Can Omega-3 fatty acid supplementation support the clinical management of drug-resistant epilepsy? A meta-analysis of randomized controlled trials

Approximately 30-40% of individuals with epilepsy develop drug-resistant epilepsy (DRE), a condition associated with substantial socioeconomic and psychological burdens for patients and their families. As standard anti-epileptic therapies often prove insufficient, alternative treatments have become a critical area of research. Dietary interventions, such as the ketogenic diet, have shown promise, and emerging evidence highlights the potential role of omega-3 fatty acids, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), due to their neuroprotective and anticonvulsant properties. However, the clinical application of omega-3 fatty acids for DRE remains uncertain due to limited high-quality randomized controlled trials (RCTs). To address this gap, we conducted a meta-analysis incorporating newly published RCTs to evaluate the clinical efficacy of omega-3 fatty acid supplementation as an adjunct to standard anti-epileptic medications in both children and adults with DRE. Our meta-analysis, incorporating high-quality RCTs, provides moderate-certainty evidence that omega-3 fatty acid supplementation, particularly at doses between 0.3 and 1.7 g/day, is associated with a reduction in seizure frequency in individuals with DRE. Notably, larger RCTs (sample size >30) demonstrated more consistent favorable outcomes. However, the evidence primarily reflects short-term effects, as the majority of included studies were of limited duration. These findings underscore the potential role of omega-3 fatty acids as an adjunctive therapy for DRE while highlighting the need for larger, long-term trials to better understand their clinical utility.