Melatonin is a hormone secreted by the pineal gland in the brain that helps regulate other hormones and maintains the body's circadian rhythm. The circadian rhythm is an internal 24-hour time-keeping system that plays a critical role in determining when we fall asleep and when we wake up. Darkness stimulates the production of melatonin while light suppresses its activity. Exposure to excessive light in the evening or too little light during the day can disrupt the body’s normal melatonin cycles. For example, jet lag, shift work, and poor vision can disrupt melatonin cycles. In addition, some experts claim that exposure to low-frequency electromagnetic fields (common in household appliances) may disrupt normal cycles and production of melatonin.

Melatonin also helps control the timing and release of female reproductive hormones. It helps determine when menstruation begins, the frequency and duration of menstrual cycles, and when menstruation ends (menopause).

Many researchers also believe that melatonin levels are related to the aging process. For example, young children have the highest levels of nighttime melatonin. Researchers believe these levels diminish as we age. In fact, the decline in melatonin may explain why many older adults have disrupted sleep patterns and tend to go to bed and wake up earlier than when they were younger. However, emerging research calls this theory into question.

In addition to its hormonal actions, melatonin has strong antioxidant effects. Preliminary evidence suggests that it may help strengthen the immune system.

If you are considering using melatonin supplements, talk to your doctor.

Insomnia

Studies suggest that melatonin supplements may help induce sleep in people with disrupted circadian rhythms (such as those suffering from jet lag or poor vision or those who work the night shift) and those with low melatonin levels (such as some elderly and individuals with schizophrenia). A review of clinical studies suggests that melatonin supplements may help prevent jet lag, particularly in people who cross five or more time zones.

A few clinical studies suggest that when taken for short periods of time (days to weeks) melatonin is significantly more effective than a placebo, or “dummy pill,” in decreasing the amount of time required to fall asleep, increasing the number of sleeping hours, and boosting daytime alertness.

Multiple human studies have measured the effects of melatonin supplements on sleep in healthy individuals. A wide range of doses has been used, often taken by mouth 30 - 60 minutes prior to sleep time. A study of 334 people aged 55 and older found that prolonged-release melatonin produced significant and clinically meaningful improvements in sleep quality, morning alertness, sleep onset latency, and quality of life in primary insomnia patients aged 55 years and over.

Osteoporosis

Melatonin has been shown to stimulate cells called osteoblasts that promote bone growth. Since melatonin levels may be lower in some older individuals such as postmenopausal women, current studies are investigating whether decreased melatonin levels contribute to the development of osteoporosis, and whether treatment with melatonin can help prevent this condition.

Menopause

Melatonin supplements may benefit menopausal women by promoting and sustaining sleep. Peri- or postmenopausal women who use melatonin supplements to regulate sleep patterns should do so only for a short period of time since long term effects are not known.

Depression

Clinical studies have found that melatonin may be useful in depression, especially associated with postmenopausal depression and anxiety. Other clinical studies show that people who suffer from major depression or panic disorder have low levels of melatonin. Healthy individuals with mild episodic depression and patients who have Seasonal Affective Disorder, (SAD -- a mild depression that correlates with fall and winter -- periods of light-phase shortening) also have lower than normal melatonin levels. Laboratory studies show that melatonin causes a surge in the chemical serotonin, which helps alleviate symptoms of depressive illness, including major and mild depression and SAD. Melatonin should be used with caution in people with depression and should be appropriately timed with light therapy and sleep-phase changes. Disruption of normal circadian rhythm by poorly timed melatonin administration may worsen depression.

Melatonin use along with certain anti-depressant medications can pose potential health risks and should only be used under direct supervision of a qualified doctor.

Benzodiazepine Withdrawal

Some clinical research has found that melatonin may assist with tapering or cessation of benzodiazepines such as diazepam (Valium), alprazolam (Xanax), or lorazepam (Ativan). Sleep quality was improved in those stopping benzodiazepine use. Although preliminary results are promising, further study is needed.

High Blood Pressure

Several controlled studies in patients with high blood pressure report small reductions blood pressure when taking melatonin by mouth (orally) or inhaled through the nose (intranasally). Better-designed research is necessary before a firm conclusion can be reached.

Breast Cancer

Several studies indicate that melatonin levels may be linked with breast cancer risk. For example, women with breast cancer tend to have lower levels of melatonin than those without the disease. In addition, laboratory experiments have found that low levels of melatonin stimulate the growth of certain types of breast cancer cells, while adding melatonin to these cells inhibits their growth. Preliminary laboratory and clinical evidence also suggests that melatonin may enhance the effects of some chemotherapy drugs used to treat breast cancer. In a study that included a small number of women with breast cancer, melatonin (administered 7 days before beginning chemotherapy) prevented the lowering of platelets in the blood. This is a common complication of chemotherapy, known as thrombocytopenia that can lead to bleeding.

