Melatonin
Also known by these names
- MLT
- N-acetyl-5-methoxytryptamine
- N-acetyl-methoxytryptamine
- Pineal hormone
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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.
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 Author
Nancy Hepp, MS, BCCT Project Manager
Read more Ms. Hepp is a science researcher and communicator who has been writing and editing educational content on varied health topics for more than 20 years. View profile. Reviewer
 Laura Pole, RN, MSN, OCNS, BCCT Senior Researcher
Read more Ms. Pole is an oncology clinical nurse specialist who has been providing integrative oncology clinical care, navigation, consultation and education services for more than 30 years. View profile. Last updated June 9, 2021.
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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.
Melatonin supplementation has been investigated for anticancer effects. Clinical studies show improved outcomes and response to conventional treatments when melatonin is used as an adjuvant (supplement). No clinical evidence shows it is effective as a first-line cancer treatment.
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 care
- Improved survival, complete response, partial response and stable disease when adding melatonin to chemotherapy, radiotherapy, supportive care, and/or palliative care, including with advanced or metastatic solid tumors
- 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)
Further small to moderately sized studies in addition to those reviews::
- Increased survival in people with skin cancer when used with chemo- and radiotherapy
- Increased survival in people with metastatic non-small cell lung cancer, with therapeutic effects seen only in patients who had "spiritual sensitivity"
- Inhibited cancer growth and promoted tumor cell death (apoptosis) in cervical cancer, ovarian cancer, colon cancer and head and neck cancers
- Counteracted metastasis in head and neck cancers
- Less aggressive ovarian cancers with higher serum levels of melatonin in clinical studies
- Enhanced the effect of tamoxifen or cisplatin in small clinical studies of solid tumors
- Favorable rates of complete response and partial response in a small, uncontrolled study of people with breast cancer when used with cyclophosphamide and other therapies
Lab and Animal Evidence
Expand list
- Reduced proliferation, promoted cell death (apoptosis), inhibited metastasis and showed other anticancer effects in several types of cancer:
- Enhanced the effect of tamoxifen or cisplatin in preclinical studies.
- Breast cancer: May reduce tumor growth (proliferation), including within breast cancer cells. Manipulating the pineal gland or the administration of melatonin lengthens the latency and reduces the incidence and growth rate of mammary tumors. Melatonin reestablished the sensitivity of breast tumors to tamoxifen and tumor regression.
- Colorectal cancer:
- Potentiated flavone-induced cell death (apoptosis) in human colon cancer cells
- Induced cell death (apoptosis) in mouse colon cancer cells in combination with a derivative of thiazolidinedione (oral hypoglycemic for type 2 diabetes, such as metformin) .
- Pancreatic cancer: proposed as an appropriate therapeutic approach for pancreatic cancer.
- Prostate cancer:
- Inhibited prostate cancer tumorigenesis and markers with oral administration in mice
- Blood from human volunteers rich in nocturnal melatonin suppressed prostate cancer signal transduction, metabolic and growth activity in mice with human prostate cancer cell xenografts. Blood from humans exposed to light at night markedly stimulated human prostate cancer growth, signal transduction and metabolic activity.
- Restored sensitivity to chemotherapy and anticancer activity in many cancer types including hormone-dependent cancers
- Inhibited angiogenesis (production of new blood vessels to supply tumor cells)
- Synergistic effects with anticancer agents such as the chemotherapy drug capecitabine
- Decreased cell survival and proliferation, and increased cell death and cellular differentiation, and also reduced rapamycin-associated toxicity to healthy cells with a combined treatment of rapamycin and melatonin .
- Enhanced the efficacy of chemotherapy and reduced chemotherapy toxicity and did not increase the toxicity of tamoxifen; chemotherapy was better tolerated in patients treated with melatonin
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.
Read more One factor that influences melatonin production is bright light. Such light exposure late in the evening—and especially blue-spectrum light such as from most television, computer, mobile phone and other screens—can disrupt melatonin production and delay the initiation of sleep. Treatments for sleep disruptions such as delayed sleep-wake phase disorder may reduce exposure to bright and blue-spectrum light in the evening.
During the day, melatonin production diminishes as our production of serotonin and cortisol increase. Bright light in the morning boosts serotonin and cortisol while also diminishing melatonin production, leading to greater wakefulness and setting the stage for the next evening's production of melatonin.
To optimize our natural melatonin cycles and benefits, research indicates that we should curb bright light in the evening and increase bright light exposure in the morning. Preliminary research also shows that bright light therapy in the morning can improve sleep in people with cancer.
