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| Melatonin
It's the hot sleeping pill, natural and cheap. Now scientists say this hormone could reset the body's aging clock turning back the ravages of time. Turning back the clock has long been the domain of crackpots and charlatans. Take one look at the claim that enthusiasts are making for melatonin, a hormone sold as a supplement in health-food stores and you'll quickly sense that nothing much has changed. Senescence, the downward spiral that we have come to associate with aging, does not have to occur," Drs. Walter Pierpaoli and William Regelson declare in their forthcoming book, "The Melatonin Miracle". "Melatonin can stop the spiral." Strip away the bombast, and it turns out these guys are on to something interesting. Like most animals we produce melatonin abundantly throughout early life. But the levels in our bloods drop slightly before puberty and decline steadily in to old age. When Pierpaoli, an Italian immunologist, restores youthful levels of the hormone in mice, they outlive their life expectancies by nearly a third. ' And his findings are consistent with a burgeoning scientific literature. Recent studies suggest that supplementing the hormone may bolster our immune systems, keep our cells from disintegrating, slow the growth of tumors and cataracts, and ward off heart disease. All that while helping us sleep better. Proven or not, melatonin is poised to become one of the hottest pills of the decade. It's cheap and readily available- a month's supply costs less than $10 in health-food stores - and it's gaining popularity among people who've heard nothing about it's anti-aging properties. Travelers and office workers are using it as an anti-dote to jet lag, stress and insomnia. And sales are soaring. One manufacturer, Source Naturals of Scotts Valley, Calif, expects to move a million jars of lozenges this year- three times the number it sold in 1993. Skeptics cringe at the thought of people gulping down a supplement whose long term effects are largely unknown. But since studies have yet to document any hazards, even scientists are taking the plunge. "I take one milligram or less every night"., says Russel Reiter, a University of Texas cellular biologist who has studied melatonin for 30 years. "I want to die young as late in life as possible and I think this hormone could help.' First identified just four decades ago, melatonin is now recognized as one of life's most ubiquitous molecules. It turns up in such diverse organisms as people and protozoa, suggesting it dates back a billion years or so. Humans secrete is cyclically from the pineal gland, a pea-size structure nestled at the center of the brain, in response to the amount of light hitting our eyes (chart). Physiologists know melatonin as the hormone that keeps us in sync with the rhythms of the day and the season. Through it's actions on other hormones, it helps determine when people sleep and horses breed, when birds migrate, dogs shed their coats and certain frogs change color. But cellular biologists have recently discovered that melatonin has an even more basic function, which is to protect oxygen-based life from the toxic effects of .... oxygen. Yes, oxygen. As we metabolize this life sustaining gas, we generate highly reactive molecules called free radicals, which can corrode our cellular membranes and damage our DNA. The process, known as oxidation, weakens our minds and muscles as we age, and contributes to at least 60 degenerative diseases, including cancer, heart disease and Alzheimer's. The body produces several enzymes to inhibit oxidation, and nutrients such as vitamin C, vitamin E and beta carotene can provide extra protection. But most of these so called antioxidants work only in certain parts of certain cells. Melatonin readily permeate any cell in any part of the body- including the brain. And as Reiter's research tear has recently shown in animal experiments the hormone can protect tissues from an amazing array of assaults. The evidence started stacking up just two years ago, when Reiter has his colleagues showed that a small dose of melatonin could shield rats from a cancer - causing chemical called safrole. Given alone safrole quickly oxidizes liver cells causing extensive DNA damage. But when rats go tiny doses of melatonin before their safrole shots, they exhibited 41 percent less damage than their untreated counterparts and those receiving a slightly larger dose of melatonin suffering just 1 percent as much liver damage as the controls. In more recent studies, Reiter's team has shown the melatonin's antioxidant can protect rats from ionizing radiation ( having the death rate from a normally lethal dose and can shield the animal's lungs from the deadly herbicide paraquat. Melatonin can also help prevent cataracts, the cloudy lesions that appear in our eyes as oxidation damages cells in the lenses. When the Texas researchers gave 18 newborn rats a toxic compound called BSO, all 18 developed cataracts within two weeks. But when 15 animals got the same treatment plus melatonin, 14 maintained perfectly clear eyes. Oxidation Isn't the only reason we fall
apart as we age. We also lose our immune function. The thymus gland shrinks
over time, sapping our ability to produce fewer of the antibody molecules
that bind with and neutralize foreign invaders, such as viruses and bacteria.
Could all of this follow from a loss of melatonin ?
