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Oral lactate slows gastric emptying and suppresses appetite in young males.
Pedersen, MGB, Søndergaard, E, Nielsen, CB, Johannsen, M, Gormsen, LC, Møller, N, Jessen, N, Rittig, N
Clinical nutrition (Edinburgh, Scotland). 2022;(2):517-525
Abstract
BACKGROUND Lactate serves as an alternative energy fuel but is also an important signaling metabolite. We aimed to investigate whether oral lactate administration affects appetite-regulating hormones, slows gastric emptying rate, and dampens appetite. METHODS Ten healthy male volunteers were investigated on two separate occasions: 1) following oral ingestion of D/L-Na-lactate and 2) following oral ingestion of isotonic iso-voluminous NaCl and intravenous iso-lactemic D/L-Na-lactate infusions. Appetite was evaluated by questionnaires and ad libitum meal tests were performed at the end of each study day. Gastric emptying rate was evaluated using the acetaminophen test. RESULTS Plasma concentrations of growth differential factor 15 (GDF15, primary outcome) increased following oral and iv administration of lactate (p < 0.001) with no detectable difference between interventions (p = 0.15). Oral lactate administration lowered plasma concentrations of acylated ghrelin (p = 0.02) and elevated glucagon like peptide-1 (GLP-1, p = 0.045), insulin (p < 0.001), and glucagon (p < 0.001) compared with iv administration. Oral lactate administration slowed gastric emptying (p < 0.001), increased the feeling of being "full" (p = 0.008) and lowered the "anticipated future food intake" (p = 0.007) compared with iv administration. Food intake during the ad libitum meal test did not differ between the two study days. CONCLUSION Oral lactate administration has a direct effect on the upper gastrointestinal tract, affecting gut hormone secretion, motility and appetite sensations which cannot be mediated through lactate in the systemic circulation alone. These data suggest that compounds rich in lactate may be useful in the treatment of metabolic disease. CLINICAL TRIAL REGISTRY NUMBER NCT0429981, https://clinicaltrials.gov/ct2/show/NCT04299815.
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Hyperlactatemia associated with diabetic ketoacidosis in pediatric intensive care unit.
Liu, J, Yan, H, Li, Y
BMC endocrine disorders. 2021;(1):110
Abstract
BACKGROUND Children with diabetic ketoacidosis often have elevated lactate. In this study, we investigated the clinical variables associated with hyperlactatemia in children with diabetic ketoacidosis. METHODS We designed a single-center retrospective descriptive study of children with diabetic ketoacidosis in a pediatric intensive care unit. RESULTS Of the 107 patients with diabetic ketoacidosis included in the analysis, 61 developed hyperlactatemia. Multivariate logistic regression analysis showed that heart rate (p = 0.003),diastolic blood pressure (p = 0.001) and stage of severity (p = 0.042) were independently associated with the development of hyperlactatemia in diabetic ketoacidosis. We found that lactate level was not significantly associated with length of hospital stay (p = 0.115) or the length of time to diabetic ketoacidosis resolution (p = 0.143). CONCLUSIONS Children with diabetic ketoacidosis presenting with severer stage, elevated heart rate and higher diastolic blood pressure may be prone to hyperlactatemia. Hyperlactatemia was not associated with length of time to DKA resolution and length of hospital stay.
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Lactate Threshold Training Program on Patients with Multiple Sclerosis: A Multidisciplinary Approach.
Amato, A, Ragonese, P, Ingoglia, S, Schiera, G, Schirò, G, Di Liegro, CM, Salemi, G, Di Liegro, I, Proia, P
Nutrients. 2021;(12)
Abstract
Physical activity could play a key role in improving the quality of life, particularly in patients with nervous system diseases such as multiple sclerosis (MS). Through lactacid anaerobic training, this study aims to investigate the effects at a bio-psycho-physical level to counteract the chronic fatigue associated with the pathology, and to improve mental health at a psychological and neurotrophic level. Eight subjects (age: 34.88 ± 4.45 years) affected by multiple sclerosis were involved. A lactate threshold training program was administered biweekly for 12 weeks at the beginning of the study (T0), at the end of the study (T1) and at 9 months after the end of the study (T2), with physical, psychological and hematochemicals parameters, and dietary habits being tested. The results obtained confirmed that lactacid exercise can influence brain-derived neurotrophic factor (BDNF) levels as well as dehydroepiandrosterone sulfate (DHEAS) levels. In addition, levels of baseline lactate, which could be best used as an energy substrate, showed a decrease after the protocol training. Self-efficacy regarding worries and concerns management significantly increased from T0 to T1. The eating attitudes test (EAT-26) did not highlight any eating disease in the patients with a normal diet enrolled in our study. Physical exercise also greatly influenced the patients psychologically and emotionally, increasing their self-esteem. Lactate threshold training, together with dietary habits, appears to exert synergic positive effects on inflammation, neural plasticity and neuroprotection, producing preventive effects on MS symptoms and progression.
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Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.
Fujioka, R, Mochizuki, N, Ikeda, M, Sato, A, Nomura, S, Owada, S, Yomoda, S, Tsuchihara, K, Kishino, S, Esumi, H
PloS one. 2018;(6):e0198219
Abstract
Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.
