HEALTH: Is this the elixir of life?

In the US, melatonin is seen as a miracle hormone that banishes illness and reverses ageing. A million people now use it. Some experts are more sceptical, says Roger Dobson
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The Independent Culture
JOYCE Leiner has been queueing for some time to get her 12 dollars' worth of capsules, tablets and lozenges. The 59-year-old has finally reached the counter of the health food shop in downtown Chicago, and picks out her week's supply. As she turns away from the assistant, she unscrews the cap of the bottle and pretends to swallow the contents for the TV cameras there to film the queue. "I'm going to be young again," she says, "and boy am I going to have fun."

For millions of middle-aged Americans, melatonin - the hormone supplement in these preparations - is seen as a cure-all that will, say its enthusiastic promoters, halt the ageing process, eliminate diseases, improve sexual prowess and perform a seemingly limitless range of other functions. But while more than a million people in the US are regular users, sceptics say the extravagance of some of the claims being made for melatonin owes more to the language of the travelling quacks who toured the Wild West a century ago, selling the elixir of life in cork-topped cough medicine bottles, than to the late 20th-century world of biochemistry.

In its natural state, melatonin is a hormone secreted by the pineal gland in the brain which is known to respond to light and effect sleep patterns. Britain's leading expert on the pineal gland and melatonin, Professor Josephine Arendt, an endocrinologist at Surrey University, has been working on the hormone since 1972 and has carried out pioneering work on its use for treating jet lag and sleep disturbance. Her concern about the new melatonin mania is that there is very little scientific evidence to support the benefits now being attributed to it. The few experiments there have been have involved the pineal glands of mice, not humans.

"The hype over melatonin is a disservice to science," she says. "It has turned a serious, interesting and useful molecule into something that can only be regarded as quackery."

Despite the recent dramatic leap in sales of the synthetic hormone in the US, melatonin is as old as humankind. When released by the pea-sized pineal gland deep inside the brain, its essential function is to control the body's biological clock, to help it know when to sleep and when to wake. The gland is behind the cerebellum and has no direct access to light and dark, but reacts to light reaching it through the eye. When there is no light, the hormone is released into the blood stream, lowering blood temperature and helping to induce sleep.

When the pineal is working efficiently, the amount of light coming in through the eyes determines the volume of melatonin produced. The pineal glands of children are larger than those of adults, and the female is larger than the male - for reasons not yet fully understood.

Though the gland has been known about for many years, it is only relatively recently that much research has been done. It was not until 1958 that melatonin was isolated by researchers. In 1963, following the publication of further research into the molecule, it became broadly accepted by scientists as a hormone.

Melatonin is easy to synthesise and several manufacturers have been producing it on a small scale for years; some also offer a so-called natural melatonin, made from the extract of animal pineal glands. Until four months ago, however, melatonin preparations had simply been gathering dust on the back shelves of health shops. The recent stampede is largely the result of a rush of new books in the US. The Melatonin Miracle, published in August, has already sold more than 100,000; Melatonin: Nature's Sleeping Pill, has sold 50,000. A third book, Melatonin: Your Body's Natural Wonder Drug, was published two months ago in the US and is destined for at least eight other countries.

This month the melatonin roadshow hits the UK with the launch of The Melatonin Miracle, a book topping the bestseller lists across the Atlantic. Though melatonin is only available in Britain on prescription for jet lag and sleep disturbance, the book's publication will probably trigger pressure for it to be made available over the counter here - just as it is in America.

The men credited with the explosion of interest in the US are the co- authors of the book, both respectable scientists - Dr William Regelson, 70-year-old professor of medicine at Virginia University's medical college, and 69-year-old Dr Walter Pierpaoli, head of research at Foundation for the Aged, an independent scientific research institution in Ancona, Italy.

Their research-based theory is that, as bodies age, the pineal gland becomes less efficient, usually from around the age of 45. The gland detects that the body is past its reproductive prime, and reduces the production of melatonin. In some elderly people, calcification of the gland occurs. "The bottom line is that nature is not interested in you unless you are reproductive," says Dr Regelson. "The essence of the future is to maintain the physiology of reproduction without reproducing."

With this bizarre take on human life and the ageing process, the melatonin lobby believes the solution is to supplement the body's own production of melatonin. This tricks the pineal gland and the body into believing all is well.

Many other scientists in this field are concerned by the claims being made for melatonin. The main plank of their argument is that the number of clinical tests on humans is very limited, or almost non-existent. They argue that the foundation for many of the claims is an extrapolation from experiments involving mice, some of them conducted nearly a decade ago.