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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:
- 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.
- 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 tumors and lymphocytopenia (low lymphocyte count), stomatitis (swelling and sores inside the mouth), cardiotoxicity and neurotoxicity in clinical trials
- 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.
Radiation Side Effects
- Potential preventive therapy for radiotherapy-induced oral mucositis.
- Prevented or minimized the unfavorable effects of radiotherapy on reduced blood cell count in rectal cancer patients receiving radiotherapy
Surgery Side Effects
- Reduced toxicity and the typical postsurgical reduction in lymphocytes when administered with low-dose interleukin-2 before surgery for gastrointestinal tract tumors
- Reduced risk of depressive symptoms in women with breast cancer after surgery in some trials but did not improve ratings of depression in another, nor have any impact on hot flashes
- See also pain, sleep effects and other side effects related to surgery below.
Sleep Effects
- Improved sleep latency, reduced pre-operative anxiety and prevented agitation in a 2018 meta-analysis
- Improved measures of sleep quality among people with breast cancer
- Increased sleep efficiency at the time of surgery and total sleep time following breast cancer surgery
- Enhanced sleep quality and sedation scores during the postoperative period in prostate cancer patients undergoing elective prostatectomy.
Other Side Effects and Symptoms
- Improved fatigue, global quality of life, and social and cognitive functioning among people with breast cancer
- No improvement in appetite, weight or quality of life compared with placebo among people with with advanced cancer and wasting (cachexia) treated with oral melatonin at night
- Decreased pain scores and tramadol consumption and subjective analgesic efficacy during the postoperative period in prostate cancer patients undergoing elective prostatectomy
Lab and Animal Evidence
Read more
Melatonin protected normal reproductive cells during chemotherapy.
Reducing Risk
Clinical Evidence
Melatonin levels, measured in blood or urine, relate to cancer risk and outcomes:
- Lower risk of breast cancer with higher nighttime levels of melatonin or melatonin supplementation
- Reduced risk of these cancers with melatonin use in epidemiological studies:
Lab and Animal Evidence
Read more
- Reduced incidence of spontaneous mammary tumors and impacted metabolic and molecular signaling mechanisms involved in human breast cancer cell growth,
Optimizing Your Terrain
- Antioxidant properties, reducing oxidative stress, a promoter of tumor growth.
- Decreased inflammation, while also modulating mitochondrial function and sexual hormones
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. However, it should be stopped five to seven days before surgery to avoid magnifying the effects of anesthesia.
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
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
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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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- Shen YQ, Guerra-Librero A et al. Combination of melatonin and rapamycin for head and neck cancer therapy: suppression of AKT/mTOR pathway activation, and activation of mitophagy and apoptosis via mitochondrial function regulation. Journal of Pineal Research. 2018 Apr;64(3).
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- Cutando A, López-Valverde A, Arias-Santiago S, DE Vicente J, DE Diego RG. Role of melatonin in cancer treatment. Anticancer Research. 2012 Jul;32(7):2747-53.
- Leproult R, Colecchia EF, L'Hermite-Balériaux M, Van Cauter E. Transition from dim to bright light in the morning induces an immediate elevation of cortisol levels. Journal of Clinical Endocrinology ad Metabolism. 2001 Jan;86(1):151-7; Nesbitt AD. Delayed sleep-wake phase disorder. Journal of Thoracic Disease. 2018 Jan;10(Suppl 1):S103-S111.
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- Haghi-Aminjan H, Asghari MH et al. The role of melatonin on chemotherapy-induced reproductive toxicity. Journal of Pharmacy and Pharmacology. 2017 Nov 23.
- Cutando A, López-Valverde A, Arias-Santiago S, DE Vicente J, DE Diego RG. Role of melatonin in cancer treatment. Anticancer Research. 2012 Jul;32(7):2747-53; Seely D, Wu P et al. Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integrative Cancer Therapies. 2012;11(4):293-303.
- Lissoni P. Is there a role for melatonin in supportive care? Support Care Cancer. 2002 Mar;10(2):110-6.
- Haghi-Aminjan H, Farhood B et al. The protective role of melatonin in chemotherapy-induced nephrotoxicity: a review of non-clinical studies. Expert Opinion on Drug Metabolism & Toxicology. 2018 Sep;14(9):937-950.
- Yeh CM, Su SC et al. Melatonin as a potential inhibitory agent in head and neck cancer. Oncotarget. 2017 Aug 9;8(52):90545-90556.
