Study Suggests Retiming Meals

Friday, January 19th 2001, 12:00 am

By: News On 6

WASHINGTON (AP) â€” The timing of meals may play an important role in resetting body clocks, concludes a study that could aid scientists hunting ways to combat long-distance travelers' jet lag.

The discovery, published in Friday's edition of the journal Science, is in rats, not travelers, scientists cautioned.

Still, ``it's noninvasive to change your eating habits,'' notes lead researcher Michael Menaker, a University of Virginia biologist. ``This would give you a reason to try it.''

But more important than the nuisance of jet lag, Menaker stressed, the discovery that the liver resets its own biological rhythms according to eating habits also could point the way to better therapy for serious liver diseases.

Everyone has a sort of master clock in the brain that controls their ``circadian rhythms,'' biological patterns such as sleep and body temperature. This brain clock is very light sensitive, the reason most people sleep at night and wake during the day. Travel to a greatly different time zone, however, and it can take a while for that master brain clock to adjust.

Then scientists discovered the brain-based clock isn't the only control of circadian rhythms. Other organs seem to have their own clocks that supplement the brain's master clock. Perhaps that's why sleep problems aren't the only jet lag symptom; lots of sufferers complain of stomach upset and other problems, too.

Menaker simulated jet lag by exposing rats to light six hours earlier than they'd normally wake. While the light-sensitive brain clock could adjust in a few days, the rats' separate liver circadian rhythms were out of sync for up to two weeks.

The liver helps control food metabolism. So Menaker, working with scientists in Norway and Japan, wondered if changing mealtimes would reset the liver's own circadian rhythm and thus help readjust the overall body clock.

They tested rats genetically engineered to carry a fluorescent-stained clock-related gene â€” when and how much the rats' liver tissue glowed under a microscope showed allowed measurement of the liver's circadian rhythms.

Rats normally sleep during the day and feed at night. Allow them food only for four hours during daylight and they rapidly act like day is night, pumping away on their exercise wheels for a few hours before the food appears. Are they just hungry? Check those liver genes under the microscope, and Menaker found that the circadian clock in the liver had shifted by 10 hours after just two days of adjusted mealtimes.

The finding is ``very important,'' said circadian rhythm expert David Earnest of Texas A&M University. ``What it proves for the first time is that feeding cycles can directly act ... on the rhythms expressed within peripheral tissues like liver,'' independent of the brain's master clock.

That doesn't mean eating habits are more important than light exposure for a person trying to prevent jet lag, Earnest cautioned â€” but that changing meal times might ``be an added bonus'' in helping reset the body clock after a long trip.

Indeed, ``it's reasonable that ... if you're going to Europe, you should a few days before start eating dinner on European time,'' Menaker said. ``The brain will shift more quickly once you get there,'' meaning the two organs might be in sync sooner thanks to the liver's head-start.

But the discovery might have much more medically important ramifications: Doctors know that some diseases are worse at certain times of day and thus try timing some medications, a field called chronotherapy. Some cholesterol drugs, for instance, work best when taken before bed so they target a cholesterol-affecting liver enzyme most active at night.

Radiation for liver cancer works on a similar pattern, Menaker said â€” it may work best with fewest side effects in the middle of the night, when patients can't get it. Yet if patients could reset their liver clock by altering meal times, ``you might get quite an advantage,'' he said.

Menaker cautions that's just a theory, but that ``it's likely all the peripheral organs have their own oscillators,'' or circadian clocks, something he is beginning experiments to test.