Tobacco Smoking and Alcohol Consumption as Risk Factors for Multiple Sclerosis Onset: A Systematic and Meta-Analyze...

Multiple sclerosis (MS) is a chronic immune-mediated disease influenced by genetic and environmental factors. Tobacco smoking and alcohol consumption are prevalent modifiable lifestyle behaviors potentially affecting MS risk, yet evidence of a role played by these factors in MS risk remains inconsistent, particularly for alcohol. To provide important information on risk and enable more robust conclusions for research and public health, we conducted a systematic review and meta-analysis to synthesize observational evidence regarding the association between tobacco smoking, alcohol consumption, and the risk of developing MS. Accordingly, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched PubMed/MEDLINE and Google Scholar for English-language observational studies published between January 2010 and January 2025. Eligible studies reported adjusted effect estimates for smoking or alcohol exposure and MS onset. Risk of bias was assessed using the Newcastle-Ottawa Scale; high-bias studies were excluded. Adjusted odds ratios (ORs) were pooled using random-effects meta-analysis (restricted maximum likelihood method). Heterogeneity was evaluated with I2 and τ2 statistics and explored via meta-regression. Eighteen studies were included (11 on smoking, 9 on alcohol). Smoking was associated with a significantly increased MS risk (pooled OR 1.40, 95% confidence interval [CI] 1.33-1.49; I2 = 34.3%). Alcohol consumption showed no significant association (pooled OR 1.11, 95% CI 0.78-1.56; I2 = 87.9%), with substantial unexplained heterogeneity. We conclude from our review of the literature that tobacco smoking is a consistent risk factor for the onset of MS, indicating the need for targeted cessation interventions. In contrast, alcohol consumption shows no clear overall effect; however, the heterogeneity of findings present in the literature, which appeared to be largely driven by a few high-impact studies, emphasizes the need for standardized future research.