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Cleveland Clinic Journal of Medicine Sep 2015In hospitalized patients, elevated serum lactate levels are both a marker of risk and a target of therapy. The authors describe the mechanisms underlying lactate... (Review)
Review
In hospitalized patients, elevated serum lactate levels are both a marker of risk and a target of therapy. The authors describe the mechanisms underlying lactate elevations, note the risks associated with lactic acidosis, and outline a strategy for its treatment.
Topics: Acidosis, Lactic; Cardiotonic Agents; Disease Management; Fluid Therapy; Humans; Oxygen Inhalation Therapy; Shock, Septic; Vasoconstrictor Agents
PubMed: 26366959
DOI: 10.3949/ccjm.82a.14098 -
Gut Microbes Jul 2017The existence of an implicit living microscopic world, composed primarily of bacteria, has been known for centuries. The exact mechanisms that govern the contribution of... (Review)
Review
The existence of an implicit living microscopic world, composed primarily of bacteria, has been known for centuries. The exact mechanisms that govern the contribution of bacteria to human health and disease have only recently become the subject of intense research efforts. Within this very evident shift in paradigms, the rational design of probiotic formulations has led to the creation of an industry that seeks to progress the engineering of probiotic bacteria that produce metabolites that may enhance human host health and prevent disease. The promotion of probiotics is often made in the absence of quality scientific and clinically plausible data. The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions) or are strain-specific (shaping an industry point of difference) for appraising a therapeutic effect. Evidence-based research should guide clinical practice, as there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. Ignoring scientifically discordant data, when sorting through research innovations and false leads relevant to the actions of probiotics, drives researcher discomfit and keeps the bar low, impeding the progress of knowledge. Biologically plausible posits are obligatory in any research effort; companies formulating probiotics often exhibit a lack of analytical understanding that then fuels questionable investigations failing to build on research capacity.
Topics: Acidosis, Lactic; Animals; Humans; Lactobacillaceae; Oxidative Stress; Probiotics; Species Specificity
PubMed: 28080206
DOI: 10.1080/19490976.2017.1279379 -
Trends in Endocrinology and Metabolism:... Apr 2024Hyperlactatemia and anemia commonly coexist and their crosstalk is a longstanding mystery with elusive mechanisms involved in physical activities, infections, cancers,... (Review)
Review
Hyperlactatemia and anemia commonly coexist and their crosstalk is a longstanding mystery with elusive mechanisms involved in physical activities, infections, cancers, and genetic disorders. For instance, hyperlactatemia leads to iron restriction by upregulating hepatic hepcidin expression. Increasing evidence also points to lactate as a crucial signaling molecule rather than merely a metabolic byproduct. Here, we discuss the mutual influence between anemia and hyperlactatemia. This opinion calls for a reconsideration of the multifaceted roles of lactate and lactylation in anemia and emphasizes the need to fill knowledge gaps, including the dose dependence of lactate's effects, its sources, and its subcellular localization.
Topics: Humans; Hyperlactatemia; Acidosis, Lactic; Lactic Acid; Anemia
PubMed: 38185594
DOI: 10.1016/j.tem.2023.12.006 -
Journal of the American Heart... May 2022Background Lactic acidosis is associated with mortality in patients with cardiogenic shock (CS). Elevated lactate levels and systemic acidemia (low blood pH) have both...
Background Lactic acidosis is associated with mortality in patients with cardiogenic shock (CS). Elevated lactate levels and systemic acidemia (low blood pH) have both been proposed as drivers of death. We, therefore, analyzed the association of both high lactate concentrations and low blood pH with 30-day mortality in patients with CS. Methods and Results This was a 2-center historical cohort study of unselected patients with CS with available data for admission lactate level or blood pH. CS severity was graded using the Society for Cardiovascular Angiography and Intervention (SCAI) shock classification. All-cause survival at 30 days was analyzed using Kaplan-Meier curves and Cox proportional-hazards analysis. There were 1814 patients with CS (mean age, 67.3 years; 68.5% men); 51.8% had myocardial infarction and 53.0% had cardiac arrest. The distribution of SCAI shock stages was B, 10.8%; C, 30.7%; D, 38.1%; and E, 18.7%. In both cohorts, higher lactate or lower pH predicted a higher risk of adjusted 30-day mortality. Patients with a lactate ≥5 mmol/L or pH <7.2 were at increased risk of adjusted 30-day mortality; patients with both lactate ≥5 mmol/L and pH <7.2 had the highest risk of adjusted 30-day mortality. Patients in SCAI shock stages C, D, and E had higher 30-day mortality in each SCAI shock stage if they had lactate ≥5 mmol/L or pH <7.2, particularly if they met both criteria. Conclusions Higher lactate and lower pH predict mortality in patients with cardiogenic shock beyond standard measures of shock severity. Severe lactic acidosis may serve as a risk modifier for the SCAI shock classification. Definitions of refractory or hemometabolic shock should include high lactate levels and low blood pH.
