Are Exogenous Ketones Good for Anxiety?

Keto4Life

Well-known member
May 24, 2021
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Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk Rats

Based on anecdotal reports of Nutritional Ketosis reducing symptoms of anxiety, this study used two different rodent models to examine whether exogenous ketone supplementation might be effective at reducing anxiety. Additionally, three different forms of exogenous ketone supplements were used in the study:
  • Ketone Ester (KE) 1,3-butanediol-acetoacetate diester
  • Ketone Salt (KS) Na/K β-hydroxybutyrate mineral salt
  • Ketone Salt mixed with Medium Chain Triglycerides (MCT) in a 1:1 ratio (KSMCT)
They also looked at two different methods of administrating the exogenous ketones and with varying dosages. Chronic administration and sub-chronic oral gavage were used. The chronic administration consisted of feeding the rodents the three different exogenous ketones formulations in their food of which they had access to all day long. The sub-chronic oral gavage consisted of one daily dose of one of the three different exogenous ketone formulations via a tube stuck down their throat. I know, that sounds like fun, right?

Chronic Administration:
  • Low-dose Ketone Ester (~10 g/kg b.w./day, Low-dose ketone ester (LKE); n = 10)
  • High-dose Ketone Ester (~25 g/kg b.w./day, high dose ketone ester (HKE); n = 10)
  • Ketone Salt (~25 g/kg b.w./day, KS; n = 9)
  • Ketone Salt + MCT (~25 g/kg b.w./day, KSMCT; n = 10)
Sub-chronic Oral Gavage:
  • Standard Diet (SD) + gavaged daily with 5 g/kg b.w./day water (SD/control; n = 11)
  • Standard Diet (SD) + gavaged daily with Ketone Ester (n = 9)
  • Standard Diet (SD) + gavaged daily with Ketone Salt (n = 9)
  • Standard Diet (SD) + gavaged daily with Ketone Salt + MCT (n = 10)
The levels of anxiety were determined by using an Elevated Plus Maze test. Essentially the longer the rats spend out in the open portions of the maze, the lower their anxiety.

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So, what did they find? Though there are several proposed mechanisms, they are still not sure exactly why they work, but they did in fact find that exogenous ketones lowered anxiety behavior in the animals. Because the results proved promising, and the fact that mechanisms of action are not fully understood, and there were slightly different efficacies within the different models, further research is warranted.

Results
“These results indicate that KS and KSMCT are the most effective after chronic treatment, while KE and KS seem to be the most effective after sub-chronic treatment in rats without pathology (SPD). In rats with pathology (WAG/Rij) KSMCT was the most effective treatment after sub-chronic administration.”

Conclusion
“In conclusion, 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.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138218/