Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents
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 effect...
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creator | 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 |
description | 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 (
= 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (
= 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. |
doi_str_mv | 10.1126/sciadv.abf6780 |
format | Article |
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= 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (
= 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.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.abf6780</identifier><identifier>PMID: 33837086</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Neuroscience ; SciAdv r-articles</subject><ispartof>Science advances, 2021-04, Vol.7 (15)</ispartof><rights>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).</rights><rights>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). 2021 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-3156994fe0416d3912fc6fd06b47e843949be35fb1569ef9fa1cb28a544d22433</citedby><cites>FETCH-LOGICAL-c390t-3156994fe0416d3912fc6fd06b47e843949be35fb1569ef9fa1cb28a544d22433</cites><orcidid>0000-0002-4760-857X ; 0000-0001-5750-3328 ; 0000-0001-7143-1236 ; 0000-0001-6668-0908 ; 0000-0001-6846-3173 ; 0000-0002-6606-2410 ; 0000-0002-2887-6667 ; 0000-0002-7415-8455 ; 0000-0002-1049-1523 ; 0000-0002-8829-8627 ; 0000-0002-8355-4900 ; 0000-0002-2934-8794 ; 0000-0001-8642-1831 ; 0000-0002-5017-9905</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034849/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034849/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33837086$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wiers, Corinde E</creatorcontrib><creatorcontrib>Vendruscolo, Leandro F</creatorcontrib><creatorcontrib>van der Veen, Jan-Willem</creatorcontrib><creatorcontrib>Manza, Peter</creatorcontrib><creatorcontrib>Shokri-Kojori, Ehsan</creatorcontrib><creatorcontrib>Kroll, Danielle S</creatorcontrib><creatorcontrib>Feldman, Dana E</creatorcontrib><creatorcontrib>McPherson, Katherine L</creatorcontrib><creatorcontrib>Biesecker, Catherine L</creatorcontrib><creatorcontrib>Zhang, Rui</creatorcontrib><creatorcontrib>Herman, Kimberly</creatorcontrib><creatorcontrib>Elvig, Sophie K</creatorcontrib><creatorcontrib>Vendruscolo, Janaina C M</creatorcontrib><creatorcontrib>Turner, Sara A</creatorcontrib><creatorcontrib>Yang, Shanna</creatorcontrib><creatorcontrib>Schwandt, Melanie</creatorcontrib><creatorcontrib>Tomasi, Dardo</creatorcontrib><creatorcontrib>Cervenka, Mackenzie C</creatorcontrib><creatorcontrib>Fink-Jensen, Anders</creatorcontrib><creatorcontrib>Benveniste, Helene</creatorcontrib><creatorcontrib>Diazgranados, Nancy</creatorcontrib><creatorcontrib>Wang, Gene-Jack</creatorcontrib><creatorcontrib>Koob, George F</creatorcontrib><creatorcontrib>Volkow, Nora D</creatorcontrib><title>Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>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 (
= 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (
= 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. 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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 (
= 19) required fewer benzodiazepines during the first week of detoxification, in comparison to those receiving a standard American (SA) diet (
= 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.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>33837086</pmid><doi>10.1126/sciadv.abf6780</doi><orcidid>https://orcid.org/0000-0002-4760-857X</orcidid><orcidid>https://orcid.org/0000-0001-5750-3328</orcidid><orcidid>https://orcid.org/0000-0001-7143-1236</orcidid><orcidid>https://orcid.org/0000-0001-6668-0908</orcidid><orcidid>https://orcid.org/0000-0001-6846-3173</orcidid><orcidid>https://orcid.org/0000-0002-6606-2410</orcidid><orcidid>https://orcid.org/0000-0002-2887-6667</orcidid><orcidid>https://orcid.org/0000-0002-7415-8455</orcidid><orcidid>https://orcid.org/0000-0002-1049-1523</orcidid><orcidid>https://orcid.org/0000-0002-8829-8627</orcidid><orcidid>https://orcid.org/0000-0002-8355-4900</orcidid><orcidid>https://orcid.org/0000-0002-2934-8794</orcidid><orcidid>https://orcid.org/0000-0001-8642-1831</orcidid><orcidid>https://orcid.org/0000-0002-5017-9905</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Neuroscience SciAdv r-articles |
title | Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents |
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