SynthesisBMC cancer2026
Exploring the impact of melatonin on cancer-related fatigue: a dose-response meta-analysis with GRADE evidence evaluation.
Synthesis in BMC cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
backgroundCancer-related fatigue (CRF) is a prevalent and debilitating symptom among patients undergoing cancer treatment, yet its management remains a clinical challenge. Previous studies evaluating the role of melatonin in CRF have yielded inconsistent findings. This meta-analysis aimed to assess the overall effect of melatonin supplementation on fatigue and to explore potential dose-response relationships.
methodsA systematic literature search was performed in PubMed, Scopus, Web of Science, and Google Scholar up to 24 August 2025. Randomized controlled trials comparing melatonin with a placebo in adult cancer patients were included. SMDs with 95% CIs were calculated using a random-effects model. Nonlinear and linear dose-response analyses were conducted, and certainty of evidence was evaluated with the GRADE approach.
resultsTwelve trials (18 effect sizes, n = 1,977) met the inclusion criteria. Pooled analysis showed a significant reduction in fatigue scores with melatonin supplementation (SMD: -0.45; 95% CI: -0.69, - 0.20; P < 0.001). Dose-response analysis revealed a significant inverse association for melatonin doses between 5 and 15 mg/day (P-nonlinearity = 0.03). Short-term interventions (≤ 4 weeks) demonstrated greater benefit, whereas longer durations showed no consistent effects. However, substantial heterogeneity (I² = 78%) and very low certainty of evidence limit the robustness of these findings.
conclusionsMelatonin supplementation may reduce fatigue in cancer patients, particularly at doses of 5-15 mg/day and with short-term use. Nonetheless, the certainty of evidence remains very low, highlighting the need for high-quality, large-scale RCTs with standardized methodologies to validate these results.
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