Human Health Effects of Aluminum and Molecular Mechanisms of its Toxicity: A Literature Review

Introduction: Aluminum, one of the most common elements in the earth’s crust, is widely used in industry, medicine and everyday life, which creates multiple pathways for its entry into the human body. Chronic accumulation of aluminum is associated with the development of neurodegenerative, renal and bone pathologies, making it necessary to update its toxicological profile.

Objective: To conduct a systematic analysis of current data on health effects of aluminum in humans and animals, including routes of exposure, mechanisms of toxicity, accumulation in target organs, and molecular aspects of its action, with an assessment of epidemiological risks for vulnerable groups of population.

Materials and Methods: We analyzed publications issued in 2001–2024 and found in PubMed, Web of Science, and eLIBRARY databases using the following keywords: aluminum, toxicity, accumulation, and metal migration, with an emphasis on experimental and epidemiological data. Of 244 search results, we selected 56 publications on the topic. Current hygienic standards were also systematized.

Results: The average daily intake of aluminum in adults is 7–9 mg, but in children and individuals with chronic renal failure, doses may exceed the permissible limits (1 mg/kg/week, EFSA) by 2–5 times. The neurotoxicity of aluminum is manifested by accumulation in the hippocampus and cerebral cortex, hyperphosphorylation of tau protein and an increased risk of dementia (RR = 2.03). Nephrotoxic effects include a 25 % decrease in glomerular filtration rate and an increase in mortality in dialysis patients (HR = 1.37). Genotoxicity is realized through the induction of oxidative stress, suppression of DNA repair, and dysregulation of histone methylation.

Conclusions: To minimize risks, it is recommended to replace aluminum adjuvants in vaccines, limit the use of aluminum cookware when preparing foods with low pH, monitor the aluminum content of baby foods. Further research should be aimed at clarifying the mechanisms of the toxic action of aluminum and assessing the effectiveness of regulatory measures to reduce exposure.

1. Soni MG, White SM, Flamm WG, Burdock GA. Safety evaluation of dietary aluminum. Regul Toxicol Pharmacol. 2001;33(1):66-79. doi: 10.1006/rtph.2000.1441

2. Nanda BB, Biswal RR, Acharya R, Rao JSB, Pujari PK. Determination of aluminium contents in selected food samples by instrumental neutron activation analysis. J Radioanal Nucl Chem. 2014;302:1471-1474. doi: 10.1007/s10967-014-3569-0

3. Razeka TMA, Kishk YFM, Khalil NSAM, Shehtaa AM. Migration of iron and aluminum from different cookwares to faba bean after cooking cycles and storage refrigerated. J Environ Sci. 2018;42(1):45-58. doi: 10.21608/jes.2018.21592

4. Li Y. Migration of metals from ceramic food contact materials. 1: Effects of pH, temperature, food simulant, contact duration and repeated-use. Food Packag Shelf Life. 2020;24:100493. doi: 10.1016/j.fpsl.2020.100493

5. Ammar HR, Saleh SM, Sivasankaran S, Albadri AEAE, Al-Mufadi FA. Investigation of element migration from aluminum cooking pots using ICP-MS. Appl Sci. 2023;13(24):13119. doi: 10.3390/app132413119

6. Jabeen S, Ali B, Khan MA, Khan MB, Hasan SA. Aluminum intoxication through leaching in food preparation. Alex Sci Exch J. 2016;37:618-626. doi: 10.21608/asejaiqjsae.2016.2539

7. Odularu AT, Ajibade PA, Onianwa PC. Comparative study of leaching of aluminium from aluminium, clay, stainless steel, and steel cooking pots. ISRN Public Health. 2013;2013:517601. doi: 10.1155/2013/517601

8. Turhan S. Aluminium contents in baked meats wrapped in aluminium foil. Meat Sci. 2006;74(4):644-647. doi: 10.1016/j.meatsci.2006.03.031

9. Nasiadek M, Sapota A. Toxic effect of dust and fumes of aluminium and its compounds on workers’ respiratory tract. Med Pr. 2004;55(6):495-500. (In Polish.)

