Biochemistry of exercise-induced metabolic acidosis
Abstract
The development of acidosis during intense exercise has traditionally been explained by the increased production of lactic acid, causing the release of a proton and the formation of the acid salt sodium lactate. On the basis of this explanation, if the rate of lactate production is high enough, the cellular proton buffering capacity can be exceeded, resulting in a decrease in cellular pH. These biochemical events have been termed lactic acidosis. The lactic acidosis of exercise has been a classic explanation of the biochemistry of acidosis for more than 80 years. This belief has led to the interpretation that lactate production causes acidosis and, in turn, that increased lactate production is one of the several causes of muscle fatigue during intense exercise. This review presents clear evidence that there is no biochemical support for lactate production causing acidosis. Lactate production retards, not causes, acidosis. Similarly, there is a wealth of research evidence to show that acidosis is caused by reactions other than lactate production. Every time ATP is broken down to ADP and P i , a proton is released. When the ATP demand of muscle contraction is met by mitochondrial respiration, there is no proton accumulation in the cell, as protons are used by the mitochondria for oxidative phosphorylation and to maintain the proton gradient in the intermembranous space. It is only when the exercise intensity increases beyond steady state that there is a need for greater reliance on ATP regeneration from glycolysis and the phosphagen system. The ATP that is supplied from these nonmitochondrial sources and is eventually used to fuel muscle contraction increases proton release and causes the acidosis of intense exercise. Lactate production increases under these cellular conditions to prevent pyruvate accumulation and supply the NAD + needed for phase 2 of glycolysis. Thus increased lactate production coincides with cellular acidosis and remains a good indirect marker for cell metabolic conditions that induce metabolic acidosis. If muscle did not produce lactate, acidosis and muscle fatigue would occur more quickly and exercise performance would be severely impaired.
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During transport, the level of activity of the muscle increased significantly, which results in increased O2 consumption.
“During transport, the level of activity of the muscle increased significantly, which results in increased O2 consumption.”
From A randomized controlled trial investigating the effect of transport duration and age at transport on surplus dairy calves: Part II. Impact on hematological variables. (2023) · cites this paper as Robergs et al., 2004
During intense musculoskeletal activity (i.e., long transportation), the production of lactic acid via glycolysis surpasses the body's lactate metabolism capacity; thus, lactic acid accumulates in the blood.
“during intense musculoskeletal activity (i.e., long transportation), the production of lactic acid via glycolysis surpasses the body's lactate metabolism capacity; thus, lactic acid accumulates in the blood”
From A randomized controlled trial investigating the effect of transport duration and age at transport on surplus dairy calves: Part II. Impact on hematological variables. (2023) · cites this paper as Robergs et al., 2004
To maintain normal blood pH, bicarbonate buffers the lactic acid, resulting in the production of water and CO2; this ultimately results in lower blood pH.
“To maintain normal blood pH, bicarbonate buffers the lactic acid, resulting in the production of water and CO2; this ultimately results in lower blood pH”
From A randomized controlled trial investigating the effect of transport duration and age at transport on surplus dairy calves: Part II. Impact on hematological variables. (2023) · cites this paper as Robergs et al., 2004
The metabolic acidosis detected in calves transported for 12 h and 16 h can be explained by an increase in muscle activity, leading to lactic acid production, via glycolysis, that surpasses the body's lactate metabolism capacity.
“The metabolic acidosis detected in calves transported for 12 h and 16 h can be explained by an increase in muscle activity, leading to lactic acid production, via glycolysis, that surpasses the body's lactate metabolism capacity”
From A randomized controlled trial investigating the effect of transport duration and age at transport on surplus dairy calves: Part II. Impact on hematological variables. (2023) · cites this paper as Robergs et al., 2004
An increase in O2 consumption increases CO2 production.
“An increase in O2 consumption increases CO2 production”
From A randomized controlled trial investigating the effect of transport duration and age at transport on surplus dairy calves: Part II. Impact on hematological variables. (2023) · cites this paper as Robergs et al., 2004
Although lactate and H+ accumulation suggest greater ATP production from glucose or glycogen, this does not always improve sprint performance.
“Previous studies indicate that although lactate and H+accumulation suggest greater ATP production from glucose or glycogen, this does not always improve sprint performance19,20.”
From Evaluating bioenergetic pathway contributions from single to multiple sprints (2024) · cites this paper as [20]
Glycolytic ATP production enhances peak sprint performance during early sprints.
“Despite this, glycolytic ATP production is known to enhance peak sprint performance during early sprints, which highlights the paradox of whether maximal glycolytic activity improves overall RSA performance20,31,36.”
From Evaluating bioenergetic pathway contributions from single to multiple sprints (2024) · cites this paper as [20]
Glycogen serves as an essential energy source for both anaerobic and aerobic pathways, and its depletion-or the reduced ability to utilize available glycogen-limits ATP resynthesis, leading to decreased endurance and performance.
“Glycogen serves as an essential energy source for both anaerobic and aerobic pathways, and its depletion—or the reduced ability to utilize available glycogen—limits ATP resynthesis, leading to decreased endurance and performance17,20,37.”
