Published on 10/18/2006

Sleep is more than a time of rest when nothing happens. It is a dynamic behavior during which important physiological changes take place, both in the brain and in the body.

Sleep is more than a time of rest when nothing happens. It is a dynamic behavior during which important physiological changes take place, both in the brain and in the body.

Sleeping can be as important to health as exercise. Not only does lack of sleep have serious impacts on both mental health (e.g., anxiety and depression) and our ability to think and function well, it also can make us more likely to become ill and can make it more difficult to recuperate when we do.

The Facts:

During the workweek, almost two-thirds of all adult Americans get fewer than the recommended eight hours of sleep a night, according to the National Sleep Foundation.

Sleep loss is associated not only with decreased vigilance and depressed mood, but also with altered hormone production. Fragmented sleep results in reduced growth hormone secretion, and even partial sleep loss one night results in higher stress hormone levels the next evening.

These effects result in decreased glucose tolerance and contribute to development of a pre-diabetic condition.(8)

Recent research shows that elderly widows and widowers whose sleep is disrupted due to bereavement-related depression have decreased levels of natural killer cells (NKCs), indicating a weakened immune system.(5)

Getting enough sleep may increase our chances of defeating infection. Research with laboratory animals shows that an animal's ability to survive bacterial infection is linked to the amount of deep sleep (non-REM) the animal gets during the first 12 hours after being infected.(11)

Total sleep deprivation can be fatal. An early study dramatically showed that after two weeks without sleep, laboratory animals lost weight despite eating more. At four weeks, the animals died, prey to an opportunistic bacterial infection.(4,10)

Interview: As Important As Exercise?

Eve Van Cauter, PhD, an endocrinologist and sleep physiologist, is a research professor of medicine at the University of Chicago.

Q. What have we learned about the links between sleep deprivation and health?

A. We can say that chronic sleep loss has a profound effect on metabolism and hormonal function. We now know that a single night of partial sleep loss is enough to result in abnormally high levels of the stress hormone, cortisol, the following afternoon and evening.(8) Our ongoing research suggests that the effects of semi-chronic sleep loss may be as profound as those of physical inactivity.

To understand why, you need to know about the two internal mechanisms that regulate sleep and wakefulness. One is the circadian clock, a small structure in the hypothalamus that generates a 24-hour rhythm that tells the body which hormones to release and which hormones to inhibit at each time of the day. Our circadian clocks control when sleep begins and how long we sleep.

The second mechanism, sleep-wake homeostasis, regulates how long we stay awake and how much we need to sleep. If you imagine homeostasis as an hourglass, the sand dripping down to the lower chamber is like the sleep-inducing substances building up while you're awake. When the lower chamber is full, the build-up of sleep-inducing substances makes us want to sleep. Upending the hourglass, or sleeping, re-empties the upper chamber.

Q. And these mechanisms affect hormone production?

A. Both underlie the daily variations of a variety of physiological parameters, including body temperature, hormonal release, carbohydrate metabolism, and cardiovascular function. (12,13,14)

The timing of the release of some hormones, such as the stress hormone, is more dependent on circadian rhythmicity. The release of other hormones, such as growth hormone that controls lean body mass and muscle strength, is more dependent on sleep-wake homeostasis.

When these two mechanisms are out of "synch," you have complete hormonal havoc. Jet lag is an excellent example, because it causes abrupt shifts in sleep-wake and light-dark cycles. The circadian hormones take several days to adjust but the homeostatic hormones shift almost immediately.

Normally, our hormonal system works with the precision of a symphony orchestra, with each player, or hormone, coming in and out at a specified time. With jet lag, some of our hormones continue to be secreted on the pre-travel schedule, and others adapt immediately.

When you try to sleep after eastward jet travel, your cortisol levels are too high so your sleep is usually fragmented and shallow.

Q. Does not getting enough sleep have an effect on metabolism?

A. In one of our studies, we wanted to find out if a common behavior - curtailing sleep to increase presumably productive waking hours - was detrimental to health. The current belief is that sleep loss has an adverse impact on brain function and impairs vigilance and mood, but not on peripheral functions, such as endocrine and cardiovascular function.

We challenged that assumption. Since we had done so much work to show that hormones are sleep-dependent, we thought it was inconceivable that a semi-chronic state of sleep loss wouldn't be associated with alterations in endocrine function or metabolism, as well as the more recognized associations with mental states and behavioral functioning.

