Background and Aims: Increasing evidence suggests that a ketogenic (high-fat, low-carbohydrate) diet intervention reduces alcohol withdrawal severity and alcohol craving in individuals with alcohol use disorder (AUD) by shifting brain energetics from glucose to ketones. We hypothesized that the ketogenic diet would reduce a brain craving signature when individuals undergoing alcohol detoxification treatment were exposed to alcohol cues. Methods: We performed a secondary analysis of functional magnetic resonance data of n=33 adults with an AUD were randomized to a ketogenic diet (n=19) or a standard American diet (n=14) and underwent three weeks of inpatient alcohol detoxification treatment. Once per week, participants performed an alcohol cue-reactivity paradigm with functional magnetic resonance imaging. We extracted brain responses to food and alcohol cues and quantified the degree to which each set of brain images shared a pattern of activation with a recently validated Neurobiological Craving Signature (NCS). We then performed a group-by-time repeated measures ANOVA to test for differences in craving signature expression between the dietary groups over the three-week treatment period. We also correlated these expression patterns with self-reported wanting ratings for alcohol cues. Results: For alcohol relative to food cues, there was a main effect of group, such that the ketogenic diet group showed lower NCS expression across all three weeks of treatment. The main effect of time and the group-by-time interaction were not significant. Self-reported wanting for alcohol cues reduced with KD compared to SA but did not correlate with the NCS score. Conclusions: A ketogenic diet reduces self-reported alcohol wanting, and induced lower brain craving signatures to alcohol cues during inpatient treatment for AUD.

The authors have declared no competing interest.

NCT03255031

This work was accomplished with support from the National Institute on Alcohol Abuse and Alcoholism, Intramural Research Program (Y1AA-3009 to Dr. Volkow). Dr. Wiers was supported by a NARSAD Young Investigator Grant (28778), and a K99/R00 grant AA026892.

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Patients provided written informed consent to participate in the study, which was approved by the Institutional Review Board at the National Institutes of Health (Combined Neurosciences White Panel). Participants were MRI scanned between October 2017 and February 2020. The study was registered at ClinicalTrials.gov (NCT03255031).

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