From Evaluating bioenergetic pathway contributions from single to multiple sprints (2024) · cites this paper as [20]
Cites
Mitochondrial Transport of Cations: Channels, Exchangers, and Permeability Transition
Bernardi, P. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.4.1127 · Cited by 1,534 · see citing works
Muscular exercise, lactic acid, and the supply and utilisation of oxygen
Hill, A., Long, C.-N.-H., & Lupton, H. (1924) · QJM · doi:10.1093/qjmed/os-16.62.135 · Cited by 1,380 · see citing works
Metabolic regulation via intracellular pH
Busa, W. B., & Nuccitelli, R. (1984) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1984.246.4.r409 · Cited by 669 · see citing works
Wollaston, W. H. (1810) · Philosophical Transactions of the Royal Society of London · doi:10.1098/rstl.1810.0002 · Cited by 624 · see citing works
Hochachka, P. W., & Mommsen, T. P. (1983) · Science · doi:10.1126/science.6298937 · Cited by 586 · see citing works
Muscle Fatigue: Lactic Acid or Inorganic Phosphate the Major Cause?
Westerblad, H., Allen, D. G., & Lännergren, J. (2002) · Physiology · doi:10.1152/physiologyonline.2002.17.1.17 · Cited by 577 · see citing works
Margaria, R., Edwards, H. T., & Dill, D. B. (1933) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1933.106.3.689 · Cited by 573 · see citing works
Latchman, D. S. (1995) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)89112-4 · Cited by 571 · see citing works
Webster’s Ninth New Collegiate Dictionary
慈继伟 (1985) · 外语教学与研究：外国语文双月刊 · Cited by 547 · see citing works
The Elements of the Science of Nutrition.
(1911) · Archives of Internal Medicine · doi:10.1001/archinte.1911.00060040141010 · Cited by 477 · see citing works
Energy supply and muscle fatigue in humans
SAHLIN, K., TONKONOGI, M., & SÖDERLUND, K. (1998) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1998.0298f.x · Cited by 419 · see citing works
Lactate content and pH in muscle samples obtained after dynamic exercise
Sahlin, K., Harris, R. C., Nylind, B., & Hultman, E. (1976) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00585150 · Cited by 418 · see citing works
Principles of Biochemistry (2nd edn)
Harris, D. (1993) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(93)90073-v · Cited by 405 · see citing works
Muscular exercise, lactic acid, and the supply and utilisation of oxygen.—Parts ӏ-ӏӏӏ
Hill, A. V., Long, C. N. H., & Lupton, H. (1924) · Proceedings of the Royal Society of London Series B Containing Papers of a Biological Character · doi:10.1098/rspb.1924.0037 · Cited by 405 · see citing works
(1990) · Journal of Applied Physiology · doi:10.1152/jappl.1990.69.5.1934 · Cited by 364 · see citing works
Anaerobic energy production and O2 deficit‐debt relationship during exhaustive exercise in humans.
Bangsbo, J., Gollnick, P. D., Graham, T. E., Juel, C., Kiens, B., Mizuno, M., & Saltin, B. (1990) · The Journal of Physiology · doi:10.1113/jphysiol.1990.sp018000 · Cited by 357 · see citing works
Protons in ischemia: Where do they come from; Where do they go to?
Dennis, S. C. (1991) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(91)91642-5 · Cited by 344 · see citing works
Lactate-proton cotransport in skeletal muscle
Juel, C. (1997) · Physiological Reviews · doi:10.1152/physrev.1997.77.2.321 · Cited by 313 · see citing works
Generation of protons by metabolic processes in heart cells
Gevers, W. (1977) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(77)80008-4 · Cited by 298 · see citing works
Wilson, M. C., Jackson, V. N., Heddle, C., Price, N. T., Pilegaard, H., Juel, C., Bonen, A., Montgomery, I., Hutter, O. F., & Halestrap, A. P. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.26.15920 · Cited by 288 · see citing works
Effect of high-intensity intermittent training on lactate and H+ release from human skeletal muscle
Juel, C., Klarskov, C., Nielsen, J., Krustrup, P., Mohr, M., & Bangsbo, J. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00303.2003 · Cited by 243 · see citing works
Anaerobic energy release in working muscle during 30 s to 3 min of exhausting bicycling
Medbø, J. I., & Tabata, I. (1993) · Journal of Applied Physiology · doi:10.1152/jappl.1993.75.4.1654 · Cited by 230 · see citing works
Karlsson, J. (1971) · PubMed · Cited by 229 · see citing works
Stewart and beyond: New models of acid-base balance
Corey, H. E. (2003) · Kidney International · doi:10.1046/j.1523-1755.2003.00177.x · Cited by 197 · see citing works
Factors influencing hydrogen ion concentration in muscle after intense exercise
Kowalchuk, J. M., Heigenhauser, G. J. F., Lindinger, M. I., Sutton, J. R., & Jones, N. L. (1988) · Journal of Applied Physiology · doi:10.1152/jappl.1988.65.5.2080 · Cited by 197 · see citing works
Regulation of lactic acid production during exercise.
