Cited by 263Barrier Structure and Function StudiesAdvanced MRI Techniques and ApplicationsCardiovascular and exercise physiology

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Lactate fuels the human brain during exercise.

Quistorff, Bjørn, Secher, Niels H., Van Lieshout, Johannes J.·2008·The FASEB Journal

DOI 10.1096/fj.08-106104

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Abstract

The human brain releases a small amount of lactate at rest, and even an increase in arterial blood lactate during anesthesia does not provoke a net cerebral lactate uptake. However, during cerebral activation associated with exercise involving a marked increase in plasma lactate, the brain takes up lactate in proportion to the arterial concentration. Cerebral lactate uptake, together with glucose uptake, is larger than the uptake accounted for by the concomitant O 2 uptake, as reflected by the decrease in cerebral metabolic ratio (CMR) [the cerebral molar uptake ratio O 2 /(glucose+½ lactate)] from a resting value of 6 to <2. The CMR also decreases when plasma lactate is not increased, as during prolonged exercise, cerebral activation associated with mental activity, or exposure to a stressful situation. The CMR decrease is prevented with combined β 1 ‐ and β 2 ‐adrenergic receptor blockade but not with β 1 ‐adrenergic blockade alone. Also, CMR decreases in response to epinephrine, suggesting that a β 2 ‐adrenergic receptor mechanism enhances glucose and perhaps lactate transport across the blood‐brain barrier. The pattern of CMR decrease under various forms of brain activation suggests that lactate may partially replace glucose as a substrate for oxidation. Thus, the notion of the human brain as an obligatory glucose consumer is not without exceptions.—Quistorff, B., Secher, N. H., and Van Lieshout, J. J. Lactate fuels the human brain during exercise. FASEB J. 22, 3443–3449 (2008)

