“I’ve heard of it,” said a friend of mine. “That’s skin pigment, isn’t it?”

She was thinking of melanin, the dark color in skin and hair. Since that conversation I’ve encountered many people who confuse the two words. Melatonin is a natural molecule made by the pineal gland, which is located in the brain. Since 1993, melatonin supplements have been available in many health food and drug stores, and through mail order catalogs.

Melatonin is made from an amino acid called tryptophan. Tryptophan is an essential amino acid, that is, the body cannot make it; we need to get it through the foods we eat. Tryptophan is found in a wide variety of foods. As we consume tryptophan during the day, the body converts it into serotonin, an important brain chemical involved with mood. Serotonin, in turn, is converted into melatonin. This conversion occurs most efficiently at night.

Melatonin helps to set and control the internal clock that governs the natural rhythms of the body. Each night the pineal gland produces melatonin which helps us fall asleep. Research about this molecule has been going on since it was discovered in 1958, but it has only been in the last few years that there has been such attention paid to melatonin. Close to a thousand articles about melatonin were published worldwide in 1994. One reason for this growing interest is that we are realizing that deep sleep is not the only byproduct of melatonin. We are learning that it has a significant influence on our hormonal, immune, and nervous systems. Research is accumulating about melatonin’s role as a powerful antioxidant, its possible anti-aging benefits, and its dream-enhancing properties. It is an effective tool to prevent or cure jet lag, an ideal substance to reset the biological clock in shift workers, and a great supplement for those who have insomnia. Melatonin also may have roles to play in the treatment of prostate enlargement, as an addition to cancer treatment, in lowering cholesterol levels, in influencing reproduction, and more. A delightful bonus is that melatonin can increase lifespan.

Melatonin and longevity

A few years ago researchers in Switzerland gave male mice melatonin in their drinking water (Maestroni, 1988). Another group of mice received plain water. At the start of the study all the mice were 19 months old (equivalent to about 60 years in humans) and healthy.

The researchers were surprised when the mice on melatonin showed such a striking improvement in their health, and most remarkably, lived so much longer! And after 5 months on melatonin, astonishing differences in the fur quality and vigor of the two groups became evident. The mean survival time of the untreated group was 25 months (78 years in humans) versus 31 months (98 years) in the melatonin-treated mice!

A similar experiment was repeated in 1991 by Pierpaoli and colleagues. The results confirmed the earlier study. Melatonin, when given regularly to middle-aged mice, increased their life span by 20%.

How would melatonin administration do in the young? To find out, Pierpaoli and colleagues gave melatonin every night to young, female mice (strain C3H/He) starting at age 12 months until death. (There are various strains of laboratory mice and the effect of a particular substance may be different on each strain. That’s why it’s important to mention which one.) These mice had not yet reached menopause. The average lifespan in this strain of mice is about 24 months. The age of 12 months (pre-menopause) would correspond roughly to age 35 in humans. To the surprise of everyone, melatonin shortened survival by 6%. A common reason was the high rate of ovarian cancer in these young mice. Apparently there are cells in the ovaries, in this strain, that overgrow when stimulated by melatonin, causing tumors. Another strain of young, female mice (NZB) was also given melatonin nightly starting at age 12 months. They lived longer. Another group of NZB strain female mice was given melatonin at 5 months of age (Pierpaoli, 1994). They also lived longer. Therefore, there is a difference in response to melatonin by different mouse strains.

How did melatonin effect mice who had already reached menopause? In an additional study, when 18 month old postmenopausal female mice (strain C57BL/ 6) were given melatonin nightly, ovarian cancer was not detected and they lived 20% longer than mice of the same age who were not given melatonin.

How can we interpret these studies in order to make practical recommendations for us humans? First we have to realize that rodents and humans may respond differently to the same medicine. We have seen that different strains of mice respond differently. However, we know by experience in countless other studies and with various other medicines that there is often a similarity between the effects of a substance on rodents and that on humans. It is also possible that if the younger, female mice had been given a lower dose of melatonin, they may have fared better. Based purely on a weight ratio, the amount of melatonin given the mice was many times the dose a human would normally use at night for sleep.

In order for us to know for certain what melatonin will do in humans when given for a lifetime, we will need to follow at least a few hundred or thousand people receiving melatonin for a few decades. Multiple groups would be needed to try different dosages. The volunteers would be advised not to take any other supplements or medicines. Such a comprehensive study is not under way at this time. And the results of such a study would not be available until well into the 21st century. What are we to do in the meantime?

