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Melatonin: Timing Is Everything

Hormone boosts immune system in short term and then ebbs -- in mice

FRIDAY, Oct. 26, 2001 (HealthDayNews) -- If you think the hormone that helps you keep day and night straight will also help keep your immune system straight -- think again, suggests a new study on mice.

So don't spring for your melatonin this weekend when you're reaching for your clock to turn it back. Many people take the over-the-counter supplement, thinking it will help them solve sleep problems or get over jet lag faster. And people with the mood ailment known as seasonal affective disorder (SAD), which is triggered by the changing daylight patterns, also take the supplement, hoping it will help. There is also some suggestion that it helps the immune system.

"What we found [was that] when animals are exposed to artificial daylight that mimics winter -- short days and very long nights -- in this species of mouse . . . the light exposures enhance the animals' immune systems," says study co-author Brian Prendergast, a postdoctoral fellow in Ohio State University's department of psychology and neuroscience in Columbus.

The melatonin at first enhances the immune systems of the deer mice, but the hormone does not work indefinitely, the study shows. And the same could be true for humans, researchers suggest.

Another expert on the hormone makes an even-stronger case against self-medicating.

Doses in the supplements of melatonin you get in health food stores are way too high; at higher doses, the dietary supplement can lower body temperature and may impact your immune system, says Dr. Richard Wurtman. He is director of the Massachussetts Institute of Technology's (MIT) clinical research center in Cambridge, Mass.

Since melatonin is produced at night, longer periods of sleep result in an increase in the hormone.

But in mice, you can't credit melatonin alone for changes in the immune system, Prendergast's study shows.

Prendergast subjected wild deer mice to artificial light for 32 weeks. Some mice had long days -- 16 hours of light a day; a second group had short days -- 8 hours of light; and a third group had long days for 20 weeks followed by short days for 12 weeks. Prendergast tested their immune functions throughout the experiment.

The immune systems of mice exposed to short days for only 12 weeks were enhanced. But the mice that had short days of light the whole time revealed the transience of the condition.

"But what we found was that after about four or five months of short days, the enhanced immune response disappears," he says.

The findings will appear in the Nov. 8 issue of Proceedings of the Royal Society of London: Biological Sciences.

"We think that after four or five months of short days, a signal is sent from the animal's brain and the brain loses the ability to respond to melatonin," Prendergast explains. It's an internal clock that allows the mouse to gear up for their reproductive season, which takes the mice about eight weeks.

"If mice waited for spring before their reproductive system began redeveloping, it would be summer before they would be ready to reproduce. That's why the reproductive system spontaneously begins operating again before winter is over and before the days begin to lengthen," he adds.

And there might be a breadcrumb trail here for humans, as well.

"Humans are not reproductively seasonal, obviously, but there are a number of aspects of our behavior that do change seasonally -- our cognitive state, our immune function," Prendergast says. "We have absolutely no idea what causes these changes in humans." The responses "could be a passive response to the weather, or they could be the output of a seasonal clock in our brain. Is this related to melatonin secretion in humans?"

"What I think is important to note is this response to short days, in mice, is controlled by melatonin, and the effect lasts only a few months, and then the animals stop responding to the hormone. So the use of melatonin as some sort of therapeutic agent in humans should take this in account," Prendergast says. "That effect might be transient in humans."

No one's sure if melatonin has anything to do with SAD, says Wurtman.

"Almost everyone assumed that seasonal depression was associated with some abnormality in blood melatonin, and light was affecting this melatonin level," he says. "But after 20 years of searching, no one has shown that this is true -- that melatonin levels are abnormal in people with SAD."

The hormone can help you sleep, but only if you take the right dose, Wurtman says.

"Eight or nine years ago, we found that if you gave children melatonin or you take it for jet lag, it could make it easier to fall asleep," Wurtman says. "But only at the right dose. Your normal level of melatonin during the day is about 10 and rises to 150 at night. You have to take the right dose to raise the melatonin level to 150."

What's the right dose?

Those health food store doses of 5 or 10 milligrams are way too much, Wurtman says. "If you take more than 0.3 milligrams, not only is melatonin less effective, it lowers body temperature at night, [so] you have a 'hangover' the next day because there's too much in your system."

In addition, he adds, "anything that causes lower body temperature may impact the immune system."

What To Do

For more on Seasonal Affective Disorder, see the National Mental Health Association, and for more on melatonin, see Scientific American and this site detailing the circadian rhythm.

If you need help turning back your clock this weekend, check out the California Energy Commission.

SOURCES: Interviews with Brian Prendergast, postdoctoral fellow, Ohio State University's department of psychology and neuroscience, Columbus; Richard Wurtman, M.D., Cecil H. Green Distinguished Professor, director, clinical research center, MIT, Cambridge, Mass.; Nov. 8, 2001, Proceedings of the Royal Society of London: Biological Sciences.
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