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

The short version

This systematic review with meta-analysis pooled 17 randomized controlled trials of ketogenic diet therapies (KDTs) for drug-resistant epilepsy, meaning epilepsy that keeps causing seizures after two or three appropriately chosen antiseizure medications have failed. About 30% of people with epilepsy fall into this group. KDTs are high-fat, low-carbohydrate, adequate-protein diets that shift the body toward burning fat and producing ketone bodies, which are fat-derived fuel molecules that may calm brain activity and support neuron energy metabolism. Several forms exist: the classical ketogenic diet, the medium-chain triglyceride (MCT) diet, the modified Atkins diet with unrestricted protein, and the low glycemic index treatment. A 2020 Cochrane review left the evidence uncertain, and this update added newer trials. Eleven trials enrolled children and six enrolled adolescents and adults, with follow-up of up to 24 months. In nearly all trials, a ketogenic diet was compared with usual care, most often an added medication. The authors searched four databases in February 2024 and again in June 2025, screened 1,193 unique records in duplicate, and pooled results as relative risks (RR) using random-effects models. Study bias was rated with the Cochrane RoB 2 tool, and confidence in each result was graded from high to very low using GRADE. In children, a 50% or greater drop in seizures was far more likely with KDT (RR 4.06, meaning roughly four times the likelihood; 49.7% versus 12.2%, or 37 more children per 100). A 90% or greater drop was borderline (RR 1.74, 95% CI 1.00 to 3.03). Adverse events were similar to usual care (RR 1.03), and dropout was not significantly different (RR 1.64, 95% CI 0.88 to 3.07). In adolescents and adults, 50% or greater seizure reduction was also more likely (RR 7.73, which translates to 16 more per 100), with moderate certainty. Near-complete seizure control (RR 13.00, with a very wide interval of 0.74 to 226.98), side effects and dropout could not be judged because of very low certainty. Reported side effects were mainly gastrointestinal and resolved when the diet stopped. Quality of life findings were mixed: one infant trial found small differences favoring medication in temperament and peer relationships, while parents in another trial reported improved alertness and sleep. The authors interpret the findings as a clinically meaningful benefit for moderate seizure reduction, strongest in children. Certainty was limited by the impossibility of blinding a diet, small event counts and high heterogeneity for some outcomes. Most trials came from high-income countries, which may limit generalizability, and publication bias could not be excluded. No trial reported hospitalizations, status epilepticus or survival. The authors call for better evidence on safety, adherence, cognition and quality of life.

Key findings

• A systematic review of 17 randomized trials found that ketogenic diets (high-fat, low-carbohydrate diets that make the body burn fat and produce ketones) made it more likely that seizures were reduced by half or more in drug-resistant epilepsy.
• In children, 49.7% of those on a ketogenic diet had a 50% or greater seizure reduction compared with 12.2% on usual care, which works out to 37 more children per 100 (moderate certainty).
• In adolescents and adults the 50% or greater reduction was also more likely (RR 7.73, a relative risk meaning the chance was several times higher), or 16 more per 100, though the confidence interval was wide.
• Side effects were mainly digestive and resolved when the diet was stopped, and dropout was not significantly different from usual care, but the certainty of this evidence was low to very low.
• Evidence on near-complete seizure control, quality of life and thinking skills was too limited to judge, and no trial reported hospital stays, prolonged seizures or survival.

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