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.
Gastroenterology. 2022 Nov;163(5):1294-1305.e3. doi: 10.1053/j.gastro.2022.07.052. Epub 2022 Aug 6.
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.
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.
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.
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.).
炎症性肠病（IBD）患者普遍存在疲劳症状，且目前仅有有限的治疗选择。基于血清色氨酸浓度降低与疲劳之间的假设关联，我们评估了补充 5-羟色氨酸对缓解期 IBD 患者疲劳的影响。
在比利时的 13 家医院进行了一项多中心、随机对照试验，共纳入 166 例 IBD 缓解期但存在疲劳症状（疲劳视觉模拟量表 [fVAS] 评分≥5 分）的患者。患者以交叉方式接受每日两次、每次 100 mg 口服 5-羟色氨酸或安慰剂治疗，连续 2 个 8 周疗程。主要终点为干预 8 周后 fVAS 评分降低≥20%的患者比例。次要结局包括血清色氨酸代谢物、慢性疾病治疗疲劳功能评估量表、抑郁、焦虑和压力评分的变化。采用线性混合模型评估干预对结局的影响。
与安慰剂相比，5-羟色氨酸治疗期间血清 5-羟色氨酸（估计平均差值，52.66ng/ml；95%置信区间 [CI]，39.34-65.98ng/ml；P<.001）和血清素（3.0ng/ml；95%CI，1.97-4.03ng/ml；P<.001）水平显著升高。安慰剂（37.6%）和 5-羟色氨酸（35.6%）治疗组达到 fVAS 评分降低≥20%的患者比例相似（P=0.830）。fVAS 评分降低（-0.18；95%CI，-0.81 至 0.46；P=0.581）和慢性疾病治疗疲劳功能评估量表评分升高（0.68；95%CI，-2.37 至 3.73；P=0.660）在 5-羟色氨酸和安慰剂治疗之间均无差异，且抑郁、焦虑和压力评分的变化也无差异。
尽管血清 5-羟色氨酸和血清素水平显著升高，但口服 5-羟色氨酸治疗并未优于安慰剂改善 IBD 相关疲劳。（试验注册：比利时联邦药品和保健产品管理局，EudraCT 编号：2017-005059-10；临床试验注册网址：ClinicalTrials.gov，NCT03574948）。
