Wonderful, fictional testimonials are being printed in the media suggesting that melatonin can possibly delay the spread of cancer, strengthen the immune system, and even slow down the aging process.  Maybe even you have been misled to believe that you can pop a pill to compensate for the decreased levels that naturally occurs, as we get older.  You may be asking yourself, what is the real story behind these tales?  Perhaps the first step in getting to the truth is to understand what melatonin is, how it works, and what the research shows. 

What is Melatonin?

It is a hormone that is manufactured by the pineal gland in the brain. It helps control your body’s internal (circadian) rhythms of body temperature, hormone secretion and sleep. Depending on the time of day that you are exposed to light, your body’s internal clock either shifts ahead or is delayed because light inhibits secretion and darkness stimulates it.  Normally, the pineal gland produces more melatonin at night than during the day. Because the production is partly affected by light, melatonin levels peak in the middle of the night and gradually decrease into the morning hours.  It appears that this hormone peaks between one and three years of age¹, and contrary to what many reports have previously indicated, the body’s secretion of it does not appear to decline as we get older², although there is some evidence to suggest that some drugs including beta-blockers and ibuprofen that may cause production to decline. 

According to Alfred Lewy, director of the Sleep and Mood Disorders Laboratory at the Oregon Health and Science University in Oregon, there doesn’t seem to be a relationship between the amount of melatonin a person makes at night and whether they get quality sleep.  There also is no indication that higher levels of melatonin will make you sleep better.  What we do know, however, is that decreased melatonin levels have been found in insomniacs of all ages³.

What Do We Know About the Uses of Melatonin?

Although most of the studies have been conducted on only a very small number of people, results of some of them indicate that melatonin may help reduce the symptoms of jet lag in some people, and it may help some people fall asleep more quickly and stay asleep without waking up frequently ^4-9.  Some studies also suggest that oral melatonin may be effective for circadian sleep disorders in blind children ^4,5,10.  There have also been some reports indicating that it has assisted people who suffer from insomnia due to abnormal decreased melatonin levels, although most of the studies conducted were shown in elderly people ^{4-5, 12-14} and have not been replicated in other age groups.  Last year, a four week study conducted at MIT showed that there was no difference found in elderly subjects who took dosages of 0.1 mg, 0.3 mg, or 3 mg of melatonin and those that took a placebo as to whether they fell asleep faster, slept longer, or awoke less frequently.  Rather, those that took melatonin were asleep 85 percent of the time that they were in bed, and those that took a placebo were asleep for 78 percent of the time they were in bed ¹⁸.  This study has important implications for this population because of their common complaint that they cannot stay asleep at night.

It has been observed that low -dose melatonin supplements have a rapid and mild sleep inducing effect, as they tend to lower alertness and body temperature in three to four hours after ingesting ^5,15-16.  In fact, a preparation of the hormone has been manufactured by a pharmaceutical company in Israel and is being tested in clinical trials for prescription drug approval as a sleep aid in Canada and Europe.  The United States, however, does not have a pharmaceutical grade melatonin product under testing for efficacy and safety and it is too early to know whether the studies overseas have passed the test.  The FDA has rendered melatonin an orphan drug for adults who suffer from minimal or no light perception, which has tremendous effects on the internal body clock and sleeping patterns. 

What Are The Recommendations For Easing Jet Lag?

It is apparent that the time at which a person takes melatonin to prevent jet lag is very important as it is liable to cause sleepiness and delay adaptation to local time if taken too early in the day.  However, researchers have not set an optimal time for administering the hormone.  A review of nine of the ten trials found that between 0.5 mg and 5.0 mg of melatonin, taken close to the target bedtime at the destination (10 p.m. to midnight), decreased jet lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 mg and 5.0 mg are similarly effective, except that people fall asleep faster and sleep better after 5 mg ¹⁷. The benefit is likely to be greater the more time zones crossed, and less for westward flights.  It also appears that the combination of melatonin along with exposure to sunlight and aerobic exercise upon arrival can help in synchronizing the body’s internal clock.

What Is The Potential Use for Alzheimer’s Disease?

In one of the most recent studies published in the December 11, 2001 issue of the journal, Biochemistry, melatonin was shown to have a potentially important role for Alzheimer’s disease.  The hormone was shown to block the formation of the protein complex amyloid beta, which is toxic to nerve cells and an underlying characteristic in the disease.   Also of interest, the researchers reported that people with this disease tend to have much lower levels of melatonin in their brains.  However, they were quick to point out that more research is needed before they can determine whether melatonin can halt or prevent Alzheimer’s disease.  Nevertheless, the possibility for the use of dietary supplements to promote brain function is an exciting aspect of the growing field of nutritional neuroscience.

What Is Our Recommendation?

