C-13-carbohydrate breath tests: Impact of physical activity on the rate-limiting step in lactose utilization

Background: (CO2)-C-13 breath tests can be used to monitor carbohydrate dig estion in the small intestine. However, after ingestion of C-13-substrates, (CO2)-C-13 excretion in breath originates from two sources: a digestive/ox idative fraction, derived from the small intestine, and a fermentation frac tion, derived from undigested substrate spill-over in the colon. In this st udy, the determinants of the digestive/oxidative fraction were analysed in order to improve the sensitivity/specificity of the C-13-carbohydrate breat h tests. Methods: C-13-carbohydrate breath tests were performed in healthy adults using C-13-lactose, pre-digested C-13-lactose, C-13-glucose, and C-1 3-galactose as substrates. The effect of exercise (bicycling, 50 W), increa sing the metabolism of digested/absorbed substrate, on the outcome of the t est was analysed. Results: In rest, no difference was observed in the 4-h c umulative percentage dose recovered in breath (4-h cPDR) after administrati on of glucose, pre-digested lactose, and lactose, which were 20.3 +/- 4.5%, 19.2 +/- 5.5%, and 19.9 +/- 4.9%, respectively. The (CO2)-C-13 excretion r ate after C-13-galactose consumption was significantly slower than after C- 13-glucose consumption. Exercise increased 4-h cPDR of C-13-glucose signifi cantly: 76.0 +/- 1.0% vs. 22.7 +/- 2.3%. This effect was also observed usin g C-13-lactose as substrate: 66.1 +/- 6.2% vs. 19.6 +/- 3.9%. One Subject h ad non-symptomatic lactose maldigestion indicated by a positive H-2 breath test. The (CO2)-C-13 breath test of this subject in rest was indistinguisha ble from that of the others (4-h cPDR 16.6 vs. 19.6 +/- 3.9%), whereas the test was clearly indicative during exercise (4-h cPDR 20.5 vs. 66.1 +/- 6.2 %). Conclusion: In healthy volunteers in rest, glucose oxidation is the rat e limiting step in lactose conversion into (CO2)-C-13. Increase of metaboli sm (for instance, by exercise) can shift this step to intestinal hydrolysis of lactose, making the C-13-lactose breath test more sensitive.