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SPECIAL COMMUNICATIONS: Contrasting Perspectives

The “Anaerobic Threshold” Concept Is Valid in Physiology and Medicine


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Medicine & Science in Sports & Exercise: May 2021 - Volume 53 - Issue 5 - p 1089-1092
doi: 10.1249/MSS.0000000000002548
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In their seminal 1964 paper, Wasserman and McIlroy (1) described how the “threshold of anaerobic metabolism” in heart failure patients could be detected not only by measurements of lactate or pH in arterial blood but also in pulmonary gas exchange. They placed their findings within the context of the pioneering work of Harrison and Pilcher (2) three decades earlier, who identified excessive CO2 output (V˙CO2) immediately after exercise in heart failure patients compared with controls. It was proposed that the “excess CO2” could not be a product of aerobic metabolism but must be released from bicarbonate when acids are buffered that were formed by anaerobic glycolysis during exercise (Fig. 1). The term coined for this concept, “the anaerobic threshold,” has been described as both a “milestone” and a “millstone” in exercise physiology (3).

The anaerobic threshold concept originally proposed by Wasserman and McIlroy (1).

Asked by his mentor Julius Comroe how he might advance detection of heart disease, Wasserman proposed that an evaluation might be best done during exercise, when the heart was being stressed. An early sign of heart failure, he proposed, would be reflected in reduced ability for O2 delivery necessary to meet the exercise-induced increase in cellular demand. Because the muscle O2 requirement would be markedly increased by the exercise, any failure of O2 transport to meet this demand would result in a metabolic acidosis (via the Pasteur effect). Thus, the context for the anaerobic threshold concept is a framework that linked inadequate O2 delivery to metabolic acidosis and excess CO2 output. In this Contrasting Perspective, I argue for the validity of this concept during exercise based on three key observations:

  • When measured by appropriate methods, there is a well-defined threshold in metabolic rate above which arterial lactate concentration increases above baseline.
  • A mechanism of excess CO2 output can be isolated to the buffering of a metabolic acidosis using pulmonary gas exchange.
  • The role of inadequate O2 delivery has yet to be ruled out as one of several mechanisms that contribute arterial lactate accumulation.


A primary observation leading to the anaerobic threshold concept was that of Owles (4). He identified a “critical level of oxygen utilization” above which lactate was increased and the CO2 combining power of the blood was reduced. Much of the criticism that the lactate profile during incremental exercise does not exhibit a satisfactorily abrupt rate of change, i.e., a “threshold” can be assuaged by considering the methods used and the extremely broad and complex range of time constants that characterize lactate formation, distribution throughout available tissue compartments, and clearance (5–7). These can account for the more logarithmic-like profiles of arterial lactate accumulation commonly observed during kinetically dependent tasks such as ramp-incremental exercise. Owles’ original study sampled blood 3–5 min after walking exercise from “convenient veins of the forearm” after immersion of the arm in hot water to “render the blood obtained more arterial in character” (4). These methodological constraints mean that Owles’ critical V˙O2 is unlikely to precisely correspond to Wasserman’s anaerobic threshold. Nevertheless, Wasserman and colleagues refined the concept to identify a V˙O2 that varies among individuals, with exercise mode or state of training, and above which a sustained increase in arterial lactate is observed. In studies using arterial sampling and sufficient time for the stabilization of lactate distribution, e.g., constant work rate exercise lasting 20 min or more, arterial lactate concentration plotted against V˙O2 demonstrates a sufficiently sharp threshold such that during exercise “just below anaerobic threshold,” arterial lactate concentration ends up at, or even below, the resting value (8).

Using their developments in breath-by-breath gas exchange measurement, Wasserman and colleagues refined methods to detect the V˙O2 corresponding to the onset of excess CO2 output across the lung during an incremental exercise test using the V-slope method, while at the same time ruling out metabolic or hyperventilatory CO2 sources (9). The stability (absence of decline) in arterial and end-tidal CO2 partial pressures at the V˙O2 associated with the threshold provides a region of “isocapnic buffering” essential to establishing that the excess V˙CO2 derives from buffering of an acidosis rather than from hyperventilation (10). This latter point is not trivial. It also alleviates concerns about a delay between an increased rate of V˙CO2 and a proton-mediated stimulation of chemoreceptor drive for ventilation (11). The result is a noninvasive determination of an individual’s V˙O2 that corresponds very closely to the metabolic rate at which lactate accumulation in the arterial blood is first observed (12), and for which bicarbonate provides >90% of the buffering of the lactate-associated protons. This aspect of the threshold concept has strong internal validity.

