TY - JOUR
T1 - Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents
AU - Wiers, Corinde E.
AU - Vendruscolo, Leandro F.
AU - van der Veen, Jan Willem
AU - Manza, Peter
AU - Shokri-Kojori, Ehsan
AU - Kroll, Danielle S.
AU - Feldman, Dana E.
AU - McPherson, Katherine L.
AU - Biesecker, Catherine L.
AU - Zhang, Rui
AU - Herman, Kimberly
AU - Elvig, Sophie K.
AU - Vendruscolo, Janaina C.M.
AU - Turner, Sara A.
AU - Yang, Shanna
AU - Schwandt, Melanie
AU - Tomasi, Dardo
AU - Cervenka, Mackenzie C.
AU - Fink-Jensen, Anders
AU - Benveniste, Helene
AU - Diazgranados, Nancy
AU - Wang, Gene Jack
AU - Koob, George F.
AU - Volkow, Nora D.
N1 - Publisher Copyright:
© 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
PY - 2021/4/9
Y1 - 2021/4/9
N2 - 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.
AB - 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.
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U2 - 10.1126/SCIADV.ABF6780
DO - 10.1126/SCIADV.ABF6780
M3 - Article
C2 - 33837086
AN - SCOPUS:85104211071
SN - 2375-2548
VL - 7
JO - Science Advances
JF - Science Advances
IS - 15
M1 - eabf6780
ER -