So we recently undertook a study with a group of young men whom we deprived of part of their sleep for six nights. We are still analyzing data, but preliminary findings suggest that, with only six days of sleep curtailment, these young men had metabolic and endocrine profiles that resemble in some ways those of men in their 60s.

When they were allowed to sleep 12-hour stretches, everything returned to normal, or better than normal. They were able to repay the sleep debt. But these were young men. If they had been older, it isn't clear whether they could have recovered that sleep debt and eliminated all the effects of sleep loss.

Q. So age makes a difference?

A. As we age, there's a decrease in the amount of sleep we can get over a given bedtime period. Starting before 40, slow wave sleep, or deep sleep, begins to decrease. By 50, we have very little deep sleep left.

Our body produces a major portion of its total daily growth hormone during deep sleep, so in the course of aging, the production of growth hormone decreases in parallel with decreasing deep sleep.(12)

That means a loss of muscle strength and muscle mass, and an increase in fat tissue. Decreased growth hormone in aging may also cause a decrease in bone density, which is particularly important for women because it can lead to osteoporosis.

Q. Can we combat those losses?

A. A few studies have shown that if you increase slow wave sleep you can increase growth hormone release. Two different experimental hypnotic drugs were used, and they both increased slow wave sleep and growth hormone at the same time and in the same proportion.

There's a lot of interest in those studies because increases in fat deposition and decreases in muscle strength and muscle mass are things we'd all like to slow down as we age.

Q. What do you hope the impact of your research will be?

A. The social world, and Anglo-Saxon culture in particular, puts a bad connotation on sleeping. If you say you sleep nine hours a night, people look at you as if you're a lazy person.

Good nutrition and regular exercise are recognized by everybody as being important to health, but people believe they can and probably should curtail their sleep as much as possible. I would like to be able to show that getting a sufficient amount of sleep is as important to health as exercising and eating well.

Interview #2: More Than Dreamland

J. Allan Hobson, MD, is director of the Laboratory of Neurophysiology at the Harvard Medical School's Department of Psychiatry. Dr. Hobson is the author of Sleep (1989), Scientific American Library.

Q. Why did it take so long for scientists to begin studying sleep?

A. For thousands of years, people thought that when you went to sleep you stopped moving and the brain stopped as well. People used to think that sleep was a kind of "null" state where nothing much happened. We rested and so did the brain.

It was curiosity about dreams, and the thought that there might be specialized phases of sleep associated with dreaming, that opened the door to studying other phases of sleep. From 1950 until around 1980, scientists were busy just getting a fix on how diverse and variegated sleep is.

That was when we began to see that sleep consists of organized activities in the brain.

When we began understanding the mechanisms of sleep - how sleep "works" - we could finally ask questions about the purpose of sleep. Is sleep solely by, of, and for the brain? By developing tools to measure physiological functions, such as endocrine levels and mental activity, we now have a way to answer many of these questions.

We've learned more about sleep in the past 60 years than we'd learned in the preceding 6,000. I think we can expect the next decades of sleep research to produce an even richer harvest of knowledge.

Q. What can we say about the function of sleep? For example, does it affect metabolism?

A. Much of the early research on sleep metabolism was done with laboratory animals to test the effects of sleep deprivation. Allan Rechtschaffen's work in the early 1980s surprised us because it showed that sleep deprivation could be fatal if it's pushed hard enough.(10)

He found no striking differences in metabolism in the first week to 10 days, but two weeks into total deprivation, Rechtschaffen's rats began to lose metabolic control. They lost weight, despite eating more.

They couldn't manage the most important function of their bodies - to keep them fueled and running. Then, they lost control of their body temperature, and they died, uniformly, at four weeks.

Q. What did they die of?

A. Research conducted by one of Rechtschaffen's students showed that the rats died of septicemia, a bacterial infection of the blood. The metabolic problems led to an immune system breakdown to the point that they couldn't mount a successful war against opportunistic infection.(4)

Q. So sleep isn't just about rest?

A. It clearly plays a role in regulating important bodily functions. It's a little like taking your car to the shop every 3,000 miles for regular maintenance. Sleep is restorative, there's no doubt about that.

It recharges our batteries. But there's also a part of sleep that re-sets our thermostats and, to take the analogy further, changