Exploring the impact of melatonin on cancer-related fatigue: a dose-response meta-analysis with GRADE evidence evaluation
Abstract
Background: Cancer-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.
Methods: A 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.
Results: Twelve 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.
Conclusions: Melatonin supplementation may reduce fatigue…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,977 participants or records.
Read the paper
Related studies
- Tryptophan Metabolism and Gut-Brain Homeostasis
- Rationale for a Multi-Factorial Approach for the Reversal of Cognitive Decline in Alzheimer’s Disease and MCI: A Review
- Prioritized Research for the Prevention, Treatment, and Reversal of Chronic Disease: Recommendations From the Lifestyle Medicine Research Summit
- Relationship between sleep disorders and gut dysbiosis: what affects what?
- The role of CLOCK gene in psychiatric disorders: Evidence from human and animal research
- Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.