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Healthy Living May Issue
MELATONIN: Agent for Rest and Rejuvenation

All was quiet in the Jones household. Suddenly there was a stirring in the bedroom. Richard rubs his eyes and looks over at the clock: "Oh, no June, we’ve overslept. It’s 7:30. Get out of bed. Wake the kids. We’ve all got to go." Suddenly all is pandemonium in the Jones household. What made the difference in those few moments? An awareness of time and its pressure. We all generally recognize that we are living in a time-pressured environment, regardless of whether or not we overslept this morning. It often seems that there are just not enough hours in the day. We find ourselves longing for more energy to accomplish all that we want or need to do. Sometimes it may seem that we are wrestling with twin enemies: frustration and fatigue.

Fatigue is a major problem worldwide. Studies from the U.S. and abroad suggest that in Western nations millions of people have significant problems with fatigue. In the United States, fatigue is one of the 10 most common reasons for visiting a physician.1 Making things worse, a significant portion of those troubled by fatigue cannot fall asleep when they go to bed. Recent U.S. data indicates that some 3.3 million patients each year visit their doctors for insomnia alone.2 Older individuals have been thought to be at greatest risk for this problem. As many as 34 percent of Americans over 65 have problems with insomnia.3

A recent study found that sleep problems are common even in young adults aged 17 to 30. Researchers surveyed about 3000 individuals regarding problems with sleep, such as: difficulty falling asleep, waking up frequently, "disrupted sleep," napping during the day, nightmares, and waking up too early or waking up tired. Only 36 percent responded that they were free of all of these indicators.4

In Western nations, insomnia and related concerns have even been documented in preschool children. For example, a German study found that 12 percent of four to five year old children had difficulties falling asleep.5 The research is clear. For a variety of reasons literally millions of people throughout the world are legitimately crying out: "Why am I so tired? And what can I do about it?"

Onto this stage stepped a nutritional supplement named melatonin. In 1993, newspapers throughout the U.S. carried word of research from the Massachusetts Institute of Technology. Scientists there had demonstrated that small amounts of melatonin acted as a natural sleep aid.6 Melatonin’s popularity grew in 1994 when the lay press reported that it could decrease jet lag.7 Interest in the compound grew further as leading periodicals continued to fan the fire. On August 7, 1995, NEWSWEEK featured melatonin.8 Since then, the compound has continued to receive rave reviews and has demonstrated its ability to generate sales of millions of dollars for bookstores and health food establishments.

When one of the world’s leading melatonin researchers, Dr. Russel J. Reiter, wrote a book in 1995 on the subject, he gave one striking indication of melatonin’s popularity. He observed that 24 different U.S. companies were then marketing the hormone. Furthermore, a steady stream of new companies was joining the marketing ranks on a monthly basis.9

Melatonin is not a foreign substance to the body, but a natural hormone produced in the body and found in certain foods. Even though melatonin supplements have been a commercial success, there is another particularly exciting line of research regarding this hormone. Namely, we are learning that we can boost melatonin production in our own bodies in natural ways, without having to resort to costly supplements. I will address this research later in the chapter and make practical suggestions on how to boost your own body’s production of this compound.

The research claims for melatonin now go far beyond its ability to enhance sleep and relieve jet lag. However, before looking at the other far-reaching effects of this natural compound, we need to look more closely at the areas of research that first ushered melatonin into the limelight. Enhancing Sleep

Israeli researchers led by D. Garfinkel looked at melatonin’s effects on a dozen individuals whose average age was 76.10

For three weeks, half of the group was given 2 mg per day of controlled-release melatonin and the other group was given a placebo. After a one week break (called a "wash out period"), the study was repeated with the other half of the subjects getting the active melatonin, while the remainder got the placebo. The results demonstrated an increase in "sleep efficiency" while on melatonin. Sleep efficiency measures the total time asleep as a percentage of the time in bed.11 It improved from 75 percent, without melatonin supplementation, to 83 percent while on the melatonin. This and other studies12,13 have also shown evidence that melatonin helps decrease the time it takes to fall asleep (19 versus 33 minutes in the Israeli data). Garfinkel and his colleagues concluded that melatonin helped to improve the efficiency of sleep although it did not improve total sleep time; this means that a person will spend a shorter time in bed to get a given amount of sleep.

