What is it about?
doi: 10.3389/fnmol.2016.00137 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 fed chronically (added to food) 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 (SMART V3.0 PLATFORM, Harvard Apparatus), 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 travelled 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. These influences may be highly beneficial for patients managing diseases with nutritional ketosis.
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Why is it important?
Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders.
Perspectives
Based on the present study, we can conclude that chronic and sub-chronic administration of exogenous ketone supplementation may be an effective way to reduce anxiety. Achieving nutritional ketosis with exogenous ketone supplementation while maintaining a normal diet might be an alternative to the KD, or may further augment the therapeutic efficacy of the KD. Therefore, it is important to understand the long-term effects of these supplements fed chronically. These preliminary data show that chronic and sub-chronic feeding of ketone supplements not only elevated blood ketone levels, but also reduced anxiety-related behavior, which can be highly beneficial for patients managing diseases with nutritional ketosis. Since achieving nutritional ketosis requires strict dietary restrictions, compliance is a major difficulty in this treatment. The administration of exogenous ketone supplements that increase ketone levels in the blood without dietary restrictions may be an effective option to those willing to reach and stay at the state of nutritional ketosis. We propose that exogenous ketone supplementation could provide an alternative method to reduce anxiety for healthy individuals, as well as those who need to maintain nutritional ketosis. Therefore, further studies are needed to determine the exact pathophysiological and molecular basis of ketone supplementation-induced changes in anxiety level.
Dr Zsolt Kovacs
Eötvös Loránd University
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This page is a summary of: Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats, Frontiers in Molecular Neuroscience, December 2016, Frontiers,
DOI: 10.3389/fnmol.2016.00137.
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