The Melatonin and Aging Sourcebook

1995

PREFACE

AT AGE THIRTY-FIVE I WAS practicing general internal medicine in a large Montreal clinic. Our patients included a number of wealthy persons who would travel to Rumania for special rejuvenating treatments. There they were prescribed various combinations of vitamins, lotions, hormones, and so on.

Our clinic in Montreal specialized in treating obesity which, as we all know, is one of the major causes of diseases such as diabetes, heart disease, cancer, arthritis, hypertension and stroke. Thus, a large part of my practice consisted of nutritional and metabolic counseling.

I was approached by one of my senior partners, Dr. David Marcus, who suggested we learn more about anti-aging therapies, and apply them in our own clinic. I found his proposal very exciting. As a medical student I had majored in biochemistry and, in fact, one of the main reasons I went to medical school was to investigate the processes involved in aging. (In medical school, I had spent several summers studying with Dr. Bernard Grad, director of McGill University’s Aging Research Center at that time.) Following Dr. Marcus’s suggestion, I began researching all the latest information on aging, trying to develop a practical approach to combat the problem.

After a thorough review of the literature it became clear to me that aging is a syndrome, or a combination of conditions, coordinated by the various hormonal systems in the body. Simply put, aging consists of an impaired ability to adapt to a hostile environment, so that a minor injury to the body can lead to more and more serious consequences. Therefore, aging can be seen as an inability, on the part of the body, to adapt to various external circumstances; and this inability to adapt properly is largely dependent on neurochemical and hormonal systems. These systems operate with the help of simple substances, called neural messengers or neurotransmitters, which are small molecules formed from the basic foods we ingest. Neurotransmitters have been known about and investigated for quite some time. We’ve all heard of substances like adrenaline, acetylcholine, noradrenaline, dopamine (used to treat Parkinson’s disease), etc.

Recently, scientists have begun investigating another important type of neurotransmitter, serotonin. Although known to be important, serotonin was largely ignored in the past, since it is found in such small quantities in the body, which made it very difficult to measure with the crude instruments available at that time. But, as research methods and technology improved, serotonin became measurable.

One day, in the course of my research, I stumbled on some data which absolutely astonished me. That data, (Table P.1), shows that the concentration of serotonin in the pineal gland is about one hundred times higher than in the rest of the brain.

Thus, my attention was captured by the pineal gland, and I embarked on an adventure of discovery for the proverbial fountain of youth or tree of life, which has fascinated me ever since.

The pineal gland has been known since ancient times. Alchemists, philosophers, physicians, and eastern mystics were all convinced that it played a key role in regulating bodily functions. Hindu yogis considered it to be the third eye, the center of occult power, the place where the soul was said to leave the body during the highest stages of meditation, and at the moment of death. Descartes believed that the pineal gland was the seat of our soul and passions.

The opinion of medical science thirty years ago was that the pineal gland was simply a vestigial organ with little significance. However, all that changed as the tools became available to measure substances in terms of picograms (1/10¹³ grams), so that now we can look inside the pineal gland, see how it works, what it does, and how it functions both as a biological clock (measuring the real biological time an organism lives) and as a regulator of all neurohormonal events (controlling production of hormones in response to past events within the body). Furthermore, animal studies have shown that it is possible to reverse the aging process by injecting a pineal-produced substance into the body. That substance is melatonin.

Researching the pineal gland, one of the few organs abandoned by medical science, became a great challenge for me, and I believe that unravelling its secrets will provide the key to solving the problem of aging. The importance of the pineal gland and its products, primarily melatonin, cannot be overestimated. Over the last fifteen years the pineal gland has gained in stature, being regarded not simply as a useless organ inside the brain, but as the regulator of regulators, the biological clock controlling human life span, and very likely the fountain of youth, since it produces substances capable of rejuvenating the body.

The search for the fountain of youth dates back to the beginning of time. When Adam and Eve were banished from the Garden of Eden they became mortal — they could no longer eat of the tree of life. It has been the dream of humankind to someday find this tree of life once again.

The aim of this book is to present information on just how far medical science has progressed in its study of the process of aging, and to suggest that it is now possible to slow down, or even reverse the aging process based on this new knowledge. I believe that we are already at a point where the human life span can be extended significantly, and that in the next twenty years or so humankind will become practically immortal, given the advances in genetics, microbiology, and the treatment of disease that are occurring almost daily.

In 1987 we published a thesis suggesting that the pineal extract melatonin can act as a rejuvenating hormone, but only when administered in the evening (Rozencwaig, R., Grad, B. R. and Ochoa, J. 1987, The role of melatonin and serotonin in aging. Med. Hypothesis. England. 23, 4: 337-352). In the same article we proposed a new and unified theory of aging, in which it was suggested that the pineal gland, and its hormone melatonin, are the key components of rejuvenation, and that melatonin is the primary substance available to us to combat the ravages of aging. Since that time, new evidence from the scientific community has appeared which supports our claim.

