Melatonin

Author

Nancy Hepp, MS, BCCT Project Manager

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Reviewer

Laura Pole, RN, MSN, OCNS, BCCT Senior Researcher

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Last updated December 23, 2020.

Also known by these names

  • MLT
  • N-acetyl-5-methoxytryptamine
  • N-acetyl-methoxytryptamine
  • Pineal hormone

Key Points

  • Before using this therapy, consult your oncology team about interactions with other treatments and therapies. Also make sure this therapy is safe for use with any other medical conditions you may have.
  • Melatonin is a hormone produced by the pineal gland in the brain.
  • Melatonin is available as a supplement used as a sleep aid.
  • Melatonin has been investigated, either by itself or as an adjuvant to conventional treatments, with several anticancer effects demonstrated. These include inhibition of cancer growth, of metastasis and of angiogenesis.
  • BCCT’s interest in melatonin derives from its possible protection of non-cancer cells from chemotherapy’s effects and its ability to reduce several symptoms associated with cancer, including sleep disruption, surgery-associated anxiety and pain.
  • Melatonin is generally safe with few side effects.
  • Melatonin supplements are widely available.

Melatonin is a hormone produced by the pineal gland in the brain that helps regulate sleep and wake cycles. Very small amounts of melatonin are found in fruits, nuts, olive oil and wine. It is also available as a supplement used as a sleep aid.

Treating the Cancer

Working against cancer growth or spread, improving survival, or working with other treatments or therapies to improve their anticancer action

Cancer acts more aggressively in people with low nighttime production of melatonin. Cancer patients with high nighttime melatonin levels tend to have better outcomes.1

Melatonin supplementation has been investigated for anticancer effects, either by itself or as an adjuvant (supplement) to conventional treatments.

Clinical Evidence

Reviews and meta-analyses:

  • Reduced risk of death at one year, including in use with chemotherapy, plus improved effect for complete response, partial response and stable disease with with solid tumors when used in conjunction with chemotherapy, radiotherapy, supportive care and palliative care2
  • Improved outcomes for one-year mortality, complete response, partial response and stable disease when adding melatonin to chemotherapy, radiotherapy, supportive care, and palliative care3
  • Increased one-year survival rate and objective tumor regression rate in patients treated with melatonin and chemotherapy compared to those receiving chemotherapy alone (with several cancers, including gastrointestinal tract neoplasms)4

Further small to moderately sized studies in addition to those reviews::

  • Increased survival in people with skin cancer when used with chemo- and radiotherapy5
  • Increased survival in people with metastatic non-small cell lung cancer, with therapeutic effects seen only in patients who had "spiritual sensitivity."6
  • Inhibited cancer growth and promoted tumor cell death (apoptosis) in cervical cancer, ovarian cancercolon cancer and head and neck cancers7
  • Counteracted metastasis in head and neck cancers8
  • Less aggressive ovarian cancers with higher serum levels of melatonin in clinical studies9
  • Enhanced the effect of tamoxifen or cisplatin insmall clinical studies.10
  • Favorable rates of complete response and partial response in a small, uncontrolled study of people with breast cancer.11

Lab and Animal Evidence

Expand list

Melatonin, Light and Sleep

Melatonin is produced naturally by the pineal gland during the early hours of night, signaling and initiating the transition from wakefulness to sleep. Individuals who experience sleep difficulties may have disrupted melatonin production.

