Biological Trace Element Research

, Volume 175, Issue 1, pp 10–16 | Cite as

Determination of Serum Trace Elements (Zn, Cu, and Fe) in Pakistani Patients with Rheumatoid Arthritis

  • Zia Ullah
  • Muhammad Ikram Ullah
  • Shabbir Hussain
  • Haiba Kaul
  • Khalid P. Lone


Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease, which mainly involves the joints. RA is prevalent worldwide with increasing prevalence in elderly people. The mechanism of RA pathogenesis is still undefined, and it is interplaying between genetic susceptibility and environmental factors. Although risk factors for RA are not fully established, various studies have focused on the role of trace elements in association with RA. Trace elements act as co-factors for most of the enzymes, and their deficiency is associated with many untoward effects on human health. The homeostatic alterations in the metabolism of trace elements may partly be due to inflammatory response in RA. The objective of the present study was to determine the serum concentrations and correlation of zinc, copper, and iron in RA patients and healthy controls. The study comprised of 61 RA patients and 61 age- and sex-related healthy individuals of Pakistani population. Serum levels of Zn, Cu, and Fe were measured in all the participants by atomic absorption spectrophotometer. Serum Zn and Fe were significantly reduced in the RA patients than those in the healthy controls. Serum Cu concentrations were found elevated in the RA patients. Correlation studies of trace elements determine that there was negative correlation between Zn and Cu in the RA patients and no correlation in the control group. It is very important to explore the deficiency of essential trace metals in biological samples of the RA patients in different populations which may be helpful for diagnosis and supplementary management of rheumatoid arthritis patients.


Rheumatoid arthritis Trace elements Correlation Pakistan 



We are grateful to University of Health Sciences, Lahore, Pakistan, for facilitating this study. We also acknowledge the patients and volunteers who participated in this research.

Compliance of Ethical Standards

The study was approved by the ethical review committee of the University of Health Sciences, Lahore, Pakistan.

