Research Blog

November 10, 2022

Biomarkers of Liver and Gallbladder Function: LDH

Optimal Takeaways

Lactate dehydrogenase (LDH) is a type of metabolic enzyme that participates in energy generation, especially when oxygen availability is limited. It converts lactate to pyruvate and vice versa, creating a flexible pool of energy substrate. LDH levels increase in liver disease and metastases, metabolic disorders, muscle or organ injury, infection, inflammation, and toxin exposure. Low LDH is uncommon but may be associated with genetic disorders, excess ascorbic acid intake, and hypoglycemia.


Conventional Lab Range: 100.00 - 200.00 IU/L  

Optimal Dx’s Optimal Range: 140.00 - 200.00 IU/L

Low levels of LDH can be seen with genetic disorders (Farhana 2021) and excess ascorbic acid intake (Pagana 2021). Low levels may be associated with hypoglycemia.

High levels of LDH can be seen with MI, pulmonary disease including pneumonia, embolism, or infarction, RBC disorders, muscle injury, kidney disease, intestinal ischemia and infarction, pancreatitis, heatstroke, strenuous exercise, muscle trauma, and RBC hemolysis. Drugs that can increase LDH include alcohol, aspirin, fluorides, narcotics, anesthetics, clofibrate, mithramycin, and procainamide (Pagana 2021).

Elevated LDH can also be associated with liver disease, bone fracture, cancer (especially liver metastases and metastatic melanoma), anemia, cellular necrosis, viral and bacterial infection (Farhana 2021), sepsis (Lu 2018), metabolic syndrome, inflammatory disorders, CVD mortality from arsenic exposure (Wu 2016), poorly controlled diabetes (Dmour 2020), pesticide exposure (Coskun 2015, Rehman 2018), and megaloblastic anemia (Galkwad 2018, Chaudhari 2015).

Overview

Lactate dehydrogenase (LDH) represents a group of oxidoreductase isoenzymes found mainly in the heart, reticuloendothelial system, lung, kidney, placenta, pancreas, liver, striated muscle, and other tissues (Pagana 2021). Concentrations are especially high in the muscle, liver, and kidney. LDH is an important participant in anaerobic metabolism as it can convert pyruvate to lactate and vice versa. Lactate produced throughout the body, especially in skeletal muscle, must be transported to the liver where LDH is able to convert it to pyruvate which then generates glucose via the Cori cycle. LDH is also able to catalyze the reverse reaction by converting pyruvate to lactate. Circulating levels of LDH can increase with increased anerobic metabolism as well as with tissue damage involving the liver, muscle, kidney, pancreas, or other organs. Evaluating the different isoenzymes of LDH can help identify the source and severity of tissue damage. Interestingly, LDH is currently the only serum biomarker that can effectively assess metastatic melanoma (Farhana 2021).

The flexibility of LDH allows glycolysis to produce lactate even under aerobic conditions and that lactate can be used for fuel by various organs including the brain, a process that can spare glucose (Henderson 2013).

Increased LDH is expected with several metabolic disorders including metabolic syndrome. Review of NHANES data revealed that those with metabolic syndrome had significantly increased risk of all-cause mortality with a mean LDH of 176–668 IU/L versus 65–149 U/L (Wu 2016). Increased LDH can reflect increasing adverse effects associated with diabetes. In one retrospective study of 62 diabetic patients, a median LDH of 328 IU/L was associated with significantly elevated glucose and BMI (Dmour 2020).

Elevated levels of LDH are seen with viral infection and may help identify increased risk for disease severity and mortality. Pooled analysis of 9 studies comprising 1,532 COVID-19 patients found that levels above 245-253 IU/L were associated with a 6-fold increased risk of severe disease and a 16-fold increased risk of mortality (Li 2020). One retrospective case-controlled study of 203 COVID-19 patients used a cut-off of 277 IU/L to predict severe disease and 359.5 IU/L to predict likelihood of mortality due to the virus (Henry 2020).

Another study of diabetics with COVID-19 found that those on metformin had significantly higher median LDH levels at 212 IU/L versus non-metformin hypoglycemic agents with a median LDH of 178.5 IU/L. Those on metformin with higher LDH had significantly more life-threatening complications than those not on metformin (Gao 2020).

Elevated LDH is seen in sepsis as well. A retrospective study of 255 septic patients found that elevated LDH of 225 IU/L or above was significantly associated with increased risk of mortality at day 28 compared to those with an LDH below 225 IU/L (Lu 2018).

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References

Chaudhari, Shubhangi, and Suparna Bindu. "Correlation of lactate dehydrogenase in megaloblastic anemia." Int J Curr Med and Appl Sci 9.1 (2015): 28-32.

Coskun, R et al. “A retrospective review of intensive care management of organophosphate insecticide poisoning: Single center experience.” Nigerian journal of clinical practice vol. 18,5 (2015): 644-50. doi:10.4103/1119-3077.158962

Dmour, Hussein H et al. “Assessment of Lactate Dehydrogenase Levels Among Diabetic Patients Treated in the Outpatient Clinics at King Hussein Medical Center, Royal Medical Services, Jordan.” Medical archives (Sarajevo, Bosnia and Herzegovina) vol. 74,5 (2020): 384-386. doi:10.5455/medarh.2020.74.384-386

Gaikwad, Amrapali L., and D. S. Jadhav. "Utility of serum lactate dehydrogenase in the diagnosis of megaloblastic anemia." Int J Res Med Sci 6 (2018): 3051-3056.

Gao, Yongchao et al. “Risk of Metformin in Patients With Type 2 Diabetes With COVID-19: A Preliminary Retrospective Report.” Clinical and translational science vol. 13,6 (2020): 1055-1059. doi:10.1111/cts.12897

Farhana, Aisha. and Sarah L. Lappin. “Biochemistry, Lactate Dehydrogenase.” StatPearls, StatPearls Publishing, 7 May 2021.

Henderson, Gregory C. “The diabetic brain during hypoglycemia: in the midst of plenty of lactate.” Diabetes vol. 62,9 (2013): 3024-6. doi:10.2337/db13-0914

Henry, Brandon Michael et al. “Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis.” The American journal of emergency medicine vol. 38,9 (2020): 1722-1726. doi:10.1016/j.ajem.2020.05.073

Li, Chang et al. “Elevated Lactate Dehydrogenase (LDH) level as an independent risk factor for the severity and mortality of COVID-19.” Aging vol. 12,15 (2020): 15670-15681. doi:10.18632/aging.103770

Lu, Jun et al. “Lactate dehydrogenase is associated with 28-day mortality in patients with sepsis: a retrospective observational study.” The Journal of surgical research vol. 228 (2018): 314-321. doi:10.1016/j.jss.2018.03.035

MG, Makloph, et al. "Do Lab Parameter Could be used as Indicators of Severity in Case of Acute Cholinestrase Inhibitor Insecticides?." Indian Journal of Forensic Medicine & Toxicology 15.2 (2021).

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 15th ed., Mosby, 2021.

Rehman, T., et al. "Combined Effect of Age and Exposure on the Levels of Different Serum Enzymes in Workers of Pesticides Formulation Factories, Pakistan." Biochem Physiol 7.238 (2018): 2.

Wu, Li-Wei et al. “Examining the association between serum lactic dehydrogenase and all-cause mortality in patients with metabolic syndrome: a retrospective observational study.” BMJ open vol. 6,5 e011186. 23 May. 2016, doi:10.1136/bmjopen-2016-011186

Tag(s): Biomarkers

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