Katz, A., & Sahlin, K. (1988) · Journal of applied physiology · doi:10.1152/jappl.1988.65.2.509 · Cited by 196 · see citing works
Harmer, A. R., McKenna, M. J., Sutton, J. R., Snow, R. J., Ruell, P. A., Booth, J., Thompson, M. W., Mackay, N., Stathis, C. G., Crameri, R. M., et al. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.89.5.1793 · Cited by 195 · see citing works
Sahlin, K. (1978) · PubMed · Cited by 189 · see citing works
Lactic acidosis as a facilitator of oxyhemoglobin dissociation during exercise
Stringer, W., Wasserman, K., Casaburi, R., Porszasz, J., Maehara, K., & French, W. (1994) · Journal of Applied Physiology · doi:10.1152/jappl.1994.76.4.1462 · Cited by 187 · see citing works
Redox state and lactate accumulation in human skeletal muscle during dynamic exercise
Sahlin, K., Katz, A., & Henriksson, J. (1987) · Biochemical Journal · doi:10.1042/bj2450551 · Cited by 185 · see citing works
Roth, D. A., & Brooks, G. A. (1990) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(90)90505-s · Cited by 182 · see citing works
Challenging beliefs: ex Africa semper aliquid novi
Noakes, T. D. (1997) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-199705000-00001 · Cited by 168 · see citing works
Anaerobic energy release in skeletal muscle during electrical stimulation in men
Spriet, L. L., Söderlund, K., Bergström, M., & Hultman, E. (1987) · Journal of Applied Physiology · doi:10.1152/jappl.1987.62.2.611 · Cited by 156 · see citing works
Lactate and contractile force in frog muscle during development of fatigue and recovery
Fitts, R. H., & Holloszy, J. O. (1976) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1976.231.2.430 · Cited by 153 · see citing works
Buffer capacity and lactate accumulation in skeletal muscle of trained and untrained men
Sahlin, K., & Henriksson, J. (1984) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1984.tb07517.x · Cited by 153 · see citing works
Studies on the subcellular pathophysiology of ischemia.
Bf, T., Wj, M., Kahng, M. W., & Aj, S. (1976) · PubMed · Cited by 143 · see citing works
Mechanisms for highly ionized magnetron sputtering
Hopwood, J., & Qian, F. (1995) · Journal of Applied Physics · doi:10.1063/1.360334 · Cited by 131 · see citing works
Skeletal muscle glycogenolysis, glycolysis, and pH during electrical stimulation in men
Spriet, L. L., Söderlund, K., Bergström, M., & Hultman, E. (1987) · Journal of Applied Physiology · doi:10.1152/jappl.1987.62.2.616 · Cited by 131 · see citing works
Muscle pH regulation: role of training
JUEL, C. (1998) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1998.0305f.x · Cited by 130 · see citing works
Contribution of tissue acidosis to ischemic injury in the perfused rat heart.
WILLIAMSON, J. R., Schaffer, S. W., Ford, C., & Safer, B. (1976) · PubMed · Cited by 130 · see citing works
Quantification of anaerobic energy production during intense exercise
Bangsbo, J. (1998) · Medicine & Science in Sports & Exercise · doi:10.1097/00005768-199801000-00007 · Cited by 126 · see citing works
Histopathology of the conduction system in the sudden infant death syndrome.
Lie, J. T., Rosenberg, H. S., & Erickson, E. E. (1976) · Circulation · doi:10.1161/01.cir.53.1.3 · Cited by 112 · see citing works
Effects of lactic acid accumulation and ATP decrease on muscle tension and relaxation
Sahlin, K., Edström, L., Sjöholm, H., & Hultman, E. (1981) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1981.240.3.c121 · Cited by 112 · see citing works
Acid-base regulation during exercise and recovery in humans
Stringer, W. W., Casaburi, R. H., & Wasserman, K. (1992) · Journal of Applied Physiology · doi:10.1152/jappl.1992.72.3.954 · Cited by 106 · see citing works
The Principles of Biochemistry
Handy, J. A. (1914) · Scientific American · doi:10.1038/scientificamerican10311914-274supp · Cited by 99 · see citing works
Surface stability of NbN single-crystal films
Talvacchio, J., Sinharoy, S., & Braginski, A. I. (1987) · Journal of Applied Physics · doi:10.1063/1.339788 · Cited by 96 · see citing works
Lactate/proton co‐transport in skeletal muscle: regulation and importance for pH homeostasis
Juel, C. (1996) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.1996.206000.x · Cited by 96 · see citing works
The roles of ion fluxes in skeletal muscle fatigue
Lindinger, M. I., & Heigenhauser, G. J. (1991) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y91-038 · Cited by 87 · see citing works
Blood Lactate: Biochemistry, Laboratory Methods, and Clinical Interpretation
Toffaletti, J. G. (1991) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408369109106865 · Cited by 82 · see citing works
Structure and Function of Mitochondrial Anion Transport Proteins
Kaplan, R. S. (2001) · The Journal of Membrane Biology · doi:10.1007/s002320010046 · Cited by 80 · see citing works
Hagberg, H. (1985) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00585346 · Cited by 80 · see citing works
The Origin of the Acidosis in Hyperlactataemia
Zilva, J. F. (1978) · Annals of Clinical Biochemistry International Journal of Laboratory Medicine · doi:10.1177/000456327801500111 · Cited by 74 · see citing works
NADH in human skeletal muscle during short-term intense exercise
Sahlin, K. (1985) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/bf00584099 · Cited by 70 · see citing works
Anaerobic metabolism in human skeletal muscle during short-term, intense activity
Spriet, L. L. (1992) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y92-023 · Cited by 68 · see citing works
Sánchez-Lavega, A., & Salazar, A. (1994) · Journal of Applied Physics · doi:10.1063/1.357720 · Cited by 58 · see citing works
Generation of protons by metabolic processes other than glycolysis in muscle cells: A critical view
Gevers, W. (1979) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(79)90446-2 · Cited by 58 · see citing works
Acid-base and electrolyte disorders : a companion to Brenner & Rector's the kidney
DuBose, T. D., & Hamm, L. L. (2002) · Saunders eBooks · Cited by 52 · see citing works
Howlett, R. A., Heigenhauser, G. J. F., & Spriet, L. L. (1999) · Journal of Applied Physiology · doi:10.1152/jappl.1999.87.5.1747 · Cited by 33 · see citing works
Thermodynamic aspects of translocation of reducing equivalents by mitochondria.
