Keller AM, Wills O, Karahalios A, Marck CH.
Background: Tobacco smoking has been implicated in multiple sclerosis (MS) onset and progression. However, findings are dispersed across reviews with differing quality and scope. Objectives: This umbrella review synthesised systematic reviews to provide a comprehensive overview of evidence, knowledge gaps, and inform future research about the effects of exposure to combustible tobacco and the use of e-cigarettes/heated tobacco products on MS onset and progression. Method: We searched CINAHL, Embase, MEDLINE, Web of Science, Cochrane and Epistemonikos for reviews published between 2014 and March 2025. Two independent reviewers assessed eligibility, extracted data, and evaluated risk of bias using the Risk Of Bias In Systematic Reviews (ROBIS) tool. This study was prospectively registered (Prospero: CRD420251033269). Results: Eleven systematic reviews, encompassing 97 unique studies, were included. Nine systematic reviews assessed MS onset and six assessed progression. Active cigarette and waterpipe smoking were consistently associated with an increased risk of MS onset, with some evidence of a dose-response relationship. Findings for passive cigarette smoking were mixed. No association was found between prenatal smoking and MS risk. Smoking was associated with a higher risk of disability progression and progression to secondary progressive MS, particularly with higher pack-years, though findings varied. Evidence on the effects of waterpipe and prenatal smoking on MS progression, and the impact of e-cigarettes/vapes on any MS outcomes was lacking. Reviews commonly reported high heterogeneity, and all were at high risk of bias. Conclusion: Observational evidence consistently links smoking with MS onset and progression. However, methodological issues and potential biases in primary data highlight the need for future high-quality research to address limitations and investigate evidence gaps.
Mult Scler Relat Disord. 2026 Aug:112:107328
Link to Pubmed