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Doan T, Massarotti E (2005) Rheumatoid arthritis: an overview of new and emerging therapies. J Clin Pharmacol 45:751–762CrossRefPubMedGoogle Scholar
  2. 2.
    Schett G (2006) Rheumatoid arthritis: inflammation and bone loss. Wien Med Wochenschr 156(1–2):34–41CrossRefPubMedGoogle Scholar
  3. 3.
    Neumann E, Lefèvre S, Zimmermann B, Gay S, Müller-Ladner U (2010) Rheumatoid arthritis progression mediated by activated synovial fibroblasts. Trends Mol Med 16:458–468CrossRefPubMedGoogle Scholar
  4. 4.
    Lipsky PE (2007) Why does rheumatoid arthritis involve the joints? N Engl J Med 356:2419–2420CrossRefPubMedGoogle Scholar
  5. 5.
    Akhter E, Bilal S, Kiani A, Haque U (2011) Prevalence of arthritis in India and Pakistan: a review. Rheumatol Int 31(7):849–855CrossRefPubMedGoogle Scholar
  6. 6.
    Khurana R, Berney SM (2005) Clinical aspects of rheumatoid arthritis. Pathophysiology 12:153–165CrossRefPubMedGoogle Scholar
  7. 7.
    Silman AJ, Hochberg MC (2001) Epidemiology of the rheumatic diseases, 2nd edn. Oxford University Press, OxfordGoogle Scholar
  8. 8.
    Turk SA, van Beers-Tas MH, van Schaardenburg D (2014) Prediction of future rheumatoid arthritis. Rheum Dis Clin North Am 40(4):753–770CrossRefPubMedGoogle Scholar
  9. 9.
    Chang K, Yang SM, Kim SH, Han KH, Park SJ, Shin JI (2014) Smoking and rheumatoid arthritis. Int J Mol Sci 15(12):22279–22295CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Yazar M, Sarban S, Kocyigit A, Isikan UE (2005) Synovial fluid and plasma selenium, copper, zinc, and iron concentrations in patients with rheumatoid arthritis and osteo arthritis. Biol Trace Elem Res 106(2):123–132CrossRefPubMedGoogle Scholar
  11. 11.
    Mertz W (1981) The essential trace elements. Science 213(4514):1332–1338CrossRefPubMedGoogle Scholar
  12. 12.
    Overbeck S, Rink L, Haase H (2008) Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Arch Immunol Ther Exp (Warsz) 56:15–30CrossRefGoogle Scholar
  13. 13.
    Prasad AS (2008) Zinc in human health: effect of zinc on immune cells. Mol Med 14:353–357CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Choy EH, Panayi GS (2001) Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 344:907–916CrossRefPubMedGoogle Scholar
  15. 15.
    Strecker D, Mierzecki A, Radomska K (2013) Copper levels in patients with rheumatoid arthritis. Ann Agric Environ Med 20(2):312–316PubMedGoogle Scholar
  16. 16.
    Kagan HM, Li W (2003) Lysyl oxidase: properties, specifity, and biological roles inside and outside of the cell. J Cell Biochem 88(4):660–672CrossRefPubMedGoogle Scholar
  17. 17.
    Schümann K, Classen HG, Dieter HH, König J, Multhaup G, Rükgauer M, Summer KH, Bernhardt J, Biesalski HK (2002) Hohenheim consensus workshop: copper. Eur J Clin Nutr 56:469–483CrossRefPubMedGoogle Scholar
  18. 18.
    Zago MP, Oteiza PI (2001) The antioxidant properties of zinc: interactions with iron and antioxidants. Free Radic Biol Med 31:266–274CrossRefPubMedGoogle Scholar
  19. 19.
    Chen H, Huang G, Su T, Gao H, Attieh ZK, McKie AT, Anderson GJ, Vulpe CD (2006) Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency. J Nutr 136:1236–1241PubMedGoogle Scholar
  20. 20.
    Swerlick RA, Korman NJ (2004) UVA and NF-B activity: ironing out the details. J Invest Dermatol 122:xi–xiCrossRefPubMedGoogle Scholar
  21. 21.
    Afridi HI, Kazi TG, Kazi N, Talpur FN, Shah F, Naeemullah FS, Arain SS, Brahman KD (2013) Evaluation of status of arsenic, cadmium, lead and zinc levels in biological samples of normal and arthritis patients of age groups (46–60) and (61–75) years. Clin Lab 59(1–2):143–153PubMedGoogle Scholar
  22. 22.
    Afridi HI, Kazi TG, Kazi N, Shah F (2012) Evaluation of status of zinc, copper, and iron levels in biological samples of normal and arthritis patients in age groups 46–60 and 61–75 years. Clin Lab 58(7–8):705–717PubMedGoogle Scholar
  23. 23.
    Afridi HI, Kazi TG, Brabazon D, Naher S (2012) Interaction between zinc, cadmium, and lead in scalp hair samples of Pakistani and Irish smokers rheumatoid arthritis subjects in relation to controls. Biol Trace Elem Res 148(2):139–147CrossRefPubMedGoogle Scholar
  24. 24.
    Nisa FU, Mumtaz A, Ullah MI, Atif M, Sami W (2014) Determination of serum zinc and magnesium levels in patients with hypothyroidism. Trace Elem Electroly 31:43–47CrossRefGoogle Scholar
  25. 25.
    Doran MF, Pond GR, Crowson CS, O'Fallon WM, Gabriel SE (2002) Trends in incidence and mortality in rheumatoid arthritis in Rochester, Minnesota, over a forty-year period. Arthritis Rheum 46(3):625–631CrossRefPubMedGoogle Scholar
  26. 26.
    Charles J, Britt H, Pan Y (2013) Rheumatoid arthritis. Aust Fam Physician 42(11):765PubMedGoogle Scholar
  27. 27.
