Urinary Mannitol Research Articles

Rapid and simultaneous determination of lactulose and mannitol in urine, by HPLC with pulsed amperometric detection, for use in studies of intestinal permeability

The lactulose/mannitol dual sugar absorption test is a non-invasive test of intestinal permeability. Its widespread use has been limited by the difficulties of analysis for carbohydrates in urine at low concentrations. We describe a "high-pressure" liquid-chromatographic method for determining lactulose and mannitol in urine, in which anion-exchange chromatography and pulsed amperometric detection are used. Sample preparation is simple and fast, and lactulose and mannitol and the internal standards arabinose and cellobiose are well resolved within 15 min. Analytical response of the method is linear with concentrations to 3 g/L, and one can detect as little as 0.3 mg of lactulose per liter of urine. Analytical recovery was between 90% and 107% for all sugars analyzed, and there was good agreement with results by a gas-chromatographic method (r = 0.993 lactulose, 0.984 mannitol). The method may potentially be applied to the study of other carbohydrates present in biological fluids at low concentrations.

Automated enzymatic assays for the determination of intestinal permeability probes in urine. 2. Mannitol

A need for a simple method for the determination of mannitol in urine has arisen because of the use of this monosaccharide in intestinal permeability tests. A rapid spectrophotometric assay for mannitol is presented based on the use of the bacterial enzyme mannitol dehydrogenase. The technique has been automated for use on the Cobas-Bio (Roche) centrifigal analyser. The assay has been shown to be highly specific for mannitol and was not affected by high concentrations of glucose, lactose or lactulose in samples. Within assay coefficient of variation was in the range 0.3 to 1.1% and 0.6 to 2.4% between assays. The technique represents a significant improvement in terms of time, simplicity and precision on existing methods.

Radionucleide tests for the assessment of intestinal permeability

14C labelled-D-mannitol and aquo (ethylene-diaminetriacetoacetic acid) 51chromium (III) (51Cr EDTA) have been evaluated as markers of intestinal permeability in twenty-four healthy control subjects, sixteen patients with recently diagnosed coeliac disease and twenty subjects with coeliac disease in remission on a gluten-free diet. The percentage excretion of 14C mannitol in urine collected for 6 h was significantly less in patients with coeliac disease (mean 6.7%) than controls (mean 13.5%). Conversely the excretion of 51Cr EDTA was significantly greater in patients with coeliac disease (mean 1.23%) compared with controls (mean 0.28%). The mean ratio of the percentage excretion of 51Cr to the percentage excretion of 14C was 0.29 in patients with untreated coeliac disease compared with 0.023 for healthy control subjects (P less than 0.001). Patients with untreated coeliac disease were clearly separated from control subjects by use of the 51Cr EDTA: 14C mannitol ratio but not by the excretion of independent markers.

Cellobiose/mannitol test: physiological properties of probe molecules and influence of extraneous factors

The influence of gastric emptying, intestinal transit, renal and hepatic function, and variations in the timing of urine collections, on the cellobiose/mannitol test of intestinal permeability has been studied. None of these extraneous factors influences the cellobiose/mannitol recovery ratio, and there is only a modest effect of renal function on urinary mannitol recovery. Cellobiose is almost totally recovered in the urine within 10 h of intravenous injection, whilst mannitol is less completely recovered, perhaps due to hepatic metabolism. The simultaneous administration of two probe molecules in the cellobiose/mannitol test, and the use of a ratio to express results, thus achieves the desired object of minimising the effect of extraneous factors on the test result. The cellobiose/mannitol test is therefore not subject to the limitations of previous tests of intestinal permeability using orally administered probe molecules, and is widely applicable as a screening test for coeliac disease.

Evaluation of mannitol for use as a probe marker of gastrointestinal permeability in man.

The absorption, metabolism, space distribution, renal excretion and natural occurrence of mannitol was studied in healthy human volunteers to determine its suitability for use as a probe marker of gastrointestinal permeability. Urinary recovery following oral loading was 8.0-39.6% of the ingested amount. Net absorption during intubation experiments in which a 30 cm segment of small intestine was perfused was 3.6% of perfusate mannitol. The slow rate of removal from the jejunum suggests that mannitol has a very low affinity for facilitated transport systems. Urinary recovery of intravenously injected mannitol approached 100% and renal clearance averaged 131 ml/min. The space distribution, progression of renal excretion and falling plasma concentration simulated that of lactulose rather than 3-0-methyl-D-glucose suggesting a mainly extracellular distribution. This was supported by measurement of erythrocyte penetration. Stool cultures degraded mannitol to products which included acid and carbon dioxide, when incubated aerobically and anaerobically. Excretion of mannitol, which was found to be naturally present in urine, was reduced but not abolished by fasting. Since mannitol occurs naturally in human urine we conclude that measurement of urinary mannitol following oral administration to assess intestinal permeability may be subject to error.

The Determination of Serum and Urine Mannitol

The Determination of Serum and Urine Mannitol