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Open AccessArticle

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

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Department of Psychology, University of South Florida, Tampa, FL 33620, USA
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Department of Molecular Pharmacology and Physiology, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA
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Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL 33620, USA
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James A. Haley VA Medical Center, Tampa, FL 33612, USA
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Shriners Hospital for Children, Tampa, FL 33612, USA
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Institute for Human and Machine Cognition, Ocala, FL 33471, USA
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Savaria Department of Biology, ELTE Eötvös Loránd University, Savaria University Centre, Károlyi Gáspár tér 4., 9700 Szombathely, Hungary
*
Author to whom correspondence should be addressed.
Nutrients 2019, 11(10), 2330; https://doi.org/10.3390/nu11102330
Received: 8 July 2019 / Revised: 30 August 2019 / Accepted: 17 September 2019 / Published: 1 October 2019
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.
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Keywords: exercise; blood glucose; blood ketone; exogenous ketone supplements; ketogenic diet exercise; blood glucose; blood ketone; exogenous ketone supplements; ketogenic diet
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Ari, C.; Murdun, C.; Koutnik, A.P.; Goldhagen, C.R.; Rogers, C.; Park, C.; Bharwani, S.; Diamond, D.M.; Kindy, M.S.; D’Agostino, D.P.; Kovács, Z. Exogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models. Nutrients 2019, 11, 2330.

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