In another study of a small group of women whose breast cancer was not improving with tamoxifen (a commonly used chemotherapy medication), adding melatonin caused tumors to modestly shrink in over 28% of the women. People with breast cancer who are considering taking melatonin supplements should consult their doctors before beginning supplementation.

Prostate Cancer

Like breast cancer, studies show that people with prostate cancer have lower melatonin levels than men without the disease. Melatonin blocks the growth of prostate cancer cells in test tube studies. In one small-scale study, melatonin (when used in combination with conventional medical treatment) improved survival rates in 9 out of 14 patients with metastatic prostate cancer. Interestingly, since meditation may cause melatonin levels to rise it appears to be a valuable addition to the treatment of prostate cancer. More research is needed before doctors can make recommendations in this area.

Cancer-related Weight Loss

Weight loss and malnutrition are concerns for people with cancer. In one study of 100 people with advanced cancer, those who received melatonin supplements were less likely to lose weight than those who did not receive the supplements.

Rheumatoid Arthritis

Melatonin levels are lower in patients with rheumatoid arthritis than in healthy individuals without arthritis. However, when arthritis patients were treated with the anti-inflammatory medication indomethacin, melatonin levels returned to normal. The chemical structure of melatonin resembles indomethacin, so researchers suspect that melatonin supplements may work similarly to this medication for people with rheumatoid arthritis. However, this theory has not been tested.

Attention Deficit Hyperactivity Disorder (ADHD)

Although melatonin supplementation does not appear to improve the key behavioral symptoms of ADHD, it may be effective in managing sleep disturbances in children with this condition.

Heart Disease

Low blood levels of melatonin are associated with heart disease, but it is not clear whether melatonin levels are low in response to having heart disease or if low levels of melatonin cause people to develop this condition. In addition, several animal studies suggest that melatonin may protect the heart from the damaging effects of ischemia (decreased blood flow and oxygen that often leads to a heart attack). However, researchers are unclear whether melatonin supplements may help prevent or treat heart disease in people. More studies are needed before scientists can draw any conclusions.

Others Uses

• Sunburn -- A few small clinical studies suggest that gels, lotions, or ointments containing melatonin may protect against redness (erythema) and other skin damage when used alone or in combination with topical vitamin E prior to exposure to UV radiation from the sun.
• Epilepsy -- Preliminary clinical research suggests that melatonin reduces the number of seizures in certain animals and may reduce seizures in people with epilepsy. However, some researchers are concerned that melatonin (1 - 5 mg per day) may actually induce seizures, particularly in children with neurologic disorders. Since this research is in the early stages, some experts suggest that doctors should administer melatonin only to a select group of people who suffer from seizures that cannot be controlled by any other type of therapy.
• Sarcoidosis -- Some doctors use melatonin to help treat sarcoidosis (a condition where fibrous tissue develops in the lungs and other tissues). A few clinical studies suggest that melatonin may be helpful for those who do not improve from conventional steroid treatment.
• Schizophrenia -- Melatonin may be a useful short-term hypnotic for schizophrenic patients with insomnia. A clinical study found that melatonin significantly improved the quality and depth of nighttime sleep, reduced the number of nighttime awakenings, and increased the duration of sleep without producing a morning hangover. Melatonin also significantly reduced sleep-onset latency, heightened freshness on awakening, improved mood, and improved daytime functioning Melatonin may be a useful short-term hypnotic for schizophrenic patients with insomnia. Melatonin could be considered for patients in whom conventional hypnotic drug therapy or higher sedative antipsychotic drug doses may be problematic.

Melatonin is available as tablets, capsules, cream, and lozenges that dissolve under the tongue.

There is currently no recommended dose for melatonin supplements. Different people will have different responses to its effects. Lower doses appear to work better in people who are especially sensitive. Higher doses may cause anxiety and irritability.

The best approach for any condition is to begin with very low doses of melatonin. Keep the dose close to the amount that our bodies normally produce (< 0.3 mg per day). You should only use the lowest amount possible to achieve the desired effect. Your doctor can help you determine the most appropriate dose for your situation, including how to increase the amount, if needed.

Pediatric

• Less than 0.3 mg/day. Although studies in children suggest that doses of 1 - 10 mg melatonin have little to no side effects, there is not enough information to clearly say that doses greater than 0.3 mg per day are safe in children under age 15. In fact, doses between 1 - 5 mg may cause seizures in this age group.

