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published in Uptown Express Oct./Nov. 1995
The interview with Dr. Russell Reiter, upon which this article was based, is available here by clicking on his name at the beginning of this sentence.
Connie LaRock, manager of General Nutrition Center in The Park shopping center in downtown Houston, reports that shipments of melatonin are being rationed by the manufacturer. John Fain, owner of A Moveable Feast, a popular natural-foods restaurant and health-food store, confirmed that there are some shortages. "We can't get any from Schiff right now," reported Fain, "but we get what we can from other reputable manufacturers--Natrol, Twinlab, Source Natural, CAL."
Melatonin was not the big news to the scientific community that it was to the average television viewer or Newsweek reader. Since 1958, when Dr. A. B. Lerner published his discovery that melatonin was manufactured in the pineal gland, thousands of articles on melatonin have appeared in the scientific literature.
The list of melatonin's potential benefits is stunning in its length and breadth, promising a longer life, freedom from debilitating illness and disease, and extending the appearance and energy of youth into the fifth and sixth decade and beyond. With no documented side effects, and after more than 30 years of careful laboratory research, melatonin can be produced easily and cheaply, offering its miracles for an average cost of eight dollars per month.
Russel Reiter, Ph.D., Professor of Neuroendocrinology with The University of Texas Health Science Center at San Antonio, has been called "the godfather of melatonin research." Reiter's book, Your Body's Natural Wonder Drug: Melatonin (Bantam Books, $22.95), co-authored with medical writer Jo Robinson, will be in the bookstores by early October, scarcely a month after release of The Melatonin Miracle (Simon & Schuster, $21.00), which inspired the Newsweek article.
With the promise of turning back the aging clock, melatonin is hot news to the general public. Reiter's book, called "the book on the subject, written by one of the worlds' leading melatonin researchers," by Andrew Weil, M.D., author of Spontaneous Healing, carries on its dust cover endorsements from a host of medical professionals with impressive credentials. Reiter has been interviewed by ABC's magazine show, 20/20, in a segment to be broadcast in October or November, and will appear on NBC's Today show on October 19. A public radio interview recorded in September has not yet been scheduled for broadcast.
Reiter supported himself in college through his association with the Reserve Officers Training Corps (R.O.T.C.) program, which obligated him to two years in the military upon graduation. Thus, in 1964, after receiving his doctorate, he was assigned to the U.S. Army Chemical Center near Baltimore. It was right after Sputnik, and looking forward to the day when astronauts would be hurtling through space on a six-month journey to Mars, the Army assigned Reiter and his colleague, Dr. Roger Hoffman, the task of isolating the hibernation factor in animals. If astronauts could be put into a state of hibernation, problems of storage of large quantities of food, water, and the excrement produced by astronauts on their long journey would be solved.
Reiter and Hoffman began to study animals that hibernate and conducted experiments changing the length of the light/dark cycle. "We noticed that certain things happened when we changed the lighting environment," says Reiter, "and this led us very quickly to melatonin and the pineal gland." Though the two never made findings relevant to hibernation, they did make important discoveries about body cycles that occur in response to changing conditions of light and darkness. The findings were so engaging to the young scientist that Reiter continued this line of research for the next 30 years. It has been, and continues to be, his life work.
Reiter describes melatonin as "a very, very interesting molecule." Produced by the pineal gland, a pea-sized organ located at the base of the brain, melatonin is manufactured while we sleep. Darkness signals the time for melatonin production to begin, and melatonin produces the drowsy state that lulls us into sleep. Science now knows that the pineal is the master gland, and melatonin is the master hormone. With melatonin as the messenger, the pineal communicates with the endocrine system and the immune system, orchestrating the work of our bodies' hormones and immune functions.
