{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T09:33:29Z","timestamp":1777714409521,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Elevating blood ketones may enhance exercise capacity and modulate adaptations to exercise training; however, these effects may depend on whether hyperketonemia is induced endogenously through dietary carbohydrate restriction, or exogenously through ketone supplementation. To determine this, we compared the effects of endogenously\u2010 and exogenously\u2010induced hyperketonemia on exercise capacity and adaptation. Trained endurance athletes undertook 6\u00a0days of laboratory based cycling (\u201crace\u201d) whilst following either: a carbohydrate\u2010rich control diet (<jats:italic>n<\/jats:italic>\u00a0=\u00a07; CHO); a carbohydrate\u2010rich diet\u00a0+\u00a0ketone drink four\u2010times daily (<jats:italic>n<\/jats:italic>\u00a0=\u00a07; Ex Ket); or a ketogenic diet (<jats:italic>n<\/jats:italic>\u00a0=\u00a07; End Ket). Exercise capacity was measured daily, and adaptations in exercise metabolism, exercise physiology and postprandial insulin sensitivity (via an oral glucose tolerance test) were measured before and after dietary interventions. Urinary \u03b2\u2010hydroxybutyrate increased by \u2053150\u2010fold and \u2053650\u2010fold versus CHO with Ex Ket and End Ket, respectively. Exercise capacity was increased versus pre\u2010intervention by ~5% on race day 1 with CHO (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05), by 6%\u20138% on days 1, 4, and 6 (all <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) with Ex Ket and decreased by 48%\u201357% on all race days (all <jats:italic>p<\/jats:italic>\u00a0&gt;\u00a00.05) with End Ket. There was an \u20533\u2010fold increase in fat oxidation from pre\u2010 to post\u2010intervention (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) with End Ket and increased perceived exercise exertion (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). No changes in exercise substrate metabolism occurred with Ex Ket, but participants had blunted postprandial insulin sensitivity (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Dietary carbohydrate restriction and ketone supplementation both induce hyperketonemia; however, these are distinct physiological conditions with contrasting effects on exercise capacity and adaptation to exercise training.<\/jats:p>","DOI":"10.14814\/phy2.15309","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T05:05:58Z","timestamp":1653541558000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["The effects of endogenously\u2010 and exogenously\u2010induced hyperketonemia on exercise performance and adaptation"],"prefix":"10.14814","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3529-3555","authenticated-orcid":false,"given":"David J.","family":"Dearlove","sequence":"first","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Soto Mota","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hauton","sequence":"additional","affiliation":[{"name":"Chemistry Research Laboratory University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Pinnick","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology and Metabolism Churchill Hospital and Oxford NIHR Biomedical Research Centre University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rhys","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford  Headington Oxford United Kingdom"},{"name":"The PET Research Centre and The MR Research Centre Aarhus University  Headington Oxford United Kingdom"},{"name":"Clarendon Laboratory Department of Physics University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roman","family":"Fischer","sequence":"additional","affiliation":[{"name":"Target Discovery Institute University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James S.O.","family":"Mccullagh","sequence":"additional","affiliation":[{"name":"Chemistry Research Laboratory University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-6526","authenticated-orcid":false,"given":"Leanne","family":"Hodson","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology and Metabolism Churchill Hospital and Oxford NIHR Biomedical Research Centre University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kieran","family":"Clarke","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pete J.","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford  Headington Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/44.3.341"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/dmr.5610050304"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v067.i01"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsm.24.4.231"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP278928"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273230"},{"key":"e_1_2_10_8_1","article-title":"Crisis of confidence averted: Impairment of exercise economy and performance in elite race walkers by ketogenic low carbohydrate, high fat (LCHF) diet is reproducible","volume":"15","author":"Burke L. M.","year":"2020","journal-title":"PLoS One"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/85.6.1511"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/2046\u20107648\u20103\u201017"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.07.010"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00915"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00290"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.721673"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000002502"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2012.12.012"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP273185"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000001700"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000002065"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.4236\/ape.2014.44024"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1983.55.2.628"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.04.015"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42255\u2010020\u20100251\u20104"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1055\/s\u20102004\u2010830512"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00806"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.22.9.1462"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2010.257"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071816-064916"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2014-093824"},{"key":"e_1_2_10_30_1","first-page":"133","article-title":"Evidence that supports the prescription of low\u2010carbohydrate high\u2010fat diets: A narrative review","volume":"51","author":"Noakes T. D.","year":"2016","journal-title":"BMJ"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00650.2010"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1971.31.3.416"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP280032"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.9.e36"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(83)90106-3"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00092.2020"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000002467"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP277831"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1980.60.1.143"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2015-094758"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22051"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500213200"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2001.281.6.E1205"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jand.2015.12.006"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7493-1_7"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469\u20107793.2001.00295.x"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108050"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2013.262709"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP271934"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00142.2010"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-11-10"}],"container-title":["Physiological Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15309","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.14814\/phy2.15309","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.14814\/phy2.15309","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T15:21:38Z","timestamp":1704208898000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.14814\/phy2.15309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5]]},"references-count":50,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["10.14814\/phy2.15309"],"URL":"https:\/\/doi.org\/10.14814\/phy2.15309","archive":["Portico"],"relation":{},"ISSN":["2051-817X","2051-817X"],"issn-type":[{"value":"2051-817X","type":"print"},{"value":"2051-817X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5]]},"assertion":[{"value":"2022-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e15309"}}