Gastroenterology. 2022 Nov;163(5):1294-1305.e3.doi: 10.1053/j.gastro.2022.07.052. Epub 2022 Aug 6.

Marie Truyens ¹, Triana Lobatón ², Marc Ferrante ³, Peter Bossuyt ⁴, Séverine Vermeire ³, Lieven Pouillon ⁴, Pieter Dewint ⁵, Anneline Cremer ⁶, Harald Peeters ⁷, Guy Lambrecht ⁸, Edouard Louis ⁹, Jean-François Rahier ¹⁰, Olivier Dewit ¹¹, Vinciane Muls ¹², Tom Holvoet ¹³, Liv Vandermeulen ¹⁴, Anneleen Peeters ¹⁵, Gerard Bryan Gonzales ¹⁶, Simon Bos ¹⁷, Debby Laukens ¹⁸, Martine De Vos ¹⁹

Author information

¹Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium; Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium.

²Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium.

³Department of Chronic Diseases & Metabolism (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), Katholieke Universiteit (KU) Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.

⁴Imelda Gastrointestinal (GI) Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium.

⁵Department of Gastroenterology, Algemeen Ziekenhuis (AZ) Maria Middelares, Ghent, Belgium; Department of Gastroenterology, University Hospital Antwerp, Antwerp, Belgium.

⁶Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium.

⁷Department of Gastroenterology, Algemeen Ziekenhuis (AZ) St-Lucas, Ghent, Belgium.

⁸Department of Gastroenterology, Algemeen Ziekenhuis (AZ) Damiaan, Ostend, Belgium.

⁹Department of Gastroenterology, Centre Hospitalier Universitaire Liège (CHU) University Hospital, Liège, Belgium.

¹⁰Department of Gastroenterology, Centre Hospitalier Universitaire (CHU) Université catholique de Louvain (UCL) Namur, Yvoir, Belgium.

¹¹Université catholique (UC) Louvain, Cliniques Universitaires Saint Luc, Brussels, Belgium.

¹²Department of Gastroenterology and Endoscopy, Saint-Pierre University Hospital Center, Université Libre de Bruxelles (ULB), Brussels, Belgium.

¹³Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium; Department of Gastroenterology, Algemeen Ziekenhuis (AZ) Nikolaas General Hospital, Sint-Niklaas, Belgium.

¹⁴Department of Gastroenterology-Hepatology, University Hospital Brussels/Free University of Brussels (VUB), Brussels, Belgium.

¹⁵Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium.

¹⁶Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Nutrition, Metabolism and Genomics Group, Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands.

¹⁷Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium.

¹⁸Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium. Electronic address: debby.laukens@ugent.be.

¹⁹Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.

Abstract

Background & aims: Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD), and only limited treatment options are available. Based on the hypothetical link between low serum tryptophan concentrations and fatigue, we determined the effect of 5-hydroxytryptophan supplementation on fatigue in patients with inactive IBD.

Methods: A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but experiencing fatigue, defined by a fatigue visual analog scale (fVAS) score of ≥5. Patients were treated in a crossover manner with 100 mg oral 5-hydroxytryptophan or placebo twice daily for 2 consecutive periods of 8 weeks. The primary end point was the proportion of patients reaching a ≥20% reduction in fVAS after 8 weeks of intervention. Secondary outcomes included changes in serum tryptophan metabolites, Functional Assessment of Chronic Illness Therapy Fatigue scale, and scores for depression, anxiety, and stress. The effect of the intervention on the outcomes was evaluated by linear mixed modeling.

Results: During 5-hydroxytryptophan treatment, a significant increase in serum 5-hydroxytryptophan (estimated mean difference, 52.66 ng/mL; 95% confidence interval [CI], 39.34-65.98 ng/mL; P < .001) and serotonin (3.0 ng/mL; 95 CI, 1.97-4.03 ng/mL; P < .001) levels was observed compared with placebo. The proportion of patients reaching ≥20% reduction in fVAS was similar in placebo- (37.6%) and 5-hydroxytryptophan (35.6%)-treated patients (P = .830). The fVAS reduction (-0.18; 95% CI, -0.81 to 0.46; P = .581) and Functional Assessment of Chronic Illness Therapy Fatigue scale increase (0.68; 95% CI, -2.37 to 3.73; P = .660) were both comparable between 5-hydroxytryptophan and placebo treatment as well as changes in depression, anxiety, and stress scores.

Conclusions: Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo. (Trial Registration: Belgian Federal Agency for Medication and Health Products, EudraCT number: 2017-005059-10 and ClinicalTrials.gov: NCT03574948, https://clinicaltrials.gov/ct2/show/NCT03574948.).