Skip to main content
Log in

Evaluation of Plasma Trace Elements in Different Stages of Nonalcoholic Fatty Liver Disease

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of metabolic syndrome. Its global prevalence is estimated between 25 and 45%, occurring mainly in overweight individuals with unhealthy dietary habits and low levels of physical activity. Many studies have investigated the association of trace elements with liver diseases, though not with NAFLD. In this work, we investigated trace element levels in plasma of patients and not-patients and their possible association with various stages of the disease. Inductively coupled plasma mass spectrometry (ICP-MS) was employed for the determination of As, Ba, Cd, Co, Cs, Cu, Fe, Rb, Sr, Tl, and Zn in the plasma of 189 free-living residents of Athens, Greece, either healthy or patients with mild, moderate, or severe NAFLD. The disease was diagnosed by abdominal ultrasound; blood samples were analyzed for total, HDL and LDL cholesterol, triglycerides, fasting glucose, fasting insulin, and liver enzymes, namely aspartate aminotransferase (AST), alanine transaminase (ALT), and γ-glutamyltransferase (Gamma-GT); insulin resistance was determined by the homeostatic model assessment (HOMA-IR). Zinc exhibited a statistically significant negative association with the severity of the disease, while cesium showed a statistically significant positive association. Moreover, thallium and iron were inversely associated with insulin levels. Trace element determination in plasma could be useful for establishing relationships with NAFLD status of patients. Further research is required for the verification and interpretation of these findings.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Levene AP, Goldin RD (2012) The epidemiology, pathogenesis and histopathology of fatty liver disease. Histopathology 61:141–152

    Article  PubMed  Google Scholar 

  2. Papandreou D, Rousso I, Mavromichalis I (2007) Update on non–alcoholic fatty liver disease in children. Clin Nutr 26:409–415

    Article  CAS  PubMed  Google Scholar 

  3. Della Corte C, Alisi A, Saccari A, De Vito R, Vania A, Nobili V (2012) Nonalcoholic fatty liver in children and adolescents: an overview. J Adolesc Health 51:305–312

    Article  PubMed  Google Scholar 

  4. Polyzos SA, Kountouras J, Mantzoros CS (2015) Leptin in nonalcoholic fatty liver disease: a narrative review. Metabolism 64:60–78

    Article  CAS  PubMed  Google Scholar 

  5. Rinella ME (2015) Nonalcoholic fatty liver disease. A systematic review. JAMA 313:2263–2273

    Article  CAS  PubMed  Google Scholar 

  6. Goh GBB, Mc Cullough AJ (2016) Natural history of nonalcoholic fatty liver disease. Dig Dis Sci 61:1226–1233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Than NN, Newsome PN (2015) A concise review of non–alcoholic fatty liver disease. Atherosclerosis 239:192–202

    Article  CAS  PubMed  Google Scholar 

  8. Sun C, Fan JG, Qiao L (2015) Potential epigenetic mechanism in non–alcoholic fatty liver disease. Int J Mol Sci 16:5161–5179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Satapathy SK, Sanyal AJ (2015) Epidemiology and natural history of nonalcoholic fatty liver disease. Semin Liver Dis 35:221–235

    Article  PubMed  Google Scholar 

  10. Sayiner M, Koenig A, Henry L, Younossi ZM (2016) Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in the United States and the rest of the world. Clin Liver Dis 20:205–214

    Article  PubMed  Google Scholar 

  11. Leite NC, CA V–N, Cardoso CRL, Salles GF (2014) Non–alcoholic fatty liver disease and diabetes: from physiopathological interplay to diagnosis and treatment. World J Gastroenterol 20:8377–8392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Malavolta M, Piacenza F, Basso A, Giacconi R, Costarelli L, Mocchegiani E (2015) Serum copper to zinc ratio: relationship with aging and health status. Mech Ageing Dev 151:93–100

    Article  CAS  PubMed  Google Scholar 

  13. Guo CH, Chen PC, Ko WS (2013) Status of essential trace minerals and oxidative stress in viral hepatitis C patients with nonalcoholic fatty liver disease. Int J Med Sci 10:730–737

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Peter ALJ, Viraraghavan T (2005) Thallium: a review of public health and environmental concerns. Environ Int 31:493–501

    Article  CAS  PubMed  Google Scholar 

  15. Jablonska–Czapla M (2015) Arsenic, antimony, chromium and thallium speciation in water and sediment samples with the LC–ICP–MS technique. Int J Anal Chem 171478. https://doi.org/10.1155/2015/171478

  16. Nordberg M, Nordberg GF (2016) Trace element research–historical and future aspects. J Trace Elem Med Biol 38:46–52

    Article  CAS  PubMed  Google Scholar 

  17. Loguercio C, De Girolamo V, Federico A, Feng SL, Crafa E, Cataldi V, Gialanella G, Moro R, Del Vecchio Blanco C (2011) Relationship of blood trace elements to liver damage, nutritional status and oxidative stress in chronic nonalcoholic liver disease. Biol Trace Elem Res 81:245–255

