{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:18:40Z","timestamp":1760059120804,"version":"build-2065373602"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Developmental epileptic encephalopathies (DEEs) are often associated with variably severe cognitive and motor impairment and frequent refractory epilepsy, with many children not achieving adequate seizure control via standard antiepileptic medications. The classic ketogenic diet (KD) has proven effective in reducing seizure frequency and\/or severity in a category of DEEs and in certain refractory epilepsies of infancy. However, its multifaceted mechanisms, e.g., epigenetic modulation, anti-inflammatory and antioxidative effects, and direct neuronal excitability changes, are balanced by a high burden and low long-term adherence. Medium-chain triglycerides (MCTs), particularly decanoic acid (C10:0), have gained attention in recent years for their potential direct inhibitory action on AMPA receptors, contributing to seizure reduction. Methods: A systematic review was conducted, including articles from January 2000 to January 2025, to explore the potential role of medium-chain triglyceride (MCT) add-on to classic KD and as MCT supplementation in free diets in the management of pediatric drug-resistant epilepsy (DRE). Results: Selected studies show how the action of MCTs, and decanoic acid in particular, is via negative modulation of AMPA receptors, with a positive impact on epileptic seizures. Conclusions: This review discusses the complexities of implementing and sustaining KD in children and presents recent pre-clinical and clinical evidence, including trials where MCTs (often enriched in decanoic acid) serve as an add-on therapy in both ketogenic and free\/unrestricted diets. The summarized findings reinforce the therapeutic potential of MCTs, highlighting both the beneficial seizure outcomes and the hurdles that remain to be addressed through future research.<\/jats:p>","DOI":"10.3390\/nu17111805","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T03:34:46Z","timestamp":1748316886000},"page":"1805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["AMPA Receptor Modulation Through Medium-Chain Triglycerides and Decanoic Acid Supports Nutritional Intervention in Pediatric Epilepsy"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4482-3506","authenticated-orcid":false,"given":"Raffaele","family":"Falsaperla","sequence":"first","affiliation":[{"name":"Department of Medical Science-Pediatrics, University of Ferrara, 44124 Ferrara, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-8430","authenticated-orcid":false,"given":"Vincenzo","family":"Sortino","sequence":"additional","affiliation":[{"name":"Pediatrics and Pediatric Emergency Department, Azienda Ospedaliero-Universitaria Policlinico \u201cRodolico-San Marco\u201d, San Marco Hospital, 95121 Catania, Italy"},{"name":"National Council of Research, Institute for Research and Biomedical Innovation (IRIB), Unit of Catania, 95126 Catania, Italy"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5780-9949","authenticated-orcid":false,"given":"Miguel Angel","family":"Soler","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Matematiche, Informatiche e Fisiche, Universit\u00e0 di Udine, 33100 Udine, Italy"}]},{"given":"Michela","family":"Spatuzza","sequence":"additional","affiliation":[{"name":"National Council of Research, Institute for Research and Biomedical Innovation (IRIB), Unit of Catania, 95126 Catania, Italy"}]},{"given":"Sara","family":"Fortuna","sequence":"additional","affiliation":[{"name":"Italian Institute of Technology (IIT), Via Melen 83, B Block, 16163 Genova, Italy"}]},{"given":"Vincenzo","family":"Salpietro","sequence":"additional","affiliation":[{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev-med-050522-034458","article-title":"Advances in Therapy for Refractory Epilepsy","volume":"76","author":"Jehi","year":"2025","journal-title":"Annu. 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