- Pineal hormone
For Patients & Caregivers
How It Works
Melatonin has not been shown to treat cancer in humans. It may improve sleep quality in some patients.
Melatonin is a hormone naturally produced by the brain in humans. The supplemental form is used to treat insomnia. 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 an antioxidant that can stimulate 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 directly applied to these cells. 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. Other studies indicate it may improve sleep quality in some patients, but whether it can be of benefit in depression or for easing withdrawal symptoms is unclear.
The American Academy of Neurology guidelines recommend using melatonin, starting with a low-dose, for children and adolescents with autism spectrum disorder and sleep disturbance if behavioral strategies have not been helpful, and if contributing coexisting conditions and use of concomitant medications have been addressed.
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 chemotherapy side effects
An analysis of clinical trials suggests melatonin may help reduce the incidence of some chemotherapy side effects. Additional trials are needed to confirm this.
To treat depression
Evidence for the use of melatonin in depression is unclear. Additional studies are needed.
To treat insomnia
Several clinical trials support this use.
To prevent and manage jet lag
A few studies suggest melatonin may be helpful for jet lag.
To treat seasonal affective disorder (SAD)
Clinical trials on melatonin for this use are lacking.
To ease withdrawal from benzodiazepines
Evidence on whether melatonin can ease withdrawal symptoms is mixed. Additional studies are needed.
For migraine prevention
A small study suggests melatonin can reduce frequency of migraine attacks.
Autism Spectrum Disorder
Clinical studies show that melatonin has beneficial effects in children and in adolescents with autism spectrum disorder
Do Not Take If
- 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.
- You are taking blood thinners such as warfarin: Caution is warranted, as a single dose of melatonin was found to decrease clotting factors in the lab tests of healthy adults. Therefore, it may increase the chance of adverse effects when used with blood-thinning drugs.
- You are taking Rhubarb: A study using human primary hepatocytes showed that concomitant use can cause metabolic disorder of melatonin.
For Healthcare Professionals
Melatonin is produced endogenously in humans by the pineal gland. Although the exact mechanism of action is unknown, it is thought to control the circadian pacemaker and promote sleep (1). Small amounts of melatonin are found in fruits, nuts, olive oil, and wine. The supplemental form is used as a sleep-aid.
Clinical studies suggest that melatonin may decrease sleep latency and improve sleep duration (2) (3) (4), although randomized trials have produced mixed data (27) (28) (29). A meta-analysis did not find any significant effects with melatonin on secondary sleep disorders associated with medical, neurological, or substance abuse disorders (5), but supplementation was reported to improve subjective sleep quality in patients with traumatic brain injury (44). Additional studies show that melatonin may decrease surgery-associated anxiety and pain (6) as well as frequency of migraine attacks (7). Data also indicate that it can reduce perioperative anxiety (30) (56), but there is insufficient evidence for its use to improve sleep in ICU patients (46), delirium in hospitalized patients (57), to improve depression or depressive symptoms (47), or for seasonal affective disorder (SAD) (48). It also did not improve nocturia in a small study of multiple sclerosis patients (53). A few studies suggest melatonin may be helpful for jet lag (51) (52). Studies on whether melatonin can help in benzodiazepine withdrawal are mixed (49) (50).
Data also suggest benefits of child-appropriate prolonged-release melatonin for long-term treatment in children and adolescents with autism spectrum disorder and insomnia (59). The American Academy of Neurology guidelines recommend using melatonin, starting with a low-dose, for children and adolescents with autism spectrum disorder and sleep disturbance if behavioral strategies have not been helpful, and if contributing coexisting conditions and use of concomitant medications have been addressed (60).
Preclinical studies suggest that melatonin has antioxidant (38) (39) and antiproliferative properties, including against breast cancer cells (40); synergistic effects with anticancer agents (8) (9) (32); and 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), but melatonin did not improve appetite, weight, or quality of life in cancer patients with cachexia (35). In studies of postmenopausal breast cancer survivors, short-term supplementation did not influence estradiol levels (36) but improved sleep quality (37). Data also suggest that melatonin may help reduce incidence of chemotherapy side effects including thrombocytopenia, asthenia, and neurotoxicity (54); cognitive function, sleep quality and depressive symptoms (61); minimize radiotherapy-induced reduction in blood cell counts (58); and protect against radiation-induced genotoxicity (62).
According to a case report, oral melatonin may delay menopause in pre-menopausal women by modulating levels of follicle stimulating hormone (FSH) and estrogen (31).
Mechanism of Action
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, it 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 is a free-radical scavenger (18) (38) and enhances antioxidative enzyme activities (39), interacting with cytosolic calmodulin and stimulating IL-4 production 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 antiproliferative effects on human breast cancer (HS578T) (19) and mouse melanoma (B16BL6, PG19) (8). Decreases in breast cancer metastasis may occur via modulation of Rho-associated kinase protein-1 expression (41). Melatonin reduces proliferation of PC-3 and LNCaP cells in mice, but has no effect on apoptosis (9). Its effect 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). Other laboratory studies suggest that melatonin behaves both as a selective estrogen receptor modulator (SERM) and as an aromatase inhibitor (42) (43). In a murine model, it modulated expression of genes crucial for DNA repair — Ogg1, Apex1, and Xrcc1 — in peripheral blood cells, to reduce X-ray-induced DNA damage (45).
- Drowsiness, alterations in sleep patterns, altered mental status, disorientation, tachycardia, flushing, pruritus, abdominal cramps, headaches, trouble sleeping, bad dreams, hypothermia (1) (2) (14) (15) (36)
- Hypothermia in autism with sleep disorder: In a 3-year-old girl whose body temperature dropped to 34°C following a single dose of melatonin. Supplementation was stopped, but hypothermia continued for 2 more days after which the temperature returned to normal value (63).
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).
Anticoagulants: Oral melatonin intake is associated with lower plasma levels of factor VIII and fibrinogen (25). Therefore, this may increase the risk of adverse effects when used with anticoagulant medications.
Rhubarb: A study using human primary hepatocytes showed that concomitant use can cause metabolic disorder of melatonin (55).