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Background
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“…and internal jugular venous concentrations assuming a resting CBF of 700ml min−1 (Jørgensen et al., 1992), adjusted according to changes in MCAvmean (Quistorff et al., 2008): 6t(0)/t(n) substrate uptake = {(t1 - t0)× [arterial– venous difference substrate1]× CBF1 + (t2 − t1) × [arterial– venous…”
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Background
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Development of a Model to Test Whether Glycogenolysis Can Support Astrocytic Energy Demands of Na+, K+-ATPase and Glutamate-Glutamine Cycling, Sparing an Equivalent Amount of Glucose for Neurons
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A tribute to Leif Hertz: The historical context of his pioneering studies of the roles of astrocytes in brain energy metabolism, neurotransmission, cognitive functions, and pharmacology identifies important, unresolved topics for future studies
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“…+ CMR glycogen )) would be stable, or increase if glycogen utilization (that was not measured in these studies) were included in the calculations (e.g., Dalsgaard, 2006 ; Dalsgaard, Quistorff, et al., 2004 ; Dalsgaard & Secher, 2007 ; Dalsgaard, Volianitis, et al., 2004 ; Quistorff et al., 2008).”
Background
Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression
Luo, Z., Huang, X., Xu, X., Wei, K., Zheng, Y., Gong, K., & Li, W. (2024) · Cancer Biology and Medicine · doi:10.20892/j.issn.2095-3941.2023.0382 · Cited by 12
“LDHB is also thought to be a scavenger of intra-cellular lactic acid 28 , while previous studies have defined the critical contribution of lactic acid as an effector metabolite associated with the inactivation of NK and T cells 23 .”
BackgroundResult
Lactate: A Theranostic Biomarker for Metabolic Psychiatry?
Caddye, E., Pineau, J., Reyniers, J., Ronen, I., & Colasanti, A. (2023) · Antioxidants · doi:10.3390/antiox12091656 · Cited by 11
“When the systemic lactate concentration is elevated from baseline such as during strenuous physical activity the brain becomes a net consumer (above ~4 mM) [84–86].”
A budget for brain metabolic water production by glucose catabolism during rest, rises in activity and sleep
Dienel, G. A., & Lauritzen, M. (2025) · Fluids and Barriers of the CNS · doi:10.1186/s12987-025-00647-8 · Cited by 13
“For example, lactate level in blood rises during extreme exercise, enters the brain, and is oxidized [123], perhaps sparing glucose for glycolysis to support ion pumping.”
Monocarboxylate transporters (MCTs) in skeletal muscle and hypothalamus of less or more physically active mice exposed to aerobic training
Scariot, P. P. M., Manchado-Gobatto, F. D. B., Beck, W. R., Papoti, M., van Ginkel, P. R., & Gobatto, C. A. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.120872 · Cited by 12
Effects of vasodilator and esmolol-induced hemodynamic stability on early post-operative cognitive dysfunction in elderly patients: a randomized trial
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Natural sources, dopaminergic and non-dopaminergic agents for therapeutic assessment of Parkinsonism in rats model
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Bicarbonate supplementation via lactate efflux improves anaerobic and cognitive performance in elite combat sport athletes
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“La, released by the muscles into the blood stream, has the ability to cross the BBB via endothelial monocarboxylate transporters (MCTs) [23] and act as an energy source and a neuro - protective factor for the brain [24, 25].”
Background
Intensity-dependent acute aerobic exercise: Effect on reactive control of attentional functions in acclimatized lowlanders at high altitude
Su, R., Wang, C., Liu, W., Han, C., Fan, J., Ma, H., Li, H., & Zhang, D. (2022) · Physiology & Behavior · doi:10.1016/j.physbeh.2022.113785 · Cited by 10
Chronic lactate exposure promotes cardiomyocyte cytoskeleton remodelling
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“Examples of the cell-cell lactate shuttles include lactate exchanges between working skeletal muscle and heart [8,9], brain [10,11], liver and kidneys [12 – 14], astrocytes and neurons [15] and viceversa (i.e., neurons and astrocytes) [16].”
