Intermittent fasting with medium‐chain triglycerides in drug‐resistant epilepsy: A pilot crossover trial

OBJECTIVE: Ketogenic dietary therapies can reduce seizure frequency in drug-resistant epilepsy, but adherence to the classical ketogenic diet is often poor. Intermittent fasting supplemented with medium-chain triglycerides (MCTs) may offer a more feasible and less restrictive alternative. We assessed whether 16:8 intermittent fasting with exogenous MCT supplementation improves seizure outcomes in adults with drug-resistant epilepsy. METHODS: This prospective, single-center, two-period crossover pilot trial included adults (≥18 years) with drug-resistant epilepsy and at least three seizures per month during the initial 4-week baseline period. Participants completed two, 12-week intervention periods-(1) 16:8 intermittent fasting plus MCT supplementation (IF-MCT) and (2) 16:8 intermittent fasting alone (IF)-separated by a 4-week washout period. Participants were allocated 1:1 to the initial sequence using deterministic alternating allocation. The primary endpoint was seizure frequency during IF-MCT compared with IF and standard therapy during the baseline period. The trial was registered with ClinicalTrials.gov (NCT06013761). RESULTS: Of 36 enrolled participants, 22 completed both intervention periods with evaluable seizure diary data and were included in per-protocol analyses. During IF-MCT, two participants (9%) achieved sustained seizure freedom. In post hoc analyses, the proportion of participants achieving earlier ≥50% seizure reduction was numerically higher during IF-MCT than during IF (Breslow: p = .233), although not statistically significant. Concentrations of ketone bodies and octanoic and decanoic acids increased during IF-MCT, without an apparent correlation with seizure reduction. SIGNIFICANCE: In this exploratory crossover pilot trial, intermittent fasting combined with MCT supplementation was associated with a numerical, although not statistically significant, reduction in seizure frequency compared with intermittent fasting alone in adults with drug-resistant epilepsy. Although the study was not powered to detect definitive differences, the observed trend suggests a potential signal of efficacy. As one of the first studies to evaluate this combined dietary approach using a crossover design, the results support further investigation in larger, adequately powered multicenter efficacy trials.