Lactate dehydrogenase (LDH) is an enzyme found inside nearly every cell in the human body. It plays an integral part in cellular energy production, facilitating the reversible conversion between lactate and pyruvate in the metabolic pathway. When cells are damaged or die, they release their internal contents, including LDH, into the bloodstream. An elevated level of LDH in the blood is a general sign of tissue damage. In cancer, high LDH levels are a non-specific marker that often correlates with disease activity and aggressiveness.
The Role of LDH in Cellular Metabolism
Cancer cells often exhibit a unique metabolic shift that fuels their rapid growth, known as aerobic glycolysis. This process, sometimes called the Warburg effect, involves breaking down glucose into lactate, even when oxygen is available for normal cellular respiration. Lactate dehydrogenase A (LDH-A) is crucial for this altered metabolism, catalyzing the final step of converting pyruvate into lactate. This reaction simultaneously regenerates NAD+, which is necessary for glycolysis to continue producing energy quickly.
Relying on this fast, though less efficient, glycolytic pathway allows cancer cells to proliferate rapidly. The resulting lactate is secreted from the tumor cell, contributing to an acidic microenvironment that supports tumor invasion and growth. The high demand for this process leads to overexpression and overactivity of the LDH-A enzyme within malignant cells. Consequently, the death or high turnover of these active cancer cells releases a significantly larger amount of LDH into the circulation.
Clinical Significance as a Cancer Marker
The measurement of serum LDH is routinely used by oncologists to gather information about a patient’s cancer status and disease trajectory. Its primary application is as a prognostic indicator, helping to predict the likely outcome or course of the disease. Higher pre-treatment LDH levels are generally associated with a greater tumor burden and a more aggressive cancer, often correlating with poorer survival rates. For instance, in metastatic melanoma, an elevated LDH level is incorporated into the American Joint Committee on Cancer (AJCC) staging system, signifying a more advanced prognosis.
LDH levels are also valuable for monitoring how effectively cancer treatment is working. A sustained decrease in serum LDH following chemotherapy or immunotherapy may indicate a positive response, suggesting the treatment is successfully destroying cancer cells and reducing tumor bulk. Conversely, a rising LDH level during or after treatment signals that the disease is progressing, recurring, or becoming resistant to the current therapeutic approach. This trend provides an early warning sign, prompting physicians to adjust the patient’s treatment plan.
The test is particularly relevant in managing hematologic malignancies, such as non-Hodgkin’s lymphoma, where it is included as a factor in the International Prognostic Index (IPI) score. Certain solid tumors, including germ cell tumors, osteosarcoma, and some types of lung cancer, also utilize LDH as a disease marker. For these cancers, the LDH level helps in the initial staging process and in determining the intensity of the treatment regimen.
Interpreting LDH Results and Limitations
When interpreting a blood test, a patient’s LDH result is compared to a laboratory-specific reference range to determine if the level is within normal limits. An elevated result simply confirms that there is an increased rate of cellular damage or turnover somewhere in the body. LDH elevation is not specific to cancer and can be caused by various common non-malignant conditions.
High LDH levels can result from liver diseases like hepatitis, or from conditions that cause the premature breakdown of red blood cells, known as hemolytic anemia. Muscle trauma, severe infections, kidney disease, and even a recent heart attack can lead to a temporary or sustained elevation of the enzyme. This lack of specificity is the main limitation of the LDH test as a standalone diagnostic tool.
Because of these numerous potential causes, physicians never rely on the LDH test alone to diagnose cancer or determine its stage. Instead, the results must be carefully considered alongside other diagnostic information, such as imaging scans, biopsies, and other blood markers. When used with a patient’s full clinical picture, the LDH test provides meaningful, real-time insight into the biological activity of the disease.