Davis, E. J., Bremer, J., & Åkerman, K. E. O. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85887-8 · Cited by 32 · see citing works
Smith, G. L., Donoso, P., Bauer, C. J., & Eisner, D. A. (1993) · The Journal of Physiology · doi:10.1113/jphysiol.1993.sp019932 · Cited by 32 · see citing works
The handbook of biochemistry and biophysics
Damm, H. C. (1966) · Medical Entomology and Zoology · Cited by 27 · see citing works
Croonian Lecture:—The laws of muscular motion
Hill, A. V. (1926) · Proceedings of the Royal Society of London Series B Containing Papers of a Biological Character · doi:10.1098/rspb.1926.0035 · Cited by 23 · see citing works
Role of mitochondrial oxidative phosphorylation in the maintenance of intracellular pH*1
Vághy, P. L. (1979) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(79)90385-7 · Cited by 19 · see citing works
Otto Meyerh of Nobel Prize for Studies of Muscle Metabolism
Shampo, M. A., & Kyle, R. A. (1999) · Mayo Clinic Proceedings · doi:10.4065/74.1.67 · Cited by 10 · see citing works
Lactic acidosis as a facilitator of oxyhemoglobin dissociation during exercise
MacRae, H., & Dennis, S. C. (1995) · Journal of Applied Physiology · doi:10.1152/jappl.1995.78.2.758 · Cited by 9 · see citing works
Raju, T. N. K. (1998) · The Lancet · doi:10.1016/s0140-6736(05)60805-7 · Cited by 7 · see citing works
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Skeletal muscle fatigue: cellular mechanisms
Allen, D. G., Lamb, G. D., & Westerblad, H. (2008) · Physiological Reviews · doi:10.1152/physrev.00015.2007 · Cited by 2,495 · see citing works
Myocardial Fatty Acid Metabolism in Health and Disease
Lopaschuk, G. D., Ussher, J. R., Folmes, C. D. L., Jaswal, J. S., & Stanley, W. C. (2010) · Physiological Reviews · doi:10.1152/physrev.00015.2009 · Cited by 2,180 · see citing works
The Science and Translation of Lactate Shuttle Theory
Brooks, G. A. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.008 · Cited by 1,486 · see citing works
Endurance exercise performance: the physiology of champions
Joyner, M. J., & Coyle, E. F. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.143834 · Cited by 1,307 · see citing works
Fragala, M. S., Cadore, E. L., Dorgo, S., Izquierdo, M., Kraemer, W. J., Peterson, M. D., & Ryan, E. D. (2019) · Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000003230 · Cited by 1,290 · see citing works
The Acidic Tumor Microenvironment as a Driver of Cancer
Boedtkjer, E., & Pedersen, S. F. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021119-034627 · Cited by 1,248 · see citing works
Electrochemical Tattoo Biosensors for Real-Time Noninvasive Lactate Monitoring in Human Perspiration
Jia, W., Bandodkar, A. J., Valdés-Ramírez, G., Windmiller, J. R., Yang, Z., Ramírez, J., Chan, G., & Wang, J. (2013) · Analytical Chemistry · doi:10.1021/ac401573r · Cited by 862 · see citing works
Haas, R., Smith, J., Rocher-Ros, V., Nadkarni, S., Montero‐Melendez, T., D’Acquisto, F., Bland, E. J., Bombardieri, M., Pitzalis, C., Perretti, M., et al. (2015) · PLoS Biology · doi:10.1371/journal.pbio.1002202 · Cited by 782 · see citing works
Lactate Threshold Concepts: How Valid are They?
