Lactic acid: New roles in a new millennium

The study of lactic acid (HLa) and muscular contraction has a long history, beginning perhaps as early as 1807 when Berzelius found HLa in muscular fluid and thought that “the amount of free lactic acid in a muscle [was] proportional to the extent to which the muscle had previously been exercised” (cited in ref. 1). Several subsequent studies in the 19th century established the view that HLa was a byproduct of metabolism under conditions of O2 limitation. For example, in 1891, Araki (cited in ref. 2) reported elevated HLa levels in the blood and urine of a variety of animals subjected to hypoxia. In the early part of the 20th century, Fletcher and Hopkins (3) found an accumulation of HLa in anoxia as well as after prolonged stimulation to fatigue in amphibian muscle in vitro. Subsequently, based on the work of Fletcher and Hopkins (3) as well as his own studies, Hill (and colleagues; ref. 4) postulated that HLa increased during muscular exercise because of a lack of O2 for the energy requirements of the contracting muscles. These studies laid the groundwork for the anaerobic threshold concept, which was introduced and detailed by Wasserman and colleagues in the 1960s and early 1970s (5–7). The basic anaerobic threshold paradigm is that elevated HLa production and concentration during muscular contractions or exercise are the result of cellular hypoxia. Table 1 summarizes the essential components of the anaerobic threshold concept. Anaerobic Threshold Concept However, several studies during the past ≈30 years have presented evidence questioning the idea that O2 limitation is a prerequisite for HLa production and accumulation in muscle and blood. Jöbsis and Stainsby (8) stimulated the canine gastrocnemius in situ at a rate known to elicit peak twitch oxygen uptake (V̇O2) and high net …