Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease: A Randomized Controlled Trial.

Edouard Louis, Martine De Vos, Debby Laukens, Simon Bos, Gerard Bryan Gonzales, Anneleen Peeters, Liv Vandermeulen, Tom Holvoet, Vinciane Muls, Olivier Dewit, Jean-François Rahier, Marie Truyens, Guy Lambrecht, Harald Peeters, Anneline Cremer, Pieter Dewint, Lieven Pouillon, Séverine Vermeire, Peter Bossuyt, Marc Ferrante, Triana Lobatón

Journal: Gastroenterology 2022;163(5):1294-1305.e3

PMID: 35940251

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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.).

Address: Department 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.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium.; Department 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.; Imelda Gastrointestinal (GI) Clinical Research Center, Imelda General Hospital, Bonheiden, Belgium.; Department of Gastroenterology, Algemeen Ziekenhuis (AZ) Maria Middelares, Ghent, Belgium; Department of Gastroenterology, University Hospital Antwerp, Antwerp, Belgium.; Department of Gastroenterology, Erasme University Hospital, Brussels, Belgium.; Department of Gastroenterology, Algemeen Ziekenhuis (AZ) St-Lucas, Ghent, Belgium.; Department of Gastroenterology, Algemeen Ziekenhuis (AZ) Damiaan, Ostend, Belgium.; Department of Gastroenterology, Centre Hospitalier Universitaire Liège (CHU) University Hospital, Liège, Belgium.; Department of Gastroenterology, Centre Hospitalier Universitaire (CHU) Université catholique de Louvain (UCL) Namur, Yvoir, Belgium.; Université catholique (UC) Louvain, Cliniques Universitaires Saint Luc, Brussels, Belgium.; Department of Gastroenterology and Endoscopy, Saint-Pierre University Hospital Center, Université Libre de Bruxelles (ULB), Brussels, Belgium.; Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium; Department of Gastroenterology, Algemeen Ziekenhuis (AZ) Nikolaas General Hospital, Sint-Niklaas, Belgium.; Department of Gastroenterology-Hepatology, University Hospital Brussels/Free University of Brussels (VUB), Brussels, Belgium.; Department of Gastroenterology, University Hospital Ghent, Ghent, Belgium.; Department 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.; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium; Vlaams Instituut voor Biotechnologie (VIB) Center for Inflammation Research (IRC), Ghent University, Ghent, Belgium.; Department 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: [email protected].; Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.

DOI: 10.1053/j.gastro.2022.07.052

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MeSH Terms: Humans, 5-Hydroxytryptophan, Serotonin, Tryptophan, Inflammatory Bowel Diseases, Fatigue, Chronic Disease