Faude, O., Kindermann, W., & Meyer, T. (2009) · Sports Medicine · doi:10.2165/00007256-200939060-00003 · Cited by 882 · see citing works
Périard, J. D., Eijsvogels, T. M. H., & Daanen, H. A. M. (2021) · Physiological Reviews · doi:10.1152/physrev.00038.2020 · Cited by 708 · see citing works
Using Recovery Modalities between Training Sessions in Elite Athletes
Barnett, A. H. (2006) · Sports Medicine · doi:10.2165/00007256-200636090-00005 · Cited by 596 · see citing works
Analysis and Interpretation of Microplate-Based Oxygen Consumption and pH Data
Divakaruni, A. S., Paradyse, A. R., Ferrick, D. A., Murphy, A. N., & Jastroch, M. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-801415-8.00016-3 · Cited by 525 · see citing works
Romero‐Garcia, S., Moreno‐Altamirano, M. M. B., Prado-Garcı́a, H., & Sánchez‐García, F. J. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00052 · Cited by 508 · see citing works
Muscle metabolic responses to exercise above and below the “critical power” assessed using 31 P-MRS
JONES, A. M., Wilkerson, D. P., DiMenna, F. J., Fulford, J., & Poole, D. C. (2007) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00731.2007 · Cited by 479 · see citing works
Lactic Acid and Exercise Performance
Cairns, S. P. (2006) · Sports Medicine · doi:10.2165/00007256-200636040-00001 · Cited by 445 · see citing works
Lactate metabolism: historical context, prior misinterpretations, and current understanding
Ferguson, B. S., Rogatzki, M. J., Goodwin, M. L., Kane, D. A., Rightmire, Z. B., & Gladden, L. B. (2018) · European Journal of Applied Physiology · doi:10.1007/s00421-017-3795-6 · Cited by 451 · see citing works
Functions of Astrocytes and their Potential As Therapeutic Targets
Kimelberg, H. K., & Nedergaard, M. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.07.006 · Cited by 409 · see citing works
Jaswal, J. S., Keung, W., Wang, W., Ussher, J. R., & Lopaschuk, G. D. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.015 · Cited by 396 · see citing works
Interaction among Skeletal Muscle Metabolic Energy Systems during Intense Exercise
Baker, J. S., McCormick, M. C., & Robergs, R. A. (2010) · Journal of Nutrition and Metabolism · doi:10.1155/2010/905612 · Cited by 394 · see citing works
Self-citationAn Examination and Critique of Current Methods to Determine Exercise Intensity
Jamnick, N. A., Pettitt, R. W., Granata, C., Pyne, D. B., & Bishop, D. J. (2020) · Sports Medicine · doi:10.1007/s40279-020-01322-8 · Cited by 424 · see citing works
Lactate in the Tumor Microenvironment: An Essential Molecule in Cancer Progression and Treatment
Pérez‐Tomás, R., & Pérez-Guillén, I. (2020) · Cancers · doi:10.3390/cancers12113244 · Cited by 395 · see citing works
Raedschelders, K., Ansley, D. M., & Chen, D. D. Y. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.11.004 · Cited by 387 · see citing works
Lactate kinetics in human tissues at rest and during exercise
van Hall, G. (2010) · Acta Physiologica · doi:10.1111/j.1748-1716.2010.02122.x · Cited by 346 · see citing works
Handbook of Fermented Meat and Poultry
(2007) · Wiley eBooks · doi:10.1002/9780470376430 · Cited by 347 · see citing works
Lactate – a signal coordinating cell and systemic function
Philp, A., Macdonald, A. L., & Watt, P. (2005) · Journal of Experimental Biology · doi:10.1242/jeb.01961 · Cited by 328 · see citing works
Faria, E. W., Parker, D., & Faria, I. E. (2005) · Sports Medicine · doi:10.2165/00007256-200535040-00002 · Cited by 321 · see citing works
Self-citationTattoo‐Based Wearable Electrochemical Devices: A Review
Bandodkar, A. J., Jia, W., & Wang, J. (2015) · Electroanalysis · doi:10.1002/elan.201400537 · Cited by 316 · see citing works
Blood flow restriction training and the exercise pressor reflex: a call for concern
Spranger, M. D., Krishnan, A. C., Levy, P. D., O’Leary, D. S., & Smith, S. A. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00208.2015 · Cited by 293 · see citing works
Lactate in human sweat: a critical review of research to the present day
Derbyshire, P. J., Barr, H., Davis, F., & Higson, S. P. J. (2012) · The Journal of Physiological Sciences · doi:10.1007/s12576-012-0213-z · Cited by 280 · see citing works
Lactate as a Metabolite and a Regulator in the Central Nervous System
Proia, P., Liegro, C. M. D., Schiera, G., Fricano, A., & Liegro, I. D. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17091450 · Cited by 280 · see citing works
pH-gated succinate secretion regulates muscle remodeling in response to exercise
Reddy, A., Bozi, L. H. M., Yaghi, O. K., Mills, E. L., Xiao, H., Nicholson, H. E., Paschini, M., Paulo, J. A., Garrity, R., Laznik-Bogoslavski, D., et al. (2020) · Cell · doi:10.1016/j.cell.2020.08.039 · Cited by 279 · see citing works
Physiological Differences Between Cycling and Running: Lessons from Triathletes
Millet, G. P., Vleck, V. E., & Bentley, D. J. (2009) · Sports Medicine · doi:10.2165/00007256-200939030-00002 · Cited by 329 · see citing works