Background
Synaptic and Non-Synaptic Mitochondria in Hippocampus of Adult Rats Differ in Their Sensitivity to Hypothyroidism
Zhuravliova, E., Barbakadze, T., Jojua, N., Zaalishvili, E., Shanshiashvili, L., Natsvlishvili, N., Kalandadze, I., Narmania, N., Chogovadze, I. S., & Mikeladze, D. (2012) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-012-9857-8 · Cited by 9
Variations in lactate during a graded exercise test due to sampling location and method
Lehnhard, R. A., Bartlett, M. F., Roche, B. M., Hinchcliff, K. W., & McKeever, K. H. (2010) · Comparative Exercise Physiology · doi:10.1017/s1755254010000255 · Cited by 9
The intracellular to extracellular proton gradient following maximal whole body exercise and its implication for anaerobic energy production
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“This assumption is not correct since even active leg muscles (Secher et al. 1977; Brooks 2002) and the brain (Quistorff et al. 2008) take up lactate during intense exercise in addition to the uptake of the liver (Nielsen et al. 2007) and the kidneys (Lauritsen et al. 2002).”
BackgroundSelf-citation
Lactate Transport via Glial MCT1 and Neuronal MCT2 Is Not Required for Synchronized Synaptic Transmission in Hippocampal Slices Supplied With Glucose
Söder, L., Baeza‐Lehnert, F., Khodaie, B., Elgez, A., Noack, L., Lewen, A., Hallermann, S., Poschet, G., Borges, K., & Kann, O. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70251 · Cited by 8
Gene Expression, Oxidative Stress, and Neurotransmitters in Rotenone-induced Parkinson’s Disease in Rats: Role of Naringin from Citrus aurantium via Blocking Adenosine A2A Receptor
Ahmed, Y. R., Naser, A. F. A., Elbatanony, M. M., El-Feky, A. M., Khalil, W. K. B., & Hamed, M. A. A. (2023) · Current Bioactive Compounds · doi:10.2174/0115734072268296231002060839 · Cited by 8
Hippocampal neurochemicals are associated with exercise group and intensity, psychological health, and general cognition in older adults
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In vivo calibration of genetically encoded metabolite biosensors must account for metabolite metabolism during calibration and cellular volume
Dienel, G. A., & Rothman, D. L. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15775 · Cited by 9
“…infusion or exhaustive exercise by in vivo MRS which has been established as a quantitative method, as well as quantitative biochemical assays (Boumezbeur et al., 2010 ; Dager et al., 1992; Quistorff et al., 2008 ; van Hall et al., 2009), questioning the overall sensor calibration procedure.”
BackgroundMethod
Exercício Físico, Humor e Bem-Estar: Considerações sobre a Prescrição da Alta Intensidade de Exercício
Miranda, R. E. E. P. C., de Mello, M. T., & Antunes, H. K. M. (2011) · Revista Psicologia e Saúde · doi:10.20435/pssa.v3i2.102 · Cited by 8
Untitled work
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The Lactate Nexus: A Molecular Bridge Linking Physical Activity, Sleep, and Cognitive Enhancement
Ablitip, A., Zheng, K., Ding, H., Cui, Y., Ma, X., & You, Y. (2026) · Biomedicines · doi:10.3390/biomedicines14010253 · Cited by 8
“Firstly, lactate is recognised as a preferred mitochondrial fuel for neurons; it enters the tricarboxylic acid (TCA) cycle more rapidly than glucose, thereby providing an efficient source of adenosine triphosphate (ATP) to support immediate synaptic activity [43–45].”
EVALUATION OF THE EFFECTS OF STERNAL VERSUS LATERAL RECUMBENCY ON TRENDS OF SELECTED PHYSIOLOGIC PARAMETERS DURING ISOFLURANE ANESTHESIA IN ZOO-HOUSED BLACK-TAILED PRAIRIE DOGS (CYNOMYS LUDOVICIANUS)
Eshar, D., Mason, D. E., Avni‐Magen, N., Kaufman, E. A., Paz, A., & Beaufrère, H. (2017) · Journal of Zoo and Wildlife Medicine · doi:10.1638/2016-0192r2.1 · Cited by 7
“The decrease in measured lactate concentrations over time is usually explained by the Cori cycle, with the liver as the organ that clears lactate from the blood but also includes lactate uptake by brain and muscle.(25)”
Background
Metabolic Studies in Brain Slices – Past, Present, and Future
Hertz, L. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00026 · Cited by 7
“Lactate serves as a partial substrate for brain metabolism during intense exercise (when its blood concentration is increased), but this does not indicate any need for lactate in addition to glucose in brain function, including ongoing activity, since during rest there is a small lactate exit from brain (Quistorff et…”