Human infants do not produce melatonin during the first few months of life, and, explains Reiter, "they typically start to sleep at night after three or four months . . . coincident with the development of the melatonin rhythm." Reiter's research team proposes that the human biological clock begins ticking, or "matures," by about four months of age, through the mechanism of melatonin. During these first few months of life, the infant's brain is "sculpting" itself through migration and division of cells. "Things are happening in the brain that melatonin, we now know, could inhibit," says Reiter. "So melatonin given to very young individuals like that may in fact prevent some of the maturational processes that occur in the brain, and so there's maybe an evolutionary reason why for the first several months that no melatonin should be present. That hasn't been proven, but there's strong evidence that that is the case. I think the body knows what it's doing when it doesn't give any melatonin immediately."
Blood levels of melatonin peak at around 6 or 7 years of age, then plummet sharply at puberty, signaling to other hormones that it is time to take over and prepare the body for reproduction. At around age 45, melatonin again begins a sharp decrease, concomitant with exterior and interior signs of aging. It is at this time that experts suggest use of melatonin supplementation would be helpful. A Moveable Feast owner John Fain states that he would discourage melatonin use in anyone under 40 unless advised by a physician to use it for a particular health problem.
Given the role melatonin apparently plays in development in infancy and puberty, it would seem unwise to artificially elevate levels in youth when physical development cycles are still in gear. Why, then, should one take it at all?
Melatonin is most widely known for its effects as a safe sleeping pill. A number of vitamin manufacturers include it as an ingredient in compounds marketed as sleep aids. Reiter relates the story of a Florida physician of his acquaintance who, now in his mid sixties, took melatonin because of sleep disturbance. A few days before talking to Uptown Express, Reiter received a letter from this physician describing some unexpected but welcome side effects from melatonin.
A jogger, who over the last four years had worked up to three miles of slow jogging each morning, the physician wrote that, within 20 days of taking melatonin, he was jogging four miles at a speed he had never before accomplished. He feels so well at the end of his daily run that he has added a course of calisthenics to his daily workout.
"What melatonin does is protect the part of the cell called the mitochondria," explains Reiter, "because that's where all the oxygen is used. You use a lot of oxygen when you're exercising, obviously. You breathe harder. And oxygen produces free radicals, especially in the part of the cell called the mitochondria. Melatonin protects the mitochondrias from damage produced by all those free radicals, and that allows for more energy production. So he [the Florida physician] immediately deduced what the potential mechanism was and that's exactly what we think it is in our testing."
Reiter takes about 1 mg. of melatonin each night before retiring. "That doesn't mean I recommend it to everyone," he states. "The reason I take it is because of my age. As you age, you lose the ability to produce melatonin like you lose so many other functions." The 59-year-old Reiter also takes melatonin because he is taking a drug which is known to suppress natural melatonin formation by the body. "There are a number of drugs on the market that prevent melatonin formation, and as a consequence, I take it to supplement myself with melatonin," he says. Reiter named aspirin and ibuprofen as two over-the-counter drugs known to block our bodies' natural production of melatonin.
And has he felt any benefits from his melatonin use? As a person who has always been active and never had low-energy problems, Reiter cannot claim the type of dramatic improvement experienced by his physician friend. "What I'm looking at is the long-term potential benefits," he states. "In other words, neurodegenerative conditions. . . . What I want to do is maintain the melatonin rhythm equivalent to that which I had when I was 20 years old."
Reiter maintains that 1 mg. of melatonin taken each night is more than sufficient to produce the desired blood levels. The 5- to 6-mg. doses recommended in some sources would give "blood levels of melatonin thousands of times higher than your normal levels," he states. "That doesn't mean they're toxic. Because we know they're not," he continues. Reiter cites examples of people who have taken doses up to 300 mg. for therapeutic reasons with no side effects.
"If you do take melatonin, then you always take it at bedtime because it's normally produced at night. It sets your circadian clock. It induces sleep. So if you take it during the day, it would be like you would be in jet lag all the time. Your clock would not be synchronized with your light/dark cycle."
It is melatonin's properties as a free-radical scavenger and powerful antioxidant that accounts for its effectiveness in preventing and alleviating a wide variety of disease conditions. The reasons melatonin has not been more widely prescribed and tested are the same as the reasons most other natural remedies have been ignored by medical researchers. Most research is financed by drug companies who are seeking a market for substances on which they own patents, an "exclusive," in other words.
"You can't patent melatonin per se," explains Reiter, "because you cannot patent a molecule that occurs in nature. If anybody holds a patent, God holds a patent on this. And as a consequence, people take out what are called use patents. If they're going to advertise it for a specific use, they can hold a patent on it. And there are several use patents on melatonin, but I don't have one of them. One of them is for sleep . . . another one is for jet lag treatment, another one is for ocular disease, glaucoma."
Reiter has done groundbreaking work on melatonin as an antioxidant over the past five years, and one would assume that he would have applied for a use patent on melatonin as an antioxidant. "It's not possible to get the patent because we've already published the material, and once the information is available to the general public you also cannot patent it," he explains, "and of course when we made our discoveries, we immediately published it in the scientific literature."
"This really hurts melatonin," he continues, "because to do these expensive long-term clinical trials in humans requires millions of dollars, and no pharmaceutical company is going to undertake a clinical study on a drug that they cannot patent." As Reiter points out, for-profit organizations such as drug companies cannot afford to invest millions proving the benefits of a substance that can be sold by anyone with the wherewithal to manufacture and market it.
"That's one of the major reasons I wrote this book," Reiter continues thoughtfully, "to point out the potential of melatonin and the difficulty with research funding because it is not patentable. We need additional research on melatonin, and it'll have to come from governmental agencies rather than from the pharmaceutical industry. This is very important for melatonin and drugs like it that cannot be patented."
"What the pharmaceutical industry wants to do is invent their own molecules," explains Reiter. "And then if they have beneficial effects, then for 17 years they have exclusive right on that molecule. Melatonin is a remarkably good drug, but not getting the testing by the pharmaceutical industry that it deserves."
One source had listed Reiter as owning a use patent on melatonin as an antioxidant. "I wouldn't mind having a patent on melatonin," he chuckles, "but I do not. And I have no vested interest in any melatonin products either. I have a vested interest from the standpoint I've worked on it all my life," he explains, "but I don't make any money from melatonin."
As in so many other areas of health, where investigation is sparse because drug companies are such an important source of research funding, the burden falls on the federal government to provide resources. Reiter is excited about two upcoming federally supported studies which will investigate melatonin as a treatment in Alzheimer's Disease and neurodegenerative conditions, one of which is anticipated to be conducted in Houston. "There's also one that's probably going to be undertaken in terms of amyotrophic lateral sclerosis, Lou Gehrig's Disease. This is also a very-high-free-radical-related disease which will potentially benefit greatly from melatonin," he states.
Studies such as Reiter describes will show their true relevance only after following study participants for 10 or 15 years. "You can only tell if you give a person these drugs over a very long period of time," states Reiter. "But we know in animals, of course, we can prevent, with melatonin, free-radical-related degenerative changes of the nervous system."
And when melatonin meets a free radical, studies have shown that a very predictable chemical reaction will occur. "It's not specific to a unique animal or a situation," explains Reiter. "It's a chemical reaction that does occur. So if it occurs in an experimental animal, it will occur in a human. So the likelihood of success is very high for these clinical trials."
Reiter offers an uncomplicated explanation of oxidation and how melatonin enters into the picture: "Free radicals have an unpaired electron," he explains, "and that makes them very toxic, because electrons like to be paired. What melatonin does is give the free radical an extra electron, so now it has a paired electron, so it's no longer toxic." In the process, Reiter instructs, the melatonin molecule becomes a one-electron radical, but a nontoxic one that is simply metabolized by the body. In short, melatonin encounters these very toxic radicals, contributes an electron, neutralizes them, and is itself used up in the process.
"The same thing happens when you park your car in the sun for a couple of years," he states. "Your paint deteriorates. This is oxidation, exchange of radicals. I've gotten telephone calls from car wax companies: Should we put melatonin in our car wax? And of course it would be just as effective in preventing that oxidation as within cells." Reiter also predicts that vitamin E in face creams and other cosmetic products will soon be replaced by melatonin, because it is a more potent antioxidant and "it's better than vitamin E in preventing degeneration of the skin."
In The Melatonin Report, a 20-page treatise sold in health-food stores, author Billie J. Sahley, Ph.D. suggests, "If you suffer from an immune system cancer such as Hodgkin's disease, leukemia, lymphoma, myeloma, or other autoimmune disorders, you should not take melatonin." Though there has been no research on melatonin's effect in these disorders, Reiter agrees with Sahley's assessment: "Autoimmune disease is an overactivity of the immune system. The immune system starts to fight itself. . . . And there is certainly some evidence that melatonin may in fact stimulate the immune system. And if it does, it stimulates an immune system that is already overstimulated; it could exacerbate or exaggerate autoimmune disease. We don't know if that's true, so I think the precaution is warranted."
Does this mean that melatonin should be avoided by persons living with AIDS? "No," states Reiter emphatically. "We outline all the reasons [in Your Body's Natural Wonder Drug: Melatonin] why an AIDS study should be done," he says. "In AIDS patients their immune system is in fact destroyed, because what happens is the virus proliferates very rapidly, and for a while the immune system can combat that virus. But eventually the virus just overwhelms the immune system and totally destroys it. So these people do not die of HIV. What they die from is infections that they get because they have no immune system. AIDS patients also have very high free-radical production. And of course melatonin is the best scavenger of these free radicals. And we think that melatonin in terms of AIDS would be a dynamite supplementary treatment. But again it hasn't been tested clinically, again for the simple reason it's going to take years to do that."
In the laboratory, melatonin has proved a potent preventative and treatment in cancer. Reiter's research team fed rats a potent cancer-causing compound, then treated them with varying doses of melatonin. They were able to achieve 99% reduction in DNA damage formation. David Blask, M.D., Ph.D., a former student of Reiter's, added melatonin to breast cancer cells grown in petri dishes. Melatonin proved a powerful inhibitor of growth of these lethal cells.
In The Melatonin Miracle, authors Walter Pierpaoli, M.D., Ph.D., William Regelson, M.D., and Carol Colman report that Italian researchers have treated cancer patients with melatonin in conjunction with traditional chemotherapy and immunotherapy. Patients receiving melatonin "showed tumor regression and lived longer with fewer side effects than those who did not receive melatonin."
"A clinical trial on human breast cancer, considering how common it is, and there's practically no treatment for it, should consider the possibility of giving melatonin. It's just crying out to be done," protests Reiter.
Currently, thousands of women are participating in clinical trials to test tamoxifen, a patented drug with severe side effects, as a breast-cancer preventative in women at high risk for breast cancer. Reiter claims that the addition of melatonin to a program including tamoxifen improves the effectiveness of tamoxifen by five- to tenfold, even while reducing tamoxifen to much smaller, and thus less toxic, doses. While thousands of women are exposed to the toxicity of tamoxifen to explore its possible effectiveness, only a few hundred women are participating in a European trial using melatonin, a nontoxic, natural substance whose effectiveness has been proved in the laboratory.
Reiter responds, "You know this is a classic example again of the pharmaceutical industry ramrodding these experiments. The reason drugs are prescription is because they are toxic. Here you have a molecule, melatonin, that occurs naturally . . . that is inhibitory of cancer, that the pharmaceutical industry doesn't touch. It's nontoxic, naturally occurring, potentially extremely helpful to cancer patients, and they won't even look at it because they can't make money."
Dr. Richard Wurtman of Massachusetts Institute of Technology (MIT), who published his research on melatonin and sleep patterns in early 1994, has publicly stated on several occasions that people should not "self-medicate" with melatonin and openly lobbies for FDA control of melatonin. Wholistic physician Julian Whitaker and others say Wurtman is motivated by the promise of enormous profits for Interneuron Pharmaceuticals Inc., a corporation of which Wurtman is founder, principal stockholder, and member of the board of directors. Interneuron owns the use patent for melatonin as a sleep aid.
