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TL:DR -- If you're not taking melatonin now, start. If you have cancer, you'd be suicidal to NOT add melatonin to what you're doing. Lots of data supports this.

I decided to post this partly because of the comment below, which I've never seen in reference to any other medicine or supplement:

Melatonin is probably the safest medical compound available, with a LD50 of infinity (it is impossible to kill an animal with industrial doses of melatonin). The only side effects reported are early morning drowsiness and “bad dreams” (when the dose is increased too rapidly). (1)

https://paulmarik.substack.com/p/cancer-hates-darkness-the-remarkable

. . . Anti-angiogenesis is one of the major mechanisms by which melatonin exerts its anticancer effects. Melatonin inhibits hypoxia-induced factor 1-α thereby preventing vascular endothelial growth factor (VEGF) expression. Melatonin also inhibits endothelial cell migration, endothelial cell invasion, and endothelial cell tube formation. It also prevents cancer cell migration via alteration of PI3K and MAPK signaling pathways in both receptor-dependent and independent manner. (11) Melatonin has been demonstrated to stimulate T cell and natural killer (NK) production and reduce regulatory T cells (Tregs). (18, 19)

Melatonin may benefit cancer patients who are also receiving chemotherapy, radiotherapy, supportive therapy, or palliative therapy by improving survival and ameliorating the side effects of chemotherapy.

Clinical studies

In addition to case studies, (20, 21) the clinical benefit of melatonin in patients with cancer is supported by the highest level of evidence, namely meta-analyses of RCTs. (22, 23) A classic systematic review of randomized trials (10 RCTs, mostly solid tumors) found that adding melatonin (typically 20 mg nightly) to chemotherapy or supportive care reduced 1‑year mortality (relative risk roughly halved) and improved tumor remission rates, with consistent effects across cancer types and doses.(22) Seely et al systematically reviewed the effects of melatonin in conjunction with chemotherapy, radiotherapy, supportive care, and palliative care on 1-year survival, complete response, partial response, stable disease, and chemotherapy-associated toxicities. (23) This analysis included 21 randomized studies, all of which studied solid tumors. The pooled relative risk (RR) for 1-year mortality was 0.63 (95% CI = 0.53-0.74; P < 0.001). Improved effects were found for complete response, partial response, and stable disease. In trials combining melatonin with chemotherapy, adjuvant melatonin decreased 1-year mortality (RR = 0.60; 95% CI = 0.54-0.67).

A triple‑blind RCT in breast cancer patients undergoing adjuvant radiotherapy (20 mg daily) showed significant reductions in fatigue, anxiety, and depression scores in the melatonin group versus placebo, suggesting a clinically meaningful improvement in radiotherapy‑related symptom burden. (24) A 2024 review of 46 clinical trials of melatonin in oncology (11 with published results) reported that the most consistent positive signals were in improved quality of life and reduced treatment‑related fatigue and sleep disruption, particularly when used adjunctively with chemotherapy or radiotherapy.(25)

Types of cancers that melatonin may be beneficial for

Melatonin may be active in several cancers including cancers of the breast, ovary, pancreas, liver, kidney, mouth, stomach, colon/rectum, brain, lung, prostate, head and neck, and various leukemias and sarcomas. (2, 9)

Dosing and cautions

Despite the expanding literature, there is currently no universally accepted “optimal” anticancer dose of melatonin. Most clinical studies have used doses substantially higher than those commonly prescribed for insomnia. The pioneering work of Paolo Lissoni and colleagues employed melatonin at a dose of 20 mg nightly in patients with advanced malignancies and reported improvements in treatment tolerance, quality of life, and, in some studies, survival outcomes when combined with standard cancer therapies. (26-28) Consequently, 20 mg at bedtime remains the best-studied dose in oncology. However, many integrative oncology practitioners now use doses ranging from 20 to 40 mg nightly, based on the hypothesis that higher concentrations may be required to achieve some of the metabolic and signaling effects observed in laboratory studies.(29, 30) While some clinicians have explored doses exceeding 50–100 mg daily, robust clinical evidence demonstrating superior anticancer efficacy at these higher doses remains lacking. [On the other hand, remember the LD:50 of "infinity"; use as much as you think might be helpful. I personally take about 500mg]

Although melatonin has an excellent safety profile, initiating therapy at the target dose may lead to transient side effects such as morning drowsiness, vivid dreams, dizziness, or headache. For this reason, a gradual titration strategy is generally recommended. Many clinicians begin with 5–10 mg at bedtime and increase the dose every one to two weeks as tolerated until a target range of 20–40 mg nightly is reached. This approach improves tolerability while allowing patients to identify the lowest effective dose that balances potential therapeutic benefit with minimal adverse effects. Most side effects diminish after several days of continued use.

. . . While it has been claimed and widely disseminated in social media that melatonin is associated with cardiac failure (abstract presented at AHA Scientific Session 2025) this study is profoundly flawed and indeed, melatonin is cardioprotective. (31-36)

(lots of graphics and references in the original)