Standardising the lactulose mannitol test of gut permeability to minimise error and promote comparability

PLoS One. 2014 Jun 5;9(6):e99256. doi: 10.1371/journal.pone.0099256. eCollection 2014.

Abstract

Background: Lactulose mannitol ratio tests are clinically useful for assessing disorders characterised by changes in gut permeability and for assessing mixing in the intestinal lumen. Variations between currently used test protocols preclude meaningful comparisons between studies. We determined the optimal sampling period and related this to intestinal residence.

Methods: Half-hourly lactulose and mannitol urinary excretions were determined over 6 hours in 40 healthy female volunteers after administration of either 600 mg aspirin or placebo, in randomised order at weekly intervals. Gastric and small intestinal transit times were assessed by the SmartPill in 6 subjects from the same population. Half-hourly percentage recoveries of lactulose and mannitol were grouped on a basis of compartment transit time. The rate of increase or decrease of each sugar within each group was explored by simple linear regression to assess the optimal period of sampling.

Key results: The between subject standard errors for each half-hourly lactulose and mannitol excretion were lowest, the correlation of the quantity of each sugar excreted with time was optimal and the difference between the two sugars in this temporal relationship maximal during the period from 2½-4 h after ingestion. Half-hourly lactulose excretions were generally increased after dosage with aspirin whilst those of mannitol were unchanged as was the temporal pattern and period of lowest between subject standard error for both sugars.

Conclusion: The results indicate that between subject variation in the percentage excretion of the two sugars would be minimised and the differences in the temporal patterns of excretion would be maximised if the period of collection of urine used in clinical tests of small intestinal permeability were restricted to 2½-4 h post dosage. This period corresponds to a period when the column of digesta column containing the probes is passing from the small to the large intestine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Aspirin / pharmacology
  • Chromatography, High Pressure Liquid / standards
  • Female
  • Gastrointestinal Transit / drug effects
  • Healthy Volunteers
  • Humans
  • Intestine, Small / drug effects
  • Intestine, Small / metabolism*
  • Lactulose / standards
  • Lactulose / urine*
  • Mannitol / standards
  • Mannitol / urine*
  • Permeability
  • Placebo Effect

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Mannitol
  • Lactulose
  • Aspirin

Grants and funding

This work was funded by the Ministry of Business Innovation and Employment (formerly Science and Innovation), New Zealand, contract number C06X0807, awarded to The New Zealand Institute for Plant and Food Research Limited. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.