Vaccarezza · PloS one 2026 · systematic review of randomized controlled trials · n=17 studies

Ketogenic diet therapies for the treatment of drug-resistant epilepsy in children and adults: A systematic review.

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Level 1 - systematic review of randomized trials

Systematic review of randomized controlled trials

PubMed 42391224 · doi:10.1371/journal.pone.0333334 · record verified 2026-08-30

What was done

Systematic review following PRISMA guidelines searching Embase, PubMed/Medline, LILACS, and Cochrane Library for randomized controlled trials (RCTs) evaluating ketogenic diet therapies (KDT) in pediatric and adult drug-resistant epilepsy with a minimum follow-up of 28 days. From 1,193 deduplicated records, 17 RCTs met inclusion criteria (11 in children ≤12 years; 6 in adolescents ≥13 years and adults), with follow-up ranging from 6 to 24 months.

What was found

In children, 37% achieved a ≥50% reduction in seizure frequency with any form of KDT (moderate-certainty evidence), and approximately 6 more children per 100 achieved a ≥90% reduction (low-certainty evidence). In adolescents and adults, KDT led to a ≥50% reduction in 16 more individuals per 100 compared to usual care (moderate-certainty evidence); effect on ≥90% reduction was uncertain. Adverse events in children showed no significant difference versus usual care (low certainty) and were uncertain in adults (very low certainty). Adherence was slightly lower with KDT, and cognitive, behavioral, and quality of life outcomes were scarce, heterogeneous, and of very low certainty.

Why it matters

This review establishes moderate-certainty evidence that ketogenic diet therapies reduce seizure frequency by at least 50% in both pediatric and adult drug-resistant epilepsy. It highlights that evidence for near-total seizure control, long-term safety, and quality-of-life benefits remains weak.

Limits

Total participant count across the 17 included RCTs was not reported in the abstract. Outcomes for high-degree seizure reduction (≥90%), adverse events, adherence, and quality of life were constrained by study scarcity, heterogeneity, imprecision, and low-to-very-low certainty evidence. Maximum follow-up was limited to 24 months.

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