Ketogenic Diet Therapy in Adolescents With Drug‐Resistant Epilepsy: An Insight From Efficacy, Mechanisms, and Clinical Applications

Epilepsy is a chronic neurological disorder marked by recurrent seizures and psychological consequences, affecting about 1% of the population. The etiology of epilepsy, according to the latest International League Against Epilepsy classification, includes structural, infectious, genetic, immune, metabolic, and unknown categories based on the underlying mechanisms. Standard treatments include anti‐seizure medications, surgery, and neuromodulation techniques such as vagus nerve stimulation and responsive neurostimulation, which reduce seizures but seldom provide a cure. Around one‐third of adolescents develop drug‐resistant epilepsy (DRE), which severely impairs mental health and quality of life, highlighting the need for alternative therapies. The ketogenic diet (KD), a high‐fat, low‐carbohydrate regimen, is a promising non‐pharmacological option. KD shifts metabolism from glucose to ketone bodies produced by the liver, stabilizing neuronal function, improving cognition, and reducing seizures. Clinical data show roughly 30% of DRE patients on KD achieve ≥ 50% seizure reduction, and some become seizure‐free. KD variants allow personalized treatment: the classic KD is most restrictive and effective for refractory cases; the medium‐chain triglyceride (MCT) diet is more flexible while boosting ketogenesis; the modified Atkins diet (MAD) is easier and popular with adolescents; and the low glycemic index treatment (LGIT) offers the fewest restrictions for lower‐risk patients. Despite its effectiveness, KD can pose social and nutritional challenges and carry potential side effects, so monitoring is essential. Nevertheless, KD remains a valuable, evidence‐based adjunct for managing DRE, can improve seizure control, and overall quality.