The unique feature of our theory lies in the fact that aging can now be attributed to changes in one particular organ, which would explain the similarity of aging in all mammals. In addition, it confirms and unifies existing scientific theories of aging. Furthermore, scientific data from experiments on animals now exists which proves that melatonin not only retards aging but actually reverses the aging process itself.

In short, it appears that melatonin and the pineal gland may very well be the key to discovering the fountain of youth.

Even if one leads a very uneventful life (i.e., not exposed to high levels of stress) the pineal life span is genetically programmed. This program can be either damaged (by mental or physical trauma) or altered in a positive sense (utilizing procedures which I will describe later on). As it turns out, the pineal gland exerts a controlling influence on the hypothalamus, which is believed to be the emotional and hormonal center of the body, as well as a gland responsible for growth development and aging.

During periods of darkness, the pineal gland is very active, producing a number of substances — melatonin in particular. The properties of melatonin, along with the other substances produced during periods of darkness, are all involved in the processes of regeneration and repair of the body. It appears that the damage done to the body during the day (from normal wear and tear, as well as stress and accidents) is repaired at night (every night) through the influence of melatonin, and other substances produced or mediated by the pineal gland.

The more I studied the effects of melatonin the more astonished I was. One factor became obvious: melatonin becomes active during periods of darkness, and not during the day. This simple observation proved to be of immense importance, since the effects of melatonin are quite different during daylight hours.

The concentration of melatonin in the pineal gland declines steadily after puberty, while the concentration of serotonin rises. Thus, the ratio of serotonin to melatonin in the diencephalon increases with age. The importance of this phenomenon will become apparent when we discuss how to combat aging.

Aging involves a breakdown in the coordination of hormonal systems. When these systems are synchronized (with the time of day) and functioning properly, the body’s adaptive capacity is well maintained and aging occurs very slowly. The hormones that control bodily functions operate in an orderly, hierarchical fashion. Several major neurohormones (neurotransmitters) are responsible for higher levels of hormonal control. These are small molecules which act on the brain and other centers, and convey messages to various parts of the body. The two major neurotransmitters are noradrenaline and serotonin.

As we have noted, the pineal gland secretes a variety of substances during hours of darkness, the most important being melatonin, which is produced from serotonin, which the gland secretes during hours of daylight. Therefore, each sunset represents a stimulus for the pineal gland to convert most of its serotonin into melatonin. Thus, the neurotransmitter serotonin, which controls many of the body’s vital functions, is totally depleted and replaced by melatonin, which acts on vital functions during hours of darkness. This phenomenon occurs every night, regardless of what activities we are involved in during the day. However, there are ways to increase or decrease melatonin levels, which we will describe later in this book.

Dr. Roman R. Rozencwaig

September 1996

INTRODUCTION

SINCE AGING OCCURS AS A RESULT of multiple processes (see Chapter 2, Figure 2.1) which uniformly lead to various diseases of the aged, it was shown that intervention with nighttime melatonin supplementation would delay and even reverse these pathologic changes and retard or possibly reverse the aging process.

It was shown that actual rejuvenation and retardation of aging in animals occurred in three ways: 1) by removal of the pituitary gland, along with proper supplementation, 2) starvation, 3) melatonin supplementation at night, and grafting of young pineals into the older animals.

The pineal gland is a biological clock which controls the hormonal system. It consists of neuronal cells which do not replicate. Thus, loss of pineal cell function or pineal cells leads to a series of reactions which cause disorganization of internal rhythms (including immunity), and other endocrine abnormalities.

In addition, melatonin works on individual cells where it produces cGMP and increases the ratio of cGMP/cAMP. It is well known that during the day cAMP is catabolic (a destructive but necessary process) whereas cGMP is an anabolic or rebuilding process which takes place during the night hours in most animals and humans.

Along with melatonin there are other methoxy-indoles produced by the pineal that function similarly, with slight differences, to melatonin. These are the minor melatonin-like substances, and they need more work for fine-tuning for melatonin effects. We (Rozencwaig and Grad) and others have also shown that the effects of serotonin are pro-aging while those of melatonin are anti-aging.

Melatonin is the best scavenger of free radicals and a great detoxifying enzyme. Thus, since melatonin decreases linearly with age, this suggests a singular cause for the uniformity of the aging process itself and the limited life span for individual species.