Coping with Jet Lag

Melatonin has been documented to help with one of the major aggravations of modern travel, namely, jet lag. A number of studies, using a variety of doses and regimens, have looked at this effect.14, 15 One report concluded that the most effective regimen involved taking melatonin on the day of the flight and continuing it for five days thereafter.16

A summary of these benefits of melatonin is shown in Figure 1: Sleep and Jet Lag Effects of Melatonin Supplements.

Aging, Healing, and General Repair

Perhaps nothing has captured the human imagination as much as the quest for a fountain of youth. Some today are suggesting that medical research may have provided at least a partial candidate for a "youth restorer" in melatonin. These sentiments grow out of the recognition that melatonin may ease the daily wear and tear that our bodies sustain. Consequently, it has been dubbed the "fix and rejuvenate" nighttime hormone.17 These healing and general repair effects of melatonin may actually help to delay some of the changes that we normally attribute to aging.

There are other lines of evidence that suggest that melatonin may help to slow the aging process. It is well known that human melatonin levels fall throughout life, as depicted in Figure 2: Fall in Melatonin Levels Through Life.18

Nighttime levels reach a peak in children between one and five years of age and decrease steadily throughout puberty. By the end of puberty, peak melatonin levels have decreased 75 percent.19 Levels continue to fall steadily throughout adult life.

Melatonin Increases the Longevity of Animals

Melatonin levels also decrease in animals as they get older. Giving melatonin to animals increases their longevity.20 Could this life span enhancement be due to some type of anti-aging effect exerted by melatonin? If so, how specifically would that effect come about? A variety of lines of research suggest that melatonin’s anti-aging effects in animals (as well as in humans, perhaps) may hinge largely on its role as a free radical scavenger.

Melatonin’s Role as an Antioxidant

The most toxic of the oxygen-free radicals is a compound called the hydroxyl radical.28 Fortunately, melatonin is an effective antioxidant in dealing with this radical. It is even more powerful than the widely touted natural antioxidant called glutathione. In one laboratory model, melatonin emerged as a five-fold more potent antioxidant than glutathione.29 Melatonin is superior to Vitamin E in handling the toxic peroxyl radical. Overall, the literature indicates that melatonin protects against free radical damage from certain carcinogens, herbicides and radiation.30 Illustrations of certain free radicals are found in Appendix VI. Melatonin’s role as an antioxidant is also illustrated in the Appendix VII.

Preventing or Helping to Fight Cancerous Tumors

We have already seen how melatonin as an antioxidant can exert a powerful effect in helping to prevent cancers through this means. However, this hormone appears to have still other anti-cancer properties. Research has demonstrated that melatonin can slow the growth of breast cancer cells.31 Some of these additional benefits in the area of cancer prevention and treatment may result from the immunostimulating properties of melatonin.

Melatonin: Is All the News Really Good?

With all of this going for it, what could get in the way of melatonin continuing to be a sweeping international success? One factor interfering with melatonin’s drive to be the world’s most popular supplement is governmental actions. England and Canada handle melatonin differently than the U.S., as shown in Figure 4: Control of Melatonin in England, Canada and the U.S.. Notice that in England and Canada the compound can only legally be obtained by prescription.43 In the United States, melatonin is considered a dietary supplement. The law forbids the FDA from reviewing compounds marketed as dietary supplements for effectiveness or safety.44 This lack of monitoring or accountability raises some concerns.

