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Iron and Parkinson's disease: A systematic review and meta-analysis.

A possible association between iron serum levels and Parkinson's disease (PD) using a meta‑analytic approach was evaluated. A systematic MEDLINE search was conducted to identify published observational, case‑control studies dealing with the association between iron blood levels and PD. In both groups, iron blood levels were extracted as means and standard deviations to calculate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity of selected studies was investigated. Then, a meta-analysis was performed applying a random effects model. Possible causes of bias were also examined. A meta-regression analysis was finally conducted to investigate whether associations varied according to specified confounding factors. Of 155 studies detected by the research strategy, a total of 23 case‑control studies with full available data were selected based on the adopted criteria. A small, around zero, overall SMD of -0.052 (95% CI, -0.303-0.2) was estimated, indicating no substantial differences between groups among selected studies. High heterogeneity among studies was detected (I2=91.42%; p<0.001). By performing a meta-regression analysis considering single available demographic, geographical and clinical covariates, no significant association was detected. Based on our systematic revision and meta-analysis of available case‑control studies, there was not sufficient evidence supporting a possible significant association between iron serum levels and PD as compared to controls. Principal reasons should be sought in the elevated methodological heterogeneity we found among available studies. A particular attention should be paid on bias and confounding effects to limit heterogeneity among studies and to facilitate the summary of results.