Nicotine Exposure and Parkinson's Disease: A Systematic Review and Meta-Analysis of Experimental Evidence
Nicotine Exposure and Parkinson's Disease: A Systematic Review and Meta-Analysis of Experimental Evidence
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Original abstract
Background: The relationship between nicotine exposure and Parkinson’s disease (PD) remains controversial. Experimental studies, particularly preclinical trials in animal models, suggest that nicotine may exert neuroprotective effects; however, this has not been adequately addressed in randomized controlled trials (RCTs) involving humans. Methods: Comprehensive searches of PubMed, Web of Science, Scopus, and Google Scholar identified 1,363 studies, of which 13 met the inclusion criteria. Random-effects meta-analysis was conducted using RevMan 5.4 and R 4.1.1. Heterogeneity was assessed using the I² statistic, publication bias using funnel plots and Egger’s test, and study quality using SYRCLE and ToxRTool criteria. The review followed PRISMA guidelines and was registered in PROSPERO (CRD420250633808). Results: Nicotine significantly reduced apoptosis (RR, 0.49; 95% CI, 0.34–0.71), oxidative stress (RR, 0.55; 95% CI, 0.41–0.73), and neuroinflammation (RR, 0.62; 95% CI, 0.49–0.79), while enhancing dopaminergic neuron survival (RR, 1.67; 95% CI, 1.35–2.06), mitochondrial function (RR, 1.55; 95% CI, 1.12–2.14), synaptic protein expression (RR, 1.52; 95% CI, 1.14–2.04), and dendritic spine density (RR, 1.47; 95% CI, 1.19–1.83). The only human randomized trial showed no clinical benefit (RR, 1.00; 95% CI, 0.84–1.49). Subgroup and meta-regression analyses identified study design, dose, duration, and model type as sources of heterogeneity. Our findings suggest that although nicotine shows preclinical promise, clinical efficacy remains unproven. Conclusion: Experimental evidence suggests that nicotine exposure confers neuroprotection against PD, however, clinical efficacy remains unproven, underscoring the need for large-scale mechanistic and translational studies to establish causal relationships in humans.