Iron Intake with Drinking Water: Bioavailability, Kinetics, and Metabolism in Humans: A Literature Review

Introduction: The issue of iron deficiency anemia remains relevant and a priority. Currently, it is diagnosed in 30 % of the world population. The analysis of its causes often disregards a whole number of factors affecting iron bioavailability.

Objective: To review publications on the iron intake with drinking water, its bioavailability, kinetics, and metabolism in humans.

Materials and methods: The search for Russian and foreign papers published in 1973-2024, with a preference given to those issued over the past 10 years, was performed in the Google, Google Scholar, Scopus, Springer, PubMed, Wiley, eLIBRARY, CyberLeninka, and StudMed databases using the following keywords: iron content and forms in water, chemical reactions, iron bioavailability and metabolism, synergism and antagonism of elements. Of 250 publications originally found, we selected 46 papers having excluded review articles and those noncompliant with the purpose of the review.

Results: We established that up to 44 % of dietary iron comes with drinking water. Low iron levels in drinking water and food products are among the factors contributing to iron deficiency anemia. Iron bioavailability depends on its form, valence, combined exposure to chelating compounds and other trace elements. Iron levels in humans are regulated by intestinal absorption, transport, storage, mobilization, and excretion. Some trace elements can compete for pathways of iron absorption. In the presence of their multitude, molecular mechanisms responsible for the absorption, transport and incorporation of iron into the heme structure can be disrupted.

Conclusions: The findings helped identify a number of factors contributing to iron deficiency in humans. We revealed a lack of epidemiological data on the causes of iron deficiency disorders in certain population groups related to drinking water of varied composition. Besides, the biochemical and kinetic mechanisms of absorption of organoiron compounds and the combined effect of trace metals on the metabolism of this element have not been fully established.

1. Kumar A, Sharma E, Marley A, Samaan MA, Brookes MJ. Iron deficiency anaemia: Pathophysiology, assessment, practical management. BMJ Open Gastroenterol. 2022;9(1):000759. doi: 10.1136/bmjgast-2021-000759

2. Stein J, Connor S, Virgin G, Ong DE, Pereyra L. Anemia and iron deficiency in gastrointestinal and liver conditions. World J Gastroenterol. 2016;22(35):7908-7925. doi: 10.3748/wjg.v22.i35.7908

3. Shokrgozar N, Golafshan HA. Molecular perspective of iron uptake, related diseases, and treatments. Blood Res. 2019;54(1):10-16. doi: 10.5045/br.2019.54.1.10

4. Ataide R, Fielding K, Pasricha SR, Bennett C. Iron deficiency, pregnancy, and neonatal development. Int J Gynaecol Obstet. 2023;162(Suppl 2):14-22. doi: 10.1002/ijgo.14944

5. Gafter-Gvili A, Schechter A, Rozen-Zvi B. Iron deficiency anemia in chronic kidney disease. Acta Haematol. 2019;142(1):44-50. doi: 10.1159/000496492

6. National Research Council. Drinking Water and Health: Volume 3. Washington, DC: The National Academies Press; 1980. doi: 10.17226/324

7. World Health Organization. Trace Elements in Human Nutrition and Health. Geneva: WHO; 1996. Accessed November 15, 2024. https://www.who.int/publications/i/item/9241561734

8. Choudhury N, Siddiqua TJ, Ahmed SMT, et al. Iron content of drinking water is associated with anaemia status among children in high groundwater iron areas in Bangladesh. Trop Med Int Health. 2022;27(2):149-157. doi: 10.1111/tmi.13710

9. Kovalchuk VK. Estimation of actual iron consumption by adolescent population in region with high content of iron in drinking water. Ekologiya Cheloveka (Human Ecology). 2015;(5):8-13. (In Russ.)

