What is the purpose and procedure of the D xylose (D-xylose) test in diagnosing malabsorption syndromes?

D-Xylose Test: Purpose and Procedure

The D-xylose test is a historically used but now largely obsolete test for detecting small bowel enteropathy that should not be routinely employed in clinical practice, as it has been superseded by endoscopic biopsy and serological testing for celiac disease. 1

Historical Purpose

The D-xylose test was designed to assess small bowel mucosal function by measuring absorption of this inert sugar. 1 The test operates on the principle that:

• D-xylose is absorbed primarily by passive diffusion through the intestinal mucosa rather than active transport 1
• Reduced absorption reflects breakdown of the intestinal barrier and increased intestinal permeability, as seen in small bowel enteropathy 1
• The test does not assess active absorptive processes or pancreatic function 1

Test Procedure

Standard Protocol

• Oral administration: 25 g of D-xylose is given orally to the patient 2, 3
• Blood sampling: Serum D-xylose levels are measured at 1 hour and/or 3 hours post-administration 4, 3
• Urine collection: Alternatively, 5-hour urinary excretion can be measured, though this is less reliable 2

Interpretation Thresholds

• 1-hour blood level <20 mg/dL indicates severe intestinal damage 4, 3
• 3-hour blood level <22.5 mg/dL improves sensitivity when combined with 1-hour testing 3
• Borderline results (20-25 mg/dL) require clinical correlation and often intestinal biopsy 4

Critical Limitations in Clinical Practice

Poor Performance Characteristics

• The test is sensitive but not specific for small bowel disease 1
• Analytical performance is poor in routine practice despite good correlation with histological abnormalities in research settings 1
• False negatives occur in 4-32.7% of cases depending on the degree of intestinal damage 4

Pre- and Post-Mucosal Confounders

• Renal function significantly affects results, as D-xylose is excreted unchanged in urine 3
• Gastric emptying, intestinal transit time, and bacterial overgrowth can all alter results 5
• Ascites, portal hypertension, and medications may interfere with absorption 5

Current Clinical Recommendations

The European Society of Gastroenterology explicitly discourages use of D-xylose testing (Grade C recommendation), as it has been superseded by superior diagnostic modalities. 1

Preferred Alternative Approaches

• For celiac disease: Antiendomysium antibody or tissue transglutaminase antibody testing as first-line 6
• For small bowel pathology: Upper endoscopy with distal duodenal biopsies provides definitive histological diagnosis 6
• For bacterial overgrowth: Hydrogen breath testing offers better specificity 6

When D-Xylose Might Still Be Considered

Despite guideline recommendations against routine use, the test may have limited utility in:

• Resource-limited settings where endoscopy and serological testing are unavailable 5
• Follow-up of celiac disease when combined with hydrogen breath testing (D-xylose breath test showed better correlation with clinical response than urinary testing) 2
• Pediatric populations with severe malabsorption when other tests are inconclusive 4

Common Pitfalls to Avoid

• Do not use D-xylose testing as a first-line diagnostic tool when serological testing and endoscopy are available 1
• Do not interpret results without considering renal function, as impaired kidney function will falsely lower serum levels 3
• Do not rely on urinary D-xylose alone, as it is less reliable than serum testing and affected by incomplete urine collection 2
• Do not assume normal results exclude disease, particularly in mild or patchy mucosal abnormalities 4
• An abnormal result is non-specific and non-diagnostic beyond confirming mucosal abnormality exists 1