Background
The value of blood lactate and lactate clearance rate in evaluating the prognosis of athletes with heat illness of varying degrees after high-intensity exercise
Li, Y., Dong, X., Li, H., & Mi, L. (2025) · BMC Sports Science Medicine and Rehabilitation · doi:10.1186/s13102-024-01042-w · Cited by 7
“Heat stroke (HS) is the most severe and life-threatening type of heat illness [31–34], and it can be divided into classic heat stroke (CHS) and exertional heat stroke (EHS) [35–37].”
Setting standards for brain collection procedures in metabolomic studies
Dienel, G. A., & Nowak, T. S. (2025) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251314331 · Cited by 6
Living high - training low model applied to C57BL/6J mice: Effects on physiological parameters related to aerobic fitness and acid-base balance
Scariot, P. P. M., Papoti, M., Polisel, E. E. C., Orsi, J. B., van Ginkel, P. R., Prolla, T. A., Manchado-Gobatto, F. D. B., & Gobatto, C. A. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.121443 · Cited by 6
Lactate shuttling as an allostatic means of thermoregulation in the brain
Kane, D. A., Foo, A. C. Y., Noftall, E. B., Brebner, K., & Marangoni, D. G. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1144639 · Cited by 5
“The human brain may release a small amount of lactate at rest, but during exercise, cerebral lactate uptake increases in proportion to the rise in arterial lactate concentration (Quistorff et al., 2008; Siebenmann et al., 2021), contributing to 27.”
Background
Acute Effects of High-Intensity Resistance Exercise on Recognition of Relational Memory, Lactate, and Serum and Plasma Brain-Derived Neurotrophic Factor
Baumgartner, N. W., Belbis, M. D., Kargl, C. K., Holmes, M. J., Gavin, T. P., Hirai, D. M., & Kao, S. (2024) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000004851 · Cited by 7
“…important during long-term memory formation (73), especially through its role in energy supply in the brain (1) when the supply of glucose dwindles (60), such as the exercise-induced shifting of glucose priority from the brain to the active muscles (37) and subsequently the reliance on lactate as…”
Proteomic Analysis of Striatum from MPTP-Treated Marmosets (Callithrix jacchus) with l-DOPA-Induced Dyskinesia of Differing Severity
Hurley, M. J., Jackson, M. J., Smith, L. A., Rose, S., & Jenner, P. G. (2013) · Journal of Molecular Neuroscience · doi:10.1007/s12031-013-0145-y · Cited by 5
A 3-day dietary manipulation affects muscle glycogen and results in modifications of carbohydrate and fat metabolism during exercise when hyperglycaemic
Malone, J. J., MacLaren, D. P. M., Campbell, I. T., & Hulton, A. T. (2020) · European Journal of Applied Physiology · doi:10.1007/s00421-020-04326-4 · Cited by 5
Molecular vehicles for therapeutic delivery of lactate in exercise and medicine
Brooks, G. A. (2026) · Sports Medicine and Health Science · doi:10.1016/j.smhs.2026.03.005 · Cited by 4
“31,32 Recent discovery of the Astrocyte-Neuron Lactate Shuttle 4,33 together and observations on men that when lactate rose during exercise, lactate substituted for glucose as brain fuel 31,34 just as it does at the whole-body level during exercise 35,36 can be interpreted to mean that lactate is…”
Lactic Acid Inhibits the Cytotoxicity of NK-92 Cells via Activating the Lactate Receptor GPR81
Huang, Y., Nie, W., Ye, S., & Chen, C. (2023) · Annual Research & Review in Biology · doi:10.9734/arrb/2023/v38i330573 · Cited by 4
Role of Cardiorespiratory Fitness, Aerobic, Exercise and Sports Participation in Female Cognition: A Scoping Review
Weber, V. M. R., Queiróga, M. R., Puranda, J. L., Semeniuk, K., Macdonald, M. L., Dantas, D. B., da Silva, D. F., & Adamo, K. B. (2024) · Sports Medicine - Open · doi:10.1186/s40798-024-00776-8 · Cited by 9
“Moreover, the reduction in BDNF after exhaustive exercise could be related to a shift in the use of additional resources (e.g., lactate for the ATP synthesis) rather than the syntheses of BDNF [45, 94].”
Background
Blood Flow Restriction Exercise for Successful Aging
Lee, D., Ji, M., & Lee, S. (2023) · Exercise Science · doi:10.15857/ksep.2023.00227 · Cited by 4
“혈중 젖산 농도의 증가는 대뇌의 젖산 흡수를 증가시킬 수 있으며, 이는 젖산이 모노카 르복실레이트 수송체(monocarboxylate transporters, MCTs)에 의해 뇌 혈관장벽(brain-blood barrier, BBB)을 통과할 수 있기 때문이다[118].”
