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Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents

2021; American Association for the Advancement of Science; Volume: 7; Issue: 15 Linguagem: Inglês

10.1126/sciadv.abf6780

2375-2548

Corinde E. Wiers, Leandro F. Vendruscolo, Jan-Willem van der Veen, Peter Manza, Ehsan Shokri‐Kojori, Danielle S. Kroll, Dana E. Feldman, Katherine McPherson, Catherine L. Biesecker, Rui Zhang, Kimberly Herman, Sophie K. Elvig, Janaina C. M. Vendruscolo, Sara A. Turner, Shanna Yang, Melanie L. Schwandt, Dardo Tomasi, Mackenzie C. Cervenka, Anders Fink‐Jensen, Helene Benveniste, Nancy Diazgranados, Gene‐Jack Wang, George F. Koob, Nora D. Volkow,

Adipose Tissue and Metabolism

Individuals with alcohol use disorder (AUD) show elevated brain metabolism of acetate at the expense of glucose. We hypothesized that a shift in energy substrates during withdrawal may contribute to withdrawal severity and neurotoxicity in AUD and that a ketogenic diet (KD) may mitigate these effects. We found that inpatients with AUD randomized to receive KD (n = 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (n = 14). Over a 3-week treatment, KD compared to SA showed lower "wanting" and increased dorsal anterior cingulate cortex (dACC) reactivity to alcohol cues and altered dACC bioenergetics (i.e., elevated ketones and glutamate and lower neuroinflammatory markers). In a rat model of alcohol dependence, a history of KD reduced alcohol consumption. We provide clinical and preclinical evidence for beneficial effects of KD on managing alcohol withdrawal and on reducing alcohol drinking.