10. Rigas AS, Ejsing BH, Sørensen E, et al. Calcium in drinking water: Effect on iron stores in Danish blood donors – Results from the Danish Blood Donor Study. Transfusion. 2018;58(6):1473. doi: 10.1111/trf.14600

11. Conrad ME, Umbreit JN. Iron absorption and transport – An update. Am J Hematol. 2020;64(4):287-298. doi: 10.1002/1096-8652(200008)64

12. Piskin E, Cianciosi D, Gulec S, Tomas M, Capanoglu E. Iron absorption: Factors, limitations, and improvement methods. ACS Omega. 2022;7(24):20441-20456. doi: 10.1021/acsomega.2c01833

13. Skalny AV. [Chemical Elements in Human Physiology and Ecology.] Moscow: ONIX 21 Century Publ.; 2004. (In Russ.)

14. Lapotyshkina NP, Sazonov RP. [Water Treatment and Water Chemistry of Heat Networks.] Moscow: Energoizdat; 1982. (In Russ.)

15. Kutergin A, Nedobukh T. The use of alumosilicate sorbent for the purification of natural waters from heavy metals. Ekologiya i Promyshlennost’ Rossii. 2020;24(3):19-23. (In Russ.) doi: 10.18412/1816-0395-2020-3-19-23

16. Kovshov AA, Novikova YuA, Fedorov VN, Tikhonova NA. Diseases risk assessment associated with the quality of drinking water in the urban districts of Russian Arctic. Vestnik Ural’skoy Meditsinskoy Akademicheskoy Nauki. 2019;16(2):215–222. (In Russ.) doi: 10.22138/2500-0918-2019-16-2-215-222

17. Kontoghiorghes GJ, Kontoghiorghe CN. Iron and chelation in biochemistry and medicine: New approaches to controlling iron metabolism and treating related diseases. Cells. 2020;9(6):1456. doi: 10.3390/cells9061456

18. Abe C, Miyazawa T, Miyazawa T. Current use of Fenton reaction in drugs and food. Molecules. 2022;27(17):5451. doi: 10.3390/molecules27175451

19. Barbusiński K. Fenton reaction – Controversy concerning the chemistry. Ecol Chem Eng. 2009;16(3):347-358.

20. Isaev AB, Magomedova AG. Advanced oxidation processes based emerging technologies for dye wastewater treatment. Vestnik Moskovskogo Universiteta. Seriya 2: Khimiya. 2022;63(4):247-268. (In Russ.)

21. Li H, Ding S, Song W, Wang X, Ding J, Lu J. The degradation of dissolved organic matter in black and odorous water by humic substance-mediated Fe(II)/ Fe(III) cycle under redox fluctuation. J Environ Manage. 2022;321:115942. doi: 10.1016/j.jenvman.2022.115942

22. Miranda LS, Wijesiri B, Ayoko GA, Egodawatta P, Goonetilleke A. Water-sediment interactions and mobility of heavy metals in aquatic environments. Water Res. 2021;202:117386. doi: 10.1016/j.watres.2021.117386

23. Kungolos A, Samaras P, Tsiridis V, Petala M, Sakellaropoulos G. Bioavailability and toxicity of heavy metals in the presence of natural organic matter. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2006;41(8):1509–1517. doi: 10.1080/10934520600754706

24. Nowack B, VanBriesen JM. Chelating agents in the environment. In: Biogeochemistry of Chelating Agents. ACS Symposium Series. 2005;910:1-18. doi: 10.1021/bk-2005-0910.ch001

25. Hathcock JN, Griffiths JC. Vitamin and Mineral Safety. 3rd ed. MacKay D, Wong A, Nguyen H, eds. Council for Responsible Nutrition, Washington, D.C.; 2013. Accessed November 15, 2024. https://www.crnusa.org/sites/default/files/files/resources/CRN-SafetyBook-3rdEdition-2014-fullbook.pdf

26. Kolosova NG, Bayandina GN, Mashukova NG, Geppe NAG. Iron exchange in the body and ways of correction of its abnormalities. Trudnyy Patsient. 2011;9(8-9):54- 58. (In Russ.)

