Advantages of deuterium‐labelled mixed triacylglycerol in studies of intraluminal fat digestion

Abstract

The 13 C-mixed triacylglcerol (MTG,1, C]octanoyl glycerol) breath test is a noninvasive measure of intraluminal fat digestion. Recovery of 13 C in breath CO 2 is incomplete (<50%) owing to sequestration of 13 C into organic molecules via the tricarboxylic acid (TCA) cycle. In addition lack of knowledge of CO 2 production rate (VCO 2 ) during the test leads to errors in the calculated percentage dose recovered (PDR). 2H sequestration into organic molecules is low ($4%) and is not influenced by factors that affect VCO 2 such as food intake or physical activity. After oxidation of 2 H-labelled macromolecules, the label appears in body water, which can be sampled O was calculated from the plateau enrichment, which was reached by 6 h in both saliva and urine. Recovery of 2 H calculated using measured TBW was compared with that using an estimated value of TBW. Mean recovery of 2 H in saliva was 99.3% and in urine was 96.4%. Errors introduced by estimating TBW were <5%. 1 -10 13 C-breath tests are particularly attractive for use in children because they are non-invasive, and pose no radiation hazard. A problem with many 13 C-breath tests is that recovery of 13 C in breath CO 2 is less than 50%, even in healthy subjects, owing to the sequestration of label into organic compounds via acetylCoA and the tricarboxylic acid (TCA) cycle. 3,11 -16 Quantitation of tracer recovery requires knowledge of carbon dioxide production rate (VCO 2 ) because labelled CO 2 originating from oxidation of the tracer is diluted by endogenously produced CO 2 from metabolism. A resting value of VCO 2 based on basal metabolic rate is often assumed, 11,14 but, even if resting VCO 2 is measured, 17,18 this may not be appropriate because subjects, especially children, rarely remain at rest for the duration of the test, which typically lasts for about 6 h. VCO 2 is increased during physical activity and after food intake; therefore, use of resting VCO 2 will underestimate the true CO 2 production rate resulting in an underestimation of the quantity of tracer recovered. 16,19 Another confounding factor for 13 C-breath tests is the natural abundance variation in the usual diet, 20,21 resulting in the need for subjects to eat a diet containing ingredients of low 13 C abundance, possibly for several days before the test and during the test. The mixed triacylglycerol (MTG) breath test was developed as an indirect measure of intraluminal fat digestion in adults with impaired pancreatic function.9,22 The 13 C [MTG] breath test has been used to assess the need for pancreatic enzyme replacement therapy in children with cystic fibrosis and to assess the ideal dose, 3,8 but it has not been widely adopted because it lacks specificity, 23 and requires frequent breath sampling over a period of 5-6 h. [1-13 C]octanoate, which is absorbed and reaches the liver via the portal vein. Less than 5% ingested 13 C is excreted in

Acetate Correction for Postabsorption Metabolism Does Not Improve the [13C]Mixed Triacylglycerol Breath Test

“…The wide variance in cPDR can be accounted for by differences in intermediary metabolism, but improvements in specificity are due to use of nonresting V CO 2 to calculate PDR. Use of 2 H‐labeled compounds, in which the label is distributed in body water and recovery is not influenced by physical activity, could prove useful in studies of macronutrient oxidation (47).…”

The carbon dioxide production rate assumption biases gastric emptying parameters in healthy adults

“…The Craig correction was employed to account for the occurrence of [ 12 C 16 O 17 O] at m/z 45. [29] Enrichment values were corrected for the linear reduction in enrichment with increased CO 2 concentrations (less than 0.6% VPDB per 1% CO 2 ) and expressed as atom fraction. [30,31] The standard deviation (SD) of 10 identical measurements was <0.1% VPDB.…”