ArticleScientific reports2024
A novel hepatocyte ketone production assay to help the selection of nutrients for the ketogenic diet treatment of epilepsy.
Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Preliminary In Vitro Screening of Structure-Dependent β-Hydroxybutyrate Responses to Dietary Fatty Acids in Hepatocyte Models.Nutrients · 2026Article
- The Ketogenic Diet Through a Metabolomic Lens: Biochemical Pathways, Therapeutic Applications, and Analytical Challenges.Nutrients · 2025Review
- Novel histone modifications and liver cancer: emerging frontiers in epigenetic regulation.Clinical epigenetics · 2025Review
- Neurostimulation for the Management of Epilepsy: Advances in Targeted Therapy.Current drug targets · 2025Review
- Role of novel protein acylation modifications in sepsis.Frontiers in immunology · 2025Review
- A novel ketogenic diet that reduces seizures and prevents liver steatosis leads to related gut microbiome changes and restores cecal short-chain fatty acid levels in the rapid kindling rat model of epileptogenesis.Gut microbes reports · 2025Article
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10 authors.
Funding
Abstract
The classic ketogenic diet is an effective treatment option for drug-resistant epilepsy, but its high fat content challenges patient compliance. Optimizing liver ketone production guided by a method comparing substrates for their ketogenic potential may help to reduce the fat content of the diet without loss in ketosis induction. Here, we present a liver cell assay measuring the β-hydroxybutyrate (βHB) yield from fatty acid substrates. Even chain albumin-conjugated fatty acids comprising between 4 and 18 carbon atoms showed a sigmoidal concentration-βHB response curve (CRC) whereas acetate and omega-3 PUFAs produced no CRC. While CRCs were not distinguished by their half-maximal effective concentration (EC50), they differed by maximum response, which related inversely to the carbon chain length and was highest for butyrate. The assay also suitably assessed the βHB yield from fatty acid blends detecting shifts in maximum response from exchanging medium chain fatty acids for long chain fatty acids. The assay further detected a dual role for butyrate and hexanoic acid as ketogenic substrate at high concentration and ketogenic enhancer at low concentration, augmenting the βHB yield from oleic acid and a fatty acid blend. The assay also found propionate to inhibit ketogenesis from oleic acid and a fatty acid blend at low physiological concentration. Although the in vitro assay shows promise as a tool to optimize the ketogenic yield of a fat blend, its predictive value requires human validation.
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