Background and aims
Fatigue is highly prevalent among patients suffering from 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.
A multicenter randomized controlled trial was performed at 13 Belgian hospitals, including 166 patients with IBD in remission but suffering from fatigue defined by a fatigue Visual Analog Scale (fVAS) ≥5. Patients were treated in a crossover manner with 100 mg oral 5-hydroxytryptophan or placebo twice daily for two consecutive periods of eight weeks. The primary endpoint was the proportion of patients reaching a ≥20% reduction in fVAS after eight weeks of intervention. Secondary outcomes included changes in serum tryptophan metabolites, FACIT-F, and scores for depression, anxiety, and stress. The effect of the intervention on the outcomes was evaluated by linear mixed modeling.
During 5-hydroxytryptophan treatment a significant increase in serum 5-hydroxytryptophan (estimated mean difference 52.66 ng/ml [39.34; 65.98], P < 0.001) and serotonin (3.0 ng/ml [1.97; 4.03], P < 0.001) 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 = 0.830). Both the fVAS reduction (-0.18 [-0.81; 0.46], P = 0.581) and FACIT-F increase (0.68 [-2.37; 3.73], P = 0.660) were comparable between 5-hydroxytryptophan and placebo treatment, as well as changes in depression, anxiety, and stress scores.
Despite a significant increase in serum 5-hydroxytryptophan and serotonin levels, oral 5-hydroxytryptophan did not modulate IBD-related fatigue better than placebo.