Cannabidiol (CBD) is a non-intoxicating phytocannabinoid which has been proposed to possess anti-inflammatory and analgesic properties. Given the potential for perceptions of pain to limit exercise performance, the aim of the present study was to investigate if 3 weeks of daily CBD supplementation (150 mg day-1) improved performance in a 10-min performance-trial on a cycle ergometer. In a randomized, double-blind and placebo-controlled study, 22 healthy participants (n = 11 male and n = 11 female) completed two 10-min performance trials on a WattBike cycle ergometer interspersed with a 3-week supplementation period. Supplementation involved either 150 mg day-1 oral CBD or 150 mg day-1 of a visually identical placebo (PLA). During trials, ratings of perceived exertion (RPE [6-20]), heart rate (HR) and blood lactate (BLa) were collected every 2 min. Mean power (W) was also taken throughout the exercise at each time point. All data were analyzed using two-way ANOVAs. There were no significant differences (P > 0.05) between CBD or PLA groups for mean power (W) during the 10-min performance trial. There were also no significant differences (P > 0.05) in any of the physiological or perceptual parameters (HR, BLa and RPE) between conditions. Three weeks supplementation of a broad-spectrum CBD supplement did not improve performance via any change in RPE during a 10-min time trial on a cycle ergometer, and as such, this evidence does not support the claim that broad-spectrum CBD supplements could be performance-enhancing in this exercise modality.

Plyometric training is characterized by high-intensity exercise which is performed in short term efforts divided into sets. The purpose of the present study was twofold: first, to investigate the effects of three distinct plyometric exercise protocols, each with varying work-to-rest ratios, on muscle fatigue and recovery using an incline-plane training machine; and second, to assess the relationship between changes in lower limb muscle strength and power and the biochemical response to the three exercise variants employed. Forty-five adult males were randomly divided into 3 groups (n = 15) performing an exercise of 60 rebounds on an incline-plane training machine. The G0 group performed continuous exercise, while the G45 and G90 groups completed 4 sets of 15 repetitions, each set lasting 45 s with 45 s rest in G45 (work-to-rest ratio of 1:1) and 90 s rest in G90 (1:2 ratio). Changes in muscle torques of knee extensors and flexors, as well as blood lactate (LA) and ammonia levels, were assessed before and every 5 min for 30 min after completing the workout. The results showed significantly higher (p < 0.001) average power across all jumps generated during intermittent compared to continuous exercise. The greatest decrease in knee extensor strength immediately post-exercise was recorded in group G0 and the least in G90. The post-exercise time course of LA changes followed a similar pattern in all groups, while the longer the interval between sets, the faster LA returned to baseline. Intermittent exercise had a more favourable effect on muscle energy metabolism and recovery than continuous exercise, and the work-to-rest ratio of 1:2 in plyometric exercises was sufficient rest time to allow the continuation of exercise in subsequent sets at similar intensity.

UNASSIGNED: Beetroot juice (BRJ) intake has been considered a practical nutritional strategy among well-trained athletes. This study aimed to assess the effects of BRJ intake on performance, cardiorespiratory and metabolic variables during a simulated 2000-meter rowing ergometer test in well-trained master rowers.
UNASSIGNED: Ten well-trained male master rowers (30-48 years) participated in a randomized, double-blind, crossover design for 3 weeks. In the first week, a researcher explained all the experimental procedures to the participants. In the next two weeks, the participants were tested in 2 rowing ergometer sessions, separated from each other by a 7-day washout period. In both strictly identical sessions, the participants randomly drank BRJ or placebo (PL) 3 hours before the start of the tests. Subsequently, the participants carried out the 2000-meter rowing ergometer tests. Oxygen saturation and blood lactate measurements were performed before starting (pretest) and at the end of the test (posttest). Performance parameters and cardiorespiratory variables were recorded during the rowing ergometer test.
UNASSIGNED: An improvement in time trial performance was observed, with a mean difference of 4 seconds (90% confidence limits ± 3.10; p ≤ 0.05) compared to PL. Relative and absolute maximaloxygenuptakeV˙O2max increased (mean difference of 2.10 mL·kg-1·min-1, 90% confidence limits ± 1.80; mean difference of 0.16 L·min-1 90% confidence limits ± 0.11, respectively; p ≤ 0.05) compared to PL. No ergogenic effect was observed on ventilatory efficiency and blood lactate concentrations after BRJ intake.
UNASSIGNED: Acute BRJ intake may improve time trial performance as well as V˙O2max in well-trained master rowers. However, BRJ does not appear to improve ventilatory efficiency.

