Pharmacokinetic effects of a single dose nutritional ketone ester supplement on brain glucose and ketone metabolism in alcohol use disorder.

Ketone ester supplementation lowered blood glucose and increased beta-hydroxybutyrate (BHB) in both AUD and healthy control groups.

• Ten participants received 395 mg/kg KE supplement
• Five participants had AUD and five were healthy controls
• Blood glucose reductions and BHB increases were observed in both groups following KE administration
• The study used a randomized crossover design with two FDG-PET brain scans per participant (one after KE, one at baseline)

Ketone ester supplementation produced a 17% reduction in brain glucose metabolism.

• Brain glucose metabolism was measured using FDG-PET scans
• The reduction was observed especially in the frontal, occipital, and cingulate cortices, as well as the hippocampus, amygdala, and insula
• No major differences in the metabolic response were observed between AUD and control groups
• The reduction suggests a rapid shift from glucose to ketone-based energy utilization

Ketone ester supplementation tripled cingulate beta-hydroxybutyrate (BHB) levels as measured by magnetic resonance spectroscopy.

• Cingulate BHB was measured using magnetic resonance spectroscopy
• Only the five AUD participants underwent MRS assessment
• BHB levels increased approximately threefold following KE administration
• Cingulate cortex BHB elevation is consistent with the observed reduction in regional glucose metabolism in that area

Ketone ester supplementation significantly reduced alcohol craving in participants with alcohol use disorder.

• Craving was assessed in the five AUD participants
• KE administration led to a significant reduction in alcohol craving compared to baseline
• This finding aligns with prior studies showing ketone therapies can lessen alcohol withdrawal and cravings
• The craving reduction occurred with a single dose of 395 mg/kg KE

Individuals with alcohol use disorder exhibit a metabolic shift away from glucose toward alternative substrates such as acetate that may serve as a treatment target.

• Acute alcohol use reduces brain glucose metabolism while increasing uptake of acetate, a byproduct of alcohol
• This metabolic shift persists in individuals with AUD
• The persistence of altered brain energy metabolism in AUD was identified as a potential treatment target
• Ketone therapies were hypothesized to exploit this metabolic vulnerability

A single ketone ester dose can rapidly shift brain energy use from glucose to ketones, supporting its potential as a therapeutic approach for AUD.

• The study used a small sample of ten participants total (five AUD, five healthy controls)
• The randomized design compared KE condition to baseline condition within subjects
• Findings support KE as a potential therapeutic approach targeting brain metabolism in AUD
• Both FDG-PET and MRS neuroimaging modalities were used to characterize the metabolic response