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Ketogenic Diet Reduces Alcohol Withdrawal Symptoms in Humans and Alcohol Intake in Rodents

A ketogenic-friendly meal and a bottle of wineHot Off the Press – April 26, 2021

Published in Science Advances by  Corinde Wiers and Leandro Vendruscolo,  et al.

Previous studies reported that people with alcohol use disorder (AUD) use less glucose and more acetate as a source of energy in the brain. This is because alcohol is broken down by the liver into acetate, which can then be used by the brain as an energy fuel. In a recently published article in Science Advances, the investigators hypothesized that when people with AUD stop drinking, there is a deficit in energy from acetate in the brain and that this deficit contributes to the symptoms of alcohol withdrawal and increased alcohol drinking in alcohol dependence.

To test this hypothesis, the investigators designed a study in which a high-fat, low-carbohydrate “ketogenic diet” intervention would compensate for the deficit of energy from acetate when patients with AUD undergo alcohol detoxification. The clinical study led by Dr. Wiers as a fellow in the Neuroimaging Laboratory of Dr. Volkow at NIAAA (currently assistant professor at the University of Pennsylvania) found that patients on the ketogenic diet needed less medication to treat alcohol withdrawal and showed less craving for alcohol compared with patients who consumed a standard American diet. A preclinical study led by Dr. Vendruscolo and Dr. Koob from the Neurobiology of Addiction Section at NIDA, found that rats with a history of a ketogenic diet drank significantly less alcohol compared to those on a regular chow diet.

Publication Information

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

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

In: Science Advances, vol. 7, no. 15, 2021.

Abstract | Links

@article{Wierseabf6780,
title = {Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents},
author = {Corinde E Wiers and Leandro F Vendruscolo and Jan-Willem van der Veen and Peter Manza and Ehsan Shokri-Kojori and Danielle S Kroll and Dana E Feldman and Katherine L McPherson and Catherine L Biesecker and Rui Zhang and Kimberly Herman and Sophie K Elvig and Janaina C M Vendruscolo and Sara A Turner and Shanna Yang and Melanie Schwandt and Dardo Tomasi and Mackenzie C Cervenka and Anders Fink-Jensen and Helene Benveniste and Nancy Diazgranados and Gene-Jack Wang and George F Koob and Nora D Volkow},
url = {https://pubmed.ncbi.nlm.nih.gov/33837086/},
doi = {10.1126/sciadv.abf6780},
year = {2021},
date = {2021-01-01},
journal = {Science Advances},
volume = {7},
number = {15},
publisher = {American Association for the Advancement of Science},
abstract = {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 textquotedblleftwantingtextquotedblright 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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

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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 textquotedblleftwantingtextquotedblright 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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  • https://pubmed.ncbi.nlm.nih.gov/33837086/
  • doi:10.1126/sciadv.abf6780

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