10. Dolgikh OV, Otavina EA, Alikina IN, Kazakova OA, Zhdanova-Zaplesvichko IG, Guselnikov MA. Peculiarities of immunoregulatory indices in children living in the conditions of aerogenous exposition by aluminum. Gigiena i Sanitariya. 2018;97(1):81-84. (In Russ.) doi: 10.18821/0016-9900-2018-97-1-81-84

11. Redgrove J, Rodriguez I, Mahadevan-Bava S, Exley C. Prescription infant formulas are contaminated with aluminium. Int J Environ Res Public Health. 2019;16(5):899. doi: 10.3390/ijerph16050899

12. Glanz JM, Newcomer SR, Daley MF, et al. Cumulative and episodic vaccine aluminum exposure in a population-based cohort of young children. Vaccine. 2015;33(48):6736- 6744. doi: 10.1016/j.vaccine.2015.10.076

13. Vecchi S, Bufali S, Skibinski DA, O’Hagan DT, Singh M. Aluminum adjuvant dose guidelines in vaccine formulation for preclinical evaluations. J Pharm Sci. 2012;101(1):17- 20. doi: 10.1002/jps.22759

14. Zhdanova-Zaplesvichko IG, Zemlyanova MA, Koldibekova YuV. Biological markers of non-carcerogenic negative impacts on the central nervous system of children in the area with exposure to aluminum production emissions. Gigiena i Sanitariya. 2018;97(5):461-469. (In Russ.) doi: 10.18821/0016-9900-2018-97-5-461-469

15. Tietz T, Lenzner A, Kolbaum AE, et al. Aggregated aluminium exposure: Risk assessment for the general population. Arch Toxicol. 2019;93(12):3503-3521. doi: 10.1007/s00204-019-02599-z

16. Hunt CD, Meacham SL. Aluminum, boron, calcium, copper, iron, magnesium, manganese, molybdenum, phosphorus, potassium, sodium, and zinc: Concentrations in common western foods and estimated daily intakes by infants; toddlers; and male and female adolescents, adults, and seniors in the United States. J Am Diet Assoc. 2001;101(9):1058-1060. doi: 10.1016/S0002-8223(01)00260-7

17. Niu Q. Overview of the relationship between aluminum exposure and health of human being. Adv Exp Med Biol. 2018;1091:1-31. doi: 10.1007/978-981-13-1370-7_1

18. Martynova MO, Kozyrev KM, Albegova ZhK. To the question of the modern concepts influence of aluminum on the living organisms. Sovremennye Problemy Nauki i Obrazovaniya. 2014;(2):302. (In Russ.) Accessed February 26, 2025. https://science-education.ru/ru/article/view?id=12441

19. Chen B, Zeng Y, Hu B. Study on speciation of aluminum in human serum using zwitterionic bile acid derivative dynamically coated C18 column HPLC separation with UV and on-line ICP-MS detection. Talanta. 2010;81(1- 2):180-186. doi: 10.1016/j.talanta.2009.11.057

20. Rahimzadeh MR, Rahimzadeh MR, Kazemi S, Amiri RJ, Pirzadeh M, Moghadamnia AA. Aluminum poisoning with emphasis on its mechanism and treatment of intoxication. Emerg Med Int. 2022;2022:1480553. doi: 10.1155/2022/1480553

21. Zemlyanova MA, Peskova EV, Stepankov MS. Proteomic profiling of blood plasma in chronic experimental exposure to aluminum oxide as a tool for predicting adverse effects from critical human organs and systems. Gigiena i Sanitariya. 2023;102(10):1125-1131. (In Russ.) doi: 10.47470/0016-9900-2023-102-10-1125-1131

22. Yokel RA, Sjögren B. Chapter 1 – Aluminum. In: Nordberg GF, Costa M, eds. Handbook on the Toxicology of Metals. 5th ed. Academic Press; 2022:1-22. doi: 10.1016/B978-0-12-822946-0.00001-5

23. Chalansonnet M, Carabin N, Boucard S, et al. Study of potential transfer of aluminum to the brain via the olfactory pathway. Toxicol Lett. 2018;283:77-85. doi: 10.1016/j.toxlet.2017.11.027

24. Oliveira RB, Carvalho AB, Jorgetti V. Bone aluminum accumulation in the current era. J Bras Nefrol. 2024;46(3):e20240023. doi: 10.1590/2175-8239-JBN-2024-0023en

25. Mirza A, King A, Troakes C, Exley C. Aluminium in brain tissue in familial Alzheimer’s disease. J Trace Elem Med Biol. 2017;40:30-36. doi: 10.1016/j.jtemb.2016.12.001

