Melatonin

Melatonin

Melatonin

Common Names

  • MLT
  • Pineal hormone

For Patients & Caregivers

Melatonin has not been shown to treat cancer in humans.

Melatonin is a hormone naturally produced by the brain in humans. Scientists believe that it controls circadian rhythms of sleep and wakefulness. Nighttime darkness causes increased production of melatonin, promoting sleep and causing a decrease in body temperature. Both elderly and depressed patients tend to have lower baseline levels of melatonin. Laboratory studies suggest that melatonin is a potent antioxidant that stimulates some aspects of the immune system, but it is not known if this effect occurs in humans. Melatonin also inhibits the growth of certain cancer cells including breast cancer and melanoma when it is directly applied to these cells in laboratory and animals studies. Studies in humans, however, do not show an anticancer effect. When used at the same time as specific chemotherapy drugs, melatonin may increase survival time.

  • To prevent or slow progression of Alzheimer’s disease
    Clinical trials have had conflicting results.
  • To prevent aging
    Clinical trials show that melatonin can help age-related sleep problems, but there is no evidence to support its use as an “anti-aging” supplement.
  • To treat cancer
    Clinical trials do not support this use, but a few studies found that a combination of melatonin with standard chemotherapy may increase survival time in cancer patients.
  • To reduce the severity of chemotherapy side effects
    In two clinical trials, melatonin did not increase blood cell counts reduced during chemotherapy or radiation therapy. One clinical trial showed that patients treated with melatonin had reduced chemotherapy-associated side effects such as weight loss and low blood platelet counts.
  • To treat depression
    Clinical trials have found melatonin effective in treating depression associated with fibromyalgia or menopause, but have not found it effective in treating major depression.
  • To treat HIV and AIDS
    No scientific evidence supports this use.
  • To treat insomnia
    Several clinical trials support this use.
  • To prevent and manage jet lag
    Clinical trials yielded mix results.
  • To treat seasonal affective disorder (SAD)
    Clinical trials have had conflicting results.
  • To ease withdrawal from benzodiazepines
    Two clinical trials have studied this use, with conflicting results.
  • For migraine prevention
    One small study suggests melatonin can reduce the frequency of migraine attack.
  • This product is regulated by the FDA as a dietary supplement. Unlike approved drugs, supplements are not required to be manufactured under specific standardized conditions. This product may not contain the labeled amount or may be contaminated. In addition, it may not have been tested for safety or effectiveness.
  • Melatonin may cause drowsiness. Patients should not drive or operate heavy machinery until familiar with the effects of melatonin.
  • Because melatonin can alter levels of estrogen, patients with hormone-sensitive cancers should consult their physicians before considering melatonin supplementation.
  • You are taking nifedipine (Procardia®): Use of melatonin and nifedipine at the same time has resulted in elevations in blood pressure and heart rate.
  • You are taking fluvoxamine (Luvox®): Fluvoxamine may increase blood levels of melatonin, resulting in sedation.
  • Headache
  • Drowsiness
  • Alterations in sleep patterns
  • Altered mental status, disorientation
  • Fast heart rate
  • Flushing
  • Itching
  • Abdominal cramps
  • Abnormally low body temperature
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For Healthcare Professionals

N-acetyl-methoxytryptamine

Melatonin is a hormonal supplement of synthetic origin, but occasionally derived from animal sources. It is used to treat insomnia, jet lag, and cancer. Melatonin is produced endogenously in humans by the pineal gland. Although the exact mechanism of action is unknown, melatonin is thought to control the circadian pacemaker and promote sleep (1).

Clinical studies suggest that melatonin may decrease sleep latency and improve sleep duration (2) (3) (4), but randomized trials yielded mixed data (27) (28) (29). No significant effects of melatonin on secondary sleep disorders associated with medical, neurological, or substance abuse disorders were found in a meta-analysis (5). Melatonin may decrease surgery-associated anxiety and pain (6) as well as the frequency of migraine attacks (7). Conclusions from a systematic review indicate that melatonin is effective in reducing perioperative anxiety but its utility as an analgesic remains inconclusive (30).

In vitro and in vivo studies suggest that melatonin has antiproliferative properties and synergistic effects with anticancer agents (8) (9) (32), as well as protective effects against adriamycin-induced cardiotoxicity (33). Clinical trials evaluating melatonin as a monotherapy or in combination with other agents and in patients with solid tumors suggest improvements in quality of life and survival time (10) (11) (12) (13). Other studies yielded conflicting results (35).

The use of oral melatonin may delay menopause by modulating levels of follicle stimulating hormone (FSH) and estrogen according to a case study (31). Patients with hormone-sensitive cancers should consult their physicians before considering melatonin supplementation.

