Shift work and jet lag are problems unique to human beings. Consider shift work. I know of no animal that shifts its schedule from day to night on a regular basis; animals are either nocturnal (night active) or diurnal (day active). Jet lag is another human invention. Although many animals travel great distances, they have the good sense to migrate north and south, keeping their journeys within one or two time zones. We human beings are the only creatures who routinely shift our work schedules and engage in transmeridian travel, throwing our body clocks out of whack.
One of the latest discoveries to emerge from the research lab is that melatonin is an effective remedy for negative symptoms in both situations. It does two jobs at once: It helps you sleep better, and it resets your body clock, reducing the problems ofjet lag and shift work alike.
What exactly is the body clock, and what does it have to do with melatonin? The term body clock refers to a tiny bundle of nerves called the suprachiasmatic nuclei, or SCN, located in the brain directly behind the eyes. The nerve cells of the SCN transmit chemical messages on a regular schedule, approximately twelve hours "on" and twelve hours "off". (The total duration of the cycle is about twenty-five hours.) This built-in rhythm is unique to SCN cells. They persist in it even if they are removed from the body, proving that the rhythm is generated from within. The SCN is believed to be the ultimate source of the body's circadian rhythms.
But there's a problem. The entire body needs to march to the beat of the body clock, yet there is no network of nerves connecting the SCN with all the cells in the body. Somehow the signal has to be conveyed to the rest of the organism. To solve this problem, the SCN signals the pineal glad to produce melatonin that is then dispersed into the circulatory system, a con'.muhication network that does, in fact, reach every cell. In essence, melatonin functions as the hands of the body clock.
Here's how the process works in more detail. A set of nerves connects the body clock to the pineal gland. The pineal gland is programmed to produce melatonin only when a chemical signal comes down that pathway. (The signal from the SCN releases a neurotransmitter called norepinephrine, which stimulates pineal cells to produce melatonin. No signal, no norepinephrine; no norepinephrmne, no melatonin.) When the body clock is in its twelve-hour "on" phase, the pathway is active and melatonin is produced. Thus melatonin is produced in lockstep with the circadian rhythm of the body clock. The hormone is absorbed into the bloodstream as soon as it is synthesized, sending a signal throughout the body that the SCN is on.
Another matter of timing must be taken care of by the body clock as well. Humans are diurnal creatures. We are programmed to be out and about while the sun is shining and to be home in bed at night. This is why melatonin, the rest-and-recuperate hormone, is produced during the dark hours. But the SCN, by itself, pays no heed to the time of day. It's like a watch that's not adjusted to local time. It may keep perfect time, but it has no built-in relationship to the rising and setting sun
Somehow the body clock has to be synchronized with the outside world. It gets synchronized by a separate pathway of nerves that leads from the eyes to the body clock. When light from the sun (or some other bright light source) shines in the eyes, a message is sent down the pathway to the body clock, switching it to the "off" phase. When the body clock is off, it sends no signal to the pineal gland, and melatonin is not produced. It is as if the sun reaches into the brain and shuts down melatonin production. About twelve hours later, the body clock turns itself back on, the signal for the pineal gland to resume production. It releases melatonin into the bloodstream, and the circulatory system carries the hormone to the body's trillions of cells. The cells "interpret" this signal as a message of darkness.
I am struck by the simplicity and effectiveness of the body's timekeeping mechanism. The eyes, a central part of the nervous system, gather information about the lighting conditions in the outside world and convey it to the body clock. The body clock sends a chemical message that activates the pineal gland. The pineal gland produces a hormone, melatonin. Melatonin circulates throughout the bloodstream, giving the body information about the time of day. Thus, the role of the pineal gland is to convert a chemical signal (norepinephrmne) into a hormone, providing a bridge between the two great information networks of the body, the nervous system and the endocrine system.
Once researchers figured out how the body keeps time, they began to wonder whether we clever humans could somehow intervene in the process. There are several situations in which the body clock fails to conform to the twenty-four-hour cycle. Night shift work and transmeridian travel are two examples. If you work the night shift or fly across time zones, your body clock will adjust eventually, but it may take about a day for each hour your schedule is shifted.
Two quite different modes of intervention came to mind. One would be to expose people to artificial bright light. The light would stand in for the sun, making the body think that the sun was rising or setting at a new time of day. A second strategy would be to give people melatonin. The timekeeping hormone would send a message of darkness, preempting the body's nocturnal production of the hormone. We now have evidence that both of these strategies work, but melatonin offers certain advantages over light therapy. It is less expensive, less time-consuming, and more portable. For these reasons and others, melatonin's ability to reset the body clock has the potential to improve the lives of millions of shift workers and frequent flyers.
I have done my share of shift work. Because melatonin is produced primarily at night, most of the hundreds of animal experiments I've conducted have taken place in the dead of the night. Today, even though I'm a senior researcher with a lab full of competent scientists to conduct the actual experiments, I almost always participate. I hate to miss the camaraderie that develops during those all-nighters. Also, ifI observe the experiments as it is being conducted, I've found, I can better interpret the results. If some inconsistency crops up in the data, for example, I can think back to what took place in the lab and perhaps come up with an explanation.
It's not just pinealogists who work the night shift, though. In the United States, approximately 10 percent of all adults have jobs that require them to stay up at odd hours. Between three and five a.m., the sleepiest time of night, as many as 10 million Americans are hard at work. In Europe, the percentage is even higher, perhaps as much as 15 percent of the adult population.
