ArticleNutrients2026
Metabolomic Profiling of Plasma in Children with Drug-Resistant Epilepsy: The Effect of the Ketogenic Diet on Energy and Amino Acid Pathways.
Article in Nutrients, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDrug-resistant epilepsy in children remains a major therapeutic challenge, and the limited efficacy of pharmacological treatment highlights the need for alternative therapeutic approaches, including the ketogenic diet (KD). Although the clinical efficacy of KD is well established, its metabolic effects are not fully understood. This study aimed to characterize the plasma metabolomic profile of children with drug-resistant epilepsy and to explore metabolic differences associated with ketogenic dietary therapy.
methodsEighteen children with drug-resistant epilepsy were enrolled, including nine receiving KD and nine receiving a standard diet. Plasma metabolomic profiling was performed using gas chromatography-mass spectrometry (GC-MS). Data were analyzed using multivariate (PCA and OPLS-DA) and univariate statistical approaches. Both variable importance in projection (VIP) scores and metabolic pathway analysis were used to support biological interpretation.
resultsA total of 462 annotated GC-MS features were retained after data filtering. OPLS-DA demonstrated clear separation between study groups (R
conclusionsKetogenic dietary therapy was associated with distinct changes in the plasma metabolomic profile of children with drug-resistant epilepsy. While the most robust findings involved β-hydroxybutyrate, citric acid, and 1,4-butanediol, the observed changes in glucose and tryptophan, as well as the amino acid-related pathway findings, should be considered exploratory and require validation in larger independent cohorts before being interpreted as biomarkers or evidence of specific metabolic mechanisms.
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