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Improvement of Neuroenergetics by Hypertonic Lactate Therapy in Patients with Traumatic Brain Injury Is Dependent on Baseline Cerebral Lactate/Pyruvate Ratio.
Quintard, H, Patet, C, Zerlauth, JB, Suys, T, Bouzat, P, Pellerin, L, Meuli, R, Magistretti, PJ, Oddo, M
Journal of neurotrauma. 2016;(7):681-7
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Abstract
Energy dysfunction is associated with worse prognosis after traumatic brain injury (TBI). Recent data suggest that hypertonic sodium lactate infusion (HL) improves energy metabolism after TBI. Here, we specifically examined whether the efficacy of HL (3h infusion, 30-40 μmol/kg/min) in improving brain energetics (using cerebral microdialysis [CMD] glucose as a main therapeutic end-point) was dependent on baseline cerebral metabolic state (assessed by CMD lactate/pyruvate ratio [LPR]) and cerebral blood flow (CBF, measured with perfusion computed tomography [PCT]). Using a prospective cohort of 24 severe TBI patients, we found CMD glucose increase during HL was significant only in the subgroup of patients with elevated CMD LPR >25 (n = 13; +0.13 [95% confidence interval (CI) 0.08-0.19] mmol/L, p < 0.001; vs. +0.04 [-0.05-0.13] in those with normal LPR, p = 0.33, mixed-effects model). In contrast, CMD glucose increase was independent from baseline CBF (coefficient +0.13 [0.04-0.21] mmol/L when global CBF was <32.5 mL/100 g/min vs. +0.09 [0.04-0.14] mmol/L at normal CBF, both p < 0.005) and systemic glucose. Our data suggest that improvement of brain energetics upon HL seems predominantly dependent on baseline cerebral metabolic state and support the concept that CMD LPR - rather than CBF - could be used as a diagnostic indication for systemic lactate supplementation following TBI.
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Effects of a new bicarbonate/lactate-buffered neutral peritoneal dialysis fluid for peritoneal failure in patients undergoing peritoneal dialysis.
Hoshino, T, Ishii, H, Kitano, T, Shindo, M, Miyazawa, H, Yamada, H, Ito, K, Ueda, Y, Kaku, Y, Hirai, K, et al
Discovery medicine. 2016;(114):81-8
Abstract
BACKGROUND The highly concentrated lactate in peritoneal dialysis fluid (PDF) has been considered to contribute to peritoneal failure in patients undergoing PD. A new PDF containing a lower lactate concentration, physiological bicarbonate concentration, and neutral pH (bicarbonate/lactate-buffered neutral PDF) was recently developed. We compared the clinical effects of this bicarbonate/lactate-buffered neutral PDF and a lactate-buffered neutral PDF. METHODS AND DESIGN Patients undergoing PD were changed from a lactate-buffered neutral PDF to a bicarbonate/lactate-buffered neutral PDF. We then investigated the changes in peritoneal functions as estimated by a peritoneal equilibration test (PET) and the following surrogate markers of peritoneal membrane failure in the drained dialysate: fibrin degradation products (FDP), vascular endothelial growth factor (VEGF), cancer antigen 125 (CA125), interleukin-6 (IL-6), and transforming growth factor beta 1 (TGF-β1). RESULTS Fourteen patients undergoing PD were enrolled. The PET results were not different before and after use of the bicarbonate/lactate-buffered neutral PDF. The FDP concentration significantly decreased from 15.60 ± 13.90 to 6.04 ± 3.49 μg/mL (p = 0.02) and the VEGF concentration significantly decreased from 37.83 ± 15.82 to 27.70 ± 3.80 pg/mL (p = 0.02), while the CA125 and IL-6 concentrations remained unchanged before and after use of the bicarbonate/lactate-buffered neutral PDF. TGF-β1 was not detected in most patients. CONCLUSION The bicarbonate/lactate-buffered neutral PDF decreased the FDP and VEGF concentrations in the drained dialysate. These results suggest that the decreased lactate level achieved by administration of bicarbonate with a neutral pH in PDF may contribute to decreased peritoneal membrane failure in patients undergoing PD.
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Lactate Clearance and Vasopressor Seem to Be Predictors for Mortality in Severe Sepsis Patients with Lactic Acidosis Supplementing Sodium Bicarbonate: A Retrospective Analysis.