Hashim, A. I., Zhang, X., Wojtkowiak, J. W., Martinez, G. V., & Gillies, R. J. (2011) · NMR in Biomedicine · doi:10.1002/nbm.1644 · Cited by 265 · see citing works
The Physiology of the World Record Holder for the Women's Marathon
JONES, A. M. (2006) · International Journal of Sports Science & Coaching · doi:10.1260/174795406777641258 · Cited by 256 · see citing works
Exercise and Blood Flow Restriction
Pope, Z. K., Willardson, J. M., & Schoenfeld, B. J. (2013) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e3182874721 · Cited by 236 · see citing works
Is lactate food for neurons? Comparison of monocarboxylate transporter subtypes in brain and muscle
Bergersen, L. H. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.11.062 · Cited by 223 · see citing works
Payen, V. L., Porporato, P. E., Baselet, B., & Sonveaux, P. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-2098-5 · Cited by 219 · see citing works
An evolutionary hybrid cellular automaton model of solid tumour growth
Gerlee, P., & Anderson, A. R. A. (2007) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2007.01.027 · Cited by 220 · see citing works
Lactic Acidosis: From Sour Milk to Septic Shock
Fall, P. J., & Szerlip, H. M. (2005) · Journal of Intensive Care Medicine · doi:10.1177/0885066605278644 · Cited by 197 · see citing works
Functions of Mature Mammalian Astrocytes: A Current View
Kimelberg, H. K. (2010) · The Neuroscientist · doi:10.1177/1073858409342593 · Cited by 199 · see citing works
Suwa, M., Nakano, H., Radak, Z. O., & Kumagai, S. (2008) · Metabolism · doi:10.1016/j.metabol.2008.02.017 · Cited by 195 · see citing works
Physiological effects of hyperchloraemia and acidosis
Handy, J. M., & Soni, N. (2008) · British Journal of Anaesthesia · doi:10.1093/bja/aen148 · Cited by 189 · see citing works
The thermoregulation system and how it works
(2018) · Handbook of Clinical Neurology · doi:10.1016/b978-0-444-63912-7.00001-1 · Cited by 186 · see citing works
Method for high‐resolution imaging of creatine in vivo using chemical exchange saturation transfer
Kogan, F., Haris, M., Singh, A. K., Cai, K., DeBrosse, C., Nanga, R. P. R., Hariharan, H., & Reddy, R. D. (2013) · Magnetic Resonance in Medicine · doi:10.1002/mrm.24641 · Cited by 176 · see citing works
Lactate as a Signaling Molecule That Regulates Exercise-Induced Adaptations
Nalbandian, M., & Takeda, M. (2016) · Biology · doi:10.3390/biology5040038 · Cited by 174 · see citing works
Thread-based multiplexed sensor patch for real-time sweat monitoring
Terse-Thakoor, T., Punjiya, M., Matharu, Z., Lyu, B., Ahmad, M., Giles, G. E., Owyeung, R. E., Alaimo, F., Baghini, M. S., Brunyé, T. T., et al. (2020) · npj Flexible Electronics · doi:10.1038/s41528-020-00081-w · Cited by 172 · see citing works
Gupta, G. S. (2022) · Inflammation · doi:10.1007/s10753-022-01680-7 · Cited by 173 · see citing works
Ergogenic Effects of Sodium Bicarbonate
McNaughton, L. R., Siegler, J. C., & Midgley, A. W. (2008) · Current Sports Medicine Reports · doi:10.1249/jsr.0b013e31817ef530 · Cited by 169 · see citing works
Lancha Junior, A. H., de Salles Painelli, V., Saunders, B., & Artioli, G. G. (2015) · Sports Medicine · doi:10.1007/s40279-015-0397-5 · Cited by 167 · see citing works
Hickey, D. P., Reid, R. C., Milton, R. D., & Minteer, S. D. (2015) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2015.09.013 · Cited by 160 · see citing works
Garami, A., Shimansky, Y. P., Rumbus, Z., Vizin, R. C. L., Farkas, N., Hegyi, J., Szakacs, Z., Solymar, M., Csenkey, A., Chiche, D. A., et al. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107474 · Cited by 159 · see citing works
Lactate metabolism in chronic liver disease
Jeppesen, J. B., Mortensen, C., Bendtsen, F., & Møller, S. (2013) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365513.2013.773591 · Cited by 157 · see citing works
Anti-fatigue activity of polysaccharides extract from Radix Rehmanniae Preparata
Tan, W. H., Yu, K.-Q., Liu, Y., Ouyang, M., Yan, M.-H., Ren, L., & Zhao, X. (2011) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2011.09.019 · Cited by 157 · see citing works
Physiological functions of peroxisome proliferator-activated receptor β
Neels, J. G., & Grimaldi, P. A. (2014) · Physiological Reviews · doi:10.1152/physrev.00027.2013 · Cited by 161 · see citing works
Review of Biguanide (Metformin) Toxicity
Wang, G. S., & Hoyte, C. O. (2018) · Journal of Intensive Care Medicine · doi:10.1177/0885066618793385 · Cited by 159 · see citing works
Wearable multiplexed biosensor system toward continuous monitoring of metabolites
Yokus, M. A., Songkakul, T., Pozdin, V. A., Bozkurt, A., & Daniele, M. A. (2020) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2020.112038 · Cited by 153 · see citing works
Redox balance is key to explaining full vs. partial switching to low-yield metabolism
van Hoek, M. J., & Merks, R. M. (2012) · BMC Systems Biology · doi:10.1186/1752-0509-6-22 · Cited by 131 · see citing works
Is fatigue all in your head? A critical review of the central governor model