And where does Reiter stand on the question of whether or not the FDA should step in and regulate the use of melatonin? "I think it would be a mistake because it's a totally nontoxic substance. And the reason Dick Wurtman lobbies for it to become a prescription drug is that he tends to make absolutely millions of dollars. He holds the patent for melatonin as a sleep aid. If melatonin is made a prescription drug and he enforces that patent, which he would do, he would be the only individual in the world who could advertise melatonin as a sleep aid specifically. . . . if there were something toxic about melatonin I'd say of course make it a prescription drug. But at this point there's no rationale for depriving its use to a lot of people, because it is nontoxic."
"I think the industry has to exercise care in terms of what they sell," he qualifies. "Melatonin is no different from any other vitamin or any other nonprescription drug that is sold, and of course we know some of those compounds have rather toxic effects. Aspirin is a good example. Ibuprofen is another example, in terms of gastrointestinal problems and liver disease. But pure melatonin is remarkable in its lack of toxicity. In fact one pharmaceutical industry advocate made the statement that it's extraordinarily nontoxic considering its potential beneficial effects. And that's a very high statement. Virtually everything that we take--even vitamins in high concentrations--are relatively toxic. That's not the case with melatonin. Melatonin has never been shown either acutely or chronically to have any significant toxicity in any animal or human to whom it's been administered."
Though human beings are living much longer than at any time in recorded history, we are still dying of one disease or another, even though we may survive into our 80s or 90s. Melatonin extended the lives of laboratory mice by completely eliminating disease. The causes of death among these pampered rodents was old age--the real thing! "You know no matter what we do we'll probably never get humans to live much beyond 110," ponders Reiter. "That will be genetically programmed. In other words, tissues can only function for so many years, and they will in fact give out. You can build the best instrumentation in the world and it's gradually going to deteriorate. And there's nothing you can do about that. So they will not die of infections, they will not die of cancer, they will not die of degenerative disease. They will die of old age."
According to Reiter, a longer life is not the ultimate goal. "Of greater interest to most people is living healthy as long as they live," he says. "And that's what we think melatonin has the capability of doing, keeping us healthy for a longer period of time. And if that also means extending life for a period of time, fine. I don't think people want to be ill from the age of 65 and then die at 85. If you're going to die at 85, of course you prefer to live healthy until near the end. And that's the secret to what I think melatonin is capable of doing."
As safe as melatonin has proved to be, there are people who shouldn't take it. If Reiter's hunch is correct, that melatonin would inhibit brain development in infants, clearly infants should never be given melatonin. It would follow that pregnant women and lactating women who are nursing should also avoid melatonin supplements. "Obviously you don't want to hurt a fetus," states Reiter. "You don't want to hurt anyone. But you take special precautions in terms of pregnancy, in terms of lactating women who are nursing, in terms of children."
It could also be supposed that, since melatonin drops at puberty, melatonin supplementation in childhood could possibly prevent normal sexual development and perhaps other forms of development necessary to reaching normal maturation. All sources state that melatonin supplementation will not guarantee eternal youth if begun before the normal midlife drop of the body's melatonin production around age 45. Sahley adds caution against use by diabetics, epileptics, and people suffering from hormonal imbalance. These disorders, she asserts, need to be the subjects of further melatonin research.
Does this mean the rest of us can just pop a pill each night at bedtime and expect to live disease-free till our cells wear out? It's likely that we need to take a hint from Pierpaoli's laboratory mice. Though the melatonin-supplemented mice lived longer than their peers by the equivalent of 25 human years, all the mice lived a healthy lifestyle. Under the watchful eyes of their patrons in white lab coats, they didn't smoke, didn't drink, and didn't hang out with the mice that did.
We humans are far more resourceful in devising countless means of self-destruction in innumerable combinations. For those who take melatonin and lead self-destructive lifestyles, its benefits are most likely to be a mirage. Leading a reasonably healthy lifestyle and taking melatonin may just produce a miracle of lifelong health, free of debilitating disease. So eat your broccoli, take your daily walk, drink lots of pure water, treat yourself like a precious object, and take your melatonin at bedtime. I'll check back with you in 2070..