Impact of medium-chain triglyceride with and without ketogenic diet in the management of drug-resistant epilepsy: a systematic review.
Level 1 - systematic review of randomized trials
Systematic review of randomized controlled trials and cohort studies
PubMed 42623429 · doi:10.1080/1028415X.2026.2720527
What was done
Authors conducted a systematic review searching PubMed, Web of Science, Scopus, and the Cochrane Library through April 2025 for randomized controlled trials and cohort studies evaluating medium-chain triglyceride (MCT) interventions with or without a ketogenic diet in patients with drug-resistant epilepsy. Methodological quality was evaluated using Joanna Briggs Institute tools and evidence certainty was assessed using GRADE. Because of substantial heterogeneity, data were synthesized narratively using a Synthesis Without Meta-analysis approach.
What was found
Twelve studies were analyzed (3 RCTs and 9 observational studies). The abstract provides qualitative findings without specific numerical values. One pediatric RCT showed no clear difference in seizure outcomes between an MCT ketogenic diet and the classical ketogenic diet, despite higher ketone levels on the classical diet, though statistical equivalence was not established. A small pediatric crossover trial suggested potential benefit from a decanoic acid (C10)-enriched ketogenic diet, and a small adult RCT showed a possible therapeutic signal for MCT supplementation alone. Observational studies reported baseline-to-follow-up improvements. Gastrointestinal adverse events were frequent across studies. Overall GRADE certainty of evidence was rated low to very low.
Why it matters
MCT-based dietary approaches provide a potentially more flexible alternative to the classical ketogenic diet for managing refractory epilepsy, though stand-alone MCT supplementation remains insufficiently supported by robust trial evidence.
Limits
The review could not perform a quantitative meta-analysis due to significant study heterogeneity. Most included evidence derives from observational designs subject to methodological bias and small RCTs, leaving equivalence to classical ketogenic diets unproven and the efficacy of non-dietary MCT supplementation highly uncertain.
Cited by
- supports Diets supplemented with medium-chain triglycerides (MCTs) work almost as effectively as standard ketogenic diets in managing epilepsy.