Neal · Epilepsia 2009 · Multicenter randomized controlled trial · n=145

A randomized trial of classical and medium-chain triglyceride ketogenic diets in the treatment of childhood epilepsy.

Cited 439 times in the scientific literature.

Level 2 - randomized trial

Individual randomized controlled trial

PubMed 19054400 · doi:10.1111/j.1528-1167.2008.01870.x · record verified 2026-08-29

What was done

Researchers conducted a randomized trial in 145 children with intractable epilepsy assigned to either a classical ketogenic diet or a medium-chain triglyceride (MCT) ketogenic diet. A total of 125 children started the diets (61 classical, 64 MCT). The study evaluated seizure frequency at 3, 6, and 12 months, tracked treatment withdrawals, measured blood ketone levels (acetoacetate and beta-hydroxybutyrate), and assessed tolerability via questionnaires.

What was found

Data from 94 children were available for analysis (45 classical, 49 MCT). Mean percentage of baseline seizures did not differ significantly between the classical and MCT groups at 3 months (66.5% vs 68.9%), 6 months (48.5% vs 67.6%), or 12 months (40.8% vs 53.2%; all p > 0.05). There were no significant differences in the proportions achieving >50% or >90% seizure reduction. Serum acetoacetate and beta-hydroxybutyrate levels were significantly higher in the classical group at 3 and 6 months (p < 0.01), as was acetoacetate at 12 months. Tolerability was similar overall, with the classical diet showing more reports of lack of energy at 3 months and vomiting at 12 months.

Why it matters

This trial demonstrates that classical and MCT ketogenic diet protocols offer comparable seizure reduction and tolerability in pediatric drug-resistant epilepsy, supporting both as viable dietary therapies.

Limits

There was substantial participant loss between randomization (n = 145) and final analysis (n = 94), which could introduce attrition bias. The abstract does not specify whether an intention-to-treat analysis was performed, does not detail blinding procedures, and provides no long-term follow-up beyond 12 months.

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