- Kouhi Habibi N, Shabestani Monfared A et al. The protective effects of melatonin on blood cell counts of rectal cancer patients following radio-chemotherapy: a randomized controlled trial. Clinical and Translational Oncology. 2019;21(6):745-752.
- Lissoni P, Brivio F et al. Immune effects of preoperative immunotherapy with high-dose subcutaneous interleukin-2 versus neuroimmunotherapy with low-dose interleukin-2 plus the neurohormone melatonin in gastrointestinal tract tumor patients. Journal of Biological Regulators and Homeostatic Agents. 1995;9(1):31-33.
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- Borazan H, Tuncer S, Yalcin N, Erol A, Otelcioglu S. Effects of preoperative oral melatonin medication on postoperative analgesia, sleep quality, and sedation in patients undergoing elective prostatectomy: a randomized clinical trial. Journal of Anesthesia. 2010 Apr;24(2):155-60.
- Haghi-Aminjan H, Asghari MH et al. The role of melatonin on chemotherapy-induced reproductive toxicity. Journal of Pharmacy and Pharmacology. 2018 Mar;70(3):291-306.
- Schernhammer ES, Hankinson SE. Urinary melatonin levels and postmenopausal breast cancer risk in the Nurses' Health Study cohort. Cancer Epidemiology, Biomarkers & Prevention. 2009 Jan;18(1):74-9.
- Posadzki PP, Bajpai R et al. Melatonin and health: an umbrella review of health outcomes and biological mechanisms of action. BMC Medicine. 2018 Feb 5;16(1):18.
- Li Y, Li S et al. Melatonin for the prevention and treatment of cancer. Oncotarget. 2017 Jun 13;8(24):39896-39921.
- Sánchez-Barceló EJ, Cos S, Fernández R, Mediavilla MD. Melatonin and mammary cancer: a short review. Endocrine-Related Cancer. 2003 Jun;10(2):153-9.
- Hill SM, Belancio VP et al. Melatonin: an inhibitor of breast cancer. Endocrine-related Cancer. 2015 Jun;22(3):R183-204.
- Sánchez-Barceló EJ, Cos S, Fernández R, Mediavilla MD. Melatonin and mammary cancer: a short review. Endocrine-Related Cancer. 2003 Jun;10(2):153-9;
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- Haghi-Aminjan H, Asghari MH et al. The role of melatonin on chemotherapy-induced reproductive toxicity. Journal of Pharmacy and Pharmacology. 2017 Nov 23.
- Yeh CM, Su SC et al. Melatonin as a potential inhibitory agent in head and neck cancer. Oncotarget. 2017 Aug 9;8(52):90545-90556.
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View All References
More Information
- Memorial Sloan Kettering Cancer Center About Herbs: Melatonin
- Mayo Clinic: Melatonin
- TRC Natural Medicines website (subscription required): in-depth information, ratings of effectiveness and safety and evaluation of specific melatonin products
- Consumer Labs: Product Review (subscription required): Melatonin Supplements Review
- Gurdev Parmar and Tina Kaczor: Textbook of Naturopathic Oncology
- Dawn Lemanne and Victoria Maizes: Advising Women Undergoing Treatment for Breast Cancer
- BCCT, KNOW Oncology and Ottawa Integrative Cancer Centre: Patient Education Brochures
- Block KI, Block PB, Gyllenhaal C: Integrative Treatment for Colorectal Cancer
- Barbara MacDonald, ND, LAc: The Breast Cancer Companion: A Complementary Care Manual: Third Edition
- Keith Block and others: A Broad-Spectrum Integrative Design for Cancer Prevention and Therapy
- Wayne Jonas, MD: Your Healing Journey: A Patient’s Guide to Integrative Breast Cancer Care
- Raymond Chang, MD: Beyond the Magic Bullet: The Anti-Cancer Cocktail
- Donald I. Abrams, MD, and Andrew T. Weil, MD: Integrative Oncology, 2nd Edition
- Neil McKinney, BSc, ND: Naturopathic Oncology, 3rd Edition
- Lise Alschuler, ND, FABNO, and Karolyn Gazella: The Definitive Guide to Cancer, 3rd Edition
- Keith I. Block, MD: Life over Cancer: The Block Center Program for Integrative Cancer Treatment
- Lorenzo Cohen and Alison Jefferies: Anticancer Living: Transform Your Life and Health with the Mix of Six
- CAM-Cancer Collaboration: CAM-Cancer
- Lone Star Medical Group: Natural Alternative Treatments
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