We have to make an intelligent decision based on the available information. There is no right or wrong answer at this time as to whether middle-aged and older people should or should not take melatonin regularly to increase their lifespan. Chronic and high dose melatonin use in the young is strongly discouraged at this time.

Different scientists familiar with these studies may endorse different courses of action. One scientist may caution, “Let’s wait a few more years before making any recommendations.” Another scientist may advocate, “If we wait, we’ll have to wait a few decades. I personally do not want to risk waiting that long; I may be 6 feet under by then. I’m 65 now and I’m having trouble sleeping at night. Melatonin provides me with great sleep. In addition to the obvious advantages of restful sleep, there’s the added bonus that it could extend my life span.” Who will eventually be proved right? No one can predict for sure at this time.

There are additional studies that support the role of melatonin and the pineal gland in life extension. It has been known for a few decades that when rodents had their pineal gland removed, they died sooner. When the pineal glands of young mice were transplanted into older mice, the older- mice lived longer and aging symptoms were postponed (Lesnikov, 1994). When young mice received the pineal gland from older mice, they died sooner.

The pineal gland releases substances other than just melatonin. These other substances, one such example is epithalamin, have a role to play in longevity; in fact, epithalamin and other pineal gland extracts have similarly produced life extension in mice (Anisimov, 1994).

The pineal gland has the means of communicating with every cell of the body through its primary hormone, melatonin. Most hormones need a receptor on the cell membrane before they can enter the cell. Not so for melatonin. As the pineal gland releases melatonin, it quickly goes into the local bloodstream and then to the rest of the body’s blood circulation. From there, melatonin finds its way to every body fluid and tissue. Because it is readily soluble in fat, melatonin has the unusual capacity to permeate into tissues and enter practically every cell of the body. (Most cell membranes are surrounded by a layer of fatty acids.) When melatonin enters the cells, it has the further ability to go directly to the DNA. Researchers speculate that the amount of melatonin reaching the DNA of every cell informs it as to which proteins to make. In November of 1994, the Journal of Biological Chemistry published a fascinating article where researchers Becker-Andre and colleagues found a specific receptor for melatonin right in the nucleus of cells. They conclude, “A nuclear signaling pathway for melatonin may contribute to some of the diverse and profound effects of this hormone.”

During infancy and childhood there is a high peak of melatonin reaching every cell. The high peak lets the cells know that the organism is young. The amount of melatonin released each night is less in middle age and even less still in old age. Therefore, as we advance in years, a lesser melatonin peak reaches the DNA in our cells. Some researchers think the pineal gland functions as the “aging clock.” The reasons for the decline in melatonin levels was discussed in chapter two. One possibility is the failure of the pineal cells. They may get overworked through the years and not function as efficiently. Perhaps supplementation with melatonin may allow the pineal gland to work less hard and preserve its optimal functions for many more years.

The decline of melatonin peak levels provides a signal to inform all cells in the body of their age i.e. it’s time to call it quits, call a lawyer to write a living will, and make the down payment for a plot at the cemetery (or cryonics arrangements for futurists). Melatonin supplementation could trick the DNA into thinking, “Maybe I miscalculated. I must be younger than I thought.”

We should not think of melatonin as the only influence on aging. In a complex organism such as the human body there are innumerable factors that are involved in the aging process. The pineal gland is only one of these factors, albeit an important one.

Some of the ways melatonin could prolong life span include it’s ability to be an antioxidant, enhance the immune system, provide deep sleep, and regulate hormonal levels. Another interesting correlation is between diet and melatonin. It is known that food restriction in rodents causes an increase in melatonin production (Stokkan, 1991). Food restriction also leads to life extension. It is too early to tell whether the increase in melatonin due to food restriction is one of the factors that leads to this longevity.

I know a number of individuals who have started to take melatonin nightly at doses ranging from 1 mg to 10 mg. They do not take melatonin necessarily for sleep, but primarily for its potential health and longevity benefits. Four of these individuals have been taking it for over two years, without apparent side effects. Some organizations involved in seeking ways for life extension are recommending to their members to use melatonin regularly.

A few pineal gland researchers have started to take melatonin for its potential health benefits. Russel Reiter, a neuroendocrinologist and foremost pineal gland researcher, is quoted in Vogue magazine, February 1995, “I’ve been taking it for years for jet lag. When we made the discovery about its antioxidant potential, I started taking it regularly.” (He takes about 1 mg nightly.)

We don’t know for certain the long-term, positive or negative, effects of melatonin use in humans then again we hardly know for certain the long-term effects of many common medicines or supplements, including aspirin and vitamins.