Skip to main content

Association Between Serum Zinc Levels and the Risk of Parkinson’s Disease: a Meta-Analysis


Recent studies have found that the serum zinc levels were associated with the risk of Parkinson’s disease (PD), but the results were inconsistent. Thus, we conducted a meta-analysis to summarize the evidence from observational studies between them. Pertinent studies were identified by a search in PubMed, Embase, and Web of science up to July, 10, 2016. Standardized mean difference (SMD) and 95% confidence intervals (CI) with random-effect model was used to combine the results. Subgroup analysis and meta-regression were also conducted. Publication bias was estimated using Begg’s regression asymmetry test. A total of 11 articles involving 822 PD patients and 777 healthy controls were included in the meta-analysis. Our meta-analysis results revealed that the serum zinc levels in PD patients were significantly lower than those in health controls (SMD = −0.779, 95%CI = [−1.323, −0.234], P < 0.001). The association was also significant oriental studies (SMD = −1.601, 95%CI = [−2.398, −0.805], P < 0.001). No publication bias was found. The current study indicated that serum zinc levels in PD patients were significantly lower than those in healthy controls.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3


  1. 1.

    Forno LS (1996) Neuropathology of Parkinson’s disease. J Neuropathol Exp Neurol 55(3):259–272

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Tanner CM, Goldman SM (1996) Epidemiology of Parkinson’s disease. Neurol Clin 14(2):317–335

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Nussbaum RL, Ellis CE (2003) Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348(14):1356–1364. doi:10.1056/NEJM2003ra020003

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Chen S, Zheng JC (2012) Translational Neurodegeneration, a platform to share knowledge and experience in translational study of neurodegenerative diseases. Translational Neurodegeneration 1(1):1. doi:10.1186/2047-9158-1-1

    Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Hirsch EC, Vyas S, Hunot S (2012) Neuroinflammation in Parkinson’s disease. Parkinsonism Relat Disord 18(Suppl 1):S210–S212. doi:10.1016/s1353-8020(11)70065-7

    Article  PubMed  Google Scholar 

  6. 6.

    Sohmiya M, Tanaka M, Tak NW, Yanagisawa M, Tanino Y, Suzuki Y, Okamoto K, Yamamoto Y (2004) Redox status of plasma coenzyme Q10 indicates elevated systemic oxidative stress in Parkinson’s disease. J Neurol Sci 223(2):161–166. doi:10.1016/j.jns.2004.05.007

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Shazia Q, Mohammad ZH, Rahman T, Shekhar HU (2012) Correlation of oxidative stress with serum trace element levels and antioxidant enzyme status in Beta thalassemia major patients: a review of the literature. Anemia 2012:270923. doi:10.1155/2012/270923

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Forsleff L, Schauss AG, Bier ID, Stuart S (1999) Evidence of functional zinc deficiency in Parkinson’s disease. Journal of alternative and complementary medicine (New York, NY) 5(1):57–64. doi:10.1089/act.1999.5.57

    CAS  Article  Google Scholar 

  9. 9.

    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol 62(10):1006–1012. doi:10.1016/j.jclinepi.2009.06.005

    Article  PubMed  Google Scholar 

  10. 10.

    Stang A (2010) Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol 25(9):603–605. doi:10.1007/s10654-010-9491-z

    Article  PubMed  Google Scholar 

  11. 11.

    Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558. doi:10.1002/sim.1186

    Article  PubMed  Google Scholar 

  12. 12.

    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ (Clinical research ed) 327(7414):557–560. doi:10.1136/bmj.327.7414.557

    Article  Google Scholar 

  13. 13.

    DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Rosenthal L, Schisterman E (2010) Meta-analysis: drawing conclusions when study results vary. Methods in molecular biology (Clifton, NJ) 594:427–434. doi:10.1007/978-1-60761-411-1_30

    Article  Google Scholar 

  15. 15.

    Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24(9):1291–1306. doi:10.1002/sim.2010

    Article  PubMed  Google Scholar 

  16. 16.

    Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ (Clinical research ed) 315(7109):629–634

    CAS  Article  Google Scholar 

  17. 17.

    Jiménez-Jiménez FJ, Molina JA, Aguilar MV, Meseguer I, Mateos-Vega CJ, González-Muñoz MJ, De Bustos F, Martínez-Salio A, Ortí-Pareja M, Zurdo M, Martínez-Para MC (1998) Cerebrospinal fluid levels of transition metals in patients with Parkinson’s disease. J Neural Transm 105(4–5):497–505

    Article  PubMed  Google Scholar 

  18. 18.

