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

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.