Association between selenium intake and epilepsy in NHANES and an independent Chinese clinical cohort

Background Selenium is an essential micronutrient involved in antioxidant defense and neuronal homeostasis. However, the association between selenium status and epilepsy remains unclear. This study aimed to investigate the association between selenium intake and epilepsy across populations and explore related clinical characteristics. Methods A two-stage observational study was conducted. First, we analyzed cross-sectional National Health and Nutrition Examination Survey (NHANES) 2013–2020 data. Weighted logistic regression assessed the association between selenium intake and epilepsy, with serum selenium as a supplementary biomarker. Second, a hospital-based case–control study was conducted, including 94 patients with epilepsy and 92 healthy controls. Logistic regression models assessed associations between selenium intake and epilepsy; analyses of cognitive impairment and drug resistance were exploratory. Results In NHANES, higher selenium intake was associated with lower odds of epilepsy after multivariable adjustment. Compared with the lowest quartile, participants in Q2 and Q3 had significantly lower odds of epilepsy. Restricted cubic spline analysis showed a decreasing association at lower selenium intake levels, which plateaued at higher levels. Serum selenium analyses yielded consistent findings. In the clinical study, patients with epilepsy had lower selenium intake than controls. Higher selenium intake was associated with lower odds of epilepsy; exploratory associations with cognitive impairment and drug resistance were imprecise. Conclusion Selenium status was associated with epilepsy, while findings for cognitive impairment and drug resistance remain uncertain. Prospective studies and intervention trials are needed to clarify causality and the potential clinical relevance of selenium supplementation.