The Neuroprotective Effects of Alpha-Tocopherol as an Anti-Inflammatory Agent: Mechanistic Insights and Therapeutic Challenges

Vitamin E (alpha-tocopherol, αToc), an antioxidant fat-soluble vitamin that prevents lipid peroxidation and modulates pro-inflammatory cytokine production, is well-known to be critical for neuroprotection. However, the underlying mechanism remains poorly understood. Accumulating evidence demonstrates that αToc influences neuroinflammatory processes. Here, we review recent research progress on the effects of αToc on neuroinflammation. Preclinical studies included in this narrative review were identified through PubMed searches using the keywords "alpha-tocopherol AND neuroinflammation or alpha-tocopherol AND brain AND inflammation". While many studies support a neuroprotective role of αToc, the magnitude and direction of its effects vary substantially depending on dosage, route of administration, types of αToc substance, sex, and experimental design. The conclusions of this review apply only to αToc and should not be extrapolated to other vitamin E isoforms. Collectively, these findings suggest that αToc exerts beneficial effects primarily under specific conditions, and that a deeper understanding of the neural mechanisms mediating its neuroprotective actions may facilitate the optimization of therapeutic strategies for neuroinflammatory diseases.