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

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.

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).

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.

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.