Highlights
- •Effects of the ketogenic diet on human plasma and urine metabolome were studied.
- •Various metabolites upstream of acetyl-CoA and propionyl-CoA were elevated.
- •Changed metabolites may hint toward developing new anti-seizure medications.
Abstract
Objective
The ketogenic diet (KD), a high-fat and low-carbohydrate diet, is effective for a
subset of patients with drug-resistant epilepsy, although the mechanisms of the KD
have not been fully elucidated. The aims of this observational study were to investigate
comprehensive short-term metabolic changes induced by the KD and to explore candidate
metabolites or pathways for potential new therapeutic targets.
Methods
Subjects included patients with intractable epilepsy who had undergone the KD therapy
(the medium-chain triglyceride [MCT] KD or the modified Atkins diet using MCT oil).
Plasma and urine samples were obtained before and at 2–4 weeks after initiation of
the KD. Targeted metabolome analyses of these samples were performed using gas chromatography-tandem
mass spectrometry (GC/MS/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS).
Results
Samples from 10 and 11 patients were analysed using GC/MS/MS and LC/MS/MS, respectively.
The KD increased ketone bodies, various fatty acids, lipids, and their conjugates.
In addition, levels of metabolites located upstream of acetyl-CoA and propionyl-CoA,
including catabolites of branched-chain amino acids and structural analogues of γ-aminobutyric
acid and lactic acid, were elevated.
Conclusions
The metabolites that were significantly changed after the initiation of the KD and
related metabolites may be candidates for further studies for neuronal actions to
develop new anti-seizure medications.
Keywords
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Article info
Publication history
Published online: March 15, 2023
Accepted:
March 15,
2023
Received in revised form:
March 7,
2023
Received:
January 29,
2023
Identification
Copyright
© 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
