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Melatonin
is secreted by the pineal gland in the brain and is important in the regulation
of many hormones in the body. Among its key roles, melatonin controls
the body's circadian rhythm, an internal 24-hour time-keeping system that
plays an important role in when we fall asleep and when we wake up. Darkness
stimulates the release of melatonin and light suppresses its activity.
Normal melatonin cycles are disrupted when we are exposed to excessive
light in the evening or too little light during the daytime. 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 (as is common in household appliances) may disrupt normal cycles
and production of melatonin.
Melatonin is also one of the hormones that controls the timing and release of
female reproductive hormones. As a result, melatonin helps determine when
menstruation begins, the frequency and duration of menstrual cycles, and when
menstruation ends (menopause). Many researchers also believe that levels of
melatonin in the body are related to the aging process. For example, young
children have the highest levels of nighttime melatonin and these levels are
thought to diminish progressively with age. This decline likely contributes to
why many older adults suffer from disrupted sleep patterns and tend to go to bed
earlier and wake up earlier in the morning than when they were younger. However,
emerging research is bringing the idea of diminished melatonin levels in the
elderly into some question. Therefore, those considering use of this supplement
should first talk to their healthcare provider about having blood levels of
melatonin checked.
In addition to its hormone actions, melatonin also has strong antioxidant properties and preliminary evidence suggests that it may help strengthen the immune system. Because melatonin is a potent hormone, it's advisable to check with a healthcare provider before using it as an antioxidant supplement.
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 placebo 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 of value for children with learning disabilities who suffer from insomnia.
Although research suggests that melatonin may be modestly effective for treating certain types of insomnia as described, few studies have investigated whether melatonin supplements are safe and effective over the long term.
Osteoporosis
Melatonin has been shown in laboratory studies to
stimulate cells called osteoblasts that promote bone growth. Given that
melatonin levels may also be lower in some older individuals such as
postmenopausal women, current studies are investigating whether or not 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, as indicated earlier, are not known.
Depression
In one small study of 10 people with a particular
type of depression known as seasonal affective disorder (depressive symptoms
that develop during the winter months when exposure to light is lessened), those
who received melatonin supplements had significant improvement in their symptoms
compared to those who received placebo. Given the small size of this study,
however, more research is needed before conclusions can be drawn regarding use
of melatonin for either seasonal affective disorder or any other type of
depression. This is particularly true since one study from the 1970s suggested
that symptoms of depression may worsen when taking melatonin.
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, it is not known 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 and 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), the addition of melatonin caused tumors to modestly shrink in over 28% of the women. People with breast cancer who are considering taking melatonin supplements should first consult a healthcare provider who can help construct a comprehensive treatment approach to be administered together with conventional care.
Prostate Cancer
Similar to breast cancer, studies of people
with prostate cancer suggest that melatonin levels are lower compared to men
without cancer, and test tube studies have found that melatonin inhibits the
growth of prostate cancer cells. In one small-scale study, melatonin (when used
in conjunction with conventional medical treatment) improved survival rates in 9
out of 14 patients with metastatic prostate cancer. Interestingly, meditation
appears to be a valuable addition to the treatment of prostate cancer. The
positive effects of meditation may be due to a rise in levels of melatonin in
the body. Although these early results are intriguing, more research is needed.
Cancer-related Weight Loss
Weight loss and malnutrition are of
great concern for people with cancer. In one study of 100 people with advanced
cancer that had spread throughout the body, those who received melatonin
supplements were less likely to lose weight than those who did not receive the
supplement.
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
In a group of patients with rheumatoid
arthritis, melatonin levels were low compared to healthy individuals without
arthritis. When treated with the anti-inflammatory medication indomethacin,
melatonin levels returned to normal. The chemical structure of melatonin
resembles indomethacin, so researchers speculate that melatonin supplements may
work similarly to this medication for people with rheumatoid arthritis. This
theory has not been tested, however.
