TY - JOUR
T1 - Effect of 5-Hydroxytryptophan on Fatigue in Quiescent Inflammatory Bowel Disease
T2 - A Randomized Controlled Trial
AU - Truyens, Marie
AU - Lobatón, Triana
AU - Ferrante, Marc
AU - Bossuyt, Peter
AU - Vermeire, Séverine
AU - Pouillon, Lieven
AU - Dewint, Pieter
AU - Cremer, Anneline
AU - Peeters, Harald
AU - Lambrecht, Guy
AU - Louis, Edouard
AU - Rahier, Jean François
AU - Dewit, Olivier
AU - Muls, Vinciane
AU - Holvoet, Tom
AU - Vandermeulen, Liv
AU - Peeters, Anneleen
AU - Gonzales, Gerard Bryan
AU - Bos, Simon
AU - Laukens, Debby
AU - De Vos, Martine
PY - 2022/11
Y1 - 2022/11
N2 - 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.)
AB - 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.)
KW - Crohn's Disease
KW - Exhaustion
KW - Neurobehavior
KW - Ulcerative Colitis
U2 - 10.1053/j.gastro.2022.07.052
DO - 10.1053/j.gastro.2022.07.052
M3 - Article
C2 - 35940251
AN - SCOPUS:85140046137
SN - 0016-5085
VL - 163
SP - 1294-1305.e3
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -