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Environmental risk factors for multiple sclerosis: a comprehensive systematic review and meta-analysis
Bruno Kusznir Vitturi1, Maria Cellerino2, Daniele Boccia2
1Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel and Kiel University, Arnold-Heller-Str 3, 24105, Kiel, Germany. z_azul@hotmail.com.
Journal of Neurology
|July 15, 2025
Summary
This review identifies key environmental risk factors for multiple sclerosis (MS), including Epstein-Barr virus (EBV) and smoking. Lower vitamin D levels were associated with reduced MS risk, highlighting potential public health interventions.
Area of Science:
- Neuroscience and Immunology
- Environmental Health and Epidemiology
Background:
- Multiple sclerosis (MS) is a central nervous system demyelinating disease with complex etiology.
- Potential contributing factors include genetics, vitamin D, body mass index (BMI), infections, and smoking.
Purpose of the Study:
- To conduct the first comprehensive systematic review and meta-analysis on environmental risk factors for MS.
- To synthesize existing evidence on the role of various environmental exposures in MS etiology.
Main Methods:
- Systematic literature search of MEDLINE, SciVerse ScienceDirect, and Web of Science.
- Inclusion of original peer-reviewed articles on adult subjects with and without MS exposed to environmental risk factors.
- Qualitative and quantitative synthesis using a random-effects model for meta-analysis of pooled effect sizes (ES).
Main Results:
- 132 publications included, analyzing data from 109,626 people with MS and 16,724,390 controls.
- Significant associations found between MS and Epstein-Barr virus (EBV) (ES=1.96), Human Herpesvirus 6 (HHV-6) (ES=2.84), and Varicella-Zoster virus (ES=1.33).
- Smoking showed a positive association (ES=1.43), while lower vitamin D levels had a negative association (ES=-0.48). Adult BMI was not associated with MS.
Conclusions:
- This review provides a comprehensive overview of environmental risk factors implicated in MS etiology.
- Findings have significant implications for public health strategies, clinical management, and future research directions in MS.
