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Melatonin

Is melatonin a miracle drug or a myth? This is what I set out to find out after several patients of mine mentioned that they were taking melatonin. At the onset of my endeavor I must admit I thought that melatonin is probably another one of the numerous "miracle drugs" that ultimately do nothing more than separate one from his or her money. When I was in medical school, melatonin was a mystery hormone secreted by an obscure gland called the pineal gland. At that time, the function of melatonin was a total enigma. Now we know much more about the pineal gland and the amazing hormone it secretes. Melatonin is a hormone that is secreted by a small gland in the center of the brain called the pineal gland. At birth there is very little melatonin secreted by this gland. It is not present until about 3 months of age. At that time, the nighttime peak of melatonin increases dramatically and reaches its peak at about 2 to 3 years of age. Then, it gradually decreases with age. Melatonin has been shown to promote sleep. Elderly people do seem to have a difficult time sleeping and it is hypothesized that this is because of the decreased secretion of melatonin. The melatonin level in the blood decreases rapidly as we wake and are exposed to sunlight in the morning. The melatonin level peaks in the middle of the night.
I decided to do a literature search and see if there was any legitimate literature supporting the assertion of melatonin being a miracle hormone. To my surprise there were over 100 articles written about melatonin that did indeed tout the amazing properties of this hormone. Some of the medical benefits that are suggested in these articles are:
1. Treating insomnia in some individuals.
2. A preventative treatment for jet lag.
3. Melatonin is the most potent antioxidant known. It protects cells from so-called free radical damage.
4. Improves the functioning of the immune system.
5. Prevents cancer probably by acting as a potent antioxidant as well as enhancing the function of the immune system.
6. Delays the aging process.
Unfortunately, most of the research has been performed in laboratory rats. The only claims that have any scientific merit in humans are the treatment of some forms of insomnia and prevention of jet lag. The other claims are totally speculation based on studies done in animals. The results of the studies done in rats certainly are tantalizing. In one study, rats lived 25% longer when they were given melatonin. The main proponent of melatonin is a scientist by the name of Russell J. Reiter. He is a University of Texas cellular biologist who has spent most of his life studying melatonin. He is so sure of the benefits of melatonin that he takes 1 mg of melatonin every night.

The Antioxidant Effect

Antioxidants are compounds that metabolize dangerous molecules in our body called free radicals. Free radicals can attack cellular membranes and even damage our DNA. Some commonly used antioxidants are Vitamin E, Beta-carotene and Vitamin C. Melatonin has been shown, at least in the lab, to be much more potent than any of these well-known antioxidants. Everyone has naturally occurring compounds that neutralize free radicals. Dr. Reiter and his colleagues have shown that small doses of melatonin can prevent rats from contracting cancer when exposed to certain cancer-causing compounds. One such compound is safrole. This compound can cause the production of free radicals that oxidize DNA, thus altering its structure. Damaged DNA can promote the development of cancer. When rats received melatonin in combination with safrole there was almost no damage to the DNA. Melatonin also prevents chemically induced cataracts in rats. Cataracts are formed by free radicals that cause damage to the cells in the lens of the eye. Free radical damage is probably involved in the etiology of many diseases such as Parkinson's disease, multiple sclerosis, Alzheimer's disease, atherosclerosis and many more. Whether or not treatment with melatonin will be beneficial remains to be seen.

Immune Function and Melatonin

Research has demonstrated that melatonin has the ability to enhance or augment the function of the immune system. It seems to be capable of neutralizing the negative effects that stress, drugs and infections have on the function of the immune system. Studies have demonstrated a stimulatory effect of melatonin on acquired immunity. Melatonin has been reported to increase natural killer cell activity.

