{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T08:23:49Z","timestamp":1765355029201,"version":"3.41.2"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"vor","delay-in-days":4,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32DA028874-11"],"award-info":[{"award-number":["T32DA028874-11"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Previous preclinical and human studies have shown that a high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal. However, the effects of KS on alcohol sensitivity are unknown.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In this single-blind, cross-over study, 10 healthy participants (3 females) were administered a single, oral dose of a KS (25\u00a0g of ketones from D-\u03b2-hydroxybutyric acid and R-1,3-butanediol) or placebo 30 minutes before an oral alcohol dose (0.25\u00a0g\/kg for women; 0.31\u00a0g\/kg for men). Assessments of breath alcohol concentration and blood alcohol levels (BAL) and responses on the Drug Effect Questionnaire were repeatedly obtained over 180 minutes after alcohol consumption. In a parallel preclinical study, 8 Wistar rats (4 females) received an oral gavage of KS (0.42\u00a0g ketones\/kg), water, or the sweetener allulose (0.58\u00a0g\/kg) followed 15 minutes later by an oral alcohol dose (0.8\u00a0g\/kg). BAL was monitored for 240 minutes after alcohol exposure.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In humans, the intake of KS before alcohol significantly blunted breath alcohol concentration and BAL, reduced ratings of alcohol liking and wanting more, and increased disliking for alcohol. In rats, KS reduced BAL more than either allulose or water.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>KS altered physiological and subjective responses to alcohol in both humans and rats, and the effects were likely not mediated by the sweetener allulose present in the KS drink. Therefore, KS could potentially reduce the intoxicating effects of alcohol.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyae009","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T18:23:32Z","timestamp":1707157412000},"source":"Crossref","is-referenced-by-count":5,"title":["Ketone Supplementation Dampens Subjective and Objective Responses to Alcohol: Evidence From a Preclinical Rat Study and a Randomized, Cross-Over Trial in Healthy Volunteers"],"prefix":"10.1093","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3136-4811","authenticated-orcid":false,"given":"Xinyi","family":"Li","sequence":"first","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenhao","family":"Shi","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dustin R","family":"Todaro","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Pond","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana I","family":"Byanyima","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sianneh A","family":"Vesslee","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rishika","family":"Reddy","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi Prakash Reddy","family":"Nanga","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine, Department of Radiology , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Kass","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijay","family":"Ramchandani","sequence":"additional","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism , National Institutes of Health, Bethesda, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1018-0450","authenticated-orcid":false,"given":"Henry R","family":"Kranzler","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janaina C M","family":"Vendruscolo","sequence":"additional","affiliation":[{"name":"National Institute on Drug Abuse, National Institutes of Health , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leandro F","family":"Vendruscolo","sequence":"additional","affiliation":[{"name":"National Institute on Drug Abuse, National Institutes of Health , Baltimore, Maryland , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2934-8794","authenticated-orcid":false,"given":"Corinde E","family":"Wiers","sequence":"additional","affiliation":[{"name":"Center for Studies of Addiction, Department of Psychiatry, University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,2,5]]},"reference":[{"key":"2024022820550248100_CIT0001","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association","year":"2013","edition":"5th ed"},{"key":"2024022820550248100_CIT0002","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3389\/fnmol.2016.00137","article-title":"Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo\/Rijswijk rats","volume":"9","author":"Ari","year":"2016","journal-title":"Front Mol Neurosci"},{"key":"2024022820550248100_CIT0003","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.3390\/nu13072167","article-title":"Ketogenic diet decreases alcohol intake in adult male mice","volume":"13","author":"Blanco-Gand\u00eda","year":"2021","journal-title":"Nutrients"},{"key":"2024022820550248100_CIT0004","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1111\/j.1530-0277.1995.tb01554.x","article-title":"Development and initial validation of a measure of drinking urges in abstinent alcoholics","volume":"19","author":"Bohn","year":"1995","journal-title":"Alcohol Clin Exp Res"},{"key":"2024022820550248100_CIT0005","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","author":"Bornebusch","year":"2021","journal-title":"Psychopharmacology (Berl)"},{"key":"2024022820550248100_CIT0006","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3389\/fnmol.2017.00129","article-title":"Nutritional