The stable isotope ketoisocaproic acid breath test as a measure of hepatic decarboxylation capacity: a quantitative analysis in normal subjects after oral and intravenous administration

Background and aims: There is no generally accepted kinetic evaluation method for the stable isotope [(13)C] ketoisocaproic acid (KIC) breath test. Differences found in the results between women and men are contradictory. Methods: Oral and intravenous breath tests using 1 mg/kg stable isotope-labelled KIC were performed in healthy male and female volunteers. A power exponential function was fitted to the mass spectrometric data of breath (13)CO(2) enrichment, allowing mathematical analysis of time-to-peak-excretion, half-excretion time, percent label recovery and parameters describing the shape of the curve. Body composition was determined using bioelectrical impedance analysis. Results: After oral administration, total label recovery after 3 h was about 22% and was not different between men (n = 7) and women (n = 8). The time to maximal label excretion was 0.67 +/- 0.12 h in men and 0.9 +/- 0.32 h in women (P = 0.028) and the excretion curve showed an initially slower rise in women compared with men. Adjusting for lean body mass or body water abrogated the sex differences. Total label recovery after intravenous administration was about 9%, suggesting that the substrate was rapidly catabolized in the muscle compartment after intravenous administration. Conclusions: The modified power exponential function described allows standardized estimates of the KIC breath test results. When corrected for body composition, there are no differences in breath test results between men and women. The comparison between oral and intravenous results provides robust evidence that the KIC breath test measures predominantly hepatic and not muscle decarboxylation and is thus a highly specific liver function test.