Probably the most sustained critique of the anaerobic threshold concept is that it is independent of O2 delivery, and therefore the “anaerobic” component of its moniker is inappropriate. In one sense, challenging this notion is futile because there is no threshold for anaerobic energy provision during exercise, given that anaerobic glycolysis and phosphocreatine breakdown—each O2-independent sources of high-energy phosphate—contribute intramuscular ATP generation at all work rates (13). Thus, we need to be clear about how the term anaerobic is being used within this critique. The question is not based on whether intramuscular lactate formation increases with increasing work rate (it does), whether it be at very low work rates or under conditions of nonlimiting intramuscular PO2 (14,15). Rather, the question is whether low PO2 provides the basis for the rapid increase in lactate formation that occurs at a particular V˙O2 and which results in increased lactate concentration in the muscle venous and, subsequently, arterial circulations. This question is not mutually exclusive with any of the inherent functions of glycolytic pyruvate production, pyruvate dehydrogenase activity, lactate dehydrogenase activity, monocarboxylate transporter activity, intercellular lactate shuttling, and pyruvate oxidation in cells that take up lactate during exercise and contribute to determining arterial lactate concentration (5,11).

The acute and dramatic rise in muscle venous lactate concentration that occurs when muscle venous PO2 falls to ~15–20 mm Hg empirically illustrates that a potentially limiting rate of O2 delivery is associated with the threshold (16). At this same V˙O2, the Bohr effect is induced, which promotes the dissociation of oxyhemoglobin and facilitates myocyte-to-mitochondrial diffusive O2 transport, precisely the moment at which muscle venous PO2 reaches its lowest level. Such a tantalizing signpost of teleologic intent is hard for a card-carrying physiologist to ignore. Experimentally reducing O2 delivery by increasing carboxyhemoglobin concentration (17) reduces the V˙O2 at the threshold by a quantitatively appropriate magnitude. However, none of these findings are sufficiently decisive to satisfy a proof. There also exist plenty of contrasting views, such as evidence that lactate efflux during exercise does not increase in proportion to the hypoxia-induced reduction in intramuscular PO2 (15). Ensemble measurements of intramuscular deoxymyoglobin concentration by magnetic resonance spectroscopy from the groups of Richardson and Jue (18) suggest that intramuscular PO2 falls from a value of ~35 mm Hg at rest to a value of ~5 mm Hg at the threshold, where it remains at all increasing metabolic rates up to peak V˙O2. This constancy of intramuscular PO2 is not unanticipated; after all, femoral venous PO2 is also constant at ~15–20 mm Hg over the same work rate range (16). A mean muscle PO2 of 5 mm Hg should be sufficient to maintain maximal flux within aerobic bioenergetic pathways. However, our knowledge of the wide heterogeneity within intramuscular O2 delivery-to-utilization ratios leads us to the probabilistic conclusion that some muscle regions, at least, are exposed to a PO2 that is limiting to aerobic metabolism (19). Thus, anaerobic or not, the jury remains in deliberation (3).


Wasserman’s aim of developing a method for early detection of heart failure has proven efficacy because the anaerobic threshold is effective in assessing severity and predicting life expectancy in these patients (20–22). Other early uses include in the assessment of exercise performance, training efficacy, or athlete identification; however, arguably, the critical power concept now shows more promise for these goals (23,24). Nevertheless, the anaerobic threshold detects the V˙O2 at which work efficiency begins to decline and ventilatory stimuli begin to increase, each of which contribute to symptoms of fatigue and dyspnea (25). Some of the most compelling current applications of the anaerobic threshold concept include judging the appropriateness to undergo major thoracic or abdominal surgery and triaging postoperative patients to a postsurgical ward, high-dependency unit, or intensive care unit. This stems from the original demonstration by Older et al. (26) that postsurgical risk of death was increased >4-fold in those with an anaerobic threshold below 11 mL·kg−1⋅min−1. A great many studies have identified associations among a range of exercise-related variables and postsurgical outcomes (27), but it is striking that the anaerobic threshold below ~10–11 mL·W⋅min−1 remains the strongest predictor of postsurgical complications and poor outcomes even when included with other outcome measures in multivariable models (28).

Overall, the utility of the anaerobic threshold concept is not without controversy. Accepting different nomenclature for the V˙O2 at which arterial blood lactate accumulates (e.g., lactate threshold, lactic acidosis threshold, or gas exchange threshold) appears to largely alleviate many critics’ concerns. However, controversy is needed. Controversy fans the flames of scientific progress. In addition, deliberations are ongoing: look no further than these Contrasting Perspectives.