Lee, SM, Kim, SE, Kim, EB, Jeong, HJ, Son, YK, An, WS
PloS one. 2015;(12):e0145181
Abstract
INTRODUCTION Initial lactate level, lactate clearance, C-reactive protein, and procalcitonin in critically ill patients with sepsis are associated with hospital mortality. However, no study has yet discovered which factor is most important for mortality in severe sepsis patients with lactic acidosis. We sought to clarify this issue in patients with lactic acidosis who were supplementing with sodium bicarbonate. MATERIALS AND METHODS Data were collected from a single center between May 2011 and April 2014. One hundred nine patients with severe sepsis and lactic acidosis who were supplementing with sodium bicarbonate were included. RESULTS The 7-day mortality rate was 71.6%. The survivors had higher albumin levels and lower SOFA, APACHE II scores, vasopressor use, and follow-up lactate levels at an elapsed time after their initial lactate levels were checked. In particular, a decrement in lactate clearance of at least 10% for the first 6 hours, 24 hours, and 48 hours of treatment was more dominant among survivors than non-survivors. Although the patients who were treated with broad-spectrum antibiotics showed higher illness severity than those who received conventional antibiotics, there was no significant mortality difference. 6-hour, 24-hour, and 48-hour lactate clearance (HR: 4.000, 95% CI: 1.309-12.219, P = 0.015) and vasopressor use (HR: 4.156, 95% CI: 1.461-11.824, P = 0.008) were significantly associated with mortality after adjusting for confounding variables. CONCLUSIONS Lactate clearance at a discrete time point seems to be a more reliable prognostic index than initial lactate value in severe sepsis patients with lactic acidosis who were supplementing with sodium bicarbonate. Careful consideration of vasopressor use and the initial application of broad-spectrum antibiotics within the first 48 hours may be helpful for improving survival, and further study is warranted.
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Arteriovenous Blood Metabolomics: A Readout of Intra-Tissue Metabostasis.
Ivanisevic, J, Elias, D, Deguchi, H, Averell, PM, Kurczy, M, Johnson, CH, Tautenhahn, R, Zhu, Z, Watrous, J, Jain, M, et al
Scientific reports. 2015;:12757
Abstract
The human circulatory system consists of arterial blood that delivers nutrients to tissues, and venous blood that removes the metabolic by-products. Although it is well established that arterial blood generally has higher concentrations of glucose and oxygen relative to venous blood, a comprehensive biochemical characterization of arteriovenous differences has not yet been reported. Here we apply cutting-edge, mass spectrometry-based metabolomic technologies to provide a global characterization of metabolites that vary in concentration between the arterial and venous blood of human patients. Global profiling of paired arterial and venous plasma from 20 healthy individuals, followed up by targeted analysis made it possible to measure subtle (<2 fold), yet highly statistically significant and physiologically important differences in water soluble human plasma metabolome. While we detected changes in lactic acid, alanine, glutamine, and glutamate as expected from skeletal muscle activity, a number of unanticipated metabolites were also determined to be significantly altered including Krebs cycle intermediates, amino acids that have not been previously implicated in transport, and a few oxidized fatty acids. This study provides the most comprehensive assessment of metabolic changes in the blood during circulation to date and suggests that such profiling approach may offer new insights into organ homeostasis and organ specific pathology.
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Effect of ingestion of medium-chain triacylglycerols on moderate- and high-intensity exercise in recreational athletes.
Nosaka, N, Suzuki, Y, Nagatoishi, A, Kasai, M, Wu, J, Taguchi, M
Journal of nutritional science and vitaminology. 2009;(2):120-5
Abstract
Medium-chain triacylglycerols (MCT) are known to hydrolyze readily and completely to fatty acids and to be metabolized more easily by beta-oxidation than long-chain triacylglycerols (LCT). Therefore, we investigated the effect of 2 wk of ingestion of food containing a small amount (6 g) of MCT on energy metabolism during moderate-intensity exercise and high-intensity exercise in recreational athletes. For comparison, the subjects were administered food containing MCT or LCT for 14 d, and were instructed to perform cycle ergometer exercise at a workload corresponding to 60% peak O(2) uptake (VO(2)) for 40 min followed by a workload corresponding to 80% peak VO(2) until exhaustion. Blood lactate concentration, VO(2), VCO(2), and rating of perceived exertion (RPE) were measured at rest and during exercise. The exercise time to exhaustion at a workload corresponding to 80% peak VO(2) was significantly (p<0.05) longer in the MCT trial (10.2+/-7.6 min; mean+/-SD) than in the LCT trial (5.8+/-3.3 min). Blood lactate concentration and RPE during exercise were significantly (p<0.05) lower after ingestion of MCT-containing food. Fat oxidation rate was higher and carbohydrate oxidation rate was lower during exercise in the MCT trial than in the LCT trial, but the differences were not significant. These results indicate that the ingestion of MCT-containing food may suppress utilization of carbohydrate for energy production because of increased utilization of fatty acids for generating energy. In conclusion, our data suggest that short-term ingestion of food containing a small amount of MCT suppresses the increase in blood lactate concentration and RPE during moderate-intensity exercise and extends the duration of subsequent high-intensity exercise, at levels higher than those achieved by ingestion of LCT-containing food.
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Effects of hypoxia on the onset of muscle deoxygenation and the lactate threshold.
Lorenz, KA, Hom, C, Lopez, J, Pozos, RS, Buono, MJ, Kolkhorst, FW
The journal of physiological sciences : JPS. 2006;(4):321-3
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Abstract
Six subjects performed two trials of incremental cycling to exhaustion under normoxic and hypoxic conditions. The lactate threshold and onset of muscle deoxygenation were highly correlated under both conditions, and during the hypoxic condition both variables shifted leftward.