Blood lactate clearance during active recovery after an intense running bout depends on the intensity of the active recovery

High-intensity exercise training contributes to the production and accumulation of blood lactate, which is cleared by active recovery. However, there is no commonly agreed intensity or mode for clearing accumulated blood lactate. We studied clearance of accumulated blood lactate during recovery at various exercise intensities at or below the lactate threshold after high-intensity interval runs that prompted lactate accumulation. Ten males repeated 5-min running bouts at 90% of maximal oxygen uptake ([Vdot]O2max), which increased blood lactate concentration from 1.0 ± 0.1 to 3.9 ± 0.3 mmol · l-1. This was followed by recovery exercises ranging from 0 to 100% of lactate threshold. Repeated blood lactate measurements showed faster clearance of lactate during active versus passive recovery, and that the decrease in lactate was more rapid during higher (60-100% of lactate threshold) than lower (0-40% of lactate threshold) (P < 0.05) intensities. The more detailed curve and rate analyses showed that active recovery at 80-100% of lactate threshold had shorter time constants for 67% lactate clearance and higher peak clearance rates than 40% of lactate threshold or passive recovery (P < 0.05). Finally, examination of self-regulated intensities showed enhanced lactate clearance during higher versus lower intensities, further validating the intensity dependence of clearance of accumulated blood lactate. Therefore, active recovery after strenuous exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner. Maximum clearance occurred at active recovery close to the lactate threshold

Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects.

We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-(2)H2]glucose, that is, D2-glucose, and [3-(13)C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (p<0.001). However, lactate fractional extraction, an index of cerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as (13)CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-(13)C]lactate tracer and (13)C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75-80% of (13)CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the injured brain. Undiminished cerebral lactate fractional extraction and uptake suggest that arterial lactate supplementation may be used to compensate for decreased CMRgluc following TBI

Blood lactate clearance after maximal exercise depends on active recovery intensity

AIM: High-intensity exercise is time-limited by onset of fatigue, marked by accumulation of blood lactate. This is accentuated at maximal, all-out exercise that rapidly accumulates high blood lactate. The optimal active recovery intensity for clearing lactate after such maximal, all-out exercise remains unknown. Thus, we studied the intensity-dependence of lactate clearance during active recovery after maximal exercise.<p></p> METHODS: We constructed a standardized maximal, all-out treadmill exercise protocol that predictably lead to voluntary exhaustion and blood lactate concentration >10 mM. Next, subjects ran series of all-out bouts that increased blood lactate concentration to 11.5±0.2 mM, followed by recovery exercises ranging 0% (passive)-100% of the lactate threshold.<p></p> RESULTS: Repeated measurements showed faster lactate clearance during active versus passive recovery (P<0.01), and that active recovery at 60-100% of lactate threshold was more efficient for lactate clearance than lower intensity recovery (P<0.05). Active recovery at 80% of lactate threshold had the highest rate of and shortest time constant for lactate clearance (P<0.05), whereas the response during the other intensities was graded (100%=60%>40%>passive recovery, P<0.05).<p></p> CONCLUSION: Active recovery after maximal all-out exercise clears accumulated blood lactate faster than passive recovery in an intensity-dependent manner, with maximum clearance occurring at active recovery of 80% of lactate threshold

Direct and indirect lactate oxidation in trained and untrained men.

Lactate has been shown to be an important oxidative fuel. We aimed to quantify the total lactate oxidation rate (Rox) and its direct vs. indirect (glucose that is gluconeogenically derived from lactate and subsequently oxidized) components (mg·kg(-1)·min(-1)) during rest and exercise in humans. We also investigated the effects of endurance training, exercise intensity, and blood lactate concentration ([lactate]b) on direct and indirect lactate oxidation. Six untrained (UT) and six trained (T) men completed 60 min of constant load exercise at power outputs corresponding to their lactate threshold (LT). T subjects completed two additional 60-min sessions of constant load exercise at 10% below the LT workload (LT-10%), one of which included a lactate clamp (LC; LT-10%+LC). Rox was higher at LT in T [22.7 ± 2.9, 75% peak oxygen consumption (Vo2peak)] compared with UT (13.4 ± 2.5, 68% Vo2peak, P < 0.05). Increasing [lactate]b (LT-10%+LC, 67% Vo2peak) significantly increased lactate Rox (27.9 ± 3.0) compared with its corresponding LT-10% control (15.9 ± 2.2, P < 0.05). Direct and indirect Rox increased significantly from rest to exercise, and their relative partitioning remained constant in all trials but differed between T and UT: direct oxidation comprised 75% of total lactate oxidation in UT and 90% in T, suggesting the presence of training-induced adaptations. Partitioning of total carbohydrate (CHO) use showed that subjects derived one-third of CHO energy from blood lactate, and exogenous lactate infusion increased lactate oxidation significantly, causing a glycogen-sparing effect in exercising muscle

