The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
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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In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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]
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Cited by
Sorted by citations
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
Myocardial Fatty Acid Metabolism in Health and Disease
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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
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Joyner, M. J., & Coyle, E. F. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.143834 · Cited by 1,307
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
Metadata
- 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 › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology (medical) › 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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