{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:38:19Z","timestamp":1791509899881,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Exogenous ketone monoester (KME) supplements rapidly increase plasma beta\u2010hydroxybutyrate (\u03b2\u2010OHB) and may impact cerebral blood flow (CBF). However, it is currently unknown how acute KME ingestion impacts resting CBF and whether differences in KME dose have differential effects on CBF regulation. The purpose of this study was to investigate the effect of two separate KME doses on resting CBF in young adults. On separate days and in a double\u2010blind, placebo\u2010controlled, cross\u2010over design, 20 participants (10 females; aged 23\u00a0\u00b1\u00a03\u00a0years) ingested either: (1) High\u2010KME (0.6\u00a0g\u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u03b2\u2010OHB); (2) Low\u2010KME (0.3\u00a0g\u00a0kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u03b2\u2010OHB); or (3) placebo drink, and quietly rested for 120\u00a0min. Global CBF (gCBF) was assessed using duplex ultrasound of the internal carotid and vertebral arteries, and transcranial Doppler ultrasound was used to assess middle cerebral artery blood velocity at baseline, 45\u00a0min and 120\u00a0min post\u2010ingestion. End\u2010tidal CO\n                      <jats:sub>2<\/jats:sub>\n                      () was measured using a gas analyser. \u03b2\u2010OHB was measured in venous blood. At 45\u00a0min post\u2010ingestion, gCBF was significantly reduced by 10.6% in Low\u2010KME and by 14.6% in High\u2010KME compared to baseline. At 120\u00a0min, gCBF returned towards baseline in Low\u2010KME, whereas gCBF was further reduced by 19.1% in High\u2010KME compared to baseline. KME dose\u2010dependent reductions in  may have contributed to these reductions in gCBF following KME ingestion. These novel findings provide a foundational characterization of the impact of KME on resting CBF, which prompts further investigation building on these results to isolate underlying mechanisms and develop dosing protocols to mitigate potential CO\n                      <jats:sub>2<\/jats:sub>\n                      disruptions.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16696-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Beta\u2010hydroxybutyrate (\u03b2\u2010OHB) is a signalling molecule and \u03b2\u2010OHB infusion increases cerebral blood flow (CBF) in humans.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Ingestion of higher doses of a ketone monoester (KME) supplement have been shown to lower blood pH and arterial CO\n                            <jats:sub>2<\/jats:sub>\n                            , which are important regulators of CBF.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            This double\u2010blind and placebo\u2010controlled cross\u2010over study tested the effects of two separate KME doses (Low\u2010KME and High\u2010KME) on resting CBF, end\u2010tidal CO\n                            <jats:sub>2<\/jats:sub>\n                            and systemic haemodynamics over a 2\u00a0h period post\u2010ingestion in young adults.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            Low\u2010KME reduced CBF 45\u00a0min post\u2010ingestion and High\u2010KME reduced CBF at both 45 and 120\u00a0min post\u2010ingestion, which corresponded with dose\u2010dependent reductions in end\u2010tidal CO\n                            <jats:sub>2<\/jats:sub>\n                            .\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The findings from this trial represent a foundational characterization of the effects of KME dose on resting CBF.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp287320","type":"journal-article","created":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T11:42:26Z","timestamp":1746963746000},"page":"2525-2541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Acute ketone monoester ingestion lowers resting cerebral blood flow: a randomized cross\u2010over trial"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9858-705X","authenticated-orcid":false,"given":"Aedan J.","family":"Rourke","sequence":"first","affiliation":[{"name":"Department of Kinesiology McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia M.S.","family":"Yong","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoff B.","family":"Coombs","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University Hamilton ON Canada"},{"name":"School of Psychology &amp; Sport Science Bangor University Bangor UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Addriana R.","family":"Odisho","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna A.","family":"Nash","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7816-0546","authenticated-orcid":false,"given":"Jack","family":"Bone","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1075-4183","authenticated-orcid":false,"given":"Baraa K.","family":"Al\u2010Khazraji","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1782-7074","authenticated-orcid":false,"given":"Jeremy J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Kinesiology McMaster University Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.206052"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17733868"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000003532"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP280682"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.5665\/sleep.1642"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/2046-7648-3-17"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.00290"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.11.032"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1996.270.5.E746"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-023-01008-y"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04483.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1961.16.3.473"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.146290"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/19390211.2023.2289961"},{"issue":"20","key":"e_1_2_6_16_1","article-title":"Ketone body \u03b2\u2010hydroxybutyrate is an autophagy\u2010dependent vasodilator","volume":"6","author":"McCarthy C.","year":"2021","journal-title":"Journal of Clinical Investigation Insight"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2020-0999"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00057.2024"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2608"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-52-1-34"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.32.3.197"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307457100"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-nutr-071816-064916"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.036459"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.095836"},{"issue":"6","key":"e_1_2_6_26_1","first-page":"1440","article-title":"Acute effects of \u03b2\u2010hydroxybutyrate on left ventricular function in young, healthy adults","volume":"135","author":"Oneglia A. 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