Low Lactate Dehydrogenase (LDH): Causes and Clinical Significance
Low LDH levels are clinically insignificant and rarely investigated because LDH elevation—not reduction—serves as the marker of tissue damage, hemolysis, and malignancy. The medical literature and clinical guidelines focus exclusively on elevated LDH as a diagnostic and prognostic tool, with no established disease states or clinical syndromes associated with low LDH values 1, 2.
Why Low LDH Is Not Clinically Relevant
LDH functions as a marker of cellular turnover and tissue damage—conditions that cause LDH to rise include hemolysis, myocardial infarction, liver disease, malignancy, and muscle injury 1, 2.
The diagnostic utility of LDH depends entirely on elevation above normal ranges, with clinical guidelines establishing thresholds for exudative pleural effusions (>2/3 upper limit of normal), tumor lysis syndrome risk (markedly elevated), and cancer prognosis (>1.5–2.5× upper limit of normal) 3.
No guidelines or research studies define pathological low LDH levels because reduced LDH activity does not correlate with any recognized disease process 1, 4, 2.
Technical Considerations for Apparent Low LDH
Pre-analytical Factors
Laboratory error or assay variability can produce falsely low results—the coefficient of variation for LDH measurement ranges from 3–8% depending on centrifugation speed and sample handling 5.
Repeat measurement is warranted if the initial LDH value appears unexpectedly low in a clinical context where elevation would be expected (e.g., suspected hemolysis, malignancy, or tissue injury) 3, 5.
Sample integrity must be verified—while hemolysis falsely elevates LDH by releasing intracellular enzyme, improper sample processing can affect measurement accuracy 1, 5.
Biological Variability
Normal LDH ranges vary by laboratory (typical reference range 313–618 IU/L), and values at the lower end of normal simply reflect individual variation in baseline cellular metabolism 6, 2.
LDH isoenzymes have tissue-specific distribution—total LDH represents the sum of five isoforms (LDH-1 through LDH-5), and low total LDH may reflect normal variation in isoenzyme expression rather than pathology 2, 7.
When to Investigate Further
Do not pursue extensive workup for isolated low LDH in an asymptomatic patient—focus clinical attention on the presenting symptoms and other laboratory abnormalities rather than the LDH value itself 1, 2.
Specific Clinical Scenarios
If low LDH occurs alongside anemia, evaluate for iron deficiency, chronic disease, or nutritional deficiencies using complete blood count, iron studies, and reticulocyte count—not LDH 8.
If low LDH is found during cancer surveillance, ensure the patient is not on treatment that suppresses cellular turnover, but recognize that declining LDH during cancer therapy indicates treatment response, not a pathological low state 1, 4.
If low LDH appears in the context of suspected hemolysis, the absence of LDH elevation effectively rules out significant hemolysis—proceed with alternative diagnoses 8.
Common Pitfalls to Avoid
Do not order LDH isoenzyme analysis for low total LDH—isoenzyme differentiation is useful only when total LDH is elevated and tissue-specific injury (e.g., myocardial infarction with LDH-1 elevation) needs confirmation 7.
Do not interpret low LDH as a marker of reduced metabolic activity or "good health"—LDH measurement has no validated role in wellness assessment or metabolic screening 2, 9.
Avoid attributing symptoms to low LDH—fatigue, weakness, or other nonspecific complaints require systematic evaluation of thyroid function, complete blood count, metabolic panel, and vitamin levels, not LDH interpretation 1, 2.