{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:11:44Z","timestamp":1784563904947,"version":"3.55.0"},"reference-count":82,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,11]]},"abstract":"\n Abstract<\/jats:title>\n \n At rest, glucose serves as the brain's primary oxidative substrate; however, when circulating lactate is elevated, lactate oxidation increases. Whether this glucose\u2010sparing effect differs when lactate is elevated via passive infusion\n versus<\/jats:italic>\n exercise remains unknown. To address this, 13\u00a0healthy adults (six females) completed protocols of: (1) intravenous sodium lactate infusion (exogenous hyperlactataemia); and (2) cycling exercise (endogenous hyperlactataemia) to matched elevations in arterial lactate concentration (\u223c4 and \u223c8\u00a0mmol\/l). Radial arterial and internal jugular venous sampling and measures of cerebral blood flow (CBF) were used to calculate cerebral metabolic rates of glucose (CMR\n Glc<\/jats:sub>\n ), lactate (CMR\n iLac<\/jats:sub>\n ), and oxygen (). The exogenous infusion protocol resulted in a higher CBF compared to exercise (\n P\u00a0<\/jats:italic>\n <\u00a00.001), despite causing systemic alkalosis (\n P\u00a0<\/jats:italic>\n <\u00a00.001). During both protocols remained unchanged across increases in lactate concentrations (\n P<\/jats:italic>\n \u00a0=\u00a00.610), while CMR\n Glc<\/jats:sub>\n decreased (lactate,\n P<\/jats:italic>\n \u00a0=\u00a00.009; condition,\n P<\/jats:italic>\n \u00a0=\u00a00.373) and CMR\n iLac<\/jats:sub>\n increased in a dose\u2010dependent manner (lactate,\n P\u00a0<\/jats:italic>\n <\u00a00.001; condition,\n P<\/jats:italic>\n \u00a0=\u00a00.972). At an arterial concentration of 8\u00a0mmol\/l, circulating lactate accounted for 24% of total cerebral oxidative metabolism. Elevated circulating lactate leads to preferential lactate oxidation and reduced glucose utilization, irrespective of whether lactate is delivered exogenously or produced endogenously.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n The human brain relies primarily on oxidative glucose metabolism; however, with age and in many pathologies cerebral glucose metabolism declines; therefore, there is interest in investigating alternative fuel sources that can meet the high energetic needs of the brain.<\/jats:p>\n <\/jats:list-item>\n \n The present study investigates whether increased lactate availability exerts a glucose\u2010sparing effect in the healthy human brain, and whether this effect is consistent across physiologically distinct states of exogenous (sodium lactate infusion) and endogenous (exercise\u2010induced) hyperlactataemia.<\/jats:p>\n <\/jats:list-item>\n \n We assessed cerebral uptake and metabolism of glucose and lactate following exercise and lactate infusion, using simultaneous arterial and jugular venous blood samples, and Duplex ultrasound.<\/jats:p>\n <\/jats:list-item>\n \n Despite stark systemic physiological differences between conditions, cerebral glucose metabolism declined in proportion to increased circulating lactate irrespective of whether it is delivered exogenously or produced endogenously.<\/jats:p>\n <\/jats:list-item>\n \n These data provide clear evidence that lactate is preferentially oxidized by the brain when made available, helping preserve glucose for non\u2010energetic roles.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp289216","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T18:06:50Z","timestamp":1759428410000},"page":"6783-6800","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Preferential lactate metabolism in the human brain during exogenous and endogenous hyperlactataemia"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4137-6840","authenticated-orcid":false,"given":"Jodie L.","family":"Koep","sequence":"first","affiliation":[{"name":"School of Health & Exercise Sciences University of British Columbia \u2013 Okanagan Kelowna BC Canada"},{"name":"Centre for Heart, Lung and Vascular Health University of British Columbia \u2013 Okanagan Kelowna BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1350-7353","authenticated-orcid":false,"given":"Jennifer S.","family":"Duffy","sequence":"additional","affiliation":[{"name":"School of Physical Education, Sport & Exercise Sciences University of Otago Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7236-1348","authenticated-orcid":false,"given":"Jay M. 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