angelic mhai: 03/22/08

Overview

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.

Uses

Insomnia

Although results are still controversial, studies suggest that melatonin supplements 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). In fact, a recent review of scientific studies found that melatonin supplements help prevent jet lag, particularly in people who cross five or more time zones.

A few 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. In addition, at least one study suggests that melatonin may improve the quality of life in people who suffer from insomnia and some experts suggest that melatonin may be helpful for children with learning disabilities who suffer from insomnia.

Although research suggests that melatonin may be modestly effective for treating certain types of insomnia, few studies have investigated whether melatonin supplements are safe and effective for long term use.

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

A recent study of postmenopausal women found that melatonin alleviated both depression and anxiety. Other 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. Experimental 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.

Eating Disorders

Melatonin levels may play a role in the symptoms of anorexia. For example, abnormally low melatonin levels may cause depressed mood in people with this condition. However, researchers do not know whether supplementation will change the course of the disease. Some researchers speculate that low melatonin levels in people with anorexia may indicate who is likely to benefit from antidepressant medications (a treatment often used for eating disorders).

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.

Sarcoidosis

Some physicians use melatonin to help treat sarcoidosis (a condition where fibrous tissue develops in the lungs and other tissues). Two case reports suggest that melatonin may be helpful for those who do not improve from conventional steroid treatment.

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.

Epilepsy

Preliminary research suggests that melatonin reduces the number of seizures in certain animals and may reduce seizures in people with epilepsy. However, not all experts agree with these findings. In fact, some researchers are concerned that melatonin (1 to 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.

Sunburn

A few small 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.

Viral Encephalitis

Although melatonin has not been scientifically evaluated for use in treating human encephalitis (inflammation of the brain), some studies suggest that this supplement may protect animals from serious complications associated with the condition and even increase their survival rates. In one study of mice infected with Venezuelan equine virus (a type of organism that causes viral encephalitis), melatonin supplements significantly lowered the presence of virus in the blood and reduced death rates by more than 80%. More studies are needed to determine whether similar treatment may offer the same protection to people with viral encephalitis.

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.

Available Forms

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

How to Take It

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 to 5 mg may cause seizures in this age group.

Adult

Insomnia: 3 mg one hour before bedtime is usually effective, although doses as low as 0.1 to 0.3 mg may improve sleep for some people. If 3 mg per night is not effective after 3 days, try 5 to 6 mg one hour before bedtime. An effective dose should produce restful sleep with no daytime irritability or fatigue.
Jet lag: 0.5 to 5 mg of melatonin one hour prior to bedtime at final destination has been successful in several studies. Another approach that has been used clinically is 1 to 5 mg 1 hour before bedtime for 2 days prior to departure and for 2 to 3 days upon arrival at final destination.
Sarcoidosis: 20 mg per day for 4 to 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 PM and 8 PM). 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.

Precautions

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

Possible Interactions

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

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, there have been a few reports suggesting 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 including 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.