ketosis affects metabolism and behavior in Sprague-Dawley rats in both control and chronic stress environments","volume":"10","author":"Brownlow","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"2024022820550248100_CIT0007","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.3390\/nu10101348","article-title":"Effect of a very low-calorie ketogenic diet on food and alcohol cravings, physical and sexual activity, sleep disturbances, and quality of life in obese patients","volume":"10","author":"Castro","year":"2018","journal-title":"Nutrients"},{"key":"2024022820550248100_CIT0008","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.cld.2012.08.002","article-title":"Alcohol metabolism","volume":"16","author":"Cederbaum","year":"2012","journal-title":"Clin Liver Dis"},{"key":"2024022820550248100_CIT0009","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/0003-9861(77)90398-8","article-title":"Transfer and reoxidation of reducing equivalents as the rate-limiting steps in the oxidation of ethanol by liver cells isolated from fed and fasted rats","volume":"183","author":"Cederbaum","year":"1977","journal-title":"Arch Biochem Biophys"},{"key":"2024022820550248100_CIT0010","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/acer.13560","article-title":"Ketogenic diet suppresses alcohol withdrawal syndrome in rats","volume":"42","author":"Dencker","year":"2018","journal-title":"Alcohol Clin Exp Res"},{"key":"2024022820550248100_CIT0011","doi-asserted-by":"crossref","first-page":"377","DOI":"10.3389\/fnmol.2017.00377","article-title":"Ketone-based metabolic therapy: is increased NAD(+) a primary mechanism","volume":"10","author":"Elamin","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"2024022820550248100_CIT0012","doi-asserted-by":"crossref","first-page":"981","DOI":"10.15585\/mmwr.mm6930a1","article-title":"Deaths and years of potential life lost from excessive alcohol use - United States, 2011-2015","volume":"69","author":"Esser","year":"2020","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"2024022820550248100_CIT0013","doi-asserted-by":"crossref","first-page":"e2239485","DOI":"10.1001\/jamanetworkopen.2022.39485","article-title":"Estimated deaths attributable to excessive alcohol use among US adults aged 20 to 64 years, 2015 to 2019","volume":"5","author":"Esser","year":"2022","journal-title":"JAMA Network Open"},{"key":"2024022820550248100_CIT0014","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/ijnp\/pyab004","article-title":"Neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals: findings from a randomized, double-blind, placebo-controlled human laboratory study","volume":"24","author":"Farokhnia","year":"2021","journal-title":"Int J Neuropsychopharmacol"},{"key":"2024022820550248100_CIT0015","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1006\/appe.1998.0168","article-title":"Effects of meal composition on blood alcohol level, psychomotor performance and subjective state after ingestion of alcohol","volume":"31","author":"Finnigan","year":"1998","journal-title":"Appetite"},{"key":"2024022820550248100_CIT0016","first-page":"G291","article-title":"Relationships between gastric emptying of solid and caloric liquid meals and alcohol absorption","volume":"257","author":"Horowitz","year":"1989","journal-title":"Am J Physiol"},{"key":"2024022820550248100_CIT0017","doi-asserted-by":"crossref","first-page":"e1340","DOI":"10.1002\/wfs2.1340","article-title":"Alcohol, its absorption, distribution, metabolism, and excretion in the body and pharmacokinetic calculations","volume":"1","author":"Jones","year":"2019","journal-title":"WIREs Forensic Science"},{"key":"2024022820550248100_CIT0018","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12986-016-0069-y","article-title":"Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague\u2013Dawley rats","volume":"13","author":"Kesl","year":"2016","journal-title":"Nutrition & Metabolism"},{"issue":"1","key":"2024022820550248100_CIT0039","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1042\/bj1120117","article-title":"Inhibition of hepatic gluconeogenesis by ethanol","volume":"112","author":"Kreb","year":"1969","journal-title":"Biochem J"},{"key":"2024022820550248100_CIT0019","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/acer.13291","article-title":"Inhalation of Alcohol Vapor: Measurement and Implications","volume":"41","author":"MacLean","year":"2017","journal-title":"Alcohol Clin Exp Res"},{"key":"2024022820550248100_CIT0020","doi-asserted-by":"crossref","first-page":"781668","DOI":"10.3389\/fpsyt.2021.781668","article-title":"Nutritional ketosis as a potential treatment for alcohol use disorder","volume":"12","author":"Mahajan","year":"2021","journal-title":"Front Psychiatry"},{"key":"2024022820550248100_CIT0021","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/j.1530-0277.1993.tb00739.x","article-title":"Development and validation of the Biphasic Alcohol Effects Scale","volume":"17","author":"Martin","year":"1993","journal-title":"Alcohol Clin Exp Res"},{"key":"2024022820550248100_CIT0022","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1042\/bj1500205","article-title":"Rate-limiting factors in the oxidation of ethanol by isolated rat liver cells","volume":"150","author":"Meijer","year":"1975","journal-title":"Biochem J"},{"key":"2024022820550248100_CIT0023","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1111\/acer.13133","article-title":"Alcohol vapor inhalation as a model of alcohol-induced organ disease","volume":"40","author":"Mouton","year":"2016","journal-title":"Alcohol Clin Exp Res"},{"key":"2024022820550248100_CIT0024","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1097\/00008877-199109000-00006","article-title":"Subjective and discriminative effects of drugs","volume":"2","author":"Preston","year":"1991","journal-title":"Behav Pharmacol"},{"key":"2024022820550248100_CIT0025","doi-asserted-by":"crossref","first-page":"e3597","DOI":"10.1210\/clinem\/dgaa483","article-title":"Oral D\/L-3-hydroxybutyrate stimulates cholecystokinin and insulin secretion and slows gastric emptying in healthy males","volume":"105","author":"Rittig","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"2024022820550248100_CIT0026","first-page":"E897","article-title":"The inhibition of gluconeogenesis following alcohol in humans","volume":"275","author":"Siler","year":"1998","journal-title":"Am J Physiol"},{"key":"2024022820550248100_CIT0027","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/acer.13264","article-title":"The influence of mixers containing artificial sweetener or different doses of carbohydrate on breath alcohol responses in females","volume":"41","author":"Smith","year":"2017","journal-title":"Alcohol Clin Exp Res"},{"key":"2024022820550248100_CIT0028","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.drugalcdep.2015.10.015","article-title":"Effects of artificial sweeteners on breath alcohol concentrations in male and female social drinkers","volume":"157","author":"Stamates","year":"2015","journal-title":"Drug Alcohol Depend"},{"key":"2024022820550248100_CIT0029","doi-asserted-by":"crossref","first-page":"848","DOI":"10.3389\/fphys.2017.00848","article-title":"On the metabolism of exogenous ketones in humans","volume":"8","author":"Stubbs","year":"2017","journal-title":"Front Physiol"},{"key":"2024022820550248100_CIT0030","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1123\/ijsnem.2019-0014","article-title":"Gastrointestinal effects of exogenous ketone drinks are infrequent, mild, and vary according to ketone compound and dose","volume":"29","author":"Stubbs","year":"2019","journal-title":"Int J Sport Nutr Exerc Metab"},{"key":"2024022820550248100_CIT0031","article-title":"Key substance use and mental health indicators in the United States: Results from the 2021 National Survey on Drug Use and Health (HHS Publication No. PEP22-07-01-005, NSDUH Series H-57)","volume-title":"Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration","author":"Substance Abuse and Mental Health Services Administration","year":"2022"},{"key":"2024022820550248100_CIT0032","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1093\/jn\/101.12.1719","article-title":"Metabolic fate of 1,3-butanediol in the rat: conversion to \u03b2-hydroxybutyrate","volume":"101","author":"Tate","year":"1971","journal-title":"J Nutr"},{"key":"2024022820550248100_CIT0033","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1111\/j.1530-0277.1989.tb00380.x","article-title":"Swift increase in alcohol metabolism in humans","volume":"13","author":"Thurman","year":"1989","journal-title":"Alcohol Clin Exp Res"},{"key":"2024022820550248100_CIT0034","doi-asserted-by":"crossref","first-page":"eabf6780","DOI":"10.1126\/sciadv.abf6780","article-title":"Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents","volume":"7","author":"Wiers","year":"2021","journal-title":"Sci Adv"},{"key":"2024022820550248100_CIT0035","doi-asserted-by":"crossref","first-page":"104852","DOI":"10.1016\/j.jff.2021.104852","article-title":"NADH and NRH as potential dietary supplements or pharmacological agents for early liver injury caused by acute alcohol exposure","volume":"87","author":"Wu","year":"2021","journal-title":"J Funct Foods"},{"key":"2024022820550248100_CIT0036","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3389\/fnut.2018.00062","article-title":"Nutritional ketosis increases NAD(+)\/NADH ratio in healthy human brain: an in vivo study by (31)P-MRS","volume":"5","author":"Xin","year":"2018","journal-title":"Front Nutr"},{"key":"2024022820550248100_CIT0037","first-page":"245","article-title":"Overview: how is alcohol metabolized by the body","volume":"29","author":"Zakhari","year":"2006","journal-title":"Alcohol Res Health"},{"key":"2024022820550248100_CIT0038","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.tifs.2016.06.004","article-title":"Recent advances in d-allulose: Physiological functionalities, applications, and biological production","volume":"54","author":"Zhang","year":"2016","journal-title":"Trends in Food Science & Technology"}],"container-title":["International Journal of Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ijnp\/advance-article-pdf\/doi\/10.1093\/ijnp\/pyae009\/56587228\/pyae009.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ijnp\/article-pdf\/27\/2\/pyae009\/56779204\/pyae009.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ijnp\/article-pdf\/27\/2\/pyae009\/56779204\/pyae009.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T20:55:25Z","timestamp":1709153725000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ijnp\/article\/doi\/10.1093\/ijnp\/pyae009\/7601198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,1]]},"references-count":39,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ijnp\/pyae009","relation":{},"ISSN":["1461-1457","1469-5111"],"issn-type":[{"type":"print","value":"1461-1457"},{"type":"electronic","value":"1469-5111"}],"subject":[],"published-other":{"date-parts":[[2024,2,1]]},"published":{"date-parts":[[2024,2,1]]},"article-number":"pyae009"}}