One of the best examples come from Pierpaoli's mouse lab. A few years ago he paired 10 young mice with 10 old ones and had a microsurgeon switch their pineal glands ( old to young and vice versa ). Before long, the youngsters were hobbling around with cataracts in their eyes and bald pitches on their backs. The old ones gained muscle and energy, and their coats grew thick and shiny. Autopsies revealed what was probably part of the reason. The young mice had all but lost their thymus glands after the pineal transplant. The oldest had had theirs restored. In other animal studies, Italian researchers
have shown that a nightly melatonin supplement can boost the performances
of the immune systems compromised by age, drug or stress. And scientists
in Israel and Switzerland have found that when mice receive melatonin,
their odd of surviving infection with encephalitis virus more than double.
Where cancer is concerned, the evidence isn't limited to mouse studied. Autopsy studies suggest that pineal calcification ( a condition that hardens the glands and reduces melatonin output) is most common in countries with high rates of breast cancer and least common in countries where breast cancer is rare. By the same token, women taking chlorpromazine, an autopsychotic medication that raises melatonin levels, enjoy unusually low rates of the disease. The explanation, says Dr. Michael Cohen of Fairfax, Va., involves estrogen. Prolonged exposure to that hormone (due to early puberty, infrequent childbearing or late menopause) increases a woman's risks of breast cancer. But melatonin dampens the release of estrogen. In fact, high melatonin levels can temporarily shut down the productive system. That's why females in most species are fertile only at certain times of year. Exploiting this principle, Cohen has combined a stiff (75 mg) dose of melatonin with progestin to create a new oral contraceptive. The drug, called B-Oval, has performed as well as conventional birth - control pills in European studies involving 1,000 women, and has shown no toxicity. Cohen plans to launch U.S. trails within two years, but his goal is not simply to market another contraceptive. If his hypothesis about melatonin, estrogen and breast tumors bears out, the new pill could help women - prevent cancer as well as unwanted pregnancies. Melatonin can also prove useful for fighting existing malignancies. Several studies have shown that it can slow the growth of human tumor cells in a test tube, and some cancer specialists are now testing its effects on patients. In a 1992 study, Dr. Paoli Lissoni and his colleagues at San Gerardo Hospital in Monza, Italy, found that a nightly melatonin supplement (10 mg) significantly improved one-year survival rates among patients with metastatic lung cancer. The same lab has since reported that melatonin can enhance the effect of interleuken-2 shots (IL-2 is a hormone that helps T cells proliferate) on cancers on the lung, kidney, liver, colon and pancreas. IL-2 causes horrific fevers and nausea at the doses normally required to tame tumors. But Lissoni's group found that the compound is effective at a fraction of the usual dose when accompanied by melatonin. Defining this hormone's true powers as an antidote to aging and chronic illness will take years, if not decades. There are countless leads to follow. Animal studies suggest that besides combating cancer, melatonin might help control cholesterol, regulate blood pressure and modulate the release of heart killing stress hormones. But today's users aren't overly concerned with any of this. Most just want a decent night's sleep - and many will tell you they've found it. Robbie Felix, a 40 year - old employment consultant in Silicon Valley, says she was a " chronic insomniac" until two years ago, when she read about melatonin on the Internet. Since then she has taken 15 to 20 milligrams every night (three to four times the typical dose), and slept soundly. "With traditional sleeping pills you're groggy the next day," she says. Not with this. Dr. Steven Bock of Rhinebeck, N.Y., author of a new book titled "Stay Young The Melatonin Way," says he has given the stuff to 300 patients and never seen a bad reaction. Dr. Ray Sahelian of Los Angeles (author of "Melatonin: Nature's Sleeping Pill ") is just as excited. "I think eventually this will make prescription sleeping all but absolute," he says. There's more at work here than the power of suggestion. Researchers have been documenting melatonin's sleep-inducing properties since the early 1980's when Dr. Richard Wurtman of MIT's Clinical Research Center started giving volunteers what are now recognized as megadoses (240 mg). Controlled studies have since established as little as a tenth of a milligram can hasten the onset of sleep, whatever the time of day. Researchers have also shown that a brief nightly regiment of 5 milligrams can help airline workers adjust to new time zones. And Dr. James Jan of Vancouver, British Columbia's Children Hospital, has reported that bedtime doses of 2,5 to 10 milligrams help establish normal sleep patterns in kids with neurological problems such as autism, epilepsy. Down syndrome and cerebral palsy. "We have tried everything." Jan recalls of the first child he treated with melatonin; "but nothing worked." After one dose of the hormone, "the parents called me and said, 'It's A Miracle!' The child slept through the night." There are plenty of drugs that can bring on sleep, but they can have well-known drawbacks. They tend to suppress the restorative dream state known