Evidence map›Paper›PMID 27999529›Full record

ArticleFrontiers in molecular neuroscience2016

Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats.

Csilla Ari, Zsolt Kovács, Gabor Juhasz, Cem Murdun, Craig R Goldhagen, Andrew P Koutnik, Angela M Poff, Shannon L Kesl, Dominic P D'Agostino

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In one paragraph

Article in Frontiers in molecular neuroscience, 2016. 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 79 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

79 citing papers in PubMed, 1 synthesis or guideline pooled it.

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  13. Strategies for optimization of hypoglycemia rat models.Animal models and experimental medicine · 2025
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19 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Csilla AriDepartment of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida Tampa, FL, USA.
Zsolt KovácsDepartment of Zoology, University of West Hungary Szombathely, Hungary.
Gabor JuhaszProteomics Laboratory, Eotvos Lorand University Budapest, Hungary.
Cem MurdunDepartment of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida Tampa, FL, USA.
Craig R GoldhagenDepartment of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida Tampa, FL, USA.
Andrew P KoutnikDepartment of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida Tampa, FL, USA.
Angela M PoffDepartment of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida Tampa, FL, USA.
Shannon L KeslDepartment of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida Tampa, FL, USA.
Dominic P D'AgostinoDepartment of Molecular Pharmacology and Physiology, Hyperbaric Biomedical Research Laboratory, Morsani College of Medicine, University of South Florida Tampa, FL, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders. The focus of this study was to determine the effects of ketone supplementation on anxiety-related behavior in Sprague-Dawley (SPD) and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We tested exogenous ketone supplements added to food and fed chronically for 83 days in SPD rats and administered sub-chronically for 7 days in both rat models by daily intragastric gavage bolus followed by assessment of anxiety measures on elevated plus maze (EPM). The groups included standard diet (SD) or SD + ketone supplementation. Low-dose ketone ester (LKE; 1,3-butanediol-acetoacetate diester, ~10 g/kg/day, LKE), high dose ketone ester (HKE; ~25 g/kg/day, HKE), beta-hydroxybutyrate-mineral salt (βHB-S; ~25 g/kg/day, KS) and βHB-S + medium chain triglyceride (MCT; ~25 g/kg/day, KSMCT) were used as ketone supplementation for chronic administration. To extend our results, exogenous ketone supplements were also tested sub-chronically on SPD rats (KE, KS and KSMCT; 5 g/kg/day) and on WAG/Rij rats (KE, KS and KSMCT; 2.5 g/kg/day). At the end of treatments behavioral data collection was conducted manually by a blinded observer and with a video-tracking system, after which blood βHB and glucose levels were measured. Ketone supplementation reduced anxiety on EPM as measured by less entries to closed arms (sub-chronic KE and KS: SPD rats and KSMCT: WAG/Rij rats), more time spent in open arms (sub-chronic KE: SPD and KSMCT: WAG/Rij rats; chronic KSMCT: SPD rats), more distance traveled in open arms (chronic KS and KSMCT: SPD rats) and by delayed latency to entrance to closed arms (chronic KSMCT: SPD rats), when compared to control. Our data indicates that chronic and sub-chronic ketone supplementation not only elevated blood βHB levels in both animal models, but reduced anxiety-related behavior. We conclude that ketone supplementation may represent a promising anxiolytic strategy through a novel means of inducing nutritional ketosis.

Indexed as

animal modelsanxietyelevated plus mazeexogenous ketone supplementsketones

Identifiers

PMID27999529
PMCPMC5138218

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Registered trials

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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.