Blood-Brain Barrier Transport of Lactate
Knudsen, G. M. (2011) · Advances in neurobiology · doi:10.1007/978-1-4614-1788-0_25 · Cited by 4
Glutamate Neurotoxicity Related to Energy Failure
Schousboe, A. (2014) · Springer eBooks · doi:10.1007/978-1-4614-5836-4_128 · Cited by 4
High-intensity circuit training improves cognitive performance independent of changes in sBDNF levels in active college students
Jiménez‐Maldonado, A., Antunes, B. M., Reyes, R. A., Rentería, I., Blanco-Salazar, A., Moncada‐Jiménez, J., Chávez-Guevara, I. A., Machado-Parra, J. P., Lira, F. S., & Rossi, F. E. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.114916 · Cited by 5
Brain glucose extraction is fixed at 10% despite twofold variability in resting cerebral blood flow in healthy humans
Duffy, J. S., Caldwell, H. G., Hoiland, R. L., Howe, C. A., Smith, K. J., Bain, A. R., MacLeod, D. B., Ainslie, P. N., & Gibbons, T. D. (2025) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251400247 · Cited by 3
“12,13 Upon brain activation, such as during physical exercise 14,15 and sensory stimulation, 2,16,17 there is an increase in CBF alongside a decrease in oxygen extraction 18 and no change in glucose extraction, 19 resulting in the disproportionate uptake of glucose relative to oxygen (i.e., AG).”
Brain aerobic glycolysis is stable during adulthood: Direct evidence from cross-brain blood sampling in 239 healthy adults
Duffy, J. S., Ainslie, P. N., Rasmussen, P., MacLeod, D. B., & Gibbons, T. D. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x251399122 · Cited by 3
Cerebral vs. Cardiovascular Responses to Exercise in Type 2 Diabetic Patients
Kim, Y.-S., van der Ster, B. J. P., Brassard, P., Secher, N. H., & LIESHOUT, J. J. V. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2020.583155 · Cited by 3
Self-citation
Revisiting Lactate in Critical Illness
Nalos, M., McLean, A. S., & Huang, S. (2013) · Springer eBooks · doi:10.1007/978-3-642-35109-9_34 · Cited by 3
“However, during increased demand on brain metabolism lactate is increasingly utilized as an energy substrate [17, 39–41].”
Background
Effects of the exercise in the cerebral blood flow and metabolism. A review
Lucas‐Cuevas, A. G., Priego‐Quesada, J. I., Pérez‐Soriano, P., & Belloch, S. L. (2015) · Journal of Human Sport and Exercise · doi:10.14198/jhse.2015.101.13 · Cited by 4
“Evidence suggests that this substrate is lactate (Dalsgaard et al., 2004; Ide et al., 2004; Quistorff et al., 2008).”
Background
A Strategy for Development of Realistic Mathematical Models of Whole-Body Metabolism
Madsen, M. F., Danø, S., & Quistorff, B. (2012) · Open Journal of Applied Sciences · doi:10.4236/ojapps.2012.21002 · Cited by 3
“This experimental approach has been applied extensively in the study of organ physiology in the past and more recently also to study of brain energy metabolism as well as muscle-brain interactions providing data on the global metabolism of the human brain in vivo [41-43] at a time resolution of less than five seconds…”
MethodSelf-citation

Authors: Quistorff, B., Secher, N. H., & Van Lieshout, J. J.
Affiliations: University of Copenhagen (DK)
Department of Internal Medicine, Medium Care Unit University of Amsterdam Amsterdam The Netherlands
ORCID: Quistorff, Bjørn
Secher, Niels H.
Venue: The FASEB Journal
Publisher: Wiley
Published: 2008-07-24
Volume: 22
Issue: 10
Pages: 3443-3449
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.08-106104
OpenAlex: W2141894573
Cited by: 262
References: 54
Citations by year: 2026: 17 · 2025: 21 · 2024: 15 · 2023: 23 · 2022: 14 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 10 · 2017: 13 · 2016: 12 · 2015: 15 · 2014: 19 · 2013: 16 · 2012: 15
FWCI: 0.92
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Pure Amsterdam UMC (submittedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics: Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
Keywords: brain energy metabolism, physical activity, glucose oxidation, beta-adrenergic receptors, epinephrine, blood-brain barrier transport, brain glucose metabolism
MeSH terms: Anaerobiosis, Brain, Glucose, Humans, Oxygen, Exercise, Lactic Acid

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Lactate fuels the human brain during exercise.

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