David C. Poole , Harry B. Rossiter , George A. Brooks and L. Bruce Gladden

J Physiol 599.3 (2021) ppp 737–767

Abstract The anaerobic threshold (AT) remains a widely recognized, and contentious, concept
in exercise physiology and medicine. As conceived by Karlman Wasserman, the AT coalesced
the increase of blood lactate concentration ([La−]), during a progressive exercise test, with an
excess pulmonary carbon dioxide output (˙VCO2 ). Its principal tenets were: limiting oxygen (O2)
delivery to exercisingmuscle→increased glycolysis, La− and H+ production→decreasedmuscle
and blood pH→with increased H+ buffered by blood [HCO3−]→increased CO2 release from
blood→increased ˙VCO2 and pulmonary ventilation. This schema stimulated scientific scrutiny
which challenged the fundamental premise that muscle anoxia was requisite for increased
muscle and blood [La−]. It is now recognized that insufficient O2 is not the primary basis for
lactataemia. Increased production and utilization of La− represent the response to increased
glycolytic flux elicited by increasing work rate, and determine the oxygen uptake (˙VO2) at which
La− accumulates in the arterial blood (the lactate threshold; LT). However, the threshold for a
sustained non-oxidative contribution to exercise energetics is the critical power, which occurs
at a metabolic rate often far above the LT and separates heavy from very heavy/severe-intensity
exercise. Lactate is nowappreciated as a crucial energy source,major gluconeogenic precursor and
signalling molecule but there is no ipso facto evidence formuscle dysoxia or anoxia. Non-invasive
estimation of LT using the gas exchange threshold (non-linear increase of ˙VCO2 versus ˙VO2 )
remains important in exercise training and in the clinic, but its conceptual basis should now be
understood in light of lactate shuttle biology.