Antioxidants and Parkinson's Disease: A Systematic Review and Meta‐Analysis of Research Evidence and Prospectives Using the Drosophila Model

ABSTRACT Parkinson's disease (PD) is the second most common neurodegenerative disorder, marked by oxidative damage to dopaminergic neurons in the substantia nigra, resulting in motor and non‐motor symptoms. Antioxidant supplements have emerged as a potential therapeutic strategy, particularly for forms unresponsive to Levodopa. Due to the limitations of human studies, animal models, especially Drosophila , have been widely used to investigate sporadic and familial PD. This systematic review and meta‐analysis aimed to evaluate the effectiveness of antioxidants in mitigating PD symptoms. We searched PubMed, Web of Science, and Google Scholar for studies published between 2000 and December 4, 2024, excluding reviews and irrelevant models or diseases. Methodological quality was assessed using the SYRCLE tool, and 82 studies met the inclusion criteria. A random‐effects model was applied using MetaEasy. Antioxidants such as terpenoids (effect size = 3.23), flavonoids (1.68), plant extracts (2.95), and others like vitamin C, melatonin, and Gastrodin (3.61) significantly improved PD outcomes. However, high heterogeneity across studies persisted. This variability may reflect differences in study design and execution. This heterogeneity may arise due to the methodological variations across studies. Our meta‐analysis highlighted the potential role of antioxidants in managing PD referring to key considerations for future research in this area.