{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:04:05Z","timestamp":1790597045436,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"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":["Experimental Physiology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Some decades ago significant scientific interest was raised by the concept of the \u2018lactate paradox\u2019 occurring during altitude acclimatization. In short, in acute hypoxia blood lactate\n                    <jats:sup>\u2212<\/jats:sup>\n                    concentration ([La]\n                    <jats:sub>b<\/jats:sub>\n                    ) is higher, compared to normoxia, at any given submaximal work rate, whereas peak [La]\n                    <jats:sub>b<\/jats:sub>\n                    at exhausting exercise is unchanged. During altitude acclimatization the [La]\n                    <jats:sub>b<\/jats:sub>\n                    vs. submaximal work rate relationship falls towards the original sea\u2010level curve, whereas peak [La]\n                    <jats:sub>b<\/jats:sub>\n                    progressively falls with increasing altitude. Upon the premise that lactate\n                    <jats:sup>\u2212<\/jats:sup>\n                    accumulation derives from lack of O\n                    <jats:sub>2<\/jats:sub>\n                    and anaerobic glycolysis, the lowered [La]\n                    <jats:sub>b<\/jats:sub>\n                    at altitude was considered \u2018paradoxical\u2019. After decades of research on the \u2018lactate shuttle\u2019 and lactate metabolism the issue should be revisited. A new scenario could be summarized as follows. Muscle and blood lactate\n                    <jats:sup>\u2212<\/jats:sup>\n                    accumulation during increasing intensity exercise reflect a mismatch between a faster \u2018speed\u2019 of glycolysis and a relatively slower speed of oxidative phosphorylation, possibly aimed at accumulating lactate\n                    <jats:sup>\u2212<\/jats:sup>\n                    in blood, to be distributed for different purposes throughout the body. Acute hypoxia further accelerates glycolysis through an enhanced sympatho\u2010adrenergic stimulation, worsens intracellular hypoxia and increases [ADP]\u2219[P\n                    <jats:sub>i<\/jats:sub>\n                    ]\/[ATP], resulting in a greater [La]\n                    <jats:sub>b<\/jats:sub>\n                    for the same absolute work rate. During altitude acclimatization the sympatho\u2010adrenergic stimulation falls, intracellular hypoxia is attenuated (mainly through a reduced O\n                    <jats:sub>2<\/jats:sub>\n                    demand), the [ADP]\u2219[P\n                    <jats:sub>i<\/jats:sub>\n                    ]\/[ATP] increase subsides, and a tighter coupling between lactate\n                    <jats:sup>\u2212<\/jats:sup>\n                    production and utilization ensues, with the end result of decreased [La]\n                    <jats:sub>b<\/jats:sub>\n                    for the same absolute work rate and lower peak [La]\n                    <jats:sub>b<\/jats:sub>\n                    . Although the perspective is radically changed, this remarkable series of metabolic adaptations appears of interest also today.\n                  <\/jats:p>","DOI":"10.1113\/ep094234","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:43:58Z","timestamp":1790595838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The \u2018lactate paradox\u2019 revisited after 35 years:\n                    <i>In memoriam<\/i>\n                    Paolo Cerretelli"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-1659","authenticated-orcid":false,"given":"Bruno","family":"Grassi","sequence":"first","affiliation":[{"name":"Department of Medicine University of Udine  Udine Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1989.67.4.1456"},{"key":"e_1_2_16_3_1","first-page":"2924","article-title":"Lactate production under fully aerobic conditions: The lactate shuttle during rest and exercise","volume":"45","author":"Brooks G. 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