While the intracellular-extracellular distribution of lactate has been suggested to play a critical role in the healthy and diseased brain, tools are lacking to noninvasively probe lactate in intracellular and extracellular spaces. Here, we show that, by measuring the diffusion of lactate with diffusion-weighted magnetic resonance (MR) spectroscopy in vivo and comparing it to the diffusion of purely intracellular metabolites, noninvasive quantification of extracellular and intracellular lactate fractions becomes possible. More specifically, we detect alterations of lactate diffusion in the APP/PS1 mouse model of Alzheimer\'s disease. Data modeling allows quantifying decreased extracellular lactate fraction in APP/PS1 mice as compared to controls, which is quantitatively confirmed with implanted enzyme-microelectrodes. The capability of diffusion-weighted MR spectroscopy to quantify extracellular-intracellular lactate fractions opens a window into brain metabolism, including in Alzheimer\'s disease.

Levilactobacillus brevis is crucial in food fermentation, particularly in sourdough production. However, the cultivation of L. brevis faces a challenge with accumulation of lactic acid, a major inhibitor. We aimed to increase the acid tolerance of L. brevis, an industrial strain for sourdough fermentation. We used the adaptive laboratory evolution (ALE) to obtain lactic acid tolerant strains. The evolved strain\'s fermentation and metabolite profiles, alongside sensory evaluation, were compared with the parental strain by using various analytical techniques. The ALE approach increased lactic acid tolerance in the evolved strain showing an increased growth rate by 1.1 and 1.9 times higher than the parental strain at pH 4.1 and 6.5, respectively. Comprehensive analyses demonstrated its potential application in sourdough fermentation, promising reduced downstream costs. The evolved strain, free from genetically modified organisms concerns, has great potential for industrial use by exhibiting enhanced growth in acidic conditions without affecting consumers\' bread preferences.

BACKGROUND: Under fasting conditions, the pathway converting gluconeogenesis precursors into muscle glycogen becomes crucial due to reduced glycogen reserves. However, there is limited research on skeletal muscle gluconeogenesis and the impact of fasting on gluconeogenic gene expression.
METHODS: Sheep fetal skeletal muscle cells cultured in vitro were used to study the effects of varying lactic acid concentrations (0 to 30 mM) and 2.5 mM glucose on the expression of gluconeogenesis-related genes after 6 h of fasting. The effects on mRNA and protein expression of key genes involved in skeletal muscle gluconeogenesis were measured by quantitative real time polymerase chain reaction (qRT-PCR), immunofluorescence, and western blotting at 48 h.
RESULTS: Fasting increased the expression of key gluconeogenic genes, fructose-1,6-bisphosphatase 2 (FBP2), glucose-6-phosphatase 3 (G6PC3), pyruvate kinase M (PKM), monocarboxylate transporter1 (MCTS1), glucose transporter type 4 (GLUT4), pyruvate carboxylase (PC), and lactate dehydrogenase A (LDHA). The mRNA levels of FBP2, G6PC3, and MCTS1 significantly decreased with glucose addition. Additionally, 10 mM lactic acid significantly promoted the expression of FBP2, PC, MCTS1, LDHA, GLUT4, and PKM while inhibiting phosphoenolpyruvate carboxykinase (PEPCK) expression. At the protein level, 10 mM lactic acid significantly increased FBP2 and PKM protein expression.
CONCLUSIONS: This study shows that fasting regulates key gluconeogenic gene expression in sheep skeletal muscle cells and highlights the role of lactic acid in inducing these gene expressions.