26. Ghorbel I, Chaabane M, Elwej A, et al. Expression of metallothioneins I and II related to oxidative stress in the liver of aluminium-treated rats. Arch Physiol Biochem. 2016;122(4):214-222. doi: 10.1080/13813455.2016.1187176

27. Valova YaV, Gizatullina AA, Smolyankin DA, et al. Assessment of MT1A and MT2A gene expression in the liver of rats during aluminum hydroxide intoxication. Nauchnyy Meditsinskiy Vestnik Yugry. 2024;40(2):37-42. (In Russ.) doi: 10.25017/2306-1367-2024-40-37-42

28. Yakupova TG, Smolyankin DA, Valova YaV, et al. Dose-dependent morphological and molecular genetic changes in rat kidneys during chronic exposure to aluminum hydroxide. Mezhdunarodnyy Vestnik Veterinarii. (In Russ.) 2025;(2):265-274. (In Russ.) doi: 10.52419/issn2072-2419.2025.2.265

29. Skalny AV, Aschner M, Jiang Y, et al. Molecular mechanisms of aluminum neurotoxicity: Update on adverse effects and therapeutic strategies. Adv Neurotoxicol. 2021;5:1-34. doi: 10.1016/bs.ant.2020.12.001

30. Kadhim A, Ben Slima A, Alneamah G, Makni M. Assessment of histopathological alterations and oxidative stress in the liver and kidney of male rats following exposure to aluminum chloride. J Toxicol. 2024;2024:3997463. doi: 10.1155/2024/3997463

31. Jackson JS, Rout P. Aluminum Toxicity. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–. Accessed December 23, 2025. https://www.ncbi.nlm.nih.gov/books/NBK609094/

32. Al-Hazmi MA, Rawi SM, Hamza RZ. Biochemical, histological, and neuro-physiological effects of long-term aluminum chloride exposure in rats. Metab Brain Dis. 2021;36(3):429-436. doi: 10.1007/s11011-020-00664-6

33. Geyikoglu F, Türkez H, Bakir TO, Cicek M. The genotoxic, hepatotoxic, nephrotoxic, haematotoxic and histopathological effects in rats after aluminium chronic intoxication. Toxicol Ind Health. 2013;29(9):780-791. doi: 10.1177/0748233712440140

34. Aschner M, Skalny AV, Santamaria A, et al. Epigenetic mechanisms of aluminum-induced neurotoxicity and Alzheimer’s disease: A focus on non-coding RNAs. Neurochem Res. 2024;49(11):2988-3005. doi: 10.1007/s11064-024-04214-9

35. Wang L. Entry and deposit of aluminum in the brain. Adv Exp Med Biol. 2018;1091:39-51. doi: 10.1007/978-981-13-1370-7_3

36. Capriello T, Di Meglio G, De Maio A, et al. Aluminium exposure leads to neurodegeneration and alters the expression of marker genes involved to parkinsonism in zebrafish brain. Chemosphere. 2022;307(Pt 1):135752. doi: 10.1016/j.chemosphere.2022.135752

37. Periasamy VS, Athinarayanan J, Alshatwi AA. Aluminum oxide nanoparticles alter cell cycle progression through CCND1 and EGR1 gene expression in human mesenchymal stem cells. Biotechnol Appl Biochem. 2016;63(3):320-327. doi: 10.1002/bab.1368

38. Ignatova AM, Zemlyanova MA. Biological assessment of the impact of aluminum oxide micro- and nanoparticles on the organism of laboratory animals in conditions of acute toxicity. Toksikologicheskiy Vestnik. 2020;(3(162)):33- 40. (In Russ.) doi: 10.36946/0869-7922-2020-3-33-40

39. Nies I, Hidalgo K, Bondy SC, Campbell A. Distinctive cellular response to aluminum based adjuvants. Environ Toxicol Pharmacol. 2020;78:103404. doi: 10.1016/j.etap.2020.103404

40. Minigalieva IA, Katsnelson BA, Privalova LI, et al. Comparative and combined toxicity of aluminium, titanium and silicon oxides nanoparticles and its alleviation with the complex of bioprotectors. Toksikologicheskiy Vestnik. 2018;(2(149)):18-27. (In Russ.) doi: 10.36946/0869- 7922-2018-2-18-27

