Production of melatonin in the pineal gland is inhibited by light (mainly blue light) and permitted by darkness. Even dim, artificial light can inhibit melatonin production to some extent, and bright light can substantially reduce production. Consequently, exposure to bright lighting before bedtime may result in difficulty going to sleep.

Insomnia and Delayed Sleep Phase Syndrome (including jet lag):

Insomnia is characterized by difficulty falling asleep, waking up frequently during the night with difficulty going back to sleep, or waking up too early in the morning. Delayed sleep phase syndrome, on the other hand, is characterized by difficulty going to sleep and difficulty waking at conventionally accepted hours. Melatonin has been shown to be beneficial for adjusting the sleep/wake circadian rhythm of delayed sleep phase syndrome. Insomnia, however, is less consistently responsive to treatment with melatonin.[fn value=1][/fn]

Melatonin has a short half-life—20 to 50 minutes. That means that in 20 to 50 minutes, if no more melatonin is added, half of what was there at the beginning will be gone. This allows the circulating melatonin to return to low levels by waking time after production has peaked (around 2 AM). It also means, however, that supplemental melatonin may not be effective for preventing night awakenings unless the supplement is given in a timed-release form. When insomniac patients older than 55 were given 2 milligrams of prolonged-release melatonin daily for three weeks, their quality of sleep and morning alertness were significantly improved. Discontinuing treatment did not cause withdrawal or rebound insomnia. [fn value=2][/fn]

For chronic insomnia in children with unmedicated ADHD (Attention Deficit Hyperactivity Disorder)[fn value=3][/fn] and in individuals with intellectual disability,[fn value=4][/fn]melatonin treatment for four weeks resulted in lessened time to sleep onset, and it increased total time asleep.

Acid-induced lesions in the esophageal lining are the major concern in GERD. Studies in rats have shown that melatonin exerts a protective effect on the linings of the esophagus and the stomach.[fn value=5][/fn] [fn value=6][/fn] When acid and pepsin were infused into the esophagus of rats, those rats pretreated with melatonin showed significantly less damage than did rats not pretreated. When humans with GERD were treated for 40 days with a formulation containing melatonin, L-tryptophan, vitamin B6, folic acid, vitamin B12, methionine, and betaine or with 20 milligrams of omeprazole (a drug that inhibits the production of gastric acid and is often used for treating GERD), 100% of those treated with the formulation containing melatonin reported complete regression of symptoms, whereas only 66% of those treated with omeprazole made that claim. No significant side effects were noted for the formulation.[fn value=7][/fn] Although more research must be done before this can become a standard treatment, there is suggestive evidence that melatonin may stimulate the contractility of the lower esophageal sphincter, thus treating the root cause of GERD rather than merely the symptoms.[fn value=8][/fn]

As an adjunct to chemotherapy, melatonin treatment has improved survival rates in patients and reduced the side effects of chemotherapy. In a randomized study, 250 late-stage cancer patients with solid tumors at varied sites were given 20 milligrams of melatonin daily plus chemotherapy or chemotherapy alone. In the group treated with melatonin, the one-year survival rate was doubled, the number of patients responding to treatment was doubled, and the side effects of chemotherapy (thrombocytopenia, neurotoxicity, cardiotoxicity, stomatitis and asthenia) were significantly decreased compared with the group treated with chemotherapy alone. [fn value=9][/fn] In a randomized study of 50 patients with brain metastases, those who received 20 mg of melatonin at 8 PM daily along with supportive therapy (steroids plus anticonvulsant drugs) had an average survival time of 9.2 months compared with 5.5 months for those who received only the supportive treatment. Furthermore, those receiving melatonin had less frequent steroid-induced metabolic and infective complications. [fn value=10][/fn] Positive effects for melatonin have been clinically observed also in breast cancer, colon cancer, lung cancer, kidney cancer, and prostate cancer.[fn value=11][/fn] [fn value=12][/fn] [fn value=13][/fn] [fn value=14][/fn] [fn value=15][/fn]Nevertheless, at this point the amount and strength of scientific evidence is considered by the medical community to be insufficient for melatonin to be officially acknowledged as a cancer-fighting agent.

Jet Lag: 0.5 to 5 mg of melatonin, taken at the target bedtime at the destination for two to five days after arrival

Analysis of studies of the effectiveness of melatonin on jet lag has shown these amounts to shorten jet lag. Doses higher than 5 milligrams are not more effective. Greatest benefit is noticed when travel is eastbound and when the number of time zones crossed is 5 or more. [fn value=16][/fn]

In a dose-finding study, 0.1 mg or 0.3 mg of melatonin significantly improved sleep efficiency (total sleep time divided by time in bed intending sleep) in adults over 50 years of age with insomnia.[fn value=17][/fn] An amount of 3 mg, though improving sleep efficiency similarly to the lower amounts, was associated with much higher serum levels of melatonin, which remained elevated above physiologically normal levels into the following day. This is thought to be undesirable, perhaps negatively affecting alertness. Furthermore, the higher melatonin levels were associated with an exaggerated hypothermia during the night.

In a 4-week study of school children with chronic sleep onset insomnia, 5 mg of melatonin advanced the time of sleep onset by over an hour.[fn value=18][/fn] Another study, on children with ADHD and chronic insomnia, found amounts of 3 or 6 mg of melatonin effective for advancing sleep onset and increasing total sleep time.3

In a dose-finding study, both amounts of melatonin were effective in advancing the time of sleep onset. The earlier the melatonin was taken, the greater was the phase advance.[fn value=19][/fn]

Cautions

Because melatonin can stimulate the immune system, it has been theorized that supplemental melatonin may be harmful to individuals with autoimmune conditions. Until further research has been done, it may be prudent for people with autoimmune conditions to avoid supplemental melatonin.