Efficacy and safety of ketogenic diets in drug-resistant epilepsy: a systematic review and meta-analysis - PubMed
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KDs and MADs are effective in reducing seizures in patients with drug-resistant epilepsy, especially in children. However, claims of seizure freedom remain uncertain. Further high-quality trials are needed to compare diets and assess long-term safety.

World J Pediatr. 2025 Nov 8. doi: 10.1007/s12519-025-00981-9. Online ahead of print.

ABSTRACT

BACKGROUND: Epilepsy affects millions of patients worldwide, and approximately one-third of patients are resistant to antiepileptic drugs. Dietary therapies, such as ketogenic diet (KD), modified Atkins diet (MAD), and low glycemic index treatment, have shown potential in seizure control. This review aims to evaluate the effectiveness and safety of these dietary interventions in reducing seizure frequency and improving related outcomes in individuals with drug-resistant epilepsy.

METHODS: A comprehensive search of PubMed, Scopus, the Cochrane Library, and Web of Science was conducted up to December 2024 and updated in May 2025. Eligible studies were randomized controlled trials and prospective cohort studies evaluating KDs in patients with drug-resistant epilepsy. The primary outcomes included seizure reduction (≥ 50%, ≥ 90%, or complete cessation), whereas the secondary outcomes included cognitive function, quality of life, and adverse events. The risk of bias was assessed via the Cochrane Risk of Bias 2 tool. Meta-analyses were performed via R (version 4.3.2), with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. Fixed- or random-effects models were applied on the basis of heterogeneity levels.

RESULTS: Dietary interventions significantly increased ≥ 50% seizure reduction [odds ratio (OR) = 3.46, 95% CI = 1.83-6.56] compared with standard care, with stronger effects in pediatric patients (OR = 10.93 vs. 2.54 in adults, P = 0.007). MAD outperformed standard care (OR = 4.04), whereas KD did not (OR = 1.83). For a ≥ 90% reduction, KD had greater efficacy (OR = 6.23) than MAD did (OR = 1.98). No significant difference was found for complete seizure resolution (OR = 1.19). Adverse events varied: constipation was most common with MAD (30.97%), whereas KD had higher rates of respiratory infections (42.77%, P < 0.0001 vs. MAD) and diarrhea (13.75% vs. 8.11%, P = 0.0017). Heterogeneity was substantial in most analyses (I2 > 75%).

CONCLUSIONS: KDs and MADs are effective in reducing seizures in patients with drug-resistant epilepsy, especially in children. However, claims of seizure freedom remain uncertain. Further high-quality trials are needed to compare diets and assess long-term safety.

PMID:41205102 | DOI:10.1007/s12519-025-00981-9

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