Retention, Fixation, and Loss of the [13C] Label: A Review for the Understanding of Gastric Emptying Breath Tests

A [13C]-breath test is a promising method for measuring gastric emptying. The methodological relevance is based on a close correspondence between gastric emptying of [13C]-acetate/octanoate (input) and pulmonary excretion of [13CO2] (output). Despite the close input-output correspondence, the pulmonary output is quite remote from the gastric input: the pulmonary output is delayed compared to the gastric input, and the total recovery of [13CO2] in the breath is incomplete. This review focuses on the kinetics of [13C]-acetate/octanoate in the body and suggests that (1) the delayed pulmonary output results from temporal retention of [13CO2] in the well-perfused tissues (heart, brain, etc.), (2) the incomplete recovery results from incorporation of the label into metabolic products (ketone bodies, amino acids, etc.) or from fixation of [13CO2] in the low-perfused tissues (bone, skeletal muscle, etc.), and (3) knowledge on the retention is the key to appropriate interpretations of breath test results. Recognition of these kinetic aspects is essential for appropriate interpretations of these breath test results.