Non-alcoholic steatohepatitis (NASH) is characterized from its early stages by a profound remodeling of the liver microenvironment, encompassing changes in the composition and activities of multiple cell types and associated gene expression patterns. Hyperpolarized (HP) 13C MRI provides a unique view of the metabolic microenvironment, with potential relevance for early diagnosis of liver disease. Previous studies have detected changes in HP 13C pyruvate to lactate conversion, catalyzed by lactate dehydrogenase (LDH), with experimental liver injury. HP ∝ -ketobutyrate ( ∝ KB) is a close molecular analog of pyruvate with modified specificity for LDH isoforms, specifically attenuated activity with their LDHA-expressed subunits that dominate liver parenchyma. Building on recent results with pyruvate, we investigated HP ∝ KB in methionine-choline deficient (MCD) diet as a model of early-stage NASH. Similarity of results between this new agent and pyruvate (~ 50% drop in cytoplasmic reducing capacity), interpreted together with gene expression data from the model, suggests that changes are mediated through broad effects on intermediary metabolism. Plausible mechanisms are depletion of the lactate pool by upregulation of gluconeogenesis (GNG) and pentose phosphate pathway (PPP) flux, and a possible shift toward increased lactate oxidation. These changes may reflect high levels of oxidative stress and/or shifting macrophage populations in NASH.

Tissue hypoxia is associated with the development of organ dysfunction and death in critically ill patients commonly captured using blood lactate. The kinetic parameters of serial lactate evaluations are superior at predicting mortality compared with single values. S-adenosylhomocysteine (SAH), which is also associated with hypoxia, was recently established as a useful predictor of septic organ dysfunction and death. We evaluated the performance of kinetic SAH parameters for mortality prediction compared with lactate parameters in a cohort of critically ill patients. For lactate and SAH, maxima and means as well as the normalized area scores were calculated for two periods: the first 24 h and the total study period of up to five days following ICU admission. Their performance in predicting in-hospital mortality were compared in 99 patients. All evaluated parameters of lactate and SAH were significantly higher in non-survivors compared with survivors. In univariate analysis, the predictive power for mortality of SAH was higher compared with lactate in all forms of application. Multivariable models containing SAH parameters demonstrated higher predictive values for mortality than models based on lactate parameters. The optimal models for mortality prediction incorporated both lactate and SAH parameters. Compared with lactate, SAH displayed stronger predictive power for mortality in static and dynamic application in critically ill patients.

In this study, the feasibility of promoting the lactic acid (LA) fermentation of food waste (FW) with iron tailings (ITs) addition was explored. The best LA yield was 0.91 g LA/g total sugar when 1 % ITs were added into the system. The mechanisms for promoting LA production were acidification alleviation effects and reduction equivalent supply of ITs. Furthermore, the addition of ITs promoted carbohydrate hydrolysis, and the carbohydrates digestibility reached 88.85 % in the 1 % ITs group. The ITs also affected the microbial communities, Lactococcus gradually replaced Streptococcus as the dominant genus, and results suggested that Lactococcus had a positive correlation with LA production and carbohydrate digestibility. Finally, the complex LAB in FW had significant effects on heavy metal removal from ITs, and the removal efficiency Cr, As, Pb, Cd, and Hg can reach 50.84 %, 26.72 %, 59.65 %, 49.75 % and 78.87 % in the 1 % ITs group, respectively.

Once considered as a \"metabolic waste,\" lactate is now recognized as a major fuel for tricarboxylic acid (TCA) cycle. Our metabolic flux analysis reveals that skeletal muscle mainly uses lactate to fuel TCA cycle. Lactate is transported through the cell membrane via monocarboxylate transporters (MCTs) in which MCT1 is highly expressed in the muscle. We analyzed how MCT1 affects muscle functions using mice with specific deletion of MCT1 in skeletal muscle. MCT1 deletion enhances running performance, increases oxidative fibers while decreasing glycolytic fibers, and enhances flux of glucose to TCA cycle. MCT1 deficiency increases the expression of mitochondrial proteins, augments cell respiration rate, and elevates mitochondrial activity in the muscle. Mechanistically, the protein level of PGC-1α, a master regulator of mitochondrial biogenesis, is elevated upon loss of MCT1 via increases in cellular NAD+ level and SIRT1 activity. Collectively, these results demonstrate that MCT1-mediated lactate shuttle plays a key role in regulating muscle functions by modulating mitochondrial biogenesis and TCA flux.