Original Contribution | Published:

Functional GI Disorders

Acute Tryptophan Depletion Alters Gastrointestinal and Anxiety Symptoms in Irritable Bowel Syndrome

The American Journal of Gastroenterology volume 101, pages 25822587 (2006) | Download Citation




To assess the effect of acute changes in serotonin (5-HT) synthesis using the acute tryptophan depletion (ATD) paradigm on gastrointestinal (GI) and mood symptoms in irritable bowel syndrome (IBS).


In a randomized double-blind crossover study, 29 subjects (18 patients with ROME II defined IBS and 11 age-matched controls) were studied under ATD and acute tryptophan increase (ATI) conditions. GI symptoms, mood and anxiety ratings, as well as plasma tryptophan concentrations were measured.


Total (and free) plasma tryptophan concentrations decreased on the ATD day in patients (73% [82%]) and controls (73% [80%]), and increased on the ATI day in patients (59% [143%]) and controls (61% [381%]). Compared with the ATD day, IBS patients reported more GI symptoms on the ATI day at +210 (p < 0.001) and at +270 (p < 0.05) min post drink. IBS patients also reported less anxiety on the ATI day compared with the ATD day at +270 min (p < 0.001). ATD and ATI did not affect these ratings in control participants. IBS patients had a lower mood compared with controls (p < 0.05), but this did not differ between the ATI and ATD days in either group.


IBS patients' GI and anxiety responses to changes in tryptophan load differ from controls. This suggests a difference in serotonergic functioning between these two groups and provides evidence to support the hypothesis that 5-HT dysfunction is involved in IBS.

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This study was funded by Avon and Wiltshire Partnership NHS Trust R and D. The sponsors had no role in study design, data collection, data analysis, data interpretation, or writing of the report. M Franklin performed the tryptophan assays. Thank you to C Rogers for statistical advice and A Rich for her help in completion of the study.

Author information


  1. Clinical Science at South Bristol, University of Bristol, Bristol, United Kingdom

    • Jonathan Shufflebotham
    •  & Chris Probert
  2. School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, Australia

    • Sean Hood
  3. Bristol Royal Infirmary, Bristol, United Kingdom

    • Julie Hendry
  4. Psychopharmacology Unit, University of Bristol, Bristol, United Kingdom

    • Dana A Hince
    • , Kelly Morris
    • , David Nutt
    •  & John Potokar


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Correspondence to John Potokar.

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