A key paper on this animal research is co-authored by Dr Pierpaoli and available from the Institute of Experimental Medicine at the Russian Academy of Medical Science. The researchers took two groups of female mice - 10 that were three to four months old, and 10 that were 18 months old - and surgically switched the pineal glands between the groups. Triangular holes were cut in the heads of the mice, and the glands extracted and transplanted. Sham operations were carried out on a control group. In these mice, the surgical procedure was carried out but the glands left in place, so as to eliminate the effects of the operation itself on the results. The young mice with old pineal glands lived on average for 510 days, the old mice with young glands for 1,021 days. The control mice lived for 719 days. The paper concluded: "Pineal cross-transplantation thus provides clear- cut evidence for the central role of the pineal gland in the initiation and progression of senescence. It offers a novel basis for interventions in the ageing process."

Research into the effects of melatonin in humans would take decades and may well prove inconclusive, its supporters argue. Regelson and Pierpaoli agree that more research is needed. "Given melatonin's promise as an age- reversing agent - and one that may prove to be an effective treatment for cancer and other life-threatening ailments - more research is desperately needed." In the meantime, they assert that the animal evidence and supportive data, some of which is anecdotal, is strong - and since melatonin isn't toxic, it is worth taking anyway.

There are, however, some orthodox and widely accepted uses of synthetic versions of the hormone. Over the last decade it has been prescribed as an aid to people suffering from jet lag, and to those with some patterns of sleep disturbance. For some it is a successful natural alternative to sleeping pills. It has also been suggested as a treatment for seasonal affective disorder (SAD), the condition which produces the symptoms of depression in winter. Dr Ian Rodin, lecturer in psychiatry at the University of Southampton, explains that SAD sufferers do secrete melatonin in a different way. He believes, though, that this may be an effect of the disorder rather than a cause. "Melatonin is a good indicator of bio-rhythms, but our feeling now is that the main cause of SAD is in a different part of the brain - and that those primary abnormalities cause the pineal gland to secrete melatonin in a different way. Giving someone melatonin is neither here nor there."

Use of the hormone is now widely accepted as effective in countering jet lag. The body will adjust naturally to the disruption of long-haul travel, but this can take up to four days. Taking synthetic melatonin resets the body clock more quickly. Professor Arendt's pioneering work on jet lag found that a melatonin supplement, taken for up to four days around the time of a flight, helps speed up the body's readjustment to different sleeping patterns. "Melatonin works in jet lag," she says, "and it is undoubtedly useful in sleep disturbance. It seems, too, to be quite helpful with elderly people and sleep problems. It is potentially useful in shiftwork, but I have never seen evidence that melatonin increases human lifespan, improves human sex life, or cures any human disease."

While accepting that there is some evidence that the hormone can increase the lifespan of mice, she says much more work is needed. "It has to be properly evaluated, with proper tests. When carrying out research, at least one other laboratory should be working in the same area."

Another sceptic is Dr David Klein, director of the world's leading melatonin research laboratory at the US Government's National Institute of Child Health and Human Development. "There aren't too many facts in this area," he warns. "I view it as a dream house, with lots of speculation, stories and observations, but not very scientific. There's a lot of loose thinking around. What has happened with melatonin is that, within the last 10 years, there has been a lot of solid research on jet lag and so on. Some clever people who sell health foods heard suggestions that it could prolong life; they knew it wasn't toxic, and they said: 'What the hell, we have nothing to lose. Let's see how it flies'."

There is one aspect of the extravagant claims, he warns, that does pose an undoubted long-term risk. "One of the problems is that it raises expectations, and also erodes the respect people have for science. That's one of the most irritating aspects of the melatonin business. People are looking for dreams, and scientists don't really have anything to do with that."

There is no damping the enthusiasm of the melatonin lobby, however. The Melatonin Miracle, its authors say , will show how "you can exceed your lifespan from the commonly projected 75 years to 120 years." The front cover proclaims melatonin as the natural age-reversing, disease-fighting, sex-enhancing hormone. The back cover explains how scientific research proves that melatonin supplements can fight heart disease and cancer, boost the immune system, lower cholesterol levels, relieve stress, improve sleep and prolong sexual vitality.

Dr Regelson says he and his colleague unsuccessfully suggested that the book be called The Discovery of the Ageing Clock. He acknowledges that there have been delays in spreading the word about melatonin. "What happened was that we presented a paper about the pineal gland and transplantation, and nothing much happened. No bells, no whistles. Someone agreed to organise a conference, but another two years went by; we got angry, decided to write a book, and it hit the press."

Dr Regelson, who is a 0.1mg of melatonin-a-day man, also gets angry over any suggestion that there may be scientific uncertainty over some of the claims. "You've got to be joking," he says. "Whoever says that is an asshole. Everything has a scientific backing; I wouldn't have stuck my neck out in this way. I'm a professor of medicine, I'm not selling soap and I make no money from the sales of melatonin. I'm trying to kick the National Institute for Ageing in the ass to get them to do something." !

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