Evidence map›Paper›PMID 38346975›Full record

ArticleCell discovery2024

Ketogenic diet-produced β-hydroxybutyric acid accumulates brain GABA and increases GABA/glutamate ratio to inhibit epilepsy.

Ya-Nan Qiao, Lei Li, Song-Hua Hu, Yuan-Xin Yang, Zhen-Zhen Ma, Lin Huang, Yan-Peng An, Yi-Yuan Yuan, Yan Lin, Wei Xu and 5 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 1 pooled it
20.9field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.

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  11. β-Hydroxybutyrate Exposure is Associated with Increased THCellular and molecular neurobiology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 2 countries.

Ya-Nan QiaoThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Lei LiDepartment of Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Song-Hua HuDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Yuan-Xin YangThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Zhen-Zhen MaThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Lin HuangThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Yan-Peng AnThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Yi-Yuan YuanThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0003-0829-3824
Yan LinThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Wei XuThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Yao LiThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China.
Peng-Cheng LinKey Laboratory for Tibet Plateau Phytochemistry of Qinghai Province, College of Pharmacy, Qinghai University for Nationalities, Xining, Qinghai, China.
Jing CaoDepartment of Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China.
Jian-Yuan ZhaoInstitute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shi-Min ZhaoThe Obstetrics & Gynaecology Hospital of Fudan University, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Metabolic Remodelling and Health, Institutes of Biomedical Sciences, and Children's Hospital of Fudan University, Fudan University, Shanghai, China. zhaosm@fudan.edu.cn.
Children's Hospital of Fudan University · CNZhengzhou University · CNFudan University · CNHarvard University · USQinghai University for Nationalities · CNShanghai Jiao Tong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced β-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy. The KD ameliorated pentetrazol-induced epilepsy in mice. Mechanistically, KD-produced BHB, but not other ketone bodies, inhibited HDAC1/HDAC2, increased H3K27 acetylation, and transcriptionally upregulated SIRT4 and glutamate decarboxylase 1 (GAD1). BHB-induced SIRT4 de-carbamylated and inactivated glutamate dehydrogenase to preserve glutamate for GABA synthesis, and GAD1 upregulation increased mouse brain GABA/glutamate ratio to inhibit neuron excitation. BHB administration in mice inhibited epilepsy induced by pentetrazol. BHB-mediated relief of epilepsy required high GABA level and GABA/glutamate ratio. These results identified BHB as the major antiepileptic metabolite of the KD and suggested that BHB may serve as an alternative and less toxic antiepileptic agent than KD.

Identifiers

PMID38346975
PMCPMC10861483
OpenAlexW4391784257

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.