Lactate dehydrogenase (LDH) is an enzyme found in almost every cell within the human body. This protein plays a fundamental role in cellular respiration, catalyzing the reversible conversion of lactate and pyruvate, two molecules central to energy production. Although LDH is abundant inside cells, it does not typically circulate in the bloodstream in high amounts. A significant increase in LDH levels in the blood is a non-specific sign that tissues throughout the body have experienced damage or destruction. When cells are injured, their internal contents, including LDH, leak out into the circulation, making it a general marker for cellular injury.
Understanding Lactate Dehydrogenase (LDH) Levels
The concentration of total LDH in the blood serum is reported in units per liter (U/L). The “normal range” is not universal and varies depending on the specific testing method used by the laboratory and the patient’s age. For most adults, the normal range for total LDH activity typically falls between 140 and 280 U/L. Infants and young children naturally have much higher baseline levels due to rapid growth and cell turnover, so their reference ranges are substantially elevated compared to adults.
To understand the source of an elevation, scientists look at five distinct forms of the enzyme, known as isoenzymes (LDH-1 through LDH-5). Each isoenzyme is structurally unique and is concentrated in specific organs or tissues. For example, LDH-1 is primarily found in the heart and red blood cells, while LDH-5 is highest in the liver and skeletal muscle. Although total serum LDH measurement is the most common test, analyzing the pattern of elevated isoenzymes can sometimes help indicate which body tissue is suffering damage.
Why LDH is Measured in Oncology
Oncologists measure LDH because cancer cells exhibit a unique metabolic preference that often leads to high serum levels of the enzyme. Unlike normal cells that primarily use oxygen to generate energy, many cancer cells rely heavily on aerobic glycolysis, often called the Warburg effect. This process involves rapidly consuming glucose and converting it into lactate, even when oxygen is available. The LDH enzyme catalyzes this final step, converting pyruvate into lactate, which sustains the cancer cell’s high rate of growth and proliferation.
High LDH levels reflect the aggressive metabolic demands of a tumor. When a tumor grows quickly, its central parts may outgrow the blood supply, leading to areas of low oxygen, or hypoxia. This low-oxygen environment further stimulates the cancer cells to rely on the LDH-driven glycolytic pathway. Additionally, a large tumor burden causes significant cellular stress and cell death, releasing the enzyme into the bloodstream. The correlation between high LDH and increased tumor burden makes it a useful marker in several malignancies.
Interpreting Elevated LDH Levels in Cancer Patients
For a cancer patient, an elevated LDH level is a piece of clinical data used by the care team to assess disease activity and help guide treatment decisions. In many cancers, a high LDH level is considered a prognostic indicator, suggesting a potentially less favorable outcome. Research across various cancer types, including melanoma, lymphoma, and small cell lung cancer, shows that patients with elevated LDH levels at diagnosis often have shorter overall survival and progression-free survival. This observation signifies a more aggressive tumor that is growing and spreading rapidly.
LDH levels are also incorporated into the staging systems for certain cancers, most notably metastatic melanoma and some types of lymphoma. An elevated LDH is formally used as a criterion to classify the disease into a more advanced or higher-risk category. This information is then used to determine the intensity and type of initial therapy.
Furthermore, trending LDH measurements over time is a common method for monitoring treatment effectiveness. A significant drop in the LDH level suggests a favorable response and a reduction in tumor burden. Conversely, LDH levels that remain high or begin to rise signal that the cancer is not responding well to therapy, is progressing, or has recurred.
Non-Cancer Factors That Influence LDH Results
A high LDH result in a cancer patient is not always a sign of cancer progression, as numerous non-malignant conditions can also cause a temporary or sustained elevation. Because the enzyme is present in so many different tissues, any event that causes widespread cell damage can lead to a rise in serum LDH.
One of the most common non-cancer causes is the benign condition of hemolysis, which is the rupture of red blood cells. Since red blood cells contain a high concentration of LDH, their breakdown can release a large amount of the enzyme into the blood. This can sometimes happen during the blood drawing process itself if the sample is handled roughly.
Strenuous physical activity, such as a marathon or intense weightlifting, can cause temporary muscle damage, leading to a spike in LDH levels that should resolve within a few days. Non-malignant diseases affecting the liver, such as hepatitis or cirrhosis, or conditions like severe anemia, can also elevate LDH significantly.
Other causes include muscle injuries, kidney disease, or certain severe infections. All of these conditions cause tissue damage that results in the enzyme leaking into the circulation. Therefore, a physician will always interpret an LDH result in the context of a patient’s overall symptoms, medical history, and other laboratory values to determine the true cause of the elevation.