Research Paper Volume 12, Issue 21 pp 21959—21970

Multiple System Atrophy (MSA) and smoking: a meta-analysis and mechanistic insights

Fan-Shuen Tseng1, , Xiao Deng2, , Yi-Lin Ong2, , Hui-Hua Li3, , Eng-King Tan2,4, ,

  • 1 Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
  • 2 Department of Neurology, National Neuroscience Institute, Singapore 169856, Singapore
  • 3 Department of Clinical Research, Singapore General Hospital, Singapore 169856, Singapore
  • 4 Duke-NUS Medical School, Singapore 169857, Singapore

Received: June 3, 2020       Accepted: August 19, 2020       Published: November 7, 2020
How to Cite

Copyright: © 2020 Tseng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: The association between cigarette smoking and multiple system atrophy (MSA) has been debated. We conducted a systematic review and a meta-analysis to investigate this link.

Results: We identified 161 articles from database searching and bibliographic review. Five case-control studies satisfied the inclusion and exclusion criteria, and 435 and 352 healthy controls and MSA patients were examined. The prevalence of MSA amongst ever smokers was lower compared to never smokers (aOR=0.57; 95% CI, 0.29-1.14), although this result did not reach statistical significance. This was also observed for current and former smokers, with a stronger association for current smokers (aOR=0.63 vs aOR=0.96).

Conclusions: There is a suggestion that smoking protects against MSA. Prospective studies in larger patient cohorts are required to further evaluate the cause-effect relationship and functional studies in cellular and animal models will provide mechanistic insights on their potential etiologic links.

Methods: PubMed and Cochrane Library were searched from inception to July 7, 2019 to identify case-control studies that analyzed smoking as an environmental risk or protective factor for MSA. Two authors independently extracted data and performed risk-of-bias and quality assessment. The random-effects model was assumed to account for between-study variance when pooling the crude and adjusted odds ratios.


aOR: adjusted odds ratio; cOR: crude odds ratio; MSA: Multiple System Atrophy.