Ketone Supplementation Attenuates Prediction Error Taste Response in Eating Disorders: A Proof-of-Concept Study

Area of Science:

• Neuroscience
• Metabolic Psychiatry
• Eating Disorder Research

Background:

• Eating disorders (EDs) involve complex pathophysiology, potentially including metabolic alterations.
• Preliminary research suggests ketogenic interventions may alleviate ED symptom severity.
• Altered prediction-error signaling is observed in ED populations.

Purpose of the Study:

• To investigate if exogenous ketone supplementation modulates neural responses in individuals with anorexia nervosa (AN) and bulimia nervosa (BN).
• To assess prediction-error signaling using electroencephalography (EEG) during a taste-based conditioning task.
• To examine the effects of beta-hydroxybutyrate (BHB) on neural sensitivity to prediction errors in EDs.

Main Methods:

• A randomized, double-blind, placebo-controlled crossover study involving 22 participants with AN and BN spectrum disorders.
• Participants received either 10g BHB or a placebo on separate days before an EEG-monitored taste-based conditioning task.
• Neural sensitivity to prediction error was indexed by reward positivity (RewP/FRN) and late positive potential (LPP) event-related potentials (ERPs).

Main Results:

• Active BHB supplementation successfully increased blood ketone levels.
• BHB significantly reduced late positive potential (LPP) sensitivity to unsigned prediction error compared to placebo (p=0.028).
• Reduced LPP sensitivity to ketones was associated with poorer self-esteem (p=0.002).

Conclusions:

• EEG measures effectively capture prediction-error processing during cue-taste learning in ED populations.
• Exogenous ketones may attenuate neural sensitivity to salient taste outcomes in individuals with EDs.
• Further research is warranted to explore clinical applications of ketone modulation in ED treatment.