Topics: Acidosis; Acidosis, Lactic; Aged; Cohort Studies; Female; Humans; Lactic Acid; Male; Shock; Shock, Cardiogenic
PubMed: 35491996
DOI: 10.1161/JAHA.121.024932 -
Indian Heart Journal 2018The use of metformin was considered a contraindication in heart failure patients because of the potential risk of lactic acidosis; however, more recent evidence has... (Review)
Review
The use of metformin was considered a contraindication in heart failure patients because of the potential risk of lactic acidosis; however, more recent evidence has shown that this should no longer be the case. We reviewed the current literature and the recent guideline to correct the misconception.
Topics: Acidosis, Lactic; Heart Failure; Humans; Hypoglycemic Agents; Metformin
PubMed: 29455774
DOI: 10.1016/j.ihj.2017.05.009 -
Military Medical Research Apr 2018Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic... (Review)
Review
Type A lactic acidosis resulted from hypoxic mitochondrial dysfunction is an independent predictor of mortality for critically ill patients. However, current therapeutic agents are still in shortage and can even be harmful. This paper reviewed data regarding lactic acidosis treatment and recommended that pyruvate might be a potential alkalizer to correct type A lactic acidosis in future clinical practice. Pyruvate is a key energy metabolic substrate and a pyruvate dehydrogenase (PDH) activator with several unique beneficial biological properties, including anti-oxidant and anti-inflammatory effects and the ability to activate the hypoxia-inducible factor-1 (HIF-1α) - erythropoietin (EPO) signal pathway. Pyruvate preserves glucose metabolism and cellular energetics better than bicarbonate, lactate, acetate and malate in the efficient correction of hypoxic lactic acidosis and shows few side effects. Therefore, application of pyruvate may be promising and safe as a novel therapeutic strategy in hypoxic lactic acidosis correction accompanied with multi-organ protection in critical care patients.
Topics: Acidosis, Lactic; Antacids; Bicarbonates; Erythropoietin; Fluid Therapy; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Pyruvic Acid; Ringer's Lactate
PubMed: 29695298
DOI: 10.1186/s40779-018-0160-y -
Physiological Reports Feb 2021Type A lactic acidosis is a potentially life-threatening complication in critically ill patients and is the hallmark of a shock state as a result of tissue hypoperfusion... (Review)
Review
Type A lactic acidosis is a potentially life-threatening complication in critically ill patients and is the hallmark of a shock state as a result of tissue hypoperfusion and dysoxia. Type B lactic acidosis results from mechanisms other than dysoxia and is a rare condition in patients with solid tumors or hematological malignancies. We present a case of a 60-year-old man with lactic acidosis who was found to have a Burkitt lymphoma related to a posttransplant lymphoproliferative disorder. Lactagenic cancers are characterized by increased aerobic glycolysis and excessive lactate formation, a phenomenon described by Warburg in 1923 that is correlated with cancer aggressiveness and poor survival. There is increased glucose utilization with the purpose of lactagenesis under fully oxygenated conditions, as lactate seems to be a potent signaling molecule for angiogenesis, immune escape, cell migration, metastasis and self-sufficient metabolism, which are five essential steps of carcinogenesis. Type B lactic acidosis in association with malignancies carries an extremely poor prognosis. Currently, effective chemotherapy seems to be the only hope for survival.
Topics: Acid-Base Equilibrium; Acidosis, Lactic; Antineoplastic Combined Chemotherapy Protocols; Burkitt Lymphoma; Humans; Male; Middle Aged; Remission Induction; Treatment Outcome; Warburg Effect, Oncologic
PubMed: 33611854
DOI: 10.14814/phy2.14737 -
Postgraduate Medical Journal Aug 2023Thiamine is present in many foods and is well recognised as an essential nutrient critical for energy metabolism. While thiamine deficiency is commonly recognised in... (Review)
Review
Thiamine is present in many foods and is well recognised as an essential nutrient critical for energy metabolism. While thiamine deficiency is commonly recognised in alcoholism, it can present in many other settings where it is often not considered and goes unrecognised. One challenging aspect to diagnosis is that it may have varied metabolic, neurological and cardiac presentations. Here we present an overview of the disorder, focusing on the multiple causes and clinical presentations. Interestingly, thiamine deficiency is likely increasing in frequency, especially among wildlife, where it is linked with changing environments and climate change. Thiamine deficiency should be considered whenever neurological or cardiological disease of unknown aetiology presents, especially in any patient presenting with lactic acidosis.
Topics: Humans; Thiamine Deficiency; Thiamine; Acidosis, Lactic; Alcoholism; Food
PubMed: 37125640
DOI: 10.1136/pmj-2022-141972 -
Physiological Reports Mar 2022The global prevalence of type 2 diabetes (T2D) is expected to exceed 642 million people by 2040. Metformin is a widely used biguanide T2D therapy, associated with rare...
