Sleep and Snake Oil

By Rachel Preiser|Saturday, March 01, 1997
As we drift into sleep, our temperatures drop, our metabolisms slow, and a chemical called melatonin begins to circulate in the blood. Melatonin is made in tiny amounts by the pineal gland, a quarter-inch-long gland at the base of the brain, and little is known about the hormone’s effects on the body. Nonetheless, health food stores around the country sell bottles of melatonin, billing it as a soporific, and thousands of users tout its powers. Yet there is now evidence that melatonin not only sometimes fails to promote sleep but in fact disrupts it.

Sleep involves a complex interplay of physiological processes in which melatonin evidently has an important role. Researchers know that the pineal begins squirting melatonin into the blood at dusk and stops at dawn. The pineal apparently responds to signals from another region in the brain- -the hypothalamus.

Although the hypothalamus lies deep within the brain, neurons link it to cells in the eye. Part of the hypothalamus--specifically, the suprachiasmatic nucleus, or scn--tracks the length of day. The scn regulates an array of chemicals, including melatonin, that govern sleep. Research over the past decade suggests that the scn fine-tunes the sleep- wake cycle--and the release of melatonin--to fit seasonal changes in day length.

When deprived of usual light cues, the body’s biological rhythms continue running but fall out of sync with the outside world. In the absence of external stimuli, rats and humans alike maintain an internalized sleep-wake cycle of about 25 hours, which falls increasingly out of step with actual day and night. But about ten years ago, investigators found that if rats kept in total darkness took nightly doses of melatonin, they could be locked into a cycle of daily torpor and nightly scurrying just as if they were witnessing the rising and setting of the sun.

Chronobiologist Benita Middleton and her colleagues at the University of Surrey in England wanted to determine whether people kept in dim-light conditions and given nightly doses of melatonin could also be kept to a normal sleep-wake cycle. The researchers put ten men in a dim suite of rooms for two weeks and monitored their sleeping patterns, heart rates, body temperatures, and other vital signs. Each man took a nightly dose of melatonin at 8 p.m. Although eight maintained a normal sleep-wake cycle, two experienced extremely fragmented sleeping and waking patterns. Their biological rhythms seemed to have been completely shot, says Middleton.

She and her colleagues thought the timing of the doses might be responsible. Although the men had all received their melatonin at the same hour, each man’s daily biological cycle differed. When Middleton examined their daily temperature cycles--body temperatures typically are lowest during deep sleep, when metabolic rates have slowed, and highest during the day--she found that the two aberrant sleepers reached their peak temperatures later in the day than the other men in the group. So although the subjects were all receiving their doses at the same hour, their biological clocks were not all identical. The two men who had trouble sleeping were, in effect, receiving melatonin at a different biological moment in their metabolic cycles.

When Middleton repeated the experiment with six new subjects, administering melatonin at a time in their temperature cycles corresponding to the time when the two troubled sleepers received theirs, she upset the sleeping patterns of two of the six. Between the two experiments, of eight people who received melatonin at the determined biological moment, four had trouble sleeping.

Psychiatrist Thomas Wehr at the National Institutes of Health, who has studied biological clocks for over a decade, says the studies are provocative. They seem to have found a vulnerable point in the clock. The interest of this is twofold: for the basic knowledge it gives us about the structure of the human biological clock; and it makes one a little cautious about taking melatonin.

At the very least, says Middleton, melatonin should not be treated as a sleeping pill. Not enough work has been done on the stuff to say categorically that it won’t have any adverse effects, she says. Wehr agrees. The public has gotten way ahead of the researchers, he says. The experiments are being done on a massive scale by people just taking melatonin without controls.
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