Dietary interventions targeting the neurolipidome in epilepsy: From preclinical models to clinical applications and future therapeutic approaches

Epilepsy is a neurological disorder affecting approximately 50 million people globally and is characterised by recurrent, unprovoked seizures resulting from abnormal, excessive synchronised firing of neurons. Developing new therapeutic targets and biomarkers is key to improving the diagnosis, treatment, and management. This scoping review examines the current literature on the preclinical and clinical applications of dietary interventions that target the neurolipidome in epilepsy. Specifically, it investigates the role of lipids in the underlying pathogenesis of epilepsy. A comprehensive search of databases was conducted to identify peer-reviewed articles published in the past ten years. Original research articles focusing on both adult and paediatric epilepsy and disrupted lipid metabolism were included, resulting in a total of 101 papers. Our review identified several key lipids implicated in the pathogenesis of epilepsy, including sphingolipids, free fatty acids, endocannabinoids, cholesterol, triglycerides, and phospholipids, and also explores the complex interactions between these lipids and their roles in the disease process. Furthermore, our study highlighted that the Ketogenic Diet (KD) and Modified Atkins Diet (MAD) have proven effective adjunctive or alternative treatments in paediatric and adult populations, improving patient quality of life and reducing seizure frequency. Additionally, treatment with lipid-based supplements, such as eicosapentaenoic acid, docosahexaenoic acid, fish oil, and cannabidiol, has been associated with a reduction in seizure rates in patients with drug-resistant epilepsy. In summary, findings from this study indicate that KD and MAD lipid-based supplements are effective for managing epilepsy in paediatrics, adults, and animal models. However, further research is necessary to elucidate the pathophysiological mechanisms underlying the role of lipids in the development and progression of epilepsy.