Of course, one can increase melatonin naturally without supplementation, but by doing so we ultimately exhaust the pineal gland, whereas supplementation with a natural melatonin has a sparing effect on the pineal. (This is similar to the exhaustion atrophy that occurs with insulin and sugar — the more sugar one eats the more insulin is produced, until such time as the insulin-producing cells no longer are able to function, which leads to mature onset diabetes.) Therefore, it is my belief that melatonin supplementation is a better way of staying young and still keeping the reserve of the pineal gland intact.

There are many other ways to increase melatonin production by the pineal cells. These include drugs such as N.A.T., HIOMT enzymes and other pharmacological methods. But, in my opinion, they too will induce the pineal production of melatonin and lead to final exhaustion of the pineal gland itself.

Since melatonin has been shown to be an up-regulator of immunity, its use in cancer has been proven many times. Starvation and pituitary removal can both be attributed to melatonin function in rejuvenating experiments, since starvation causes an increase in melatonin; and melatonin with thyroid supplement acts as a functional pituitectomy.

Melatonin also has a stabilizing effect on the central nervous system. It reduces the onset of epilepsy, produces sleep similar to that of a young adult’s, without a hangover, and helps migraine patients. In addition, it has been suggested that melatonin deficiency may play a part in Parkinson’s disease and other psychoneurological disorders.

Recently we studied several patients with dyslexia where small doses of melatonin improved their sleep and daytime concentration (Rozencwaig and Grad). Also, we found a topical application of melatonin dissolved in alcohol combined with propylene glycol produced hair growth in balding men whose ages varied from 25 - 75 (Rozencwaig and Grad). (This has also been reported by other research teams.) Melatonin supplementation from early morning auto-urine drinking is demonstrated in the practice of yogis who drink first morning urine to induce a meditative/hypnotic state. (Mills, M. and Faunce, T.A., 1991. Medical Hypothesis, 936: 195-199).

Parkinson’s disease and melatonin have also been related in both animal and human studies. Administration of L-dopa increases pineal melatonin, and chronic oral administration of melatonin improves tremors and rigidity in Parkinson’s patients. Melatonin was also shown to antagonize the effects of beta MSH, thus reducing stimulation for melanin; and melatonin may decrease the incidence of melanoma.

In addition, the beneficial effects of L-tryptophan and pyridoxine supplementation in tardive dyskinesia (Sandyk, et al. 1990, Int. J. of Neuroscience, 52: 85-92) can be related to melatonin release in these patients.

P.E. Kloeden, et al., (1993, Exp. Gerontol. Mar-Apr, 28, 2: 109-118) have suggested that genetic switching triggered for melatonin signal induces changes in supporting biological structures such as hormonal and other control systems. Pierpaoli’s experiments (see Abstracts, Chapter 2 and References, Chapter 4) provide key involvement of melatonin in the aging process; their theory proposes that melatonin acts directly in switching on genes.

In an article in a book titled, Where Science and Magic Meet (Shaftesbury, England: Element Books, 1991, Chapter 4, 84-113) by Serena Roney Dougal, the author expresses a link betweeen the pineal gland and the psychic chakra as understood in various metaphysical and spiritual teachings.

Jeh I Chang, et al., (1993, Pharmacology 42: 191-97) propose that melatonin may act as an endogenous hypotensive factor, and is an antiserotonin which decreases BP (blood pressure) at the levels of the hypothalamus.

In addition, melatonin has been shown to be as potent as indocid, and to inhibit platelet aggregation. Melatonin also inhibits platelet function at the stage preceding the cycloprygonase dependency factor.

Melatonin also increases CD4 and helper cells which may be used in cancer, and possibly in AIDS treatment.

Reiter, et. al., 1995 (Melatonin in edible plants identified by radio immunoassay and by H.P.L.C. J. of Pin. Res. 18:28-31) studied melatonin levels of different foods and found that bananas and tomatoes had the highest content. Other foods may also be important such as avocados, plums and walnuts — which are all high in seratonin.

In my experiments I have used pure melatonin from both the Sigma Chemical Company and ICN which make 99.8% pure melatonin. The melatonin used in all cases was synthetic since it is difficult and expensive to use melatonin from animals.

I would suggest that the slaughter of animals be done at night when melatonin production is at the highest. I would also advocate the use of melatonin from food during the evening hours. I found that it was important to begin melatonin supplementation (at 3 mg. per evening) only after ages 35-40, since there are reports that melatonin adminstration early in life may lead to ovarian cancers.

I have personally treated metastatic cancers with 6 mg. of melatonin and 4 mg. of cyproheptadine to increase the ratio of melatonin to serotonin. My results on about twenty patients are excellent, with tumor regression and even disappearance.

The future development of melatonin and methoxy indoles is infinitely large and I find that most conditions that don’t respond well to medication will respond well to melatonin and cyproheptadine.

The cGMP produced by melatonin is lipid soluble and can incorporate in DNA as a Guanyl base. Guanyl base has been shown to