as REM. They lose their effect over time. They're addictive if used too often, and at high doses they can kill you. Researchers have yet to report any of these problems with melatonin. When government scientists set out to find melatonin's "LD 50" - the dose that's lethal to 50 percent of the animals receiving it - they couldn't make a rich enough concentrate to kill a mouse. And when researchers fed human volunteers 6 grams (6,000 mg) of the stuff every night for a month, stomach discomfort and some residual sleepiness were the only reported side effects. Even so, experts differ sharply on whether melatonin should be bold like sea-weed in health stores. "Every time someone writes about this stuff," says Wurtman, "I get the sinking feeling that more people are going to run out and take it." Wurtman is as excited as anyone about the hormone's potential. His own company, Interneuron Pharmaceutical, has a patent pending on a melatonin - based sleeping pill (the chemical itself can't be patented). But he worries that we know less about the hormone than we think we do. "Is it safe to take while you're asks. Is it safe to take the Prozac? No one really knows." If the FDA regulates melatonin as a drug, manufacturers would have to address such questions before marketing it. They would also have to show that their ingredients were pure and their production methods sound. Says Wurtman, "You'd have a better idea of what you were buying." For now, consumers are stuck deciding for themselves whether to trust what they read on a label. There's no reason to assume that melatonin is any more hazardous than other unregulated supplements. And as enthusiasts like a point out, regulated prescription drugs still carry plenty of risks. So far, the FDA has shown little interest in controlling melatonin. The agency simply warns the users that they take it "without any assurance that it is safe or that it will have any beneficial effect." It's a worthy admonition, but it's not likely to turn people away. The promise is too rich: a good night's sleep, compete with dreams of a rip-roaring 105th birthday party. Forget Prozac. Throw away those anti-oxidants and magic time release vitamins. Start thinking Melatonin. In case you haven't been on planet earth for the last eight months Melatonin is believed to be THE nightcap. This all natural time-clock is being toted as everything from an elixir of youth to the greatest free-radical exterminator of them all. Until recently a few crack-pot alternative-medicine enthusiasts and international travelers were the only ones dosing themselves with 'nature's own sleeping pill.' But last August melatonin madness was born. The explosion took place after the normally conservative Newsweek printed a story touting melatonin's possible health-benefits and citing the contents of the capsule as an antidote for certain diseases and... an anti-aging remedy. It didn't take too long (48 hours) before almost as many health stores and authors in the USA were writing about - or selling - the product as there were people rushing out to buy it. Demand kept growing until some large drug stores in New York reported selling as many as 6 000 bottles a day. As melatonin mania grew, so did its wild
health claims.
The natural hormone has become the hottest stuff since....well....since Prozac. What exactly is melatonin comprised of? And how does it work? Every human being produces their own melatonin.
This pea-size structure at the center of the brain is known as the body's clock. The pineal gland pumps out about 100 picograms per milliliter at night and falls to levels nine-tenths lower during the day. Normally, melatonin begins to rise around 9.30 p.m. and drops again in the early morning. That's why melatonin has been nicknamed 'the night hormone.' But, as the human body ages, the pineal
gland calcifies
Dr. Al Lewy, a professor of psychiatry at the Oregon Health Science University in Portland, was one of the pioneers whose work with melatonin, showed that low doses of the hormone are highly effective for older patients. Lewy's studies have shown that small doses - equivalent to those the body produces normally - can replace the falling levels and also realign a person's disturbed sleep cycle. This accounts for the reason that so many travelers rely on melatonin to combat jet-lag. In addition to this Melatonin is non-addictive and proponents claim that it does not produce the serious side effects associated with 'sleeping pills'. But nowadays, the claims are becoming more grandiose. The hype and hoopla accompanying melatonin, is by no means restricted to its bedtime qualities. Cheerleaders tell us to imagine melatonin - a drug that can reverse the ravages of age, extend life, prevent cancer, Alzheimers and Aids, improve sex, eliminate depression, provide oxidation, induce vivid dreams, make on feel more energetic, live longer - and prevent jet lag. It's the anti-aging claims that are having the greatest impact on nations of aging baby boomers, It's hardly surprising those queues keep growing longer and longer. As far as antioxidants claims go, melatonin has been acknowledged by many researchers as one of the elite antioxidants in the body. Directly and indirectly melatonin is said to exert a powerful antioxidant effect which is metabolized in all body tissue. Some reports say that melatonin is the most powerful anti-oxidant of all Professor Russel Reiter, Ph.D., professor of neuroendocrinology at the University of Texas at San Antonio, has been studying melatonin for more than thirty-four years.