The Anti-aging Effect

This is the most tantalizing assertion that some researchers have made about the benefits of melatonin. The claims are based on a prominent theory of aging that suggests that the anatomical and functional degeneration that organs undergo during aging is a consequence of accumulated free radical damage. If this theory is true, it would follow that prevention of oxidative damage by free radicals would promote longevity. Obviously, this would be hard to prove in humans since the life span is so long. On the other hand, rats have a much shorter life span and they don't object to being test subjects, so much research has been performed on them. Rats that are given daily doses of melatonin actually live 25% longer. Another study showed that when the pineal gland of an infant rat is grafted in the body of an old rat, a similar improvement in life span was observed. The older rats became more active and physiologically younger. It was hypothesized that an increased production of melatonin is the cause of the improved longevity.

Side Effects

Fortunately, there have been no significant adverse reactions from taking melatonin reported in the literature as far as I can tell. Doses of melatonin that are sold in health food stores are much higher than the doses ordinarily used in most studies in humans. Dr. Richard Wurtman of MIT's Clinical Research Center is doing studies on humans using melatonin to induce sleep. He feels that a more appropriate dose would be in the 0.5 mg. range. Dr. Wurtman has urged caution in using the health food store brand of melatonin.

A Word of Caution

Health food stores market melatonin as a dietary supplement and therefore it is not subject to the U.S. Food and Drug Administration regulations. The regulation of the dietary supplement market place is despicable to say the least. This category of compounds would include herbs. For the most part the claims made about these products are totally unsupported by legitimate medical research. Much of the time these companies do not have any medical research supporting their products. They do not have to show that their products have any definite positive effects. The products are not manufactured according to any set standards. The manufacturers can make almost any claims they want as long as they word their claims carefully. The purity of the products is totally unregulated, meaning you may get a different concentration of a supplement from one bottle to the next or from one manufacturer to the next. A real-life example of problems related to the "health-food" market place is exemplified by L-tryptophan. It was marketed for insomnia several years ago. It caused a condition called the eosinophilia-myalgia syndrome that resulted in 38 deaths and over 1500 reported cases. It was caused by contamination of the product which is a direct result of the lack of regulation.

Conclusion

Melatonin does seem to have some potential. I certainly don't think it would hurt to take melatonin on an occasional basis to try to prevent jet lag. On the other hand, I think we need to use caution in taking melatonin until more studies show a definite benefit in humans. The shelves of pharmacies are packed with numerous medicines that have theoretical properties that can improve health and longevity. Unfortunately, they rarely prove to be of any help and occasionally are harmful. For instance, vitamin E and beta-carotene have both been proven to not be helpful and possibly be harmful.

References

1. Reiter RJ, et al. A review of the evidence supporting melatonin's role as an antioxidant. J Pineal Res 1995 Jan; 18(1):1-11
2. Reiter RJ, et al. Melatonin as a free radical scavenger: implications for aging and age-related diseases. Ann N Y Acad Sci 1994 May 31;719:1-12
3. Poon AM, et al. Evidence for a direct action of melatonin on the immune system.Biol Signals 1994 Mar-Apr;3(2):107-17
4. Herbal Roulette. Consumer Reports November 1995 pg. 698-705
5. Cowley G. Melatonin. Newsweek 1995 Aug 7;46-49
6. Hearn W. Melatonin caution: Latest majic bullet may not hit target. American Medical News 1995 Nov 6;20-30.
7. Reiter RJ, et al. Melatonin, hydroxyl radical-mediated oxidative damage, and aging: a hypothesis. J Pineal Res 1993 May;14(4):151-68
8. Maestroni GJ. T-helper-2 lymphocytes as a peripheral target of melatonin. J Pineal Res 1995 Mar;18(2):84-9
9. Kloeden PE, et al. Timekeeping in genetically programmed aging. Exp Gerontol 1993 Mar-Apr;28(2):109-18
10. Kloeden PE, et al. Artifical life extension. The epigenetic approach. Ann N Y Acad Sci 1994 May 31:719:474-82

The information provided above is offered as a community service about health-care issues and is not a substitute for individual consultation. Advice on individual problems should be obtained from your personal physician. This information is based on research by the author and represents his interpretation of the literature.

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Readers may send questions to our email address. This column is for informational purposes only and is not a substitute for professional or medical advice.

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