41. Zaitseva NV, Zemlyanova MA, Stepankov MS, Ignatova AM. Scientific forecasting of toxicity and evaluation of hazard potential of aluminum oxide nanoparticles for human health. Ekologiya Cheloveka (Human Ecology). 2018;(5):9- 15. (In Russ.) doi: 10.33396/1728-0869-2018-5-9-15

42. Chappard D. Effects of aluminum on cells and tissues. Morphologie. 2016;100(329):49-50. doi: 10.1016/j.morpho.2016.04.001

43. Klein GL. Aluminum toxicity to bone: A multisystem effect? Osteoporos Sarcopenia. 2019;5(1):2-5. doi: 10.1016/j.afos.2019.01.001

44. Wang F, Kang P, Li Z, Niu Q. Role of MLL in the modification of H3K4me3 in aluminium-induced cognitive dysfunction. Chemosphere. 2019;232:121-129. doi: 10.1016/j.chemosphere.2019.05.099

45. Li X, Hu C, Zhu Y, Sun H, Li Y, Zhang Z. Effects of aluminum exposure on bone mineral density, mineral, and trace elements in rats. Biol Trace Elem Res. 2011;143(1):378-385. doi: 10.1007/s12011-010-8861-4

46. Zhao C, Xu N, Zhang W, Zhao C. Changes of some elements in rat’s tissues except nerve centre with both ovariectomy and chronic aluminum toxication and the effects of estrogen supplement. Wei Sheng Yan Jiu. 2009;38(1):99-103. (In Chinese.)

47. Bellés M, Albina ML, Sanchez DJ, Corbella J, Domingo JL. Effects of oral aluminum on essential trace elements metabolism during pregnancy. Biol Trace Elem Res. 2001;79(1):67-81. doi: 10.1385/BTER:79:1:67

48. Rondeau V, Commenges D, Jacqmin-Gadda H, Dartigues JF. Relation between aluminum concentrations in drinking water and Alzheimer’s disease: An 8-year follow-up study. Am J Epidemiol. 2000;152(1):59-66. doi: 10.1093/aje/152.1.59

49. Abu-Taweel GM, Ajarem JS, Ahmad M. Neurobehavioral toxic effects of perinatal oral exposure to aluminum on the developmental motor reflexes, learning, memory and brain neurotransmitters of mice offspring. Pharmacol Biochem Behav. 2012;101(1):49-56. doi: 10.1016/j.pbb.2011.11.003

50. Giorgianni CM, D’Arrigo G, Brecciaroli R, et al. Neurocognitive effects in welders exposed to aluminium. Toxicol Ind Health. 2014;30(4):347-356. doi: 10.1177/0748233712456062

51. Mold M, Chmielecka A, Rodriguez MRR, et al. Aluminium in brain tissue in multiple sclerosis. Int J Environ Res Public Health. 2018;15(8):1777. doi: 10.3390/ijerph15081777

52. Mouro VGS, Menezes TP, Lima GDA, et al. How bad is aluminum exposure to reproductive parameters in rats? Biol Trace Elem Res. 2018;183(2):314-324. doi: 10.1007/s12011-017-1139-3

53. Dey M, Singh RK. Chronic oral exposure of aluminum chloride in rat modulates molecular and functional neurotoxic markers relevant to Alzheimer’s disease. Toxicol Mech Methods. 2022;32(8):616-627. doi: 10.1080/15376516.2022.2058898

54. Liu Y, Yuan Y, Xiao Y, et al. Associations of plasma metal concentrations with the decline in kidney function: A longitudinal study of Chinese adults. Ecotoxicol Environ Saf. 2020;189:110006. doi: 10.1016/j.ecoenv.2019.110006

55. Hsu CW, Weng CH, Lee CC, et al. Association of low serum aluminum level with mortality in hemodialysis patients. Ther Clin Risk Manag. 2016;12:1417-1424. doi: 10.2147/TCRM.S113829

56. Panhwar AH, Kazi TG, Naeemullah, et al. Evaluated the adverse effects of cadmium and aluminum via drinking water to kidney disease patients: Application of a novel solid phase microextraction method. Environ Toxicol Pharmacol. 2016;43:242-247. doi: 10.1016/j.etap.2016.03.017