    Forte G, Alimonti A, Pino A, Stanzione P, Brescianini S, Brusa L, Sancesario G, Violante N, Bocca B (2005) Metals and oxidative stress in patients with Parkinson’s disease. Annali dell’Istituto superiore di sanita 41(2):189–195

    CAS  PubMed  Google Scholar 

  19. 19.

    Qureshi GA, Qureshi AA, Memon SA, Parvez SH (2006) Impact of selenium, iron, copper and zinc in on/off Parkinson’s patients on L-dopa therapy. J Neural Transm Suppl 71:229–236

    CAS  Article  Google Scholar 

  20. 20.

    Gellein K, Syversen T, Steinnes E, Nilsen TI, Dahl OP, Mitrovic S, Duraj D, Flaten TP (2008) Trace elements in serum from patients with Parkinson’s disease—a prospective case-control study: the Nord-Trondelag health study (HUNT). Brain Res 1219:111–115. doi:10.1016/j.brainres.2008.05.002

    CAS  Article  PubMed  Google Scholar 

  21. 21.

    Nikam S, Nikam P, Ahaley SK, Sontakke AV (2009) Oxidative stress in Parkinson’s disease. Indian Journal of Clinical Biochemistry : IJCB 24(1):98–101. doi:10.1007/s12291-009-0017-y

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ahmed SSSJ, Santosh W (2010) Metallomic profiling and linkage map analysis of early parkinson’s disease: a new insight to aluminum marker for the possible diagnosis. PLoS One 5(6)

  23. 23.

    Baillet A, Chanteperdrix V, Trocmé C, Casez P, Garrel C, Besson G (2010) The role of oxidative stress in amyotrophic lateral sclerosis and Parkinson’s disease. Neurochem Res 35(10):1530–1537

    CAS  Article  PubMed  Google Scholar 

  24. 24.

    Fukushima T, Tan X, Luo Y, Wang P, Song J, Kanda H, Hayakawa T, Kumagai T, Kakamu T, Tsuji M, Hidaka T, Mori Y (2013) Heavy metals in blood and urine and its relation to depressive symptoms in Parkinson’s disease patients. Fukushima J Med Sci 59(2):76–80

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Younes-Mhenni S, Aissi M, Mokni N, Boughammoura-Bouatay A, Chebel S, Frih-Ayed M, Kerkeni A, Bost M, Chazot G, Sfar MT, Sfar MH (2013) Serum copper, zinc and selenium levels in Tunisian patients with Parkinson’s disease. La Tunisie Medicale 91(6):402–405

    CAS  PubMed  Google Scholar 

  26. 26.

    Zhao H-W, Lin J, Wang X-B, Cheng X, Wang J-Y, Hu B-L, Zhang Y, Zhang X, Zhu J-H (2013) Assessing plasma levels of selenium, copper, iron and zinc in patients of Parkinson’s disease. PLoS One 8(12). doi:10.1371/journal.pone.0083060

  27. 27.

    Verma AK, Keshari AK, Raj J, Kumari R, Kumar T, Sharma V, Singh TB, Srivastava S, Srivastava R (2016) Prolidase-associated trace elements (Mn, Zn, Co, and Ni) in the patients with Parkinson’s disease. Biol Trace Elem Res 171(1):48–53. doi:10.1007/s12011-015-0503-4

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Ooi TC, Mohammad NH, Sharif R (2014) Zinc carnosine protects against hydrogen peroxide-induced DNA damage in WIL2-NS lymphoblastoid cell line independent of poly (ADP-ribose) polymerase expression. Biol Trace Elem Res 162(1–3):8–17. doi:10.1007/s12011-014-0153-y

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Kara E, Gunay M, Cicioglu I, Ozal M, Kilic M, Mogulkoc R, Baltaci AK (2010) Effect of zinc supplementation on antioxidant activity in young wrestlers. Biol Trace Elem Res 134(1):55–63. doi:10.1007/s12011-009-8457-z

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Eide DJ (2011) The oxidative stress of zinc deficiency. Metallomics : Integrated Biometal Science 3(11):1124–1129. doi:10.1039/c1mt00064k

    CAS  Article  Google Scholar 

Download references


This work was supported by the National Nature Science Foundation of China [grant numbers 8157315, U1204823, and 81573243], Science and Technology Foundation for Innovation Talent of Henan Province [grant number 154200510010], and Dietary Nutrition Research and Education Foundation of Danone [grant number DIC2013-06].

Author information



Corresponding author

Correspondence to Wenjie Li.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sun, H., Liu, X., Ge, H. et al. Association Between Serum Zinc Levels and the Risk of Parkinson’s Disease: a Meta-Analysis. Biol Trace Elem Res 179, 45–51 (2017).

Download citation


  • Serum zinc levels
  • Parkinson’s disease
  • Meta-analysis