Levetiracetam and Peripheral Oxidative Stress Biomarkers in Epilepsy: A Systematic Review of Human Evidence.

Oxidative stress is implicated in epilepsy, but seizures, disease severity, diet, comorbidity and treatment all influence circulating redox biomarkers. We systematically reviewed human evidence on levetiracetam (LEV) under three estimands: within-person change, LEV-treated epilepsy versus healthy controls, and LEV versus other antiseizure medications. PubMed/MEDLINE, Cochrane Library, Web of Science and Scopus were searched from inception to 15 July 2026 (PROSPERO CRD420261448016; OSF HXA4U). Eleven non-randomized studies contributed 297 participants-the sum of LEV subgroups with analysable biomarker data, not the total enrolled populations. Effect estimates with 95% confidence intervals were calculated here wherever reporting permitted; none could be derived for four studies, and those derived are wide, inconsistent in direction, or from designs that cannot attribute change to LEV. Meta-analysis was inappropriate: definitions, matrices, assays, estimands and variance reporting were incompatible. Certainty was very low for every outcome-domain/comparator body, and a sensitivity analysis excluding one report failing a post hoc source-verifiability check (10 studies, 265 participants) changed no conclusion. This review's contribution is not an estimate of LEV's redox effect but a demonstration of why the literature cannot establish one: the human evidence is not of sufficient validity to support or refute such an effect.