Weir, J. P., Beck, T. W., Cramer, J. T., & Housh, T. J. (2006) · British Journal of Sports Medicine · doi:10.1136/bjsm.2005.023028 · Cited by 150 · see citing works
Gagaoua, M., Terlouw, C. E. M., Mullen, A. M., Franco, D., Warner, R. D., Lorenzo, J. M., Purslow, P. P., Gerrard, D. E., Hopkins, D. L., TROY, D. J., et al. (2020) · Meat Science · doi:10.1016/j.meatsci.2020.108311 · Cited by 150 · see citing works
Carbohydrate metabolism in meat animals
Pösö, A. R., & Puolanne, E. (2005) · Meat Science · doi:10.1016/j.meatsci.2004.12.017 · Cited by 146 · see citing works
Tissue-Resident Alveolar Macrophages Do Not Rely on Glycolysis for LPS-induced Inflammation
Woods, P. S., Kimmig, L. M., Meliton, A. Y., Sun, K. A., Tian, Y., O’Leary, E. M., Gökalp, G. A., Hamanaka, R. B., & Mutlu, G. M. (2019) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2019-0244oc · Cited by 145 · see citing works
The Metabolic Fates of Pyruvate in Normal and Neoplastic Cells
Prochownik, E. V., & Wang, H. (2021) · Cells · doi:10.3390/cells10040762 · Cited by 145 · see citing works
Metformin and other antidiabetic agents in renal failure patients
Lalau, J., Arnouts, P., Sharif, A., & Broe, M. E. D. (2014) · Kidney International · doi:10.1038/ki.2014.19 · Cited by 144 · see citing works
Hultmann, L., Phú, T. M., Tobiassen, T. I., Aas-Hansen, Ø., & Rustad, T. (2012) · Food Chemistry · doi:10.1016/j.foodchem.2012.03.038 · Cited by 141 · see citing works
Effect of Recovery Mode on Repeated Sprint Ability in Young Basketball Players
Castagna, C., Abt, G., Manzi, V., Annino, G., Padua, E., & D'Ottavio, S. (2008) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0b013e31816a4281 · Cited by 141 · see citing works
Lactate oxidation at the mitochondria: a lactate-malate-aspartate shuttle at work
Kane, D. A. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00366 · Cited by 142 · see citing works
Robey, R. B., Weisz, J., Kuemmerle, N. B., Salzberg, A. C., Berg, A. S., Brown, D. G., Maurer, L. L., Palorini, R., Al‐Mulla, F., Al-Temaimi, R. A., et al. (2015) · Carcinogenesis · doi:10.1093/carcin/bgv037 · Cited by 138 · see citing works
Lactate: a multifunctional signaling molecule
Lee, T.-Y. (2021) · Journal of Yeungnam Medical Science · doi:10.12701/yujm.2020.00892 · Cited by 136 · see citing works
Singh, N. K., Chung, S., Chang, A., Wang, J., & Hall, D. A. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115097 · Cited by 137 · see citing works
Neuromuscular Function after a Bout of Low-Load Blood Flow–Restricted Exercise
Cook, S. B., Murphy, B. G., & LaBarbera, K. E. (2013) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31826c6fa8 · Cited by 133 · see citing works
Kuwahara, H., Horie, T., Ishikawa, S., Tsuda, C., Kawakami, S., Noda, Y., Kaneko, T., Tahara, S., Tachibana, T., Okabe, M., et al. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.02.011 · Cited by 129 · see citing works
Lactic acid buffering, nonmetabolic CO2 and exercise hyperventilation: A critical reappraisal
Péronnet, F., & Aguilaniu, B. (2005) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2005.04.005 · Cited by 128 · see citing works
Seheult, J. N., Fitzpatrick, G. J., & Boran, G. P. (2016) · Clinical Chemistry and Laboratory Medicine (CCLM) · doi:10.1515/cclm-2016-0438 · Cited by 128 · see citing works
Hooren, B. V., & Peake, J. M. (2018) · Sports Medicine · doi:10.1007/s40279-018-0916-2 · Cited by 134 · see citing works
Smith, A. E., Walter, A. A., Graef, J. L., Kendall, K. L., Moon, J. R., Lockwood, C. M., Fukuda, D. H., Beck, T. W., Cramer, J. T., & Stout, J. R. (2009) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-6-5 · Cited by 123 · see citing works
The Science of Speed: Determinants of Performance in the 100 m Sprint
Majumdar, A. S., & Robergs, R. A. (2011) · International Journal of Sports Science & Coaching · doi:10.1260/1747-9541.6.3.479 · Cited by 122 · see citing works
Self-citationpH inactivation of phosphofructokinase arrests postmortem glycolysis
England, E. M., Matarneh, S. K., Scheffler, T. L., Wachet, C., & Gerrard, D. E. (2014) · Meat Science · doi:10.1016/j.meatsci.2014.07.019 · Cited by 120 · see citing works
Terlouw, C. E. M., Picard, B. B., Deiss, V., Berri, C., Hocquette, J.-F. J.-F., Lebret, B., Lefèvre, F., Hamill, R. M., & Gagaoua, M. (2021) · Foods · doi:10.3390/foods10010084 · Cited by 120 · see citing works
Leal‐Junior, E. C. P., Lopes‐Martins, R. Á. B., Baroni, B. M., Marchi, T. D., Rossi, R. P., Grosselli, D., Generosi, R. A., de Godoi, V., Basso, M., Mancalossi, J. L., et al. (2009) · Photomedicine and Laser Surgery · doi:10.1089/pho.2008.2350 · Cited by 118 · see citing works
Leal‐Junior, E. C. P., Lopes‐Martins, R. Á. B., de Almeida, P., Ramos, L., Iversen, V. V., & Bjordal, J. M. (2009) · European Journal of Applied Physiology · doi:10.1007/s00421-009-1321-1 · Cited by 117 · see citing works
Hall, M. M., Rajasekaran, S., Thomsen, T. W., & Peterson, A. R. (2016) · PM&R · doi:10.1016/j.pmrj.2015.10.018 · Cited by 119 · see citing works
A "Lactatic" Perspective on Metabolism
