Selenium and Other Trace Elements in the Etiology of Parkinson's Disease: A Systematic Review and Meta-Analysis of Case-Control Studies

Neuroepidemiology. 2020;54(1):1-23. doi: 10.1159/000502357. Epub 2019 Aug 27.


Background: Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's dementia. Whereas the exact etiology of PD remains unknown, risk of developing PD seems to be related to a combination of genetic and environmental factors. This also includes abnormal exposure to trace elements of nutritional and toxicological interest.

Objectives: In this systematic review and meta-analysis, we summarized the results of case-control studies comparing levels of selenium, copper, iron, and zinc in PD patients and controls in either blood (whole blood, serum/plasma) or cerebrospinal fluid (CSF).

Methods: We performed a systematic PubMed search selecting studies reporting trace element levels in different specimens of patients and controls. We performed a meta-analysis using a random-effect model to compute the weighted mean differences (WMD) and corresponding 95% CI of selenium, copper, iron, and zinc levels in the blood or CSF of patients and their matched controls.

Results: We retrieved 56 papers reporting data for selenium (cases/controls: 588/721), copper (2,190/2,522), iron (2,956/3,469), and zinc (1,798/1,913) contents in CSF and blood. Cases showed considerably higher levels of selenium in CSF compared with controls (+51.6%; WMD 5.49; 95% CI 2.82 to 8.15), while levels in serum were similar (-0.2%; WMD -0.22; 95% CI -8.05 to 7.62). For copper, cases showed slightly higher levels in CSF and slightly lower concentrations in serum (+4.5%; WMD 1.87; 95% CI -3.59 to 7.33, and -4.5%; WMD -42.79; 95% CI -134.35 to 48.76, respectively). A slight increase was also found for CSF iron -levels (+9.5%; WMD 9.92; 1.23 to 18.61), while levels were -decreased in serum/plasma (-5.7%; WMD -58.19; 95% CI -106.49 to -9.89) and whole blood (-10.8%; WMD -95.69; 95% CI -157.73 to -33.65). Conversely, for zinc cases exhibited lower levels both in CSF (-10.8%; WMD -7.34; 95% CI -14.82 to 0.14) and serum/plasma (-7.5%; WMD -79.93; 95% CI -143.80 to -16.06). A longer duration of the disease tends to be associated with overall lower trace element levels in either CSF or blood.

Conclusions: Due to the study findings and the greater relevance of the CSF compartment compared with the circulating peripheral ones, this meta-analysis suggests that overexposure in the central nervous system to selenium, and possibly to copper and iron, may be a risk factor of the disease, while zinc might have a protective -effect.

Keywords: Copper; Etiology; Iron; Parkinson’s disease; Selenium; Zinc.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Case-Control Studies
  • Humans
  • Parkinson Disease / etiology*
  • Selenium* / adverse effects
  • Selenium* / blood
  • Selenium* / cerebrospinal fluid
  • Trace Elements* / adverse effects
  • Trace Elements* / blood
  • Trace Elements* / cerebrospinal fluid


  • Trace Elements
  • Selenium