{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:23:53Z","timestamp":1768566233104,"version":"3.49.0"},"posted":{"date-parts":[[2023,9,26]]},"group-title":"Addiction Medicine","reference-count":35,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,9,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background and Aims<\/jats:title>\n                  <jats:p>Increasing evidence suggests that a ketogenic (high-fat, low-carbohydrate) diet intervention reduces alcohol withdrawal severity and alcohol craving in individuals with alcohol use disorder (AUD) by shifting brain energetics from glucose to ketones. We hypothesized that the ketogenic diet would reduce a brain craving signature when individuals undergoing alcohol detoxification treatment were exposed to alcohol cues.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed a secondary analysis of functional magnetic resonance data of n=33 adults with an AUD were randomized to a ketogenic diet (n=19) or a standard American diet (n=14) and underwent three weeks of inpatient alcohol detoxification treatment. Once per week, participants performed an alcohol cue-reactivity paradigm with functional magnetic resonance imaging. We extracted brain responses to food and alcohol cues and quantified the degree to which each set of brain images shared a pattern of activation with a recently validated \u2018Neurobiological Craving Signature\u2019 (NCS). We then performed a group-by-time repeated measures ANOVA to test for differences in craving signature expression between the dietary groups over the three-week treatment period. We also correlated these expression patterns with self-reported wanting ratings for alcohol cues.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For alcohol relative to food cues, there was a main effect of group, such that the ketogenic diet group showed lower NCS expression across all three weeks of treatment. The main effect of time and the group-by-time interaction were not significant. Self-reported wanting for alcohol cues reduced with KD compared to SA but did not correlate with the NCS score.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A ketogenic diet reduces self-reported alcohol wanting, and induced lower brain craving signatures to alcohol cues during inpatient treatment for AUD.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.09.25.23296094","type":"posted-content","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:25:10Z","timestamp":1695774310000},"source":"Crossref","is-referenced-by-count":3,"title":["Ketogenic diet reduces a neurobiological craving signature in alcohol use disorder"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2934-8794","authenticated-orcid":false,"given":"Corinde E.","family":"Wiers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Manza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gene-Jack","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora D.","family":"Volkow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023093009350738000_2023.09.25.23296094v1.1","doi-asserted-by":"crossref","unstructured":"American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders. Washington DC.","DOI":"10.1176\/appi.books.9780890425596"},{"key":"2023093009350738000_2023.09.25.23296094v1.2","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1038\/s41386-021-01248-3","article-title":"A neuroeconomic signature of opioid craving: How fluctuations in craving bias drug-related and nondrug-related value","volume":"47","year":"2022","journal-title":"Neuropsychopharmacology"},{"key":"2023093009350738000_2023.09.25.23296094v1.3","doi-asserted-by":"crossref","unstructured":"Blanco-Gand\u00eda, M.D.C. , R\u00f3denas-Gonz\u00e1lez, F. , Pascual, M. , Reguil\u00f3n, M.D. , Guerri, C. , Mi\u00f1arro, J. , and Rodr\u00edguez-Arias, M. (2021). Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice. Nutrients 13.","DOI":"10.3390\/nu13072167"},{"key":"2023093009350738000_2023.09.25.23296094v1.4","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s00213-020-05735-1","article-title":"Effects of ketogenic diet and ketone monoester supplement on acute alcohol withdrawal symptoms in male mice","volume":"238","year":"2021","journal-title":"Psychopharmacology (Berl)"},{"key":"2023093009350738000_2023.09.25.23296094v1.5","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1007\/s00213-018-4887-7","article-title":"New steps for treating alcohol use disorder","volume":"235","year":"2018","journal-title":"Psychopharmacology"},{"key":"2023093009350738000_2023.09.25.23296094v1.6","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16669366"},{"key":"2023093009350738000_2023.09.25.23296094v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.01.032"},{"key":"2023093009350738000_2023.09.25.23296094v1.8","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/acer.13560","article-title":"Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats","volume":"42","year":"2018","journal-title":"Alcohol Clin Exp Res"},{"key":"2023093009350738000_2023.09.25.23296094v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(81)90189-2"},{"key":"2023093009350738000_2023.09.25.23296094v1.10","doi-asserted-by":"crossref","unstructured":"Farokhnia, M. , Grodin, E.N. , Lee, M.R. , Oot, E.N. , Blackburn, A.N. , Stangl, B.L. , Schwandt, M.L. , Farinelli, L.A. , Momenan, R. , Ramchandani, V.A. , and Leggio, L. (2017). Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals. Mol Psychiatry.","DOI":"10.1038\/mp.2017.226"},{"key":"2023093009350738000_2023.09.25.23296094v1.11","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1176\/appi.ajp.21121207","article-title":"Transdiagnostic Connectome-Based Prediction of Craving","volume":"180","year":"2023","journal-title":"Am J Psychiatry"},{"key":"2023093009350738000_2023.09.25.23296094v1.12","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1001\/jamapsychiatry.2022.1970","article-title":"Neuropsychoimaging Measures as Alternatives to Drug Use Outcomes in Clinical Trials for Addiction","volume":"79","year":"2022","journal-title":"JAMA Psychiatry"},{"key":"2023093009350738000_2023.09.25.23296094v1.13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65153"},{"key":"2023093009350738000_2023.09.25.23296094v1.14","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/s41593-022-01228-w","article-title":"A neuromarker for drug and food craving distinguishes drug users from non-users","volume":"26","year":"2023","journal-title":"Nat Neurosci"},{"key":"2023093009350738000_2023.09.25.23296094v1.15","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.11406"},{"key":"2023093009350738000_2023.09.25.23296094v1.16","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1038\/s41593-022-01246-8","article-title":"An fMRI marker of drug and food craving","volume":"26","year":"2023","journal-title":"Nat Neurosci"},{"key":"2023093009350738000_2023.09.25.23296094v1.17","doi-asserted-by":"crossref","unstructured":"Li, X. , Shi, Z. , Byanyima, J. , Morgan, P.T. , Van Der Veen, J.W. , Zhang, R. , Deneke, E. , Wang, G.J. , Volkow, N.D. , and Wiers, C.E. (2022). Brain glutamate and sleep efficiency associations following a ketogenic diet intervention in individuals with Alcohol Use Disorder. Drug Alcohol Depend Rep 5.","DOI":"10.1016\/j.dadr.2022.100092"},{"key":"2023093009350738000_2023.09.25.23296094v1.18","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.ajem.2017.02.002","article-title":"The emergency medicine management of severe alcohol withdrawal","volume":"35","year":"2017","journal-title":"Am J Emerg Med"},{"key":"2023093009350738000_2023.09.25.23296094v1.19","doi-asserted-by":"publisher","DOI":"10.1046\/j.1360-0443.1998.937109113.x"},{"key":"2023093009350738000_2023.09.25.23296094v1.20","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2021.781668"},{"key":"2023093009350738000_2023.09.25.23296094v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2008.07.018"},{"key":"2023093009350738000_2023.09.25.23296094v1.22","doi-asserted-by":"publisher","DOI":"10.1097\/01.nrl.0000340787.30542.41"},{"key":"2023093009350738000_2023.09.25.23296094v1.23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s13011-016-0081-2","article-title":"A narrative review of alcohol consumption as a risk factor for global burden of disease","volume":"11","year":"2016","journal-title":"Subst Abuse Treat Prev Policy"},{"key":"2023093009350738000_2023.09.25.23296094v1.24","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.appet.2009.09.009","article-title":"State craving, food availability, and reactivity to preferred snack foods","volume":"54","year":"2010","journal-title":"Appetite"},{"key":"2023093009350738000_2023.09.25.23296094v1.25","doi-asserted-by":"publisher","DOI":"10.1037\/0021-843X.91.3.199"},{"key":"2023093009350738000_2023.09.25.23296094v1.26","doi-asserted-by":"publisher","DOI":"10.15288\/jsa.1982.43.1157"},{"key":"2023093009350738000_2023.09.25.23296094v1.27","unstructured":"Sobell, L.C. , and Sobell, M.B. (1996). \u201cTimeline Followback: User\u2019s Guide - A calendar method for assessing alcohol and drug use.\u201d. (Toronto: Addiction Research Foundation)."},{"key":"2023093009350738000_2023.09.25.23296094v1.28","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1002\/oby.22051","article-title":"A Ketone Ester Drink Lowers Human Ghrelin and Appetite","volume":"26","year":"2018","journal-title":"Obesity (Silver Spring)"},{"key":"2023093009350738000_2023.09.25.23296094v1.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2012.08.057"},{"key":"2023093009350738000_2023.09.25.23296094v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROPHARM.2017.01.012"},{"key":"2023093009350738000_2023.09.25.23296094v1.31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1306011110"},{"key":"2023093009350738000_2023.09.25.23296094v1.32","doi-asserted-by":"crossref","unstructured":"Wechsler, D. (1999). Wechsler Abbreviated Scale of Intelligence. San Antonio, TX: The Psychological Corporation.","DOI":"10.1037\/t15170-000"},{"key":"2023093009350738000_2023.09.25.23296094v1.33","doi-asserted-by":"crossref","unstructured":"Wiers, C.E. , Vendruscolo, L.F. , Van Der Veen, J.W. , Manza, P. , Shokri-Kojori, E. , Kroll, D.S. , Feldman, D.E. , Mcpherson, K.L. , Biesecker, C.L. , Zhang, R. , Herman, K. , Elvig, S.K. , Vendruscolo, J.C.M. , Turner, S.A. , Yang, S. , Schwandt, M. , Tomasi, D. , Cervenka, M.C. , Fink-Jensen, A. , Benveniste, H. , Diazgranados, N. , Wang, G.J. , Koob, G.F. , and Volkow, N.D. (2021). Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents. Sci Adv 7.","DOI":"10.1126\/sciadv.abf6780"},{"key":"2023093009350738000_2023.09.25.23296094v1.34","doi-asserted-by":"crossref","unstructured":"Wiers, C.E. , Zhao, J. , Manza, P. , Murani, K. , Ramirez, V. , Zehra, A. , Freeman, C. , Yuan, K. , Wang, G.J. , Demiral, S.B. , Childress, A.R. , Tomasi, D. , and Volkow, N.D. (2020). Conscious and unconscious brain responses to food and cocaine cues. Brain Imaging Behav.","DOI":"10.1007\/s11682-020-00258-x"},{"key":"2023093009350738000_2023.09.25.23296094v1.35","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-021-01124-0"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.09.25.23296094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:41:50Z","timestamp":1768506110000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2023.09.25.23296094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":35,"URL":"https:\/\/doi.org\/10.1101\/2023.09.25.23296094","relation":{},"subject":[],"published":{"date-parts":[[2023,9,26]]},"subtype":"preprint"}}