People vary a great deal in their ability to tolerate shift work. It's been said that in a given group of a hundred shift workers, ten will enjoy working at night and will have no trouble adapting to the schedule; twenty will hate it and will quit as soon as possible; and seventy will have a hard time adapting but will stick with the job for a variety of reasons, including higher pay. Of the reluctant seventy, a high percentage will be plagued with a disorder called shift maladaptation syndrome. Typical signs of this syndrome are chronic sleep problems, indigestion, ulcers, depression, chronic illness, an increased risk of miscarriages, heart attack, and coronary artery disease. The seriousness of these health problems gives new meaning to the term graveyard shift.
Working at cross-purposes to your biological rhythms is harder on your body than it first might appear. Imagine that, tonight, you have to switch your regular schedule to night work. your scheduled work hours are eleven p.m. to seven a.m. You head off for work at ten-thirty at night, just when your pineal gland is producing a strong surge of melatonin. The hormone signals your heart to slow down, your blood vessels to relax, your body temperature to lower, and your digestion to grind to a hah. You have just entered the Sleep Zone. To fight off a wave of sleepiness, you stop at a fast-food restaurant and gulp down a sixteen-ounce container of coffee, which helps you feel more alert. (Unbeknownst to you, the coffee, which is inhibiting your production of melatonin.) But your stomach, which has already closed down for the night, resents the hot dark brew, and you feel a bit queasy.
You arrive at work and struggle gamely to stay alert, but at times during the eight-hour shift, particularly around two or three in the morning, you almost fall asleep on your feet. You feel cold, unmotivated. Your reaction time is slow. Your brain feels half asleep. One reason for this slump is that you are producing peak amounts of melatonin.
When the shift ends at seven a.m., you are weary and ready for bed. But your body clock has not had time to shift to the new schedule and is sending a signal to your pineal gland that it's time to wake up, shutting down your production of melatonin. As your melatonin level falls, your temperature rises, your pulse quickens, and you feel more alert. The drive home in the bright morning sun makes matters worse by further inhibiting your production of melatonin. Now you are wide-awake.
When you arrive home, you're surrounded by dozens of external signs telling you that it's time to wake up, not to go to bed - the morning paper is on the breakfast table; coffee is brewing; the kids are eating their cereal; the hosts on the morning TV news show are wishing you a cheery good day. The whole world seems to be conspiring to keep you awake.
Yet you have to sleep. You eat breakfast and shower, then turn in for the "night". You flop into bed - but sleep does not come. Your heart seems to be racing. Your mind is alert and active. Your hearing seems especially acute. (Does your neighbor have to use his gas-powered leaf blower in the morning?) Even though you desperately need to sleep, every cell in your body seems wide-awake.
If you stick with your new work schedule, your body clock may or may not adjust to the new routine. Studies show that you have the greatest likelihood of adapting if you are relatively young and happen to be a night owl. If you are thirty and older and function best in the morning hours, you are a poor candidate for shift work and are more likely to suffer from shift maladaption syndrome. Even though you continue to show up for work every night, your body clock will remain on strike.
A great deal of effort has gone into finding new therapies and techniques to help shift workers cope. Left to their own devices, many shift workers practice the art of self-medication. At night, they load up on coffee or other stimulants so they can stay awake. In the morning, they wind down by drinking alcohol or taking sleeping pills.
A more promising approach is bright light therapy. Shift workers who are exposed to bright light at the right time of day can shift their biological rhythm so it is in harmony with their work schedule. The bright light substitutes for the sun, convincing their body clock that the sun is shining at night. In a matter of five or six days, they are producing high amounts of melatonin during the day, when they need to sleep, and low amounts at night, when they need to work.
There are two ways that shift workers can increase their light quotient: (1) They can work in a highly illuminated environment, which may require the cooperation of management; or (2) they can purchase a light box and use the device at home. For maximum benefit, however, workers must avoid bright light during the day. They are encouraged to avoid the sunlight or wear very dark glasses or goggles.
Melatonin is a more practical and less costly remedy than light therapy. It, too, resets the body clock, making it the "first clinically viable pharmacological agent that influences the human circadian pacemaker." By sending a message of darkness to the body clock, it causes the body clock to believe the sun is setting in the morning. After about a week of melatonin supplementation, the biological rhythms of many shift workers are more in harmony with their nocturnal schedules. As an added bonus, the signal that melatonin sends to the body clock is so powerful that it overrides the conflicting message from the sun. That means that shift workers can be out in the sun in the daytime and still have their bodies convinced it is night.
Researchers at Oregon Health Sciences University (OHSU) are now studying melatonin's effects on a group of nurses who work the night shift at a nearby Kaiser Hospital. The nurses work ten-hour days, arriving at work at 9:30 p.m. and leaving at 7:30 a.m. They stay on this schedule for seven days, then have a full week off. (It is called a 7-70 shift.) The nurses take either a small dose of melatonin (0.5 milligrams in an immediate-release format) or a placebo at around nine in the morning, just before they go to sleep. The results are preliminary, but so far, this simple, convenient, and inexpensive treatment has reset the body clocks of a number of nurses who have had difficulty adapting.
Meanwhile, some shift workers have gotten a jump on the researchers and are taking melatonin on their own. Says one of the OHSU researchers, "We have to be careful to screen the participants in our study to make sure they haven't been taking melatonin all along."