Lactate Metabolism in Patients with Metastatic Colorectal Cancer¹

The possible effect of tumor glycolysis on whole-body lactate metabolism has not been previously measured in humans. Using an isotope tracer technique, we found increased rates of lactate production in 20 patients with metastatic colorectal cancer compared to 13 control subjects of comparable age and sex (15.6 ± 1.3 µmol/kg/min versus 10.4 ± 0.6 µmol/kg/min; p < 0.01). The cancer patients were characterized by a moderately increased rate of lactate oxidation (p < 0.05), a 2-fold increase in nonoxidative lactate disposal (p < 0.001), and an increased percentage of glucose derived from lactate (p < 0.01). There was a direct correlation between venous plasma lactate concentrations and lactate production rates. There was also a direct correlation between lactate production rates and the percentage of respiratory CO₂ derived from plasma lactate, the rates of lactate oxidation, the rates of nonoxidative lactate disposal, and the percentage of plasma glucose derived from plasma lactate. These observed results correlated poorly with tumor burden, and no correlation was observed between increased lactate production and the following clinical or biochemical parameters: ambulatory status, histological differentiation, weight change, carcinoembryonic antigen titer, hemoglobin, WBC, presence or absence of hepatic metastases, O₂ consumption, CO₂ production, respiratory quotient, plasma free fatty acids, glucose, and immunoreactive insulin concentrations. This study emphasizes that metabolic heterogeneity with respect to lactate metabolism exists within an apparently homogeneous group of patients with colorectal cancer.