Effective reduction in seizure severity and prevention of a fatty liver by a novel low ratio ketogenic diet composition in the rapid kindling rat model of epileptogenesis.

Autor: Meeusen H; Amsterdam UMC location University of Amsterdam, Dept of (Neuro)pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands; Danone Research & Innovation, Utrecht, the Netherlands., Kalf RS; Amsterdam UMC location University of Amsterdam, Dept of (Neuro)pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands; Danone Research & Innovation, Utrecht, the Netherlands., Broekaart DWM; Amsterdam UMC location University of Amsterdam, Dept of (Neuro)pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands., Silva JP; Danone Research & Innovation, Utrecht, the Netherlands., Verkuyl JM; Danone Research & Innovation, Utrecht, the Netherlands., van Helvoort A; Danone Research & Innovation, Utrecht, the Netherlands; NUTRIM - Institute of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands., Gorter JA; Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands., van Vliet EA; Amsterdam UMC location University of Amsterdam, Dept of (Neuro)pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands; Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: e.a.vanvliet@uva.nl., Aronica E; Amsterdam UMC location University of Amsterdam, Dept of (Neuro)pathology, Amsterdam Neuroscience, Meibergdreef 9, Amsterdam, the Netherlands; Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, the Netherlands.
Jazyk: angličtina
Zdroj: Experimental neurology [Exp Neurol] 2024 Sep; Vol. 379, pp. 114861. Date of Electronic Publication: 2024 Jun 12.
DOI: 10.1016/j.expneurol.2024.114861
Abstrakt: Drug-resistant epilepsy patients may benefit from non-pharmacological therapies, such as the ketogenic diet (KD). However, its high fat content poses compliance challenges and metabolic risks. To mitigate this, we developed a novel KD composition with less fat and additional nutrients (citrate, nicotinamide riboside, and omega-3 fatty acids) for ketone-independent neuroprotection. The efficacy, metabolic and neuropathological effects of the novel KD and a classic KD were compared to a control diet in the rapid kindling model of temporal lobe epilepsy. Both KD groups entered ketosis before kindling onset, with higher ketone levels in the classic KD group. Remarkably, rats on the novel KD had slower progression of behavioral seizures as compared to rats on a control diet, while this was not the case for rats on a classic KD. Both KDs reduced electrographic after-discharge duration, preserved neurons in the dorsal hippocampus, and normalized activity in open field tests. The novel KD, despite lower fat and ketone levels, demonstrated effective reduction of behavioral seizure severity while the classic KD did not, suggesting alternative mode(s) of action are involved. Additionally, the novel KD significantly mitigated liver triglyceride and plasma fatty acid levels compared to the classic KD, indicating a reduced risk of long-term liver steatosis. Our findings highlight the potential of the novel KD to enhance therapeutic efficacy and compliance in epilepsy patients.
Competing Interests: Declaration of competing interest H. Meeusen, J.P. Silva, J.M. Verkuyl and A. van Helvoort were under employment by Danone Nutricia Research during this study. The remaining authors have no conflicts of interest.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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