    Cooper GS, Bynum ML, Somers EC (2009) Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun 33:197–207CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM (2002) How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum 46(2):357–365CrossRefPubMedGoogle Scholar
  29. 29.
    Harrison MJ, Farragher TM, Clarke AM, Manning SC, Bunn DK, Symmons DP (2009) Association of functional outcome with both personal and area-level socioeconomic inequalities in patients with inflammatory polyarthritis. Arthritis Rheum 61:1297–1304CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Camacho EM, Verstappen SM, Symmons DP (2012) Association between socioeconomic status, learned helplessness, and disease outcome in patients with inflammatory polyarthritis. Arthritis Care Res 64(8):1225–1232Google Scholar
  31. 31.
    Brewer GJ (2003) Copper in medicine. Curr Opin Chem Biol 7:207–212CrossRefPubMedGoogle Scholar
  32. 32.
    Mayadah H, AL-Jamma S, Saad M, Alhasani, Mowafak K, Hassan (2010) Serum concentration of zinc copper, manganese and iron in rheumatoid arthritis. Raf J Sci 21(2):19–28Google Scholar
  33. 33.
    Söderlin MK, Petersson IF, Geborek P (2012) The effect of smoking on response and drugsurvival in rheumatoid arthritis patients treated with their first anti-TNF drug. Scand J Rheumatol 41(1):1–9CrossRefPubMedGoogle Scholar
  34. 34.
    Önal S, Nazıroğlu M, Çolak M, Bulut V, Flores-Arce MF (2011) Effects of different medical treatments on serum copper, selenium and zinc levels in patients with rheumatoid arthritis. Biol Trace Elem Res 142:447–455CrossRefPubMedGoogle Scholar
  35. 35.
    Sahebari M, Ayati R, Mirzaei H, Sahebkar A, Hejazi S, Saghafi M, Saadati N, Ferns GA, Ghayour-Mobarhan M. (2015) Serum trace element concentrations in rheumatoid arthritis. Biol Trace Elem ResGoogle Scholar
  36. 36.
    Mazzetti I, Grigolo B, Borzì RM, Meliconi R, Facchini A (1996) Serum copper and zinc superoxide dismutase levels in patients with rheumatoid arthritis. Int J Clin Lab Res 26:245CrossRefPubMedGoogle Scholar
  37. 37.
    Taneja SK, Mandal R (2009) Assessment of mineral status (Zn, Cu, Mg and Mn) in rheumatoid arthritis patients in Chandigarh, India. Rheumatol Rep 1(1):e5CrossRefGoogle Scholar
  38. 38.
    Louro MO, Cocho JA, Mera A, Tutor JC (2000) Immunochemical and enzymatic study of ceruloplasmin in rheumatoid arthritis. J Trace Elem Med Biol 14(3):174–178CrossRefPubMedGoogle Scholar
  39. 39.
    Colak M, Bingol NK, Ayhan O, Avci S, Bulut V (2001) Serum copper, zinc and selenium levels in rheumatoid arthritis. Romatizma Cilt 16(2):66–71Google Scholar
  40. 40.
    Farid YZ, Mohammed AK, Mohammed IS (2005) Serum copper and zinc levels and copper/zinc ratio in patients with rheumatoid arthritis. Iraqi J Med Sci 4(1):49–56Google Scholar
  41. 41.
    Ala S, Shokrzadeh M, Pur Shoja AM, Saeedi Saravi SS (2009) Zinc and copper plasma concentrations in rheumatoid arthritis patients from a selected population in Iran. Pak J Biol Sci 12(14):1041–1044CrossRefPubMedGoogle Scholar
  42. 42.
    Mierzecki A, Strecker D, Radomska K (2011) A pilot study on zinc levels in patients with rheumatoid arthritis. Biol Trace Elem Res 143:854–862CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    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 1 beta and tumor necrosis factor alpha. Clin Rheumatol 17(5):378–382CrossRefPubMedGoogle Scholar
  44. 44.
    Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, Knutson MD, Ganz T, Cousins RJ (2005) Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci U S A 02:6843–6848CrossRefGoogle Scholar
  45. 45.
    Kim S, Watanabe K, Shirahata T, Watarai M (2004) Zinc uptake system (znuA locus) of Brucellaabortus is essential for intracellular survival and virulence in mice. J Vet Med Sci 66:1059–1063CrossRefPubMedGoogle Scholar
  46. 46.
    Huda MA, Al-Zubaidi MA (2012) Evaluation of trace elements in iraqi patients with rheumatoid arthritis by using atomic absorption spectrophotometer. Iraqi J Pharm Sci 21(2):77–84Google Scholar
  47. 47.
    Nikolaisen C, Figenschau Y, Nossent JC (2008) Anaemia in early RA is associated with interleukin 6-mediated bone marrow suppression, but has no effect on disease course or mortality. J Rheumatol 35(3):380–386PubMedGoogle Scholar
  48. 48.
    Powanda MC, Biesel WR (1982) Hypothesis: leukocyte endogenous mediator/endogenous pyrogen/lymphocyte-activating factor modulates the development of nonspecific and specific immunity and affects nutritional status. Am J Clin Nutr 35:23–29Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of BiochemistryUniversity of Health SciencesLahorePakistan
  2. 2.Department of Biochemistry, Faculty of Biological SciencesQuaid i Azam University IslamabadIslamabadPakistan
  3. 3.Research Laboratories, Shifa College of MedicineShifa Tameer-e-Millat University IslamabadIslamabadPakistan
  4. 4.Department of Physiology and Cell BiologyUniversity of Health SciencesLahorePakistan

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