The global prevalence of type 2 diabetes (T2D) is expected to exceed 642 million people by 2040. Metformin is a widely used biguanide T2D therapy, associated with rare but serious events of lactic acidosis, in particular with predisposing conditions (e.g., renal failure or major surgery). Imeglimin, a recently approved drug, is the first in a new class (novel mode of action) of T2D medicines. Although not a biguanide, Imeglimin shares a chemical moiety with Metformin and also modulates mitochondrial complex I activity, a potential mechanism for Metformin-mediated lactate accumulation. We interrogated the potential for Imeglimin to induce lacticacidosis in relevant animal models and further assessed differences in key mechanisms known for Metformin's effects. In a dog model of major surgery, Metformin or Imeglimin (30-1000 mg/kg) was acutely administered, only Metformin-induced lactate accumulation and pH decrease leading to lactic acidosis with fatality at the highest dose. Rats with gentamycin-induced renal insufficiency received Metformin or Imeglimin (50-100 mg/kg/h), only Metformin increased lactatemia and H concentrations with mortality at higher doses. Plasma levels of Metformin and Imeglimin were similar in both models. Mice were chronically treated with Metformin or Imeglimin 200 mg/kg bid. Only Metformin produced hyperlactatemia after acute intraperitoneal glucose loading. Ex vivo measurements revealed higher mitochondrial complex I inhibition with Metformin versus slight effects with Imeglimin. Another mechanism implicated in Metformin's effects on lactate production was assessed: in isolated rat, liver mitochondria exposed to Imeglimin or Metformin, only Metformin (50-250 µM) inhibited the mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH). In liver samples from chronically treated mice, measured mGPDH activity was lower with Metformin versus Imeglimin. These data indicate that the risk of lactic acidosis with Imeglimin treatment may be lower than with Metformin and confirm that the underlying mechanisms of action are distinct, supporting its potential utility for patients with predisposing conditions.
Topics: Acidosis, Lactic; Animals; Diabetes Mellitus, Type 2; Dogs; Humans; Hypoglycemic Agents; Lactic Acid; Metformin; Mice; Rats; Renal Insufficiency; Triazines
PubMed: 35274817
DOI: 10.14814/phy2.15151 -
The Journal of Extra-corporeal... Mar 2017The normal blood lactate level is 0-2 mmol/L, and a value above 3-5 mmol/L is variably used to define hyperlactatemia. In cardiac surgical patients, hyperlactatemia can... (Review)
Review
The normal blood lactate level is 0-2 mmol/L, and a value above 3-5 mmol/L is variably used to define hyperlactatemia. In cardiac surgical patients, hyperlactatemia can arise from both hypoxic and non-hypoxic mechanisms. The major non-hypoxic mechanism is likely stress-induced accelerated aerobic metabolism, in which elevated lactate results from a mass effect on the lactate/pyruvate equilibrium. The lactate/pyruvate ratio is normal (<20) in this circumstance. Hyperlactatemia can also result from impaired global or regional oxygen delivery, in which case the lactate/pyruvate ratio is typically elevated (>20). Lactate is a strong anion that is virtually fully dissociated at physiological pH. As such, increased lactate concentration reduces the strong ion difference and exerts an acidifying effect on the blood. Hyperlactatemia in cardiac surgery patients has been categorized as either early or late onset. Early-onset hyperlactatemia is that which develops in the operating room or very early following intensive care unit (ICU) admission. Early-onset hyperlactatemia is strongly associated with adverse outcome and probably arises as a consequence of both hypoxic (e.g., microcirculatory shock) and non-hypoxic (accelerated aerobic metabolism) mechanisms. By contrast, late-onset hyperlactatemia is a benign, self-limiting condition that typically arises within 6-12 hours of ICU admission and spontaneously resolves within 24 hours. Late onset hyperlactatemia occurs in the absence of any evidence of global or regional tissue hypoxia. The mechanism of late onset hyperlactatemia is not understood. Hyperlactatemia is a common accompaniment to treatment with β-agonists such as epinephrine. Epinephrine-induced hyperlactatemia is thought to be due to accelerated aerobic metabolism and requires no specific intervention. Irrespective of the cause, the presence of hyperlactatemia should trigger a search for remedial causes of impaired tissue oxygenation, bearing in mind that normal-or even supranormal-indices of global oxygen delivery may exist despite regional tissue hypoperfusion.
Topics: Acidosis, Lactic; Biomarkers; Cardiac Surgical Procedures; Humans; Hyperlactatemia; Hypoxia; Lactic Acid; Metabolic Clearance Rate; Models, Cardiovascular; Oxygen; Pyruvic Acid
PubMed: 28298660
DOI: No ID Found