Dr. Brooks’ elegant perspective (29) draws on several historic and recent lines of evidence in attempt to expose sophistic reasoning underlying the anaerobic threshold concept. His position primarily focuses on the concepts that: i) lactate turnover (production and clearance) cannot be inferred from measures of concentration alone and (ii) cellular lactate production is evident even in well-oxygenated tissues.

There is no disagreement—at least, from me—that in Dr. Brooks’ words, “lactate is produced and disposed of continuously under fully aerobic conditions.” Nor that “lactatemia during exercise and other conditions is a biomarker for the presence of appropriate physiological strain responses.” If there were to be one physiologic inference made from the observation that arterial lactate concentration that is raised above basal, it would be that the organism is under some form of metabolic stress. During exercise, the kinetic response of arterial lactate concentration is discriminatory for intensity domains defining aerobic power-output ranges that result in common physiologic profiles of cardiorespiratory and metabolic stress, termed moderate-, heavy-, and very heavy-intensity exercise (30). There is even renewed interest in the concept of lactate as an oncometabolite, regulating transcriptional activity of cancer-related genes including, among many others, hypoxia inducible factor 1α (31). On these oxygen-related points—I anticipate—there will be little debate from Dr. Brooks.

I even venture to suggest that Dr. Brooks and I will agree on at least one other oxygen-related point of lactate production: that is, the accumulation of lactate—and its associated proton—within the muscle capillary during exercise is a vital facilitator of increased oxygen extraction and the ability to continue to increase the rate of mitochondrial oxidative phosphorylation (16). This is due to the action of blood acidification on the oxyhemoglobin dissociation curve (the Bohr effect), which reduces the affinity of heme for oxygen and facilitates diffusive O2 transport specifically adjacent to mitochondria that are bathed in a cytosol undergoing high glycogenolytic flux. Individuals with phosphorylase deficiency (McArdle disease), who lack the capacity to effectively acidify the muscle capillary during exercise, become intolerant at a far lower fractional O2 extraction than controls with normal glycogenolytic physiology (32). Therefore, under conditions of increasing exercise intensity, I wholeheartedly agree with Dr. Brooks that “lactate production is an important strain response the purpose of which is to mitigate stress.”

Hence, what is it about the anaerobic threshold concept that is so egregious that we should abandon it from physiology and medicine? Dr. Brooks reminds us that well-oxygenated tissues produce lactate (29,33) and can do so under conditions where the NAD+/NADH redox couple becomes more oxidized (34), indicating simultaneous lactate production and NADH entry to the electron transport system via mitochondrial shuttles, i.e., aerobic glycogenolysis/glycolysis. Despite conceptual weaknesses with the anaerobic threshold (and they do exist), evidence that lactate formation occurs in well-oxygenated tissue is not evidence either for or against. This finding does not relate to the core critique of the concept: whether lactate formation accelerates, and arterial lactate accumulation begins, consequent to insufficient myocellular PO2 (termed dysoxia [35]). Thus, is dysoxia the basis for the threshold? As stated in my original perspective, technical constraints in our ability to measure the relevant variables mean that the jury is still out. Precisely because we lack the essential evidence, it is important for users of the anaerobic concept bear in mind that lactate is “at the fulcrum of metabolism” (29) and may be influenced by a very wide range of metabolic events, including lactate formation, lactate clearance, blood flow distribution, and of course O2 delivery, among many others.


What if dysoxia was conclusively identified as unrelated to the anaerobic threshold? In such a case, I would argue that there remains both validity and utility in the concept of a threshold in metabolism defined by events that are dependent on anaerobic glycogenolysis/glycolysis.

I ask whether there exists a “threshold” metabolic rate at which “anaerobic” glycogenolysis/glycolysis, i.e., cytosolic NADH oxidation through the conversion of pyruvate to form lactate, progresses at a rate sufficient to overwhelm clearance pathways and accumulate arterial lactate. The answer is, there is. Prolonged steady-state exercise shows a metabolic rate above basal, below which arterial lactate accumulation is maintained at, or even below, the resting value (8). This physiologic event was originally termed the anaerobic threshold by Wasserman and McIlroy (1) and occurs at approximately 50% of V˙O2 peak in the average healthy individual (36).

I also ask whether there exist exercise intensity domains, defined by the kinetics of arterial lactate accumulation, that separate states of “wholly aerobic” energy transfer (at the whole-organism level) from those which are not, and which strongly predict endurance exercise performance in sport or mortality in hospitalized patients. To each, the answers are yes (23,37,38).

Given these threshold behaviors that reflect cellular metabolic strain, let us not throw out the baby with the bathwater.

The author sincerely thank Dr. L. Bruce Gladden and Dr. Kathy E. Sietsema for their authoritative feedback in shaping this perspective.

The author declares no conflicts of interest and source of funding.


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