Influence of melatonin supplementation on cancer-related fatigue: a meta-analysis of randomized controlled trials

Previous studies that evaluated the influence of melatonin supplementation on cancer-related fatigue (CRF) revealed inconsistent results. The present meta-analysis was performed to systematically evaluate the influence of melatonin on the severity of fatigue in patients with cancer.

Relevant randomized controlled trials (RCTs) were acquired by conducting a comprehensive search in the PubMed, Embase, and Cochrane Library databases. Only RCTs published as full-length English-language articles were included. A random-effects model was utilized to combine the findings by incorporating its potential influence.

Nine RCTs were included for the meta-analysis. Compared to the placebo, melatonin supplementation improved the symptoms of fatigue of these patients (standardized mean difference [SMD]: -0.23, 95% confidence interval [CI]: -0.44 to -0.01, p = 0.04, I² = 53%). The univariate analysis suggested that the treatment duration was significantly correlated with the improvement of melatonin supplementation on CRF (coefficient =  -0.0063, p = 0.02), which largely explains the source of heterogeneity (adjusted R² = 83.7%). The subgroup analysis revealed significantly improved fatigue in studies with treatment durations of ≥13 weeks, but not in studies with treatment durations of <13 weeks (SMD: -0.38 vs. 0.06, p for subgroup difference = 0.02). The further subgroup analysis suggested that the results were not significantly influenced by the type of cancer, status (advanced cancer or overall cancer), sample size, treatment (active anticancer treatment or palliative care only), dose of melatonin, or scale for evaluating fatigue symptoms.

Melatonin supplementation may relieve CRF, especially for intervention durations of ≥13 weeks.