BACKGROUND Dicarboxylic acids are water-soluble, contrary to monocarboxylic acids, and have a metabolic pathway intermediate between those of lipids and carbohydrates. Our goal was to investigate the plasma turnover and oxidation rate of dodecanedioic acid (C12) in eight healthy male volunteers. METHODS A simultaneous infusion of both cold (0.24 mmol/min corresponding to 0.396 kcal/min) and radiolabeled (1.62 microCi/min) C12 free acid was performed. Blood specimens were sampled over a period of 360 minutes, and 24-hour urine samples were collected to measure the levels of C12 by high-performance liquid chromatography and liquid scintillation. Indirect calorimetry was continuously performed, and expired 14CO2 was collected. Binding of C12 in human plasma was determined in separate experiments using equilibrium dialysis. RESULTS A linear one-compartment model was used to describe the kinetics of labeled C12. Its volume of distribution was 139.02 +/- 10.84 mL/kgbw (mean +/- SE), and its plasma elimination constant was 0.01 +/- 0.004 min-1. The 24-hour urinary excretion of C12 was 3.14 +/- 0.96 mmol, corresponding to about 7% of the administered dose. The amount of C12 oxidized, expressed as percent oxidation, was equal to 35.44 +/- 1.64%. The mean basal value of npRQ (0.80 +/- 0.006) significantly (p < .02) decreased during the infusion to 0.78 +/- 0.01, which is a value close to that theoretically calculated (0.77). The oxidation of free fatty acids was significantly increased at the end of the C12 infusion, whereas the glucose oxidation was reduced to about 50%. CONCLUSIONS The experimental data suggest that C12 might represent a fuel substrate immediately available for tissue energy requirements, because a relevant amount of C12 is promptly oxidized. Its prompt oxidation and its conversion to succinic acid support the use of dodecanedioic acid in parenteral nutrition, especially in insulin-resistance conditions in which glucose uptake and oxidation is impaired.