Adult

• Insomnia: 3 mg 1 hour before bedtime is usually effective, although doses as low as 0.1 -0.3 mg may improve sleep for some people. If 3 mg per night is not effective after 3 days, try 5 - 6 mg 1 hour before bedtime. An effective dose should produce restful sleep with no daytime irritability or fatigue.
• Jet lag: 0.5 - 5 mg of melatonin 1 hour prior to bedtime at final destination has been successful in several studies. Another approach that has been used clinically is 1 - 5 mg 1 hour before bedtime for 2 days prior to departure and for 2 - 3 days upon arrival at final destination.
• Sarcoidosis: 20 mg per day for 4 - 12 months. Take melatonin to treat this specific health condition only under medical supervision. Do not take melatonin supplements long-term without consulting your doctor.
• Depression: 0.125 mg twice in the late afternoon, each dose 4 hours apart (for example, 4 p.m. and 8 p.m.). People with depression tend to be particularly sensitive to the effects of melatonin -- meaning that a very low dose is generally enough to achieve the desired outcomes.

Because of the potential for side effects and interactions with medications, people should take dietary supplements only under the supervision of a knowledgeable health care provider.

Some people may experience vivid dreams or nightmares when they take melatonin. Overuse or incorrect use of melatonin may disrupt circadian rhythms. Melatonin can cause drowsiness if taken during the day. If you experience morning drowsiness after taking melatonin at night take a lower dose. Additional side effects include stomach cramps, dizziness, headache, irritability, decreased libido, breast enlargement in men (called gynecomastia), and decreased sperm count.

Pregnant or nursing women should not take melatonin as it could interfere with fertility.

Some studies show that melatonin supplements actually worsened symptoms of depression. For this reason, individuals with depression should consult their doctor before using melatonin supplements.

Although many researchers believe that melatonin levels diminish with age, emerging evidence has brought this theory into question. Since findings are inconsistent, people older than 65 years of age should consult their doctor before taking melatonin supplements, so blood levels of this hormone can be monitored appropriately.

If you are being treated with any of the following medications, you should not use melatonin without first discussing it with your health care provider.

Antidepressant medications -- In an animal study, melatonin supplements reduced the antidepressant effects of desipramine and fluoxetine. More research is needed to determine whether these effects would occur in people. In addition, fluoxetine (a member of a class of drugs called selective serotonin reuptake inhibitors, or SSRIs) has led to measurable depletion of melatonin in people.

Antipsychotic medications -- A common side effect of antipsychotic medications used to treat schizophrenia is a condition called tardive dyskinesia, a movement disorder of the mouth characterized by a constant chewing motion and darting action of the tongue. In a study of 22 people with schizophrenia and tardive dyskinesia caused by antipsychotic medications, those who took melatonin supplements had significantly reduced mouth movements compared to those who did not take the supplements.

Benzodiazepines -- The combination of melatonin and triazolam (a benzodiazepine medication used to treat anxiety and sleep disorders) improved sleep quality in one study. In addition, a few reports have suggested that melatonin supplements may help individuals stop using long-term benzodiazepine therapy. (Benzodiazepines are highly addictive.)

Blood pressure medications -- Melatonin may reduce the effectiveness of blood pressure medications like methoxamine and clonidine. In addition, medications in a class called calcium channel blockers (such as nifedipine, verapamil, diltiazem, amlodipine, nimodipine, felodipine, nisoldipine, and bepridil) may decrease melatonin levels.

Use of beta-blockers (another class of high blood pressure medications that includes propranolol, acebutolol, atenolol, labetolol, metoprolol, pindolol, nadolol, sotalol, and timolol) may reduce melatonin production in the body.

Blood-thinning medications, anticoagulants -- Melatonin may increase the risk of bleeding from anticoagulant medications such as warfarin.

Interleukin-2 -- In one study of 80 cancer patients, use of melatonin in conjunction with interleukin-2 led to more tumor regression and better survival rates than treatment with interleukin-2 alone.

Nonsteroidal anti-inflammatory drugs (NSAIDs) -- NSAIDs such as ibuprofen may reduce the levels of melatonin in the blood.

Steroids and immunosuppressant medications -- People should not take melatonin with corticosteroids or other medications used to suppress the immune system because the supplement may cause them to be ineffective.

Tamoxifen -- Preliminary research suggests that the combination of tamoxifen (a chemotherapy drug) and melatonin may benefit certain patients with breast and other cancers. More research is needed to confirm these results.

Other Substances -- Caffeine, tobacco, and alcohol can all diminish levels of melatonin in the body while cocaine and amphetamines may increase melatonin production.

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