Melatonin for Stage IV Cancer
Also known as: N-acetyl-5-methoxytryptamine
High-dose melatonin enhances anti-tumor immunity and may improve chemotherapy efficacy while reducing toxicity.
Mechanism of Action
Melatonin at pharmacological doses (20mg+) enhances NK cell activity, promotes CD4+ T helper response, inhibits tumor angiogenesis through VEGF suppression, induces apoptosis via MT1 receptor-mediated Bax activation, and reduces chemotherapy-induced immunosuppression.
General mechanism: Pineal hormone. Mitochondrial antioxidant, Nrf2 activator, NLRP3 inhibitor, circadian regulator, anti-amyloid, immunomodulator.
Current Evidence
Meta-analyses show improved 1-year survival when melatonin is added to chemotherapy. Reduced chemotherapy side effects (thrombocytopenia, neurotoxicity). Over 20 RCTs support adjunctive use.
Clinical Status: Extensive clinical data for adjunctive cancer use. 20mg nightly standard in trials. Available OTC.
Safety Profile
Extremely safe even at high doses. Drowsiness. No addiction potential. May affect reproductive hormones at very high doses.
Key Research Questions
- Can melatonin enhance checkpoint inhibitor efficacy through immune modulation?
- Does melatonin's circadian effect influence optimal dosing timing for cancer?