J Stud Alcohol Drugs. 2025 Dec 15. doi: 10.15288/jsad.25-00285. Online ahead of print.

ABSTRACT

OBJECTIVE: Alcohol use disorder is highly prevalent with known associations to poor health and memory. Diet interventions are a useful tool that have the potential to help many, as they are relatively non-invasive and accessible. The ketogenic diet (KD) is a high fat, low carbohydrate diet that has been used for decades to reduce seizures in children with epilepsy. In the current study, the effects of 3 weeks of KD on alcohol use and anxiety, and post-alcohol anxiety, sociability and memory were assessed in C57BL/6J mice.

METHOD: In Experiment 1 and 1a, mice were allowed to drink alcohol for 8 weeks using the intermittent drinking in the dark paradigm. Across the last 3 weeks of drinking, mice were fed either KD or a standard chow diet and tested for performance in a Barnes maze. In Experiment 2, mice were fed either KD or standard diet for 3 weeks and observed for anxiety and social behaviors, and memory. Experiment 2a extended this work using a small number of male mice that were injected with alcohol for 1 week prior to behavioral assessment.

RESULTS: Overall, our findings suggest a therapeutic effect of KD on alcohol consumption and post-alcohol deficits.

CONCLUSIONS: Benefits were independent of effects on generalized anxiety yet support a more specific effect of KD to increase exploration and reduce behavioral inhibition. This study did not investigate the neurobiology mediating these effects and future research for this is now needed.

PMID:41395988 | DOI:10.15288/jsad.25-00285

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