    Article  Google Scholar 

  18. Schnabl B, Czech B, Valletta D, Weiss TS, Kirovski G, Hellerbrand C (2011) Increased expression of Zinc finger protein 267 in non–alcoholic fatty liver disease. Int J Clin Exp Pathol 4:661–666

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Tan M, Schmidt RH, Beier JI, Watson WH, Zhong H, States JC, Arteel GE (2011) Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice. Toxicol Appl Pharmacol 257:356–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hyder O, Chung M, Cosgrove D, Herman JM, Li Z, Firoozmand A, Gurakar A, Koteish A, Pawlik TM (2013) Cadmium exposure and liver disease among US adults. J Gastrointest Surg 17:1265–1273

    Article  PubMed  PubMed Central  Google Scholar 

  21. Go YM, Sutliff RL, Chandler JD, Khalidur R, Kang BY, Anania FA, Orr M, Hao L, Fowler BA, Jones DP (2015) Low–dose cadmium causes metabolic and genetic dysregulation associated with fatty liver disease in mice. Toxicol Sci 147:524–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Kalafati IP, Dimitriou M, Borsa D, Vlachogiannakos J, Revenas K, Kokkinos A, Ladas SD, Dedoussis GV (2018) Fish intake interacts with TM6SF2 gene variant to affect NAFLD risk: results of a case-control study. Eur J Nutr. https://doi.org/10.1007/s00394-018-1675-4

  23. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ (2012) The diagnosis and management of non–alcoholic fatty liver disease: practice guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology and the American Gastroenterological Association. Hepatology 55:2005–2023

    Article  PubMed  Google Scholar 

  24. Castera L, Vilgrain V, Angulo P (2013) Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol Hepatol 10:666–675

    Article  CAS  PubMed  Google Scholar 

  25. Friedewald WT, Levi RI, Fredrickson DS (1972) Estimation of the concentration of low–density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502

    CAS  PubMed  Google Scholar 

  26. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta–cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419

    Article  CAS  PubMed  Google Scholar 

  27. Jin L, Liu J, Ye B, Ren A (2014) Concentrations of selected heavy metals in maternal blood and associated factors in rural areas in Shanxi Province, China. Environ Int 66:157–164

    Article  CAS  PubMed  Google Scholar 

  28. Batáriová A, Spěváčková V, Beneš B, Čejchanová M, Šmíd J, Černá M (2006) Blood and urine levels of Pb, Cd and Hg in the general population of the Czech Republic and proposed reference values. Int J Hyg Environ Health 209:359–366

    Article  CAS  PubMed  Google Scholar 

  29. US EPA (1997) Definition and procedures for the determination of the method detection limit. App B, Part 136:343–345. (40 CFR Ch (7–1–12 edition)

  30. Falq G, Zeghnoun A, Pascal M, Vernay M, Le Strat Y, Garnier R, Olichon D, Bretin P, Castetbon K, Fréry N (2011) Blood lead levels in the adult population living in France the French Nutrition and Health Survey (ENNS 2006–2007). Environ Int 37:565–571

    Article  CAS  PubMed  Google Scholar 

  31. Cesbron A, Saussereau E, Mahieu L, Couland I, Guerbet M, Goullé JP (2013) Metallic profile of whole blood and plasma in a series of 106 healthy volunteers. J Anal Toxicol 37:401–405

    Article  CAS  PubMed  Google Scholar 

  32. Yuan Y, Xiao Y, Yu Y, Liu Y, Feng W, Qiu G, Wang H, Liu B, Wang J, Zhou L, Liu K, Xu X, Yang H, Li X, Qi L, Zhang X, He M, Hu FB, Pan A, Wu T (2018) Associations of multiple plasma metals with incident type 2 diabetes in Chinese adults: the Dongfeng-Tongji cohort. Environ Pollut 237:917–925

    Article  CAS  PubMed  Google Scholar 

  33. Gatiatulina ER, Popova EV, Polyakova VS, Skalnaya AA, Agletdinov EF, Nikonorov AA, Skalny AV, Tinkov AA (2017) Evaluation of tissue metal and trace element content in a rat model of non–alcoholic fatty liver disease using ICP–DRC–MS. J Trace Elem Med Biol 39:91–99

    Article  CAS  PubMed  Google Scholar 

  34. Stamoulis I, Kouraklis G, Theocharis S (2007) Zinc and the liver: an active interaction. Dig Dis Sci 52:1595–1612

    Article  CAS  PubMed  Google Scholar 

  35. Goode HF, Kelleher J, Walker BE (1990) Relationship between zinc status and hepatic functional reserve in patients with liver disease. Gut 31:694–697