Gladden, L. B. (2008) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31815fa580 · Cited by 113 · see citing works
Gerdle, B. U. C., Ghafouri, B., Ernberg, M. M., & Larsson, B. (2014) · Journal of Pain Research · doi:10.2147/jpr.s59144 · Cited by 111 · see citing works
Role of metabolic stress for enhancing muscle adaptations: Practical applications
de Freitas, M. C., Gerosa-Neto, J., Zanchi, N. E., Lira, F. S., & Rossi, F. E. (2017) · World Journal of Methodology · doi:10.5662/wjm.v7.i2.46 · Cited by 117 · see citing works
Serum lactate as a novel potential biomarker in multiple sclerosis
Amorini, A. M., Nociti, V., Petzold, A., Gasperini, C., Quartuccio, M. E., Lazzarino, G., Pietro, V. D., Belli, A., Signoretti, S., Vagnozzi, R., et al. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.005 · Cited by 111 · see citing works
Thomas, C., Bishop, D. J., Lambert, K., Mercier, J. G., & Brooks, G. A. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00250.2011 · Cited by 110 · see citing works
Regulation of post-mortem glycolysis in ruminant muscle
Ferguson, D. M., & Gerrard, D. E. (2014) · Animal Production Science · doi:10.1071/an13088 · Cited by 108 · see citing works
A ‘New’ Method to Normalise Exercise Intensity
Lansley, K. E., DiMenna, F. J., Bailey, S. J., & JONES, A. M. (2011) · International Journal of Sports Medicine · doi:10.1055/s-0031-1273754 · Cited by 108 · see citing works
Proteomic biomarkers of beef colour
Gagaoua, M., Hughes, J. M., Terlouw, C. E. M., Warner, R. D., Purslow, P. P., Lorenzo, J. M., & Picard, B. B. (2020) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2020.05.005 · Cited by 107 · see citing works
Applying physicochemical principles to skeletal muscle acid-base status
Lindinger, M. I., Kowalchuk, J. M., & Heigenhauser, G. J. F. (2005) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00225.2005 · Cited by 107 · see citing works
Effects of Four Recovery Methods on Repeated Maximal Rock Climbing Performance
Heyman, E., de Geus, B., MERTENS, I., & MEEUSEN, R. R. (2009) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318195107d · Cited by 106 · see citing works
Bendable Electro-chemical Lactate Sensor Printed with Silver Nano-particles
Abrar, M. A., Dong, Y., Lee, P. K., & Kim, W. S. (2016) · Scientific Reports · doi:10.1038/srep30565 · Cited by 106 · see citing works
Metcalfe, R. S., Koumanov, F., Ruffino, J. S., Stokes, K., Holman, G. D., Thompson, D., & Vollaard, N. B. J. (2015) · European Journal of Applied Physiology · doi:10.1007/s00421-015-3217-6 · Cited by 104 · see citing works
e, J. E., Bishop, D. J., Hill-Haas, S. V., DAWSON, B. T., & Goodman, C. (2005) · European Journal of Applied Physiology · doi:10.1007/s00421-005-0056-x · Cited by 104 · see citing works
Extracellular vesicles and energy metabolism
Ronquist, G. K. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.10.044 · Cited by 101 · see citing works
Influence of pacing strategy on O2 uptake and exercise tolerance
JONES, A. M., Wilkerson, D. P., Vanhatalo, A., & Burnley, M. (2008) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/j.1600-0838.2007.00725.x · Cited by 99 · see citing works
Choi, Y. M., Ryu, Y., & Kim, B. C. (2007) · Meat Science · doi:10.1016/j.meatsci.2006.11.009 · Cited by 98 · see citing works
The tortuous path of lactate shuttle discovery: From cinders and boards to the lab and ICU
Brooks, G. A. (2020) · Journal of sport and health science/Journal of Sport and Health Science · doi:10.1016/j.jshs.2020.02.006 · Cited by 99 · see citing works
Garami, A., Pákai, E., McDonald, H. A., Reilly, R. M., Gomtsyan, A. R., Corrigan, J. J., Pintér, E., Zhu, D., Lehto, S. G., Gavva, N. R., et al. (2018) · Acta Physiologica · doi:10.1111/apha.13038 · Cited by 95 · see citing works
Wu, H., Huang, H., & Zhao, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1211221 · Cited by 96 · see citing works
- Authors
- Robergs, R. A., Ghiasvand, F., & Parker, D.
- Affiliations
- University of New Mexico (US)
- ORCID
- Robergs, Robert A.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2004-09
- Volume
- 287
- Issue
- 3
- Pages
- R502-R516
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2171756298
- Cited by
- 1,304
- References
- 66
- Citations by year
- 2026: 58 · 2025: 60 · 2024: 71 · 2023: 75 · 2022: 82 · 2021: 82 · 2020: 71 · 2019: 54 · 2018: 81 · 2017: 62 · 2016: 53 · 2015: 51 · 2014: 70 · 2013: 63 · 2012: 58
- FWCI
- 74.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology (publishedVersion)
- PubMed (publishedVersion)
- Faculty of Health
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- lactic acidosis, lactic acid production, muscle fatigue, proton release, ATP regeneration, glycolysis, phosphagen system, mitochondrial respiration, oxidative phosphorylation, pyruvate accumulation, NAD+ regeneration, exercise performance
- MeSH terms
- Acidosis, Acidosis, Lactic, Animals, Buffers, Humans, Models, Biological, Protons, Exercise, Lactic Acid, History, 18th Century, History, 20th Century
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