多发性硬化症中的褪黑素补充：临床、影像、生物标志物及安全性结局的系统综述。
完整摘要 · 中文译文
目的：褪黑素可能作用于与多发性硬化（MS）相关的免疫、氧化和昼夜节律通路，但其临床获益和安全性特征仍不明确。本系统评价评估了口服褪黑素补充剂在成人MS患者中的疗效和安全性。 方法：我们检索了MEDLINE（通过PubMed）、Scopus、Web of Science核心合集和Cochrane对照试验中心注册库（CENTRAL），检索时间自建库至2026年8月15日，纳入随机和前瞻性非随机干预研究。两名评价者独立筛选研究、提取数据，并使用RoB 2或ROBINS-I评估偏倚风险。鉴于存在显著的临床和方法学异质性，我们遵循SWiM指南，在未进行meta分析的情况下综合了研究结果，并使用GRADE对证据确定性进行分级。我们在PROSPERO注册了方案（CRD420251167112）。 结果：我们纳入了10项独立研究，报告于17篇出版物中，共涵盖435名参与者。其中9项为随机试验（两项为交叉设计），1项为前瞻性非随机干预研究。褪黑素剂量范围为0.5-300 mg/天，治疗持续时间从2周至14个月。证据未显示复发活动、残疾进展或新发MRI活动减少。小型研究提示睡眠、疲劳、疼痛、躯体功能、认知、情绪、自主神经功能、身体成分以及炎症、代谢或氧化应激生物标志物可能存在改善，但这些结果不一致且少有重复。剂量为0.5-25 mg/天 尽管部分参与者中止了治疗且不良事件报告仍不完整，总体耐受性良好。在300 mg/天剂量下，四名接受褪黑素治疗的参与者中有三人出现高转氨酶血症，停药后缓解，其中一例在再激发后复发。所评估的每一项结局的证据确定性均为低或极低。 结论：当前证据不支持褪黑素在多发性硬化（MS）中具有疾病修饰作用。任何症状性或生物标志物方面的获益均需在更大规模、设计良好的试验中加以确认，且高剂量褪黑素可能带来有意义的肝脏风险。
完整摘要 · 英文原文
PURPOSE: Melatonin may act on immune, oxidative, and circadian pathways relevant to multiple sclerosis (MS), yet its clinical benefits and safety profile remain unclear. This systematic review assessed the efficacy and safety of oral melatonin supplementation in adults with MS. METHODS: We searched MEDLINE (via PubMed), Scopus, Web of Science Core Collection, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception through August 15, 2026, and included randomized and prospective non-randomized intervention studies. Two reviewers independently selected studies, extracted data, and assessed risk of bias using RoB 2 or ROBINS-I. Given substantial clinical and methodological heterogeneity, we synthesized findings without meta-analysis, following SWiM guidance, and rated certainty of evidence with GRADE. We registered the protocol in PROSPERO (CRD420251167112). RESULTS: We included 10 independent studies, reported across 17 publications, covering 435 participants. Nine were randomized trials (two of them crossover designs), and one was a prospective non-randomized intervention study. Melatonin doses spanned 0.5-300 mg/day, with treatment durations from 2 weeks to 14 months. The evidence did not show reductions in relapse activity, disability progression, or new MRI activity. Small studies suggested possible improvements in sleep, fatigue, pain, physical function, cognition, mood, autonomic function, body composition, and inflammatory, metabolic, or oxidative-stress biomarkers, but these results were inconsistent and rarely replicated. Doses of 0.5-25 mg/day were generally well tolerated, though some participants discontinued treatment and adverse-event reporting remained incomplete. At 300 mg/day, three of four melatonin-treated participants developed hypertransaminasemia, which resolved after withdrawal and recurred on rechallenge in one case. Certainty of evidence was low or very low for every outcome assessed. CONCLUSION: Current evidence does not support a disease-modifying effect of melatonin in MS. Any symptomatic or biomarker benefits need confirmation in larger, well-designed trials, and high-dose melatonin may carry meaningful hepatic risk.