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Managing Side Effects and Promoting Wellness

Managing or relieving side effects or symptoms, reducing treatment toxicity, supporting quality of life or promoting general well-being

Clinical Evidence

Melatonin may improve quality of life by reducing side effects and symptoms. In addressing symptoms commonly associated with cancer and treatments, melatonin has shown these effects:

Chemotherapy Side Effects

  • Reduced frequency of chemotherapy-induced side-effects:29
    • Weakness (asthenia)
    • Low blood platelet count (thrombocytopenia)
    • Inflammation of the mouth and lips (stomatitis)
    • Damage to the heart (cardiotoxicity)
    • Damage to nerves (neurotoxicity)
    • Loss of strength and energy
  • Protected normal reproductive cells during chemotherapy, decreasing  cell death, while also improving reproductive health and function, reducing injury during chemotherapy.30
  • Reduced occurrences of hair loss (alopecia), anemia, weakness or lack of energy (asthenia), nausea and vomiting, low blood pressure and low platelet levels (thrombocytopenia) in pooled analyses of patients with solid tumors31 and lymphocytopenia (low lymphocyte count), stomatitis (swelling and sores inside the mouth), cardiotoxicity and neurotoxicity in clinical trials32
  • Protective effects against kidney damage (nephrotoxicity) caused by different chemotherapy agents such as cyclophosphamide, cisplatin, doxorubicin, methotrexate, oxaliplatin, etoposide and daunorubicin in non-clinical studies.33

Radiation Side Effects

  • Potential preventive therapy for radiotherapy-induced oral mucositis.34
  • Prevented or minimized the unfavorable effects of radiotherapy on reduced blood cell count in rectal cancer patients receiving radiotherapy35

Surgery Side Effects

  • Reduced toxicity and the typical postsurgical reduction in lymphocytes when administered with low-dose interleukin-2 before surgery for gastrointestinal tract tumors36
  • Reduced risk of depressive symptoms in women with breast cancer after surgery in some trials37 but did not improve ratings of depression in another, nor have any impact on hot flashes38
  • See also pain, sleep effects and other side effects related to surgery below.

Sleep Effects

Other Side Effects and Symptoms

  • Improved fatigue, global quality of life, and social and cognitive functioning among people with breast cancer43
  • No improvement in appetite, weight or quality of life compared with placebo among people with with advanced cancer and cachexis (wasting syndrome) treated with oral melatonin at night44
  • Decreased pain scores and tramadol consumption and subjective analgesic efficacy during the postoperative period in prostate cancer patients undergoing elective prostatectomy.45

Lab and Animal Evidence

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Reducing Risk

Clinical Evidence

Melatonin levels, measured in blood or urine, relate to cancer risk and outcomes:

Lab and Animal Evidence

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Optimizing Your Terrain

  • Antioxidant  properties,52  reducing oxidative stress, a promoter of tumor growth.53  
  • Decreased inflammation, while also modulating mitochondrial function and sexual hormones54

Cautions

Melatonin is generally considered safe, although a doctor’s supervision is recommended. Melatonin has a very low toxicity profile and is not associated with significant side effects.55 However, it should be stopped five to seven days before surgery to avoid magnifying the effects of anesthesia.56

Melatonin use at recommended doses typically does not lead to dependency, habituation or a drug hangover, all common issues with many pharmaceutical sleep aids.

Access

Melatonin supplements are widely available and are generally affordably priced.

Dosing

BCCT does not recommend therapies or doses, but only provides information for patients and providers to consider as part of a complete treatment plan. Patients should discuss therapies with their physicians, as contraindications, interactions and side effects must be evaluated. 

Levels of active ingredients of natural products can vary widely between and even within products. See Quality and Sources of Herbs, Supplements and Other Natural Products.

Dosage recommendations are available from these sources:

Integrative Programs, Protocols and Medical Systems

For more information about programs and protocols, see our Integrative Programs and Protocols page.

Non-cancer Uses of Melatonin

BCCT has not reviewed the effectiveness of this therapy for non-cancer uses.

  • Alzheimer's disease
  • Amyotrophic lateral sclerosis (ALS)
  • Migraine headaches
  • Periodontal disease
  • Protozoan parasitic infections
  • Sleep disturbances due to insomnia, jet lag, shift work and other situations

Note: BCCT has not conducted an independent review of research of melatonin. This summary draws from the Memorial Sloan Kettering Cancer Center’s About Herbs, Mayo Clinic and other sources as noted.

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