Therapeutic Efficacy of Intermittent Ketogenesis in Modulating Adenosine Metabolism, Immune Response, and Seizure Severity in Refractory Temporal Lobe Epilepsy: A Pilot Human Study.

Abstract

Temporal lobe epilepsy (TLE) is a common neurological disorder characterized by recurrent seizures originating in the temporal lobe, often affecting patients' physical, cognitive, and social well-being. Despite the availability of antiseizure medication (ASMs), approximately 30% of TLE patients exhibit drug-resistant seizures, emphasizing the need for alternative therapeutic approaches. Ketogenic diets, known for their anticonvulsant effects, have shown promise in managing drug-resistant epilepsy. However, their demanding high-fat, low-carbohydrate regimens pose significant adherence challenges. Medium-chain triglyceride (MCT) offers a viable alternative by inducing ketosis periodically without the need for continuous dietary restrictions. This study evaluated seizure severity, biochemical markers, and immune-related factors in TLE patients. The intervention group received neuro-Capridin caprylate and caprate (n-CAP), while the control group did not. Significant findings included increased plasma ATP and adenosine levels in the treatment group, along with higher expression of ADORA1 and CD73 and reduced expression of ADK. Corresponding protein changes were observed, with increased CD73 and decreased ADK levels. Caprylate and Caprate also elevated regulatory T cells and reduced proinflammatory cytokines (TNF-α, IL-6, IL-1β). These changes were associated with significant reductions in seizure severity and frequency. Intermittent ketogenesis through the consumption of Caprylate and Caprate effectively reduced seizures and improved immune and metabolic markers in drug-resistant TLE patients. These findings highlight its potential as a complementary therapy, warranting further exploration of its long-term impact and underlying molecular mechanisms.