Melatonin
Hormone adjunct: SIRT1/3 ↑, mTOR ↓, apoptosis ↑; strong evidence for chemo/radiation tolerance in breast/lung/colorectal/prostate.
Forms: Immediate-release tablets (3-10 mg) · Extended-release capsules (2-5 mg)
Key Takeaway
Circadian hormone that activates SIRT1/3, downshifts mTOR, and promotes apoptosis; repeatedly improves chemo-tolerance and sometimes response rates in clinical studies.
Evidence at a glance
Numerous RCTs/meta-analyses for toxicity mitigation; mechanistic ties to sirtuins/mTOR; adjunct OS/PFS signals in solid tumors.
How it may work
Melatonin engages MT1/MT2 and mitochondrial targets to activate SIRT1/3, improving DNA repair and metabolic efficiency. It inhibits PI3K/Akt/mTOR signaling, enhances p53/p21, and increases caspase-mediated apoptosis. As an adjunct, it reduces chemo/radiotherapy toxicity (myelosuppression, mucositis, neurotoxicity) and may improve response in specific settings.
Targets & pathways
Curated mechanistic targets reported for this agent — how it may act on cells, not proof of a clinical effect.
Often studied / combined with
Combinations reported in the literature, not a protocol or a recommendation.
- Doxorubicin: Amplified apoptosis and cardioprotection in breast cancer.
- Curcumin: Cooperative SIRT1/mTOR modulation in lung models.
- Resveratrol: Enhanced mTOR inhibition and DNA repair in colorectal cancer.
- Quercetin: Synergistic antioxidant/apoptosis effects in prostate cancer.
Overlapping mechanisms
- Sirtuin: Overlaps with resveratrol/others; may not add incrementally.
- mTOR ↓: Redundant with metformin/rapalogs; monitor for GI effects.
Safety & interactions
Severity and how well-established each signal is are shown separately. Verify everything with your oncologist or pharmacist — absence here does not mean safe.
- sedativesCautionModerateTheoreticalAdditive CNS depression.
- blood_thinnersMonitorLowTheoreticalMay enhance anticoagulant effects.
- DoxorubicinSynergizeLowTheoreticalReduces cardiotoxicity while boosting efficacy.
Timing
- Bedtime: Aligns with natural peak; 30-60 min before sleep.
- HS: Nightly for circadian entrainment.
References
- PMC8123278: Melatonin in breast cancer adjuvant therapy
- PMC12314884: SIRT1 activation mechanisms
- PMC7260648: mTOR inhibition in colorectal cancer
- PMC7488244: Apoptosis enhancement with chemo
- DOI 10.3390/nu13020523: Synergy with doxorubicin in breast models
- PMC10221542: Combination with curcumin in lung cancer
Research
No published studies for Melatonin yet
New studies appear here once they’ve been reviewed. Browse all studies.
Dose: as studied, not a recommendation
Ranges seen in adjunct / practice use: 10–40 mg/night (po) Bedtime; titrate from 3 mg, Oncology adjunct 20-40 mg HS; lower for sleep (3-5 mg); sustained-release for circadian mimicry..
Trials studying Melatonin
Loading current trials from ClinicalTrials.gov… Search ClinicalTrials.gov →
Appears in these protocol claims
Melatonin is named in these protocols discussed online. Listed for transparency: being part of a protocol is not evidence that it works, and OncoForge does not endorse them.
- Gerson, Gonzalez, Budwig, RSO, IPT, and Other Long-Running Claims : Older alternative or clinic-based approaches with strong testimonial communities and major evidence disputes.