ATP-Sensitive Potassium Channel-Mediated Lactate Effect on Orexin Neurons: Implications for Brain Energetics during Arousal

Active neurons have a high demand for energy substrate, which is thought to be mainly supplied as lactate by astrocytes. Heavy lactate dependence of neuronal activity suggests that there may be a mechanism that detects and controls lactate levels and/or gates brain activation accordingly. Here, we demonstrate that orexin neurons can behave as such lactate sensors. Using acute brain slice preparations and patch-clamp techniques, we show that the monocarboxylate transporter blocker α-cyano-4-hydroxycinnamate (4-CIN) inhibits the spontaneous activity of orexin neurons despite the presence of extracellular glucose. Furthermore, fluoroacetate, a glial toxin, inhibits orexin neurons in the presence of glucose but not lactate. Thus, orexin neurons specifically use astrocyte-derived lactate. The effect of lactate on firing activity is concentration dependent, an essential characteristic of lactate sensors. Furthermore, lactate disinhibits and sensitizes these neurons for subsequent excitation. 4-CIN has no effect on the activity of some arcuate neurons, indicating that lactate dependency is not universal. Orexin neurons show an indirect concentration-dependent sensitivity to glucose below 1mM, responding by hyperpolarization, which is mediated by ATP-sensitive potassium channels composed of Kir6.1 and SUR1 subunits. In conclusion, our study suggests that lactate is a critical energy substrate and a regulator of the orexin system. Together with the known effects of orexins in inducing arousal, food intake, and hepatic glucose production, as well as lactate release from astrocytes in response to neuronal activity, our study suggests that orexin neurons play an integral part in balancing brain activity and energy supply

L-lactate reduces ischemic white matter injury and modulates HCA1 oligodendrocyte expression in an in vivo mouse model of focal ischemia

L-lactate is a metabolite that is oxidized preferentially to glucose under conditions of high metabolic stress. The discovery and localization of the lactate receptor HCA1 in various brain regions suggests that lactate is additionally an important signaling molecule in the brain. Lactate is neuroprotective in various ischemia paradigms, reduces axonal injury in vitro and is avidly utilized by oligodendrocytes (OLs). The protective potential of L-lactate to reduce white matter (WM) injury in a mouse stroke model was investigated.N/

Is Lactate an Oncometabolite? Evidence Supporting a Role for Lactate in the Regulation of Transcriptional Activity of Cancer-Related Genes in MCF7 Breast Cancer Cells.

Lactate is a ubiquitous molecule in cancer. In this exploratory study, our aim was to test the hypothesis that lactate could function as an oncometabolite by evaluating whether lactate exposure modifies the expression of oncogenes, or genes encoding transcription factors, cell division, and cell proliferation in MCF7 cells, a human breast cancer cell line. Gene transcription was compared between MCF7 cells incubated in (a) glucose/glutamine-free media (control), (b) glucose-containing media to stimulate endogenous lactate production (replicating some of the original Warburg studies), and (c) glucose-containing media supplemented with L-lactate (10 and 20 mM). We found that both endogenous, glucose-derived lactate and exogenous, lactate supplementation significantly affected the transcription of key oncogenes (MYC, RAS, and PI3KCA), transcription factors (HIF1A and E2F1), tumor suppressors (BRCA1, BRCA2) as well as cell cycle and proliferation genes involved in breast cancer (AKT1, ATM, CCND1, CDK4, CDKN1A, CDK2B) (0.001 < p < 0.05 for all genes). Our findings support the hypothesis that lactate acts as an oncometabolite in MCF7 cells. Further research is necessary on other cell lines and biopsy cultures to show generality of the findings and reveal the mechanisms by which dysregulated lactate metabolism could act as an oncometabolite in carcinogenesis

Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain