What Is LDH? Elevated LDH in Cancer Patients

Lactate dehydrogenase (LDH), which is found in most body tissues, is an enzyme. It participates in cellular respiration, the process that converts nutrients into energy for cells.

Although LDH is abundant in cells, it is not normally present in high concentrations in the blood, so LDH blood test levels are generally low. However, if tissues are damaged by injury or various diseases, blood LDH levels rise.

The most common causes of elevated blood LDH are:

• liver disease
• heart attack
• anemia
• infections
• advanced stages of certain cancers and blood cancers such as lymphoma and leukemia

Doctors may use the LDH test to help diagnose these conditions.

This article explains the LDH test, its uses and what the results may mean.

What Is LDH?

Lactate dehydrogenase (LDH) is an enzyme found in almost all body tissues, including:

• muscles
• liver
• heart
• pancreas
• kidneys
• brain
• blood cells

The LDH enzyme helps convert lactate, a product of a sugar molecule, into pyruvate, which cells then use for energy.

If disease or injury damages cells, LDH is released into the bloodstream. Measuring LDH levels in the blood can therefore tell doctors how much cell damage has occurred.

There are different forms of LDH found in various tissues, called isoenzymes.

• LDH1 in the heart
• LDH2 in the reticuloendothelial system (liver, spleen, lungs) and red blood cells
• LDH3 in the lungs
• LDH4 in the kidneys
• LDH5 in the liver and skeletal muscle

What Does Elevated LDH Mean, and What Does the Test Measure?

Doctors use LDH tests to determine whether there is tissue damage inside the body that they cannot see externally. They may also use LDH tests to monitor conditions that can damage tissues, for example:

• hemolytic anemia (anemia due to red blood cell breakdown)
• muscular dystrophy (progressive muscle weakness and wasting)
• liver disease
• kidney disease
• lung disease
• certain infections
• advanced stages of certain cancers and blood cancers such as lymphoma and leukemia.

The LDH test may also help doctors determine whether chemotherapy is working during cancer treatment. However, LDH is not used as part of routine monitoring for every type of cancer.

Normal LDH Levels

Normal blood LDH levels for adults are generally 140-280 U/L(units/liter). Doctors use a person's symptoms and signs of underlying disease to help interpret the data.

Babies and young children generally have substantially higher normal LDH levels. For example, normal levels are 135–750 U/L in newborns and 180–435 U/L in children up to 12 months old.

How Is an LDH Test Performed?

LDH levels are measured by analyzing a blood sample taken from the arm in a biochemistry laboratory. Taking the sample is generally straightforward and takes only a few minutes.

Sometimes doctors may also measure LDH using samples of other body fluids, such as those from the spinal cord or lungs.

Elevated LDH

LDH is found in many cells, so high levels can indicate various conditions, including:

• hemolytic anemia
• infections such as COVID-19 or meningitis
• muscle injury
• stroke
• certain cancers
• heart attack
• liver disease
• muscular dystrophy
• pancreatitis

As shown above, LDH rises in many conditions and therefore cannot be used as a diagnostic test on its own. To diagnose a suspected condition, the LDH test result is interpreted together with other tests.

Cancers That Cause Elevated LDH

As mentioned above, LDH levels rise in response to tissue damage or during disease. In particular, in advanced stages of certain cancers, LDH levels may rise as the tumor burden in the body increases.

Cancer cells have a different metabolism from normal cells, providing enough biomaterial and energy for unlimited proliferation. Reprogrammed energy metabolism also contributes to metastasis (spread), resistance to cell death and other malignant characteristics.

Accelerated energy production from glucose is an important aspect of cancer metabolism, as reported by Warburg in 1956 (see Hallmarks of Cancer). Increased activity in energy production from glucose in cancer cells provides precursors for biomolecules involved in cellular structures and processes. The LDH enzyme, which is necessary for converting lactate into pyruvate, is therefore closely associated with various cancers.

Higher LDH levels have been associated with shorter survival in various cancers. A study of 2500 patients with non-small cell lung cancer found that normal baseline serum LDH levels were significantly associated with better survival. Similar reports have been made for colorectal, nasopharyngeal, breast, prostate and germ cell cancers, and melanoma.

Low LDH

Unusually low LDH levels are very rare. Most of the time, they are not considered harmful. However, unusually low LDH levels may indicate a genetic condition known as LDH deficiency. People can inherit this condition from a parent. It interferes with how cells use energy.

There are two types of LDH deficiency. LDH-A deficiency causes fatigue, muscle pain and exercise intolerance. It can also cause the breakdown of muscle tissue known as rhabdomyolysis. This releases the protein myoglobin, which can damage the kidneys.

A person with LDH-B deficiency may have no signs or symptoms.

LDH During Pregnancy

Elevated LDH levels during pregnancy may indicate preeclampsia. This is a serious complication that causes high blood pressure and increases the risk of the following additional problems for the parent and fetus:

• kidney damage
• liver damage
• placental problems
• pulmonary edema
• hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome
• epileptic seizures
• death of the parent or baby

The main signs of preeclampsia are high blood pressure, protein in the urine and elevated LDH. If a pregnant person has severe preeclampsia, LDH may rise to 400 U/L, which is 1.6 times the normal level.

Preeclampsia improves after a person gives birth. Until then, doctors monitor the condition, recommend rest and plan blood pressure monitoring and treatment.

If a pregnant person with preeclampsia is close to their due date, doctors may recommend an earlier delivery. In some cases, doctors may use various medicines to reduce the risk of complications.

Summary

The LDH test is a blood test used to detect elevated levels of the enzyme lactate dehydrogenase. High levels may indicate various conditions, including stroke, certain cancers, heart attack and infections.

High LDH levels during pregnancy may indicate preeclampsia, which causes high blood pressure. Low LDH levels are very rare and generally not harmful, but may indicate LDH deficiency.