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

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

Original languageEnglish
Article numbereabf6780
JournalScience Advances
Volume7
Issue number15
DOIs
Publication statusPublished - Apr 2021

ID: 67031636