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

Nutrients. 2019 Oct 1;11(10):2330. doi: 10.3390/nu11102330.


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.

Keywords: blood glucose; blood ketone; exercise; exogenous ketone supplements; ketogenic diet.

Publication types

  • Comparative Study

MeSH terms

  • 3-Hydroxybutyric Acid / pharmacology*
  • Acetoacetates / pharmacology*
  • Animals
  • Biomarkers
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Butylene Glycols / pharmacology*
  • Carbohydrate Metabolism, Inborn Errors / blood
  • Carbohydrate Metabolism, Inborn Errors / genetics
  • Carbohydrate Metabolism, Inborn Errors / physiopathology
  • Carbohydrate Metabolism, Inborn Errors / therapy*
  • Diet, Ketogenic*
  • Dietary Supplements*
  • Disease Models, Animal
  • Down-Regulation
  • Epilepsy, Absence / blood
  • Epilepsy, Absence / genetics
  • Epilepsy, Absence / physiopathology
  • Epilepsy, Absence / therapy*
  • Glucose Transporter Type 1 / deficiency
  • Glucose Transporter Type 1 / genetics
  • Male
  • Mice, Knockout
  • Monosaccharide Transport Proteins / blood
  • Monosaccharide Transport Proteins / deficiency*
  • Monosaccharide Transport Proteins / genetics
  • Physical Exertion
  • Rats, Sprague-Dawley
  • Rest
  • Time Factors


  • Acetoacetates
  • Biomarkers
  • Blood Glucose
  • Butylene Glycols
  • Glucose Transporter Type 1
  • Monosaccharide Transport Proteins
  • Slc2a1 protein, mouse
  • 1,3-butylene glycol
  • acetoacetic acid
  • 3-Hydroxybutyric Acid

Supplementary concepts

  • Glut1 Deficiency Syndrome