Abstract
Stroke remains a leading cause of disability and mortality worldwide, and the preventive role of antioxidants is of great clinical interest. The present study aimed to clarify the relationship between circulating α-tocopherol and stroke by performing a meta-analysis of prospective studies. The Web of Knowledge, Embase, Scopus, Cochrane Library and PubMed databases were searched through January 2026 for relevant studies. Risk ratios (RRs) and the corresponding 95% confidence intervals (CIs) were extracted to estimate the association of circulating α-tocopherol with stroke risk. In total, six cohort studies involving 104,209 participants and 2,194 events were identified. The results indicated that a high circulating α-tocopherol level was associated with a 22% lower stroke risk (RR, 0.78; 95% CI, 0.70-0.87). Additionally, a higher circulating α-tocopherol level was associated with a reduced stroke risk in the ischemic stroke (RR, 0.80; 95% CI, 0.72-0.90), body mass index >25 (RR, 0.80; 95% CI, 0.72-0.89), physical activity adjusted (RR, 0.69; 95% CI, 0.57-0.84) and physical activity not adjusted (RR, 0.83; 95% CI, 0.73-0.94) subgroups, but not for the hemorrhagic stroke (RR, 0.65; 95% CI, 0.41-1.01) subgroup. Dose-response analysis indicated that each 5 mg/l increment in circulating α-tocopherol was associated with an average 8% lower stroke risk (RR, 0.92; 95% CI, 0.85-0.98). In conclusion, the findings of the present meta-analysis indicates that an increased circulating α-tocopherol level may be related to lower ischemic but not hemorrhagic stroke risk. Notably, while physical activity is a critical determinant of stroke risk, the protective association of α-tocopherol remains significant and is further strengthened after accounting for this factor. This suggests that α-tocopherol may play a vital role in stroke prevention, particularly within the context of active lifestyle management.