  • Alzheimer’s disease
  • Antiaging
  • Cancer treatment
  • Chemotherapy side effects
  • Depression
  • Drug withdrawal symptoms
  • HIV and AIDS
  • Insomnia
  • Jet lag
  • Migraine prophylaxis
  • Seasonal affective disorder (SAD)

Melatonin is an endogenously produced indolamine hormone secreted by the pineal gland in humans. Nocturnal secretion is regulated by circadian rhythms and nighttime darkness (17), and melatonin is thought to control the circadian pacemaker and promote sleep. Ironically, melatonin is associated with wakefulness and activity in nocturnal animals (14). As levels of melatonin increase, an associated drop in core body temperature occurs. Both elderly and depressed patients tend to have lower basal levels of melatonin (2).

Melatonin appears to be a potent free-radical scavenger (18), interacting with cytosolic calmodulin and stimulating the production of IL-4 in bone marrow T-lymphocytes (1). In vitro and animal studies suggest that antitumor effects may occur through antimitotic or immunomodulatory activity. In vitro studies demonstrate that melatonin has antiproliferative effects on human breast cancer (HS578T) (19) and mouse melanoma (B16BL6, PG19) (8). Melatonin reduces proliferation of PC-3 and LNCaP cells in mice, but has no effect on apoptosis (9). The effect of melatonin on tumor cell growth may be mediated in part by melatonin receptor signaling. (20) (21) In endometrial cancer cells, it interferes with estrogen receptor expression (22).

  • Melatonin may cause drowsiness. Patients should not drive or operate heavy machinery until familiar with the effects of melatonin.
  • Because melatonin can alter estrogen levels, patients with hormone-sensitive cancers should consult their physicians before considering melatonin supplementation.

Drowsiness, alterations in sleep patterns, altered mental status, disorientation, tachycardia, flushing, pruritus, abdominal cramps, headache, hypothermia (1) (2) (14) (15)

Nifedipine: Concomitant administration of melatonin and nifedipine has resulted in elevations in blood pressure and heart rate (16).
CYP1A2 substrates: Melatonin inhibits CYP1A2 and may increase the bioavailability of substrate drugs, like fluvoxamine (23) (26) (34).

Patients taking blood-thinning medications should use melatonin with caution as a single dose decreased coagulation factors in healthy adults (25).


  1. Brzezinski A. Melatonin in humans. N Engl J Med 1997;336:186-95.

  2. Avery D, Lenz M, Landis C. Guidelines for prescribing melatonin. Ann Med 1998:30:122-30.

  3. Peres MF, et al. Melatonin, 3 mg, is effective for migraine prevention. Neurology. 2004 Aug 24;63(4):757.

  4. Cos S, Garcia-Bolado A, Sanchez-Barcelo EJ. Direct antiproliferative effects of melatonin on two metastatic cell sublines of mouse melanoma (B18BL6 and PG19). Melanoma Res 2001;11:197-201.

  5. Sack RL, Lewy AJ, Hughes RJ. Use of melatonin for sleep and circadian rhythm disorders. Ann Med 1998;30:115-21.

  6. Reppert SM, Weaver DR. Melatonin Madness. Cell 1995;83:1059-62.

  7. Ram PT, Dai J, Yuan L, et al. Involvement of the mt1 melatonin receptor in human breast cancer.Cancer Lett. May 28 2002;179(2):141-150.

  8. Watanabe M, Kobayashi Y, Takahashi N, et al. Expression of melatonin receptor (MT1) and interaction between melatonin and estrogen in endometrial cancer cell line.J Obstet Gynaecol Res. Aug 2008;34(4):567-573.

  9. Hartter S, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.

  10. DeMuro RL, et al. The absolute bioavailability of oral melatonin. J Clin Pharmacol 2000;40:781-4.

  11. Wirtz PH, Spillmann M, Bartschi C, et al. Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. J Pineal Res. Mar 2008;44(2):127-133.

  12. Gögenur I, Kücükakin B, Bisgaard T, et al. The effect of melatonin on sleep quality after laparoscopic cholecystectomy: a randomized, placebo-controlled trial. Anesth Analg. 2009 Apr;108(4):1152-6.

  13. Yousaf F, Seet E, Venkatraghavan L, Abrishami A, Chung F. Efficacy and Safety of Melatonin as an Anxiolytic and Analgesic in the Perioperative Period: A Qualitative Systematic Review of Randomized Trials. Anesthesiology. 2010 Sep 3. [Epub ahead of print]

  14. Diaz BL, Llaneza PC. Endocrine regulation of the course of menopause by oral melatonin: first case report. Menopause. 2008 Mar-Apr;15(2):388-92.

  15. Ruiz-Rabelo J, Vázquez R, Arjona A, et al. Improvement of capecitabine antitumoral activity by melatonin in pancreatic cancer. Pancreas. 2011 Apr;40(3):410-4.

  16. Aydemir S, Ozdemir I, Kart A. Role of exogenous melatonin on adriamycin-induced changes in the rat heart. Eur Rev Med Pharmacol Sci. 2010 May;14(5):435-41.

  17. Chang TK, Chen J, Yang G, et al. Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin. J Pineal Res. 2010 Jan;48(1):55-64.

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