Danger of Long Term Effects Are Unknown

Even if we could be assured that all melatonin supplements were 100 percent pure and contained just as much of the compound as they promised, there are still several lingering doubts. Despite the initial suggestions of melatonin’s safety, what are the potential long-term problems with taking large amounts of a supplement with such far-reaching effects? Even Dr. Reiter, one of melatonin’s biggest proponents, was constrained to admit as recently as 1995 that most melatonin studies had involved only small numbers of people and that we do not yet know who should not be taking melatonin supplements.49 In fact, doses taken far above normal physiologic levels of many supplements over a period of time often cause more problems than they address.50

An ironic twist to one of melatonin’s earliest claims to fame is worth noting at this point. Jet lag actually worsened in a group who were assigned to begin taking the supplement several days before travel rather than waiting until the day of their flight. The implication of this finding is that taking melatonin on a regular basis may prevent some of the beneficial effects of the compound when needed. 51

How to Increase Our Melatonin Levels

If a plant foreman desires to improve production on an assembly line, the likelihood of success will be increased if he is thoroughly acquainted with every aspect of the production process. Similarly, if we want to optimize our melatonin levels, we must understand how the body makes this vital hormone.

Melatonin production occurs in the pineal gland, a tiny organ that is located in the exact center of the brain.60 Its location is shown in Figure 6: Pineal Anatomy.

This gland is only about the size of a kernel of corn and has the shape of a miniature pinecone. Its appearance explains the roots of its name: the Latin pinealis is derived from pinea which means pinecone.61 As a testament to its importance, the pineal gland is the first gland to form during human fetal development. It is clearly distinguishable a mere three weeks after conception.62

It is important to note that the pineal gland is more than just a melatonin factory. At least four important compounds are secreted by this tiny gland,63, 64 as listed in Figure 7: Pineal Gland Secretions.

There are several steps in the chemical production of melatonin. They are outlined in Figure 8: Steps in the Production of Melatonin. For those acquainted with biochemistry, a biochemical flow chart of the biosynthesis of melatonin is included in Appendix VIII.

Regulation of Melatonin Production

In spite of what may seem like a very straightforward chemical process, the body carefully regulates melatonin production.65 The process is largely controlled by the light-dark cycle. Optimal melatonin production only occurs at night and is dependent on a dark environment. Nighttime levels generally peak around 2 A.M. to 3 A.M., as depicted in Figure 9: Melatonin Level Variations Throughout the Day.

In those wee hours of the night, melatonin levels are five to ten times higher than during the day.66 The light-dark regulation of melatonin occurs through an intricate system. The process begins with our eyes and optical nerves which carry information about environmental lighting to an area of the brain called the hypothalamus. Within the hypothalamus lies a small control center(called the Suprachiasmatic Nucleus) that lies above a place where the optic nerves cross after leaving the back of each eye. This control center regulates melatonin production. In a normal daylight situation, the control center is sending messages to the pineal gland that block the release of a key chemical messenger called norepinephrine (NE) that is needed for the pineal to make melatonin. The absence of this messenger ensures that no melatonin is made. In order for the gland to produce melatonin, the chemical messenger (NE) must be made and released into the gland.

These critical functions of this control center have caused some chronobiologists (those who specialize in research on our timed internal rhythms) to refer to this center (Suprachiasmatic Nucleus) as "the body clock." Dr. Russel Reiter has explained further that the control center actually has an internal clock that is either on or off. If the clock is on, it allows the pineal to produce melatonin; if is off, it does not. The clock is on for about 12 hours and off for about 12 hours. Daylight is what keeps this internal clock on schedule.

When a person goes to sleep in a dark room, the eyes now initiate a change in pineal regulation. The presence of darkness is perceived by the eyes, which through a series of intricate nerve connections send messages instructing a group of cells (called the Superior Cervical Ganglion) to make that key chemical messenger (norepinephrine) previously mentioned. This group of cells lies near the top of the spinal cord and has direct nerve connections into the pineal gland, so this task sounds as if it could easily be accomplished. However, the key chemical messenger, even though it is produced, cannot be released into the gland until a parallel phenomenon also occurs. At the same time that the group of cells is making the chemical messenger, nerve pathways stimulated by the darkness tell the hypothalamus’ control center to release its blocking effect on the release of the chemical messenger. It is this combination of messages that leads to an outflow of the messenger into the pineal gland, and the gland then begins to produce melatonin and feeds it into the bloodstream.