In 1992 Reiter discovered melatonin's antioxidant properties. "The reason organs become dysfunctional as we age is accumulated free radical damage caused by anti-oxidants. . . If we can delay that damage, we can delay the consequences of aging," Reiter writes. Reiter - who authored Melatonin: Your Body's Natural Wonder Drug (Bantam -) - contends that daily doses of melatonin can delay age-related illnesses prevent cataracts and heart disease, epilepsy, diabetes, Parkinson's and Alzheimer's. Dr. Steven Bock agrees with Reiter. In his book - 'Stay Young The Melatonin Way,'- Bock claims that melatonin acts directly on cells as an antioxidant, protecting them from the chemical compounds ('free radicals') that have been implicated in cancer and many other diseases. Bock adds. "The essence of what we've discovered in aging is a system governed by a clock. We've discovered the clock - it's the pineal gland. And melatonin keeps it going. We're not talking about immortality, we're talking about quality of life in later years." But, not everybody is excited by the claims. Not by a long shot. Many scientists, say it's just too early to make such promises - even if the substance does show considerable promise in many areas of medicine. They worry that consumer consumption has gone way beyond scientific certainty into the dangerous realm of old-fashioned hocus pocus and faith-health. They ask what happened to good old fashioned anti-agers like good sex, exercise, meditation, laughter, love, and a glass of wine with dinner?. The Canadian Government ended melatonin's over-the-counter status in 1995 - forcing scientists to prove its safety in human trials before it can come back as a drug. Indeed, America is the only country where melatonin can be sold over the counter. For its part the FDA in America has shown
little interest in controlling melatonin. The agency simply warns that
This may be a worthy admonition, but it's not likely to turn people away. And the fact that the product is so reasonably priced ensures crowded counters and giddy profits. (In essence, the FDA by law, can't regulate the sale of the hormone because it is readily available in foods and can therefore be sold as a supplement and not as a drug.) Dr. Dan Oren of the National Institute of Mental Health in the USA - an expert on circadian rhythms of the body - and several of his colleagues are worried about the flood of attention focused on melatonin. "This is a substance unregulated by the Food and Drug Administration (FDA), which has brought droves of people into health stores where they buy it as a dietary supplement. But our bodies are in a delicate balance and melatonin is, I think, at the crux of that balance. I believe that this is not a frivolous substance; it's a very important body compound. My assumption is that there is a reason why it's not there at certain times in order for us to function best. And if one starts getting it into one's system at a time of day when it's not supposed to be there, there may be untoward effects," he complains. Oren compares melatonin with L-tryptophan (sleeping pill), and he says "A few years ago in the United States we had a disaster with L-tryptophan, which at that time was thought to be a great sleeping pill. It was sold in an unregulated, uncarefully formulated way in the absence of any FDA regulation. "Unfortunately, contaminated batches of L-tryptophan were sold. Fifteen hundred people developed eiasinophilia myalgia syndrome. Twenty four of them died, and others suffered permanent neurologic damage because of a contaminant that got into the manufacturing process." Many of Oren's colleagues concur that melatonin has not been on the market long enough to test for long term effects - and - they say - there could be serious side-effects. South African physicians are conservative in their approach to Melatonin. Several physicians claimed that they did not know enough about the hormone to comment on it. And a neurologist who had been studying the hormone for many years, said that he had grave doubts about the extravagant claims being made. "Dr. Harry Seftel, Professor of General Medicine at Wits University said "I haven't had enough experience with melatonin to give an objective opinion, but my general assessment is that these things appear on the market and wild claims are made. Apart from the sleep issue - which may have some benefit - anything such as anti-aging must be treated with extreme skepticism. "Unless and until proper clinical trials have been done over a large period of time with a large number of people nobody can make proper claims," said Seftel. In South Africa, as in the United Kingdom, The Medicines Control Council, (MCC) have issued a directive prohibiting the sale of melatonin over the counter pending registration of the product. The MCC's stance is - there are unproven claims on melatonin - and melatonin is a hormone. All hormones have to be registered by the MCC as medicines. However, this has not stopped the flood of sales or inquiries for melatonin in South Africa. Many pharmacies - who don't want to be left behind in the 'melatonin mania cure-all' - sell the product illegally. Bottles are virtually flying out of their hidden under the counter destinations. Small wonder, rumbling reactions are erupting. For instance, all consumers - even in the USA are warned not to take melatonin:
Is this not an oxymoron? Melatonin is supposed to cure depression - so why not take it if one is prone to depression? And, if melatonin can't be combined with other hormones, what should menopausal and peri-menopausal baby boomers do? After all they comprise a large proportion of the melatonin market. Gynecologists insist women take estrogen - otherwise known as hormone replacement therapy (HRT) to combat osteoporosis and premature aging. But, they are unable to combine estrogen hormones with melatonin hormones. Must boomers make a choice between - either ditching estrogen and risking osteoporosis and other menopausal ailments - and - settle instead for melatonin, The mother of all 'natural youth and sleeping pills'?. And, contraindicated when taken together with Prozac. Please..... give me a break..... It's 1996. Will anybody who isn't taking Prozac put their hands up! Can anybody survive in this crazy world without 'THE happy pill'? Or is the new melatonin cult going to have boomers flush their prosaic down the line....making the choice to rage instead of age? In the meanwhile I must rush. I need to get a bottle of melatonin before my chemist runs out of stock. |
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