A lifelong insomniac, Julie Austin never had a problem sleeping when she took a capsule of L-tryptophan.
But then, in 1989, the nutritional supplement was pulled from the market after being linked to hundreds of cases of a rare blood disorder.
Before it was recalled, though, Austin, 28, bought "a whole case." But when that supply was exhausted, "There was nothing to take. I don't like taking prescription sleeping pills because of the side effects. So I just stayed up all night."
Now, the Los Angeles woman is sleeping soundly again, thanks to the hormone melatonin, the latest star on the natural health scene.
So many Americans are popping melatonin capsules that health-food stores have difficulty keeping them in stock. The melatonin craze has also produced no less than six books and, in August, a glowing report in normally restrained Newsweek magazine. ". . . Melatonin could help us prevent, and even treat, the most common afflictions of old age," it gushed.
It's that type of pronouncement that makes many health experts cringe. While melatonin has indeed been shown to be effective in the treatment of some sleep disorders, no research has shown that it works for other ailments.
"The hype is ahead of the controlled studies," says Dr. John H. Renner, director of the Consumer Health Information Research Institute in Independence, Mo., who calls melatonin promising but experimental.
Nevertheless, melatonin's public reputation is that of a wonder drug.
Says Dr. Richard Wurtman, a sleep researcher at the Massachusetts Institute of Technology: "There are no published clinical studies on the safety or efficacy of giving these doses repeatedly. There is no evidence that melatonin in any dose has any useful effect on life span, cancer, AIDS, heart disease, oxidation, etcetera, in people."
He has studied the effects of melatonin on sleep for more than a decade, and says he is optimistic that the hormone may eventually prove useful in the treatment of some sleep disorders.
But consumers treating themselves with health-food-store preparations of melatonin are gambling with their health, Wurtman charges, because melatonin--like L-tryptophan--is not under the regulatory purview of the Food and Drug Administration and could be sold in formulations that are unpure or even dangerous.
"It was the absence of such an FDA regulation that led to the L-tryptophan disaster," Wurtman says. "I would hate to see history repeat itself."
Melatonin's sudden burst of popularity is the result of word-of-mouth praise for the supplement among travelers who have long used it as an antidote to jet lag.
The hormone is secreted naturally from the pineal gland--the pebble-sized gland in the center of the brain. When humans are exposed to darkness, the pineal gland releases melatonin to keep our body clocks in sync with daylight and darkness and to help us sleep. But when light hits the retina (at daybreak or if you switched on a bright light during a 2 a.m. trip to the bathroom), it signals the pineal gland to cease production.
Melatonin is at its highest levels in childhood and declines as we age, which may explain why elderly people often have difficulty sleeping, says Russell J. Reiter, a University of Texas-San Antonio biologist who studies melatonin.
Says Wurtman: "The good news is, when you give people tiny doses of melatonin--0.3 milligrams, which is about one-tenth of the health-food-store stuff--it raises their blood levels to what they would normally be at nighttime and makes them sleepy. This dose can also be used to shift biological rhythms."
For example, someone who changes from a 3-to-11-p.m. shift to an 11-p.m.-to-7-a.m. shift might use melatonin at selected times to ease the transition.
But Wurtman says further clinical studies are needed, as well as a manufacturing process that guarantees purity. He is one of half a dozen scientists who have filed patents for a melatonin-based drug.
Most people, however, aren't waiting for the FDA to approve an expensive prescription drug. Alternative-health practitioner Jocelyne Eberstein prescribes melatonin frequently for patients who have sleep problems. Some people dislike powerful prescription sleep drugs because they can cause side effects such as grogginess.
But the Los Angeles practitioner is cautious about using melatonin for conditions other than sleep.
"Until the research fully pans out, you have to be careful," she says.
Renner, whose office investigates health trends to uncover fraud or quackery, expresses concern that people with sleep problems will forgo a diagnostic evaluation in favor of a quick melatonin fix.
"I think people with severe sleep disturbances should be examined because there are many causes of not sleeping," he says. "So instead of turning to a pill, I think they need to make sure they are getting enough exercise, not napping, not taking herbs with stimulants, or caffeine or alcohol. There is not one cause of insomnia."
Sleep isn't the only reason Americans are infatuated with melatonin. Reiter is among several researchers studying the hormone for its effects on various diseases.
The author of the new book "Melatonin: Your Body's Natural Wonder Drug" (Bantam), Reiter claims it's melatonin's role as an antioxidant that has triggered its superstar status.
"That it's an antioxidant is very well-established," he says. But it's unclear whether the body produces enough melatonin to be an effective antioxidant or whether supplements are needed, he says.
When oxygen is metabolized, molecules called free radicals are produced that can damage DNA. Reiter's experiments on rats have shown that preventive doses of melatonin can act as an antioxidant to prevent DNA damage from exposure to a carcinogen. Antioxidants are substances--such as vitamins C and E and beta carotene--that protect against damage from free radicals.
More recently, he says, he took high doses of melatonin and exposed a sample of his blood to ionizing radiation. The result was that DNA damage was reduced by 60%, contrasted with blood samples not fortified with melatonin.
Unlike other antioxidants, which affect only some cell tissues, melatonin circulates widely in the body, including in the brain.
"Melatonin traverses the blood-brain barrier very easily," Reiter says. "This is important in the context of free radical-related diseases that affect the brain.
"I'm not saying melatonin is a miracle drug and is going to prevent these diseases. But we do think it can play a significant role in reducing the severity or preventing some of these conditions."
But unlike its acceptance as a sleep aid, melatonin is not embraced by most researchers as an effective antioxidant for humans.
"The fragmentary studies in animals are largely unconvincing and, in any case, irrelevant," Wurtman says. "We know that rats and people both secrete melatonin at nighttime, but people are sleeping at nighttime and rats are mostly awake. So the hormone clearly does different things in laboratory rats and in people."
But Dr. Steven Bock, a family practitioner in Rhinebeck, N.Y., agrees with Reiter that melatonin is a good bet as an antioxidant.
Consumers, Bock says, are loath to wait for science to produce the final word about melatonin, especially when the hormone appears to be nontoxic, even in huge doses.
"I know there are no risks for me. So I'll take it now and watch," says Bock, author of "Stay Young the Melatonin Way" (Dutton, 1995).
Reiter says that individuals have consumed as much as 300 milligrams daily with no ill effects other than feeling sleepy.
Capsules are usually sold in one milligram or three milligram doses, although "one-fifth of a milligram" produces sleepiness in many people, Reiter says.
"The risks are nil," Bock says. "But [misuse] is the unfortunate thing about something trendy. Someone may decide to take two melatonin capsules, and they're five milligrams each. People should read about melatonin or take the literature on it to their doctor and discuss it."
Despite its nontoxicity, additional safety questions surround melatonin because there is no regulatory oversight of the manufacturing process. It is widely believed that a contaminant introduced during the manufacturing process caused the L-tryptophan disaster.
"No one should take melatonin now because the preparation sold in health-food stores has not been shown to be pure, and some of them we have found to be quite impure," Wurtman says.
Adds Renner: "Melatonin is coming out of an industry with self-admitted problems with quality control. There is no way I would recommend [people take melatonin] right now without further study and research."
Even Reiter, a cheerleader for melatonin, advises consumers to consult with a doctor before taking it.
"I don't think people should take melatonin indiscriminately--as innocuous as it is."