Light-dark signals are fed through the optical nerves to a control center in the brain where our "body clock" is located. This clock, in turn, tells the pineal gland not to produce melatonin when the daylight signal is transmitted from the eyes. When the dark signal from the eyes is received by the control center, it triggers the gland to produce melatonin, which is fed into the bloodstream.67

Animal tests indicate that melatonin can also be produced directly by the retina. Under conditions of darkness, this tissue on the back of the eye can act alone in producing melatonin.68

Melatonin is not stored in the pineal gland; it leaves the gland through simple diffusion.69 Its half-life is short during the initial few minutes, followed by a second longer phase.70 As a result we cannot rely on yesterday’s melatonin for today. We need a liberal supply of melatonin each evening.

Some of the factors involved in the body’s production of melatonin are shown in Figure 10: Factors Involved in the Production of Melatonin. Boosting Melatonin Naturally

How can we now apply the understanding of the chemistry and regulation of melatonin in such a way as to increase the production of this vital hormone by our own bodies? The remainder of the chapter will provide answers to this question.

Get Exposure to Bright Light Early in the Day

One of the first and highly respected studies probing the daylight/melatonin connection was published in 1988. Researchers in Finland found that rats who were exposed to natural daylight had significantly higher evening melatonin levels than another group of rats who had an equal amount of exposure to artificial light.71 The difference in melatonin levels of the two groups is shown in Figure 11: Natural Light is Best for Melatonin Production.

Outdoor light is incredibly more intense than the artificial variety. Outdoor light can reach 3000 lux on a bright sunny day.72 A bright indoor environment may provide only 400 lux, less than 15 percent of daylight brightness.73 This medical research verifies the counsel given by Ellen White a century ago, quoted in Figure 12: Sunlight - Nature's Natural Healing Agent.74 There is an interesting observation regarding a special need for more sunlight as we get older. Consider these three facts:
  • Melatonin appears to slow the aging process.
  • The older we get, the less melatonin output we have.
  • Natural light exposure in daytime increases melatonin output at night.
We conclude that to slow the aging process, we can boost our melatonin output by being exposed to more sunlight, which helps to offset the natural weakening of melatonin production. Ellen White understood this need for the elderly to get more sunlight, according to her statement shown in Figure 13: Older People need more Sunlight.75

Bright light, such as sunlight, also may increase serotonin production in the daytime which can in turn prevent depression and fatigue.76

Exercise Boosts Melatonin

An early study by Carr and colleagues looked at seven healthy women. They demonstrated that one hour of exercise on a stationary bicycle could double or triple melatonin levels.78 Other studies have also demonstrated that physical exercise can boost melatonin levels.79

Eat Foods Rich in Melatonin

Melatonin is present in many foods. Eating foods rich in natural melatonin80 can raise melatonin levels in the bloodstream. Foods rich in melatonin are listed in Figure 15: Foods High in Melatonin.81,82

Summing Up

Melatonin is a compound with incredible promise. We are just beginning, however, to learn about its side effects. The use of large amounts of melatonin supplements may in some cases pose significant harm. The most prudent approach seems to emphasize natural lifestyle approaches that boost levels of this remarkable hormone. To some this may sound too simple. It may even sound strangely reminiscent of those things our mothers and grandmothers emphasized: a healthful diet, regular physical exercise, regularity in sleeping, avoiding late night activities, sunshine, etc. Despite the simplicity of these measures, medical research is demonstrating their effectiveness. However, there are some things that even mom and grandma did not recognize: the importance of foods high in tryptophan and melatonin, and the dangers of drugs once thought innocent.

Our growing understanding of melatonin may, indeed, change the way we attempt to answer that oft-posed question, "Why am I so tired?" When we struggle with personal fatigue issues, we may find ourselves running down a mental checklist of factors that affect melatonin levels. Such an approach is calculated to help the majority of people safely boost their energy levels, minimize fatigue, and experience a whole host of other benefits.

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