016; 22: 7908-7925.
9. Nielsen OH, Soendergaard C, Vikner ME, Weiss G. Rational Management of Iron-Deficiency Anaemia in Inflammatory Bowel Disease. Nutrients 2018; 10.
10. Salgado W, Jr., Modotti C, Nonino CB, Ceneviva R. Anemia and iron deficiency before and after bariatric surgery. Surg Obes Relat Dis 2014; 10: 49-54.
11. Elli L, Norsa L, Zullo A et al. Diagnosis of chronic anaemia in gastrointestinal disorders: A guideline by the Italian Association of Hospital Gastroenterologists and Endoscopists (AIGO) and the Italian Society of Paediatric Gastroenterology Hepatology and Nutrition (SIGENP). Dig Liver Dis 2019; 51: 471-483.
12. Cremonesi P, Caramazza I. Chemical and biological characterization of iron-protein succinylate (ITF 282). Int J Clin Pharmacol Ther Toxicol 1993; 31: 40-51.
13. Raja KB, Jafri SE, Dickson D et al. Involvement of iron (ferric) reduction in the iron absorption mechanism of a trivalent iron-protein complex (iron protein succinylate). Pharmacol Toxicol 2000; 87: 108-115.
14. Deriu lM, M. Assorbimento in Rapporto con il Pasto di un Composto di Ferro Coniugato con Proteine Succinilate. Riforma Med 1988; 103: 389-390.
15. Bianchi FM, Cavassini GB, Leo P. Iron protein succynilate in the treatment of iron deficiency: potential interaction with H2-receptor antagonists. Int J Clin Pharmacol Ther Toxicol 1993; 31: 209-217.
16. Rayado B CJ, Fernández-Esteban J, et al. Estudio comparativo entre 2 proteínas férricas en la prevención de la anemia ferropénica gestacional. Clin Invest Ginecol Obstet 1996; 24: 46-50.
17. Cremonesi P, Acebron A, Raja KB, Simpson RJ. Iron absorption: biochemical and molecular insights into the importance of iron species for intestinal uptake. Pharmacol Toxicol 2002; 91: 97-102.
18. Danisi M, Guerresi E, Landucci G et al. Serum iron concentrations following administration of two different iron preparations. J Int Med Res 1987; 15: 374-378.
19. De Petris GB, A. Rizza, F. Scotti, A. Dobrilla, G. Studio sull'assorbimento del ferroproteinsuccinilato, un composto a base di ferro coniugato con proteine succinilate, in confronto con gluconato di ferro. Basi Raz Ter 1988; XVIII: 145-148.
20. Cogo R, De Luca P, Mastrantoni M. Evaluation of the siderohaemic curve after loading administration of iron--protein--succinylate to gastrectomized subjects: a controlled study. J Int Med Res 1990; 18: 225-227.
21. Martinez Frances A, Leal Martinez-Bujanda J. Efficacy and tolerability of oral iron protein succinylate: a systematic review of three decades of research. Curr Med Res Opin 2020; 1-11.
22. Scremin S, Caprioglio L. [The efficacy and tolerability of ferroproteinsuccinylate in iron deficiency]. Boll Chim Farm 1988; 127: 44s-49s.
23. De Renzo A, Buffardi S, Frigeri F et al. [Efficacy and tolerability of iron protein-succinyl versus ferritin in sideropenic anemia]. Recenti Prog Med 1987; 78: 562-565.
24. Liguori L. Iron protein succinylate in the treatment of iron deficiency: controlled, double-blind, multicenter clinical trial on over 1,000 patients. Int J Clin Pharmacol Ther Toxicol 1993; 31: 103-123.
25. Pujol Farriols R, Anglada Oriol M, Formiga Perez F et al. [Iron protein-succinylate in the treatment of adult iron-deficiency anemia]. An Med Interna 2002; 19: 651-652.
26. Popovska. Out-Patiend treatment of sideropenic anemi with Legofer.
27. Ambrosini A. [The activity and tolerability of ferroproteinsuccinylate in the treatment of iron deficiency in surgery]. Boll Chim Farm 1988; 127: 40s-43s.