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Zolfaghari H, Askari G, Siassi F, Feizi A, Sotoudeh G (2016) Intake of nutrients, fiber and sugar in patients with nonalcoholic fatty liver disease in comparison to healthy individuals. Int J Prev Med 7:98. https://doi.org/10.4103/2008-7802.188083

    Article  PubMed  PubMed Central  Google Scholar 

  37. Alimonti A, Bocca B, Mannella E, Petrucci F, Zennaro F, Cotichini R, D'Ippolito C, Agresti A, Caimi S, Forte G (2005) Assessment of reference values for selected elements in a healthy urban population. Ann Ist Super Sanita 41:181–187

    CAS  PubMed  Google Scholar 

  38. Zoli A, Altomonte L, Caricchio R, Galossi A, Mirone L, Ruffini MP, Magaró M (1998) Serum zinc and copper in active rheumatoid arthritis: correlation with interleukin 1β and tumor necrosis factor–α. Clin Rheumatol 17:378–382

    Article  CAS  PubMed  Google Scholar 

  39. Mousavi SN, Faghihi A, Motaghinejad M, Shiasi M, Imanparast F, Amiri HL, Shidfar F (2018) Zinc and selenium co–supplementation reduces some lipid peroxidation and angiogenesis markers in a rat model of NAFLD–fed high fat diet. Biol Trace Elem Res 181:288–295

    Article  CAS  PubMed  Google Scholar 

  40. Britton LJ, Subramaniam VN, Crawford DH (2016) Iron and non-alcoholic fatty liver disease. World J Gastroenterol 22:8112–8122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Orban E, Schwab S, Thorand B, Huth C (2014) Association of iron indices and type 2 diabetes: a meta-analysis of observational studies. Diabetes Metab Res Rev 30:372–394

    Article  CAS  PubMed  Google Scholar 

  42. Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PW, Wood RJ (2002) Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort. Am J Clin Nutr 76:1375–1384

    Article  CAS  PubMed  Google Scholar 

  43. Bowers K, Yeung E, Williams MA, Qi L, Tobias DK, Hu FB, Zhang C (2011) A prospective study of prepregnancy dietary iron intake and risk for gestational diabetes mellitus. Diabetes Care 34:1557–1563

    Article  PubMed  PubMed Central  Google Scholar 

  44. Qiu C, Zhang C, Gelaye B, Enquobahrie DA, Frederick IO, Williams MA (2011) Gestational diabetes mellitus in relation to maternal dietary heme iron and nonheme iron intake. Diabetes Care 34:1564–1569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Melnikov P, Zanoni LZ (2009) Clinical effects of cesium intake. Biol Trace Elem Res 135:1–9

    Article  CAS  PubMed  Google Scholar 

  46. Padilla MA, Elobeid M, Ruden DM, Allison DB (2010) An examination of the association of selected toxic metals with total and central obesity indices: NHANES 99–02. Int J Environ Res Public Health 7:3332–3347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Minoia C, Sabbioni E, Apostoli P, Pietra R, Pozzoli L, Gallorini M, Nicolaou G, Alessio L, Capodaglio E (1990) Trace element reference values in tissues from inhabitants of the European community. I. A study of 46 elements in urine, blood, and serum of Italian subjects. Sci Total Environ 95:89–105

    Article  CAS  PubMed  Google Scholar 

  48. Kiliç GA, Kutlu M (2010) Effects of exogenous metallothionein against thallium-induced oxidative stress in rat liver. Food Chem Toxicol 48:980–987

    Article  CAS  PubMed  Google Scholar 

  49. Petit P, MM L–M (1992) Potassium channels of the insulin–secreting B cell. Fundam Clin Pharmacol 6:123–134

    Article  CAS  PubMed  Google Scholar 

  50. Yang SN, Shi Y, Yang G, Li Y, Yu J, Berggren PO (2014) Ionic mechanisms in pancreatic β cell signaling. Cell Mol Life Sci 71:4149–4177

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the grant “Obesity and metabolic syndrome: dietary intervention with Greek raisins in NAFLD / NASH. Investigation of molecular mechanisms” reviewed and approved by the Greek Secretariat for Research and Technology (Cooperation 890/2009).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nick Kalogeropoulos.

Ethics declarations

The study was approved by the Ethics Committee of Harokopio University of Athens (35/25-07-2012), based on the Helsinki Declaration.

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Asprouli, E., Kalafati, I.P., Sakellari, A. et al. Evaluation of Plasma Trace Elements in Different Stages of Nonalcoholic Fatty Liver Disease. Biol Trace Elem Res 188, 326–333 (2019). https://doi.org/10.1007/s12011-018-1432-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-018-1432-9

Keywords

Navigation