Despite all the publicity, scientists do not know exactly what taking a dietary supplement of melatonin does to the human body in the long-term.  We do know that it can help regulate sleep, prevent jet lag, and may serve as a remedy for insomnia.    But claims that melatonin can slow or reverse aging, fight cancer, and strengthen the immune system are far from proven.

If you are considering its use as a sleep aid, you should know that supplements sold in stores typically contain many times the amount of melatonin produced by your body and if taken improperly, can actually disrupt your sleep cycle.   And, because we do not know the effects of continuous usage, it is our recommendation to wait until there is more research in this area. 

Preparations come in either an artificial (synthetic) form or a biological form found in humans or animals. The artificial form of melatonin is made from chemicals in a lab, while the biological form usually is taken from animals, such as cows. The biological form is not recommended because it may transmit disease that can cause illness.  There are also concerns about the quality and purity of the supplements. Because melatonin isn't considered a drug, the Food and Drug Administration doesn't regulate the safety of the supplements before they go on the market. 

Melatonin does have some possible drug interactions as it can interfere with immunosuppressive drugs and case reports suggest that it may be contraindicated for people taking warfarin ^1,17. Those with liver disease should avoid this supplement because the liver plays a key role in its metabolism and usage might result in high concentrations that might have adverse effects ⁵.  Finally, people who suffer from epilepsy should avoid taking melatonin because a case report indicated that it increased the incidence of seizures.

Nevertheless, we do feel that occasional short-term use for most people for the prevention of jet lag appears to be safe and the incidence of side effects reported has been low.  Therefore, if you are planning an overseas trip for business or pleasure this summer and are considering the use of melatonin to ease the “lag”, remember that it is ALWAYS best to speak with your personal physician before taking any over the counter drug or dietary supplement. 

References:

1. Pheatt N, ed.  Nonherbal Dietary Supplements.  Pharmacist’s Letter Continuing Education Booklet 1998:98(4):1-51.
2. Zeitzer J.M, Daniels, J.E., Duffy J.F., et al.  Do plasma melatonin concentrations decline with age?  Am J Med 199:107(5):432-436.
3. The Review of Natural Products by Facts and Comparisons.  St Louis, MO: Wolters Kluwer Co., 1999.
4. Martindale W. Martindale the Extra Pharmacopeia.  Pharmaceutical Press, 1999.
5. Micromedex ® Healthcare Series: Micromedex Inc., Englewood, CO. Vol. 101.
6. Suhner A, et al.  Compartitive study to determine the optimal melatonin dosage form for the alleviation of jet lag.  Chronobiol Int 1998:15(6): 655-6.
7. Petrie K, et al.  A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatry 1993:33(7): 526-30.
8. Claustrat B, et al.  Melatonin and jet lag: confirmatory result using a simplified protocol.  Biol Psychiatry 1992:32(8): 705-11.
9. Petrie K. et al.  Effect of melatonin on jet lag after long haul flights.  British Medical J 1989; 298(6674): 705-7.
10. Sack R.L., et al.  Melatonin administration to blind people: phase advances and entrainment.  J Biol Rhythms 191:6(3): 249-61.
11. FDA Orphan Drug Act: http://www.fda.gov/orphan/oda.htm
12. Garfinkel D, et. Al.  Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995:346(8974): 541-4.
13. James S.P et. Al.  Melatonin administration in insomnia.  Neuropsychopharmacotherapy 1990:3(1): 19-23.
14.  Haimov I, Lavie P, Laudon M. et. Al.  Melatonin replacement therapy of elderly insomniacs.  Sleep 1995:18(7): 598-603
15. Attenburrow M.E., Cowen P.J., Sharpley A.L.  Low dose melatonin improves sleep in healthy middle-aged subjects.  Psychophamacology 1996:126(2): 179-81.
16. Arendt J. Melatonin.  British Medical J 1996:312(7041): 1242-1243.
17. Cochrane Database Syst Rev 2001;(1): CD001520
18. J. Clin. Endocrinol. Metab. 86: 4727, 2001.

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Angela Marks is the Director of Operations for Cooper Concepts, Inc., a division of The Cooper Aerobics Center. Cooper Concepts, Inc. develops and markets health-related products including the Cooper Complete® vitamins and supplements. The division is also responsible for the weekly radio show "Healthy Living Radio with Dr. Ken Cooper." Prior to her current position, she was the Project Director for the initial research study on the Cooper Complete® multivitamin. She co-authored "Effect of Cooper Complete on Glucose Levels" published in Diabetes, 60th Scientific Sessions.

Marks received a bachelors of science degree in education with an emphasis on health promotion from Baylor University and is currently pursuing an MBA. She is also certified by the Cooper Institute as a health promotion director, a physical fitness specialist and in the biomechanics of strength training. Well versed on a variety of health and wellness topics, Marks' expertise lies in the discussion of supplementations and vitamins.