28. Manfredi B, Finelli F. [A new therapeutic approach to iron deficiency]. Clin Ter 1987; 123: 25-39.
29. Veneroni G CS, Tripodi S, et al. Studio clinico controllato in doppio cieco sull’efficacia terapeutica e sulla tollerabilità di un nuovo prodotto a base di ferro organico. Policlin Sez Med 1996; 103: 21–29.
30. Peyrin-Biroulet L, Williet N, Cacoub P. Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review. Am J Clin Nutr 2015; 102: 1585-1594.
31. WHO Report. Iron Deficiency Anemia. 2001.
32. Camaschella C. Iron deficiency. Blood 2019; 133: 30-39.
33. Tolkien Z, Stecher L, Mander AP et al. Ferrous sulfate supplementation causes significant gastrointestinal side-effects in adults: a systematic review and meta-analysis. PLoS One 2015; 10: e0117383.
34. DeLoughery TG. Safety of Oral and Intravenous Iron. Acta Haematol 2019; 142: 8-12.
35. Bayraktar UD, Bayraktar S. Treatment of iron deficiency anemia associated with gastrointestinal tract diseases. World J Gastroenterol 2010; 16: 2720-2725.
36. Pogliani E SA, Acuto G. Clinical efficacy and tolerability of iron protein succinylate in comparison to slow release iron sulphate in sideropenic anemia. 1990.
37. Lee T, Clavel T, Smirnov K et al. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut 2017; 66: 863-871.
38. Constante M, Fragoso G, Lupien-Meilleur J et al. Iron Supplements Modulate Colon Microbiota Composition and Potentiate the Protective Effects of Probiotics in Dextran Sodium Sulfate-induced Colitis. Inflamm Bowel Dis 2017; 23: 753-766.
39. Yilmaz B, Li H. Gut Microbiota and Iron: The Crucial Actors in Health and Disease. Pharmaceuticals (Basel) 2018; 11.
40. Mahalhal A, Williams JM, Johnson S et al. Oral iron exacerbates colitis and influences the intestinal microbiome. PLoS One 2018; 13: e0202460.
41. Parmanand BA, Kellingray L, Le Gall G et al. A decrease in iron availability to human gut microbiome reduces the growth of potentially pathogenic gut bacteria; an in vitro colonic fermentation study. J Nutr Biochem 2019; 67: 20-27.
42. Simonyte Sjodin K, Domellof M, Lagerqvist C et al. Administration of ferrous sulfate drops has significant effects on the gut microbiota of iron-sufficient infants: a randomised controlled study. Gut 2019; 68: 2095-2097.
43. Cherayil BJ, Ellenbogen S, Shanmugam NN. Iron and intestinal immunity. Curr Opin Gastroenterol 2011; 27: 523-528.
44. Heidelbaugh JJ. Proton pump inhibitors and risk of vitamin and mineral deficiency: evidence and clinical implications. Ther Adv Drug Saf 2013; 4: 125-133.
45. Hamano H, Niimura T, Horinouchi Y et al. Proton pump inhibitors block iron absorption through direct regulation of hepcidin via the aryl hydrocarbon receptor-mediated pathway. Toxicol Lett 2020; 318: 86-91.
46. Aymard JP, Aymard B, Netter P et al. Haematological adverse effects of histamine H2-receptor antagonists. Med Toxicol Adverse Drug Exp 1988; 3: 430-448.
47. Lam JR, Schneider JL, Quesenberry CP, Corley DA. Proton Pump Inhibitor and Histamine-2 Receptor Antagonist Use and Iron Deficiency. Gastroenterology 2017; 152: 821-829 e821.
48. Vinnakota RD, Brett AS. Iron Deficiency Anemia Associated With Acid-Modifying Medications: Two Cases and Literature Review. Am J Med Sci 2019; 357: 160-163.
49. Steenackers N, Van der Schueren B, Mertens A et al. Iron deficiency after bariatric surgery: what is the real problem? Proc Nutr Soc 2018; 77: 445-455.
50. Mimura EC, Bregano JW, Dichi JB et al. Comparison of ferrous sulfate and ferrous glycinate chelate for the treatment of iron deficiency anemia in gastrectomized patients. Nutrition 2008; 24: 663-668.
51. Garcia-Casal MN, Layrisse M. The effect of change in pH on the solubility of iron bis-glycinate chelate and other iron compounds. Arch Latinoam Nutr 2001; 51: 35-36.