{"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":1791509899586,"version":"4.3.4"},"reference-count":56,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T00:00:00Z","timestamp":1633305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MSH\u2010141980"],"award-info":[{"award-number":["MSH\u2010141980"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000245","name":"Michael Smith Foundation for Health Research","doi-asserted-by":"publisher","award":["Grant\u2010in\u2010Aid: JL support by Scholar Award (16890)"],"award-info":[{"award-number":["Grant\u2010in\u2010Aid: JL support by Scholar Award (16890)"]}],"id":[{"id":"10.13039\/501100000245","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Adults with obesity are at increased risk of neurocognitive impairments, partly as a result of reduced cerebral blood flow and brain\u2010derived neurotrophic factor (BDNF). Ketone supplements containing \u03b2\u2010hydroxybutyrate (\u03b2\u2010OHB) are a purported therapeutic strategy for improving brain health in at\u2010risk populations. We tested the hypothesis that short\u2010term \u03b2\u2010OHB supplementation will elevate cerebral blood flow and BDNF, as well as improve cognition in adults with obesity. In a placebo\u2010controlled double\u2010blind, cross\u2010over design, 14 adults with obesity (10 females; aged\u00a056\u00a0\u00b1\u00a012\u00a0years; body mass index\u00a0=\u00a033.8\u00a0\u00b1\u00a06.9\u00a0kg\u00a0m<jats:sup>\u20132<\/jats:sup>) consumed 30\u00a0mL (12\u00a0g) of \u03b2\u2010OHB or placebo thrice\u2010daily for 14\u00a0days. Blood flow (<jats:italic>Q<\/jats:italic>) and cerebrovascular conductance (CVC) were measured in the common carotid (CCA), internal carotid (ICA) and vertebral (VA) arteries by duplex ultrasound. BDNF was measured by an enzyme\u2010linked immunosorbent assay. Cognition was assessed by the digit\u2010symbol substitution (DSST), Stroop and task\u2010switching tests. Following 14\u00a0days of ketone supplementation, we observed significant improvements in cerebrovascular outcomes including <jats:italic>Q<\/jats:italic><jats:sub>CCA<\/jats:sub> (+12%), <jats:italic>Q<\/jats:italic><jats:sub>VA<\/jats:sub> (+11%), VA<jats:sub>CVC<\/jats:sub> (+12%) and VA shear rate (+10%). DSST performance significantly improved following ketone supplementation (+2.7 correct responses) and improved DSST performance was positively associated improvements in cerebrovascular outcomes including <jats:italic>Q<\/jats:italic><jats:sub>CCA<\/jats:sub>, CCA<jats:sub>CVC<\/jats:sub>, <jats:italic>Q<\/jats:italic><jats:sub>VA<\/jats:sub> and VA<jats:sub>CVC<\/jats:sub>. By contrast to one hypothesis, \u03b2\u2010OHB did not impact fasting serum and plasma BDNF. \u03b2\u2010OHB supplementation improved cognition in adults with obesity, which may be partly facilitated by improvements in cerebral blood flow. \u03b2\u2010OHB supplementation was well\u2010tolerated and appears to be safe for cerebrovascular health, suggesting potential therapeutic benefits of \u03b2\u2010OHB in a population at risk of neurocognitive impairment.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp14839-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>People with obesity are at increased risk of neurocognitive dysfunction, partly as a result of \u2010induced reductions in cerebral blood flow (CBF) and brain\u2010derived neurotrophic factor (BDNF).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Ketone supplements containing \u03b2\u2010hydroxybutyrate (\u03b2\u2010OHB) reduce postprandial hyperglycaemia, which may increase CBF and BDNF, thereby protecting against obesity\u2010related cognitive dysfunction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We show for the first time that 14\u00a0days of thrice\u2010daily \u03b2\u2010OHB supplementation improves aspects of cognition and increases cerebrovascular flow, conductance and shear rate in the extracranial arteries of adults with obesity.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our preliminary data indicate a significant positive relationship between elevated CBF and improved cognition following \u03b2\u2010OHB supplementation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This trial provides a foundation for the potential non\u2010pharmacological therapeutic application of \u03b2\u2010OHB supplementation in patient groups at risk of hyperglycaemic cerebrovascular disease and cognitive dysfunction.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp281988","type":"journal-article","created":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T22:57:19Z","timestamp":1633474639000},"page":"4763-4778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Short\u2010term ketone monoester supplementation improves cerebral blood flow and cognition in obesity: A randomized cross\u2010over trial"],"prefix":"10.1113","volume":"599","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1782-7074","authenticated-orcid":false,"given":"Jeremy J.","family":"Walsh","sequence":"first","affiliation":[{"name":"School of Health and Exercise Sciences Centre for Heart, Lung and Vascular Health University of British Columbia Okanagan  Kelowna BC Canada"},{"name":"Department of Kinesiology McMaster University  Hamilton ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah G.","family":"Caldwell","sequence":"additional","affiliation":[{"name":"School of Health and Exercise Sciences Centre for Heart, Lung and Vascular Health University of British Columbia Okanagan  Kelowna BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Neudorf","sequence":"additional","affiliation":[{"name":"School of Health and Exercise Sciences Centre for Heart, Lung and Vascular Health University of British Columbia Okanagan  Kelowna BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip N.","family":"Ainslie","sequence":"additional","affiliation":[{"name":"School of Health and Exercise Sciences Centre for Heart, Lung and Vascular Health University of British Columbia Okanagan  Kelowna BC 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