Labeled CO2 production and oxidative vs nonoxidative disposal of labeled carbohydrate administered at rest

Carbon isotopes (*C) have been extensively used in man to describe oxidative vs nonoxidative disposal of an exogenous load of labeled carbohydrate (*C-CHO) at rest in various experimental situations. It is hypothesized that V*CO2 reflects *C-CHO oxidation. However, when glycogen is synthesized through the indirect pathway (which is responsible for ∼50% of glycogen storage), *C could be lost, diluted, and exchanged in the pyruvate-lactate pool, in the pool of tricarboxylic acid cycle intermediates, as well as at the entrance of the tricarboxylic acid cycle, and along the pathway of gluconeogenesis. This could result in a lower *C/C in the glycogen stored than in the CHO administered, in an increased production of *CO2, and, respectively, in an overestimation and an underestimation of the oxidative and nonoxidative disposal of the CHO load. Results from the present experiment offer a support to this hypothesis. Over a 10-hour period after ingestion of a 13C-pasta meal (313 ± 10 g dry mass or 258 ± 8 g of glucose) in 12 healthy subjects (6 men and 6 women), exogenous CHO oxidation computed from V13CO2 (recovery factor, 0.54) significantly exceeded total CHO oxidation computed by indirect respiratory calorimetry corrected for urea excretion: 154.2 ± 2.6 vs 133.5 ± 3.2 g. In an additional study conducted in rats, 13C/12C in glycogen stores was significantly ∼50% lower than in the 13C-CHO ingested, over a wide range of enrichment. These results suggest that because of dilution, loss, and exchange of *C in the indirect pathway of glycogen synthesis, the oxidative vs nonoxidative disposal of exogenous *C-CHO cannot be accurately tracked from V*CO2.