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 animal species and may reduce seizures in
people with epilepsy. However, not all experts agree with these findings. In
fact, concern has been raised that melatonin (1 to 5 mg per day) may actually
induce seizures, particularly in children with neurologic disorders. Given that
the research is in a very premature stage, some experts suggest that melatonin
should be administered by healthcare providers to only a select group of people
who suffer from seizures that cannot be controlled by any other type of
therapy.
Sunburn
A few small-scale studies suggest that gels, lotions,
or ointments containing melatonin may protect against redness (erythema) and
other skin damage when used either 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, however, to determine whether similar
treatment may offer the same protection to people with viral encephalitis.
Heart Disease
Low levels of melatonin in the blood have been
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 predispose
people to developing this condition. In addition, several studies in rats
suggest that melatonin may protect the hearts of these animals from the damaging
effects of ischemia (decreased blood flow and oxygen that often leads to a heart
attack). It is not known from this information, however, whether melatonin
supplements may help prevent or treat heart disease in people. More research and
scientific information is needed before conclusions can be drawn.
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 range for melatonin supplements. Different people will be more sensitive or less sensitive to its effects. For those especially sensitive, lower doses may work effectively while a higher dose could cause anxiety and irritability. The best approach for any condition is to begin with very low doses of melatonin that match the amounts our bodies normally make on a daily basis (< 0.3 mg) and keep the dose to a minimum. Your healthcare provider can help guide what is best and most appropriate, including how to increase the amount as needed.
Pediatric
- Less than 0.3 mg/day
Although studies including small numbers of children suggest that doses of 1-10 mg melatonin have little to no side effects, there is not enough information at this point 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. Until more information is available, it is safest to keep the dose close to the amount that our bodies normally produce (< 0.3 mg per day).
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 three days, try 5-6 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 one hour before bedtime for two 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. Use of melatonin to treat this specific health condition should only be done under medical supervision. Do not take melatonin supplements long-term without consulting your healthcare provider.
- Depression: 0.125 mg twice in the late afternoon, each dose four 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 get the desired outcomes.
Precautions
Because of the potential for side effects and interactions with medications, dietary supplements should be taken 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 could disrupt circadian rhythms. Melatonin can cause drowsiness if taken during the day. Individuals experiencing morning drowsiness after taking melatonin at night should take less of the supplement. Additional side effects that have been reported from melatonin include stomach cramps, dizziness, headache, irritability, decreased libido, breast enlargement in men (called gynecomastia), and decreased sperm count.
Melatonin could interfere with fertility and also should not be taken by pregnant or nursing women.
A 1973 study including only 4 people with depression found that melatonin supplements actually worsened symptoms of the condition. For this reason, individuals with depression should consult a healthcare practitioner before using melatonin supplements.
Although many researchers believe that levels of melatonin diminish with age, emerging evidence has brought this theory into question. Given these inconsistent findings, people older than 65 years of age should consult a healthcare practitioner before taking melatonin supplements so that 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 talking to your healthcare 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 for the treatment of 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
Melatonin should
not be taken 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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Review Date: April 2002Reviewed By: Participants in the review process include: Ruth DeBusk, RD, PhD, Editor, Nutrition in Complementary Care, Tallahassee, FL; Jacqueline A. Hart, MD, Department of Internal Medicine, Newton-Wellesley Hospital, Harvard University and Senior Medical Editor Integrative Medicine, Boston, MA; Gary Kracoff, RPh (Pediatric Dosing section February 2001), Johnson Drugs, Natick, Ma; Steven Ottariono, RPh (Pediatric Dosing section February 2001), Veteran's Administrative Hospital, Londonderry, NH. All interaction sections have also been reviewed by a team of experts including Joseph Lamb, MD (July 2000), The Integrative Medicine Works, Alexandria, VA;Enrico Liva, ND, RPh (August 2000), Vital Nutrients, Middletown, CT; Brian T Sanderoff, PD, BS in Pharmacy (March 2000), Clinical Assistant Professor, University of Maryland School of Pharmacy; President, Your Prescription for Health, Owings Mills, MD; Ira Zunin, MD, MPH, MBA (July 2000), President and Chairman, Hawaii State Consortium for Integrative Medicine, Honolulu, HI.
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