Evidence map›Paper›PMID 29325899›Full record

ReviewNeuropharmacology2018

Do ketone bodies mediate the anti-seizure effects of the ketogenic diet?

Timothy A Simeone, Kristina A Simeone, Carl E Stafstrom, Jong M Rho

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neuropharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 6 pooled it
8.6field-weighted citation impact, top 2% 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

80 citing papers in PubMed, 6 syntheses or guidelines pooled it, 135 citations in OpenAlex.

  1. Pooled it
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  5. Pooled it
  6. Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2020
    Pooled it
  7. Trial
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  18. Pharmacological inhibition of ENT1 enhances the impact of specific dietary fats on energy metabolism gene expression.Proceedings of the National Academy of Sciences of the United States of America · 2024
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 2 countries.

Timothy A SimeoneDepartment of Pharmacology, Creighton University School of Medicine, Omaha, NE, USA.
Kristina A SimeoneDepartment of Pharmacology, Creighton University School of Medicine, Omaha, NE, USA.
Carl E StafstromDepartment of Neurology, and Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jong M RhoDepartment of Pediatrics, Department of Clinical Neurosciences, and Department of Physiology and Pharmacology, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada. Electronic address: jong.rho@ahs.ca.
Creighton University · USJohns Hopkins University · USUniversity of Calgary · CA

Funding

PPARgamma, Epilepsy and TherapeuticsR01NS085389 · NINDS · CREIGHTON UNIVERSITY · PI SIMEONE, TIMOTHY A. · 2014 to 2018
$1.5M
Adenosine, Hypocretin and Sleep Disorder Comorbidities Associated with EpilepsyR01NS072179 · NINDS · CREIGHTON UNIVERSITY · PI SIMEONE, KRISTINA A · 2012 to 2016
$1.5M
CIHR MOP-119594CIHR PJT-148871NINDS NIH HHS R01 NS072179NINDS NIH HHS R01 NS085389
6 · The paper itself

Abstract

Although the mechanisms underlying the anti-seizure effects of the high-fat ketogenic diet (KD) remain unclear, a long-standing question has been whether ketone bodies (i.e., β-hydroxybutyrate, acetoacetate and acetone), either alone or in combination, contribute mechanistically. The traditional belief has been that while ketone bodies reflect enhanced fatty acid oxidation and a general shift toward intermediary metabolism, they are not likely to be the key mediators of the KD's clinical effects, as blood levels of β-hydroxybutyrate do not correlate consistently with improved seizure control. Against this unresolved backdrop, new data support ketone bodies as having anti-seizure actions. Specifically, β-hydroxybutyrate has been shown to interact with multiple novel molecular targets such as histone deacetylases, hydroxycarboxylic acid receptors on immune cells, and the NLRP3 inflammasome. Clearly, as a diet-based therapy is expected to render a broad array of biochemical, molecular, and cellular changes, no single mechanism can explain how the KD works. Specific metabolic substrates or enzymes are only a few of many important factors influenced by the KD that can collectively influence brain hyperexcitability and hypersynchrony. This review summarizes recent novel experimental findings supporting the anti-seizure and neuroprotective properties of ketone bodies.

Indexed as

AnimalsAnticonvulsantsDiet, KetogenicHumansKetone BodiesSeizuresAnticonvulsantsKetone BodiesAcetoacetateBeta-hydroxybutyrateEpilepsyKetogenic dietKetone bodiesNeuroprotection

Identifiers

PMID29325899
PMCPMC5858992
OpenAlexW2783271998

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.