27. Espina A, Cañamares MV, Jurašeková Z, Sanchez-Cortes S. Analysis of iron complexes of tannic acid and other related polyphenols as revealed by spectroscopic techniques: Implications in the identification and characterization of iron gall inks in historical manuscripts. ACS Omega. 2022;7(32):27937-27949. doi: 10.1021/acsomega.2c01679

28. Xu T, Zhang X, Liu Y, et al. Effects of dietary polyphenol supplementation on iron status and erythropoiesis: A systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2021;114(2):780-793. doi: 10.1093/ajcn/nqab068

29. Ashmead HD. The absorption and metabolism of iron amino acid chelate. Arch Latinoam Nutr. 2001;51(1 Suppl 1):13-21.

30. Olivares M, Pizarro F. Bioavailability of iron bis-glycinate chelate in water. Arch Latinoam Nutr. 2001;51(1 Suppl 1):22-25.

31. Rebrov VG, Gromova OA. [Vitamins, Macro- and Microelements.] Moscow: GEOTAR-Media; 2008. (In Russ.)

32. Milman NT. A review of nutrients and compounds, which promote or inhibit intestinal iron absorption: Making a platform for dietary measures that can reduce iron uptake in patients with genetic haemochromatosis. J Nutr Metab. 2020;2020(1):7373498. doi: 10.1155/2020/7373498

33. Shamov IA, Gasanova PO. Ferrum, absorption, transport. Vestnik Gematologii. 2016;12(1):31-38. (In Russ.)

34. Roth MP, Meynard D, Coppin H. Regulators of hepcidin expression. Vitam Horm. 2019;110:101-129. doi: 10.1016/bs.vh.2019.01.005

35. Milto IV, Suhodolo IV, Klimenteva TK, Prokopieva VD. Molecular and cellular bases of iron metabolism in humans. Biochemistry (Moscow). 2016;81(6):549–564. doi: 10.1134/S0006297916060018

36. Lapenko VV, Bikbulatova LN, Minyaylo LA, Kharkov VV. Hygienic assessment of iron content in pipeline water of administrative centers of the north of Tyumen Region. Zdorov’e Naseleniya i Sreda Obitaniya. 2022; 30(3):53-58. (In Russ.) doi: 10.35627/2219-5238/2022-30-3-53-58

37. Han G, Yang K, Zeng J, Zhao Y. Dissolved iron and isotopic geochemical characteristics in a typical tropical river across the floodplain: The potential environmental implication. Environ Res. 2021;200:111452. doi: 10.1016/j.envres.2021.111452

38. Levi S, Ripamonti M, Moro AS, Cozzi A. Iron imbalance in neurodegeneration. Mol Psychiatry. 2024;29(4):1139–1152. doi: 10.1038/s41380-023-02399-z

39. Chen WJ, Kung GP, Gnana-Prakasam JP. Role of iron in aging related diseases. Antioxidants (Basel). 2022;11(5):865. doi: 10.3390/antiox11050865

40. Baudry J, Kopp JF, Boeing H, Kipp AP, Schwerdtle T, Schulze MB. Changes of trace element status during aging: Results of the EPIC–Potsdam cohort study. Eur J Nutr. 2020;59(7):3045–3058. doi: 10.1007/s00394-019-02143-w

41. Wang X, Zhao Y, Wu X, Cui L, Mao S. Editorial: Trace element chemistry and health. Front Nutr. 2022;9:1034577. doi: 10.3389/fnut.2022.1034577

42. Słota M, Wąsik M, Stołtny T, et al. Relationship between lead absorption and iron status and its association with oxidative stress markers in lead-exposed workers. J Trace Elem Med Biol. 2021;68:126841. doi: 10.1016/j.jtemb.2021.126841

43. Abbaspour N, Hurrell R, Kelishadi R. Review on iron and its importance for human health. J Res Med Sci. 2014;19(2):164–174.

44. Angelova MG, Petkova-Marinova TV, Pogorielov MV, Loboda AN, Nedkova-Kolarova VN, Bozhinova AN. Trace element status (iron, zinc, copper, chromium, cobalt, and nickel) in iron-deficiency anaemia of children under 3 years. Anemia. 2014;2014:718089. doi: 10.1155/2014/718089

45. Permyakov EA. Metal binding proteins. Encyclopedia. 2021;1(1):261-292. doi: 10.3390/encyclopedia1010024

46. Yuan G, Curtolo F, Deng Y, et al. Highly dynamic polynuclear metal cluster revealed in a single metallothionein molecule. Research (Wash D C). 2021;2021:9756945. doi: 10.34133/2021/9756945