Lactate (La) has long been at the center of controversy in research, clinical, and athletic settings. Since its discovery in 1780, La has often been erroneously viewed as simply a hypoxic waste product with multiple deleterious effects. Not until the 1980s, with the introduction of the cell-to-cell lactate shuttle did a paradigm shift in our understanding of the role of La in metabolism begin. The evidence for La as a major player in the coordination of whole-body metabolism has since grown rapidly. La is a readily combusted fuel that is shuttled throughout the body, and it is a potent signal for angiogenesis irrespective of oxygen tension. Despite this, many fundamental discoveries about La are still working their way into mainstream research, clinical care, and practice. The purpose of this review is to synthesize current understanding of La metabolism via an appraisal of its robust experimental history, particularly in exercise physiology. That La production increases during dysoxia is beyond debate, but this condition is the exception rather than the rule. Fluctuations in blood [La] in health and disease are not typically due to low oxygen tension, a principle first demonstrated with exercise and now understood to varying degrees across disciplines. From its role in coordinating whole-body metabolism as a fuel to its role as a signaling molecule in tumors, the study of La metabolism continues to expand and holds potential for multiple clinical applications. This review highlights La's central role in metabolism and amplifies our understanding of past research.

Through much of the history of metabolism, lactate (La−) has been considered merely a dead-end waste product during periods of dysoxia. Congruently, the end product of glycolysis has been viewed dichotomously: pyruvate in the presence of adequate oxygenation, La− in the absence of adequate oxygenation. In contrast, given the near-equilibrium nature of the lactate dehydrogenase (LDH) reaction and that LDH has a much higher activity than the putative regulatory enzymes of the glycolytic and oxidative pathways, we contend that La− is always the end product of glycolysis. Cellular La− accumulation, as opposed to flux, is dependent on (1) the rate of glycolysis, (2) oxidative enzyme activity, (3) cellular O2 level, and (4) the net rate of La− transport into (influx) or out of (efflux) the cell. For intracellular metabolism, we reintroduce the Cytosol-to-Mitochondria Lactate Shuttle. Our proposition, analogous to the phosphocreatine shuttle, purports that pyruvate, NAD+, NADH, and La− are held uniformly near equilibrium throughout the cell cytosol due to the high activity of LDH. La− is always the end product of glycolysis and represents the primary diffusing species capable of spatially linking glycolysis to oxidative phosphorylation.

Key pointsr A slow adjustment of skeletal muscle oxygen uptake (V O 2 ) to produce energy during exercise predisposes to early fatigue.r In human studies,V O 2 kinetics are slow when exercise is initiated from an elevated baseline; this is proposed to reflect slow blood flow regulation and/or recruitment of muscle fibres containing few mitochondria.r To investigate this, we measuredV O 2 kinetics in canine muscle, with experimental control over muscle activation and blood flow.r We found thatV O 2 kinetics remained slow when contractions were initiated from an elevated baseline despite experimentally increased blood flow and uniform fibre activation.r These data challenge our current understanding of the control of muscleV O 2 and demand consideration of new alternative mediators forV O 2 control.Abstract Oxygen uptake kinetics (τV O 2 ) are slowed when exercise is initiated from a raised metabolic rate. Whether this reflects the recruitment of muscle fibres differing in oxidative capacity, or slowed blood flow (Q ) kinetics is unclear. This study determined τV O 2 in canine muscle in situ, with experimental control over muscle activation andQ during contractions initiated from rest and a raised metabolic rate. The gastrocnemius complex of nine anaesthetised, ventilated dogs was isolated and attached to a force transducer. Isometric tetanic contractions (50 Hz; 200 ms duration) via supramaximal sciatic nerve stimulation were used to manipulate metabolic rate: 3 min stimulation at 0.33 Hz (S1), followed by 3 min at 0.67 Hz (S2). Circulation was initially intact (SPON), and subsequently isolated for pump-perfusion (PUMP) above the greatest value in SPON. MuscleV O 2 was determined contraction-by-contraction using an ultrasonic flowmeter and venous oximeter, and normalised to tension-time integral (TTI). τV O 2 /TTI and τQ were less in S1 SPON (mean ± S.D.: 13 ± 3 s and 12 ± 4 s, respectively) than in S2 SPON (29 ± 19 s and 31 ± 13 s, respectively; P < 0.05). τV O 2 /TTI was unchanged by pump-perfusion (S1 PUMP , 12 ± 4 s; S2 PUMP , 24 ± 6 s; P < 0.001) despite increased O 2 delivery; at S2 onset, venous O 2 saturation was 21 ± 4% and 65 ± 5% in SPON and PUMP, respectively.V O 2 kinetics remained slowed when contractions were initiated from a raised metabolic rate despite uniform muscle stimulation and increased O 2 delivery. The intracellular mechanism may relate to a falling energy state, approaching saturating ADP concentration, and/or slowed mitochondrial activation; but further study is required. These data add to the evidence that muscleV O 2 control is more complex than previously suggested.

Three parallel squat protocols with equal total work volume were used to determine the metabolic response of resistance exercise with different practical training protocols combining program variables in the way that they are typically prescribed in field. Sixteen men able to back squat 1.5 times their body weight participated in the study. Individualized muscular endurance (ME), strength (STR), and hypertrophy (HYP) squat workouts were developed based on a 1 repetition maximum back squat. Each protocol was performed 3-7 days apart in random order. Venous blood was obtained after 5 minutes of seated rest both before and after each workout for ammonium and lactate analysis. The ME protocol (79.8 μM [SD = 45.4], 95% confidence interval [CI]: 55.7-104.0) produced a greater change of plasma ammonium than both the HYP (45.3 μM [SD = 34.5], 95% CI: 26.9-63.6, p = 0.017) and STR (31.7 μM [SD = 52.3], 95% CI: 3.9-59.6, p = 0.006) protocols. Change of blood lactate concentration from resting levels to postexercise levels was significantly different (p = 0.005) between ME (6.1 mM [SD = 2.9], 95% CI: 4.6-7.7) and STR (3.9 mM [SD = 2.5], 95% CI: 2.6-5.2) protocols. The main finding of this study is that blood ammonium and lactate seem to accumulate in response to an increasing number of repetitions with decreasing rest time between sets. As consequence, a greater number of repetitions should be added to a resistance workout, along with a shorter rest time between sets when training for events that induce a large metabolic load. The metabolic accumulation associated with high repetition exercise may represent the need for longer recovery time between these types of workouts compared with workouts using a low number of repetitions.

It is unclear if the higher S100B concentration in football players playing at least 50 plays was caused by exercise or hits. Therefore, if serum S100B is to be used as a biomarker of impacts, and possible brain injury in sport, exercise time and intensity should be taken into account as confounding variables.