Kd. Wutzke et al., EVALUATION OF ORO-COECAL TRANSIT-TIME - A COMPARISON OF THE LACTOSE-[C-13, N-15]UREIDE (CO2)-C-13-BREATH AND THE LACTULOSE H-2-BREATH TEST IN HUMANS, European journal of clinical nutrition, 51(1), 1997, pp. 11-19
Objective: The lactulose H-2-breath test is the most widely used non-i
nvasive approach for evaluation of orocoecal transit time (OCTT). In t
he present study, doubly-labelled lactose-[C-13, N-15]ureide (DLLU) wa
s synthesized to investigate the OCTT in comparison to the conventiona
l lactulose H-2-breath test. Additionally, the bacterial breakdown rat
e (BBR) and rate of elimination and the metabolic pathways of the clea
vage products of DLLU ((CO2)-C-13, [N-15]urea, and (NH3)-N-15) were in
vestigated. Design and subjects: In a first study, DLLU was administer
ed as a single oral-pulse-labelling (dosage: one gram) either without
and after pretreatment of five grams of unlabelled lactoseureide (LU)
on the day prior to the study to twelve healthy adult volunteers after
breakfast. Breath and urine were collected in one and two hour-interv
als, respectively, over a one-day period. C-13-enrichment in breath as
well as N-15-enrichment in urine fractions were measured by continuou
s flow-isotope ratio mass spectrometry (CF-IRMS). In a second study, l
actulose was administered to the same subjects (dosage: ten grams). Br
eath was collected in quarter, half and one hour-intervals over a ten
hour-period. Hydrogen concentration in breath was analysed using an el
ectrochemical detector. Results: The comparison of the lactose-[C-13]u
reide (CO2)-C-13-breath test and the lactulose H-2-breath test showed
that the mean increase of the C-13-enrichment in CO2 occurred 1.18 h l
ater than the mean increase of H-2 in breath. The resulting OCTTs deri
ved from the two methods were 3.02 +/- 1.4 and 1.84 +/- 0.5 h (P < 0.0
5) and the corresponding BBRs were 9.63 +/- 3.4 and 6.07 +/- 1.7 h (P
< 0.01), respectively. The N-15-enrichment of urinary urea and ammonia
without and after pretreatment with LU started between two and three
hours after DLLU-administration. The cumulative percentage urinary exc
retion of the N-15- and C-13-tracer was 29.9% and 13.6% respectively,
and was slightly increased after LU-pretreatment to 32.1% and 14.6% of
the dose administered. A total of 35.2% of the C-13 was found to be e
xhaled and remained approximately constant after LU-pretreatment (36.2
%). Conclusions: The use of the lactulose H-2-breath test for evaluati
on of the OCTT showed a statistically significant shortening of 1.18 h
in comparison to the lactose-[C-13]ureide (CO2)-C-13-breath test in h
ealthy adults. The most important limitations of the lactulose H-2-bre
ath test are its low specificity and sensitivity due to dose-dependent
accelerations of OCTT, interfering H-2-rise from malabsorbed dietary
fibre and H-2-non-producers. In contrast, our lactose-[C-13]ureide (CO
2)-C-13-breath test was confirmed to avoid these disadvantages and to
yield reliable results. This test is recommended especially if higher
sensitivity and specificity is required, if IRMS-technique is availabl
e and if lactulose H-2-tests lead to insufficient results.