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Exogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models.

Nutrients
October 1, 2019
Csilla Ari et al. (11 authors)
Comparative StudyJournal ArticleAnimal Study
Study Details

Study Goal

The researchers aimed to determine whether exogenous ketones could effectively reduce blood glucose levels in various rodent models, both with and without pathology, and under different conditions (rested, post-exercise, acute, sub-chronic, and chronic administration).

Results Summary

Exogenous ketones (KE, KS, KSMCT, KEKS, KEMCT) significantly reduced blood glucose levels in rested and post-exercise states across different rodent models and age groups, with some formulations showing sustained effects over days or weeks.

Population

WAG/Rij rats (absence epilepsy model), GLUT1 deficiency syndrome mice, wild-type Sprague Dawley rats, and non-pathological animals of varying ages.

Effective Dosage

Not specified

Duration

Varied (acute: 1h, sub-chronic: 24h to 7 days, chronic: up to 10 weeks)

Interactions

None mentioned

Extracted Claims (15)
InterventionDirectionEndpointPopulationDosageImpactClaim #
ketogenic diet (KD)
decrease
absolute glucose
-
-
reduces
#1
ketogenic diet (KD)
decrease
insulin
-
-
reduces
#2
ketogenic diet (KD)
increase
fatty acid oxidation
-
-
increasing
#3
ketogenic diet (KD)
increase
ketogenesis
-
-
increasing
#4
ketogenic diet (KD)
increase
circulating levels of β-hydroxybutyrate (βHB), acetoacetate (AcAc), and acetone
-
-
increasing
#5
exogenous ketones
increase
blood ketone levels
-
-
elevate
#6
KE, KS, KSMCT
decrease
blood glucose level
rested WR rats
after 1 h of treatment
had lower
#7
KE, KSMCT
decrease
blood glucose level
rested WR rats
after 24 h
had lower
#8
KE, KSMCT, KEKS, KEMCT
decrease
glucose levels
WR rats after exercise
after 1 h
had lowered
#9
KEKS, KEMCT
decrease
glucose levels
WR rats after exercise
after 7 days
had lowered
#10
KE
decrease
glucose levels
GLUT1D mice without exercise
at week 2 and week 6 during a 10 weeks long chronic feeding study
resulted in significantly lower
#11
KD and KE
decrease
blood glucose
4-month-old SPD rats in the post-exercise trials
-
significantly lower
#12
KEMCT
decrease
blood glucose
1-year-old SPD rats in the post-exercise trials
-
significantly lower
#13
KSMCT
decrease
blood glucose levels
SPD rats
After seven days
most significantly reduced
#14
exogenous ketones
decrease
blood glucose levels
various rodent models of different ages, with and without pathology
-
efficacious in reducing
#15
Abstract

Diseases involving inflammation and oxidative stress can be exacerbated by high blood glucose levels. Due to tight metabolic regulation, safely reducing blood glucose can prove difficult. The ketogenic diet (KD) reduces absolute glucose and insulin, while increasing fatty acid oxidation, ketogenesis, and circulating levels of β-hydroxybutyrate (βHB), acetoacetate (AcAc), and acetone. Compliance to KD can be difficult, so alternative therapies that help reduce glucose levels are needed. Exogenous ketones provide an alternative method to elevate blood ketone levels without strict dietary requirements. In this study, we tested the changes in blood glucose and ketone (βHB) levels in response to acute, sub-chronic, and chronic administration of various ketogenic compounds in either a post-exercise or rested state. WAG/Rij (WR) rats, a rodent model of human absence epilepsy, GLUT1 deficiency syndrome mice (GLUT1D), and wild type Sprague Dawley rats (SPD) were assessed. Non-pathological animals were also assessed across different age ranges. Experimental groups included KD, standard diet (SD) supplemented with water (Control, C) or with exogenous ketones: 1, 3-butanediol (BD), βHB mineral salt (KS), KS with medium chain triglyceride/MCT (KSMCT), BD acetoacetate diester (KE), KE with MCT (KEMCT), and KE with KS (KEKS). In rested WR rats, the KE, KS, KSMCT groups had lower blood glucose level after 1 h of treatment, and in KE and KSMCT groups after 24 h. After exercise, the KE, KSMCT, KEKS, and KEMCT groups had lowered glucose levels after 1 h, and in the KEKS and KEMCT groups after 7 days, compared to control. In GLUT1D mice without exercise, only KE resulted in significantly lower glucose levels at week 2 and week 6 during a 10 weeks long chronic feeding study. In 4-month and 1-year-old SPD rats in the post-exercise trials, blood glucose was significantly lower in KD and KE, and in KEMCT groups, respectively. After seven days, the KSMCT group had the most significantly reduced blood glucose levels, compared to control. These results indicate that exogenous ketones were efficacious in reducing blood glucose levels within and outside the context of exercise in various rodent models of different ages, with and without pathology.

Medical Subject Headings (MeSH)
3-Hydroxybutyric AcidAcetoacetatesAnimalsBiomarkersBlood GlucoseButylene GlycolsCarbohydrate Metabolism, Inborn ErrorsDiet, KetogenicDietary SupplementsDisease Models, AnimalDown-RegulationEpilepsy, AbsenceGlucose Transporter Type 1MaleMice, KnockoutMonosaccharide Transport ProteinsPhysical ExertionRats, Sprague-DawleyRestTime Factors
Study Links
Quality Scores
SafetyNot Assessed
Efficacy85/10
Quality75/10
Citation Metrics
Total Citations30
Citations/Year5.0
Relative Citation Ratio1.45
NIH Percentile64%
Research Impact Scores
APT Score0.50
Weight Score1.13
Normalized Score0.69
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