Abstract
The association between alcohol consumption and Parkinson's disease (PD) risk remains unclear, whereas smoking has an inverse relationship with the disease. This study systematically reviewed and meta-analyzed 16 studies (2014-2024) from PubMed, Scopus, Web of Science, MEDLINE, and the Cochrane Library to assess the relationship between alcohol intake and PD risk, examining sex differences, dose-response patterns, smoking interactions, and genetic factors. Alcohol consumption was classified as low, moderate, or heavy, considering beverage type, sex, smoking status, and gene-environment interactions. Random-effects meta-analyses were used to evaluate sex-stratified and subtype-specific associations. PD progression, Mendelian randomization (MR), and gene-environment results were narratively synthesized. Sex-stratified analyses showed inverse associations between alcohol consumption and PD risk versus non-drinkers (lifetime relative risk [LRR] = -0.35 to -0.62), with significant effects in women and no association in low-level drinkers. Subtype analyses indicated protective effects for liquor (RR = -0.12) and wine (RR = -0.16), but not for low-level drinkers. Combined alcohol and smoking exposure produced the greatest PD risk reduction (LRR = -0.37), with pooled estimates confirming an inverse association (LRR = -0.20, I(2) = 90.1%). However, MR and gene-environment studies showed inconsistent evidence. Light-to-moderate alcohol consumption, particularly wine and liquor, may reduce PD risk, with the strongest effects when combined with smoking. These findings highlight the combined effects of sex, genetic susceptibility, and lifestyle factors. Further longitudinal and MR studies stratified by sex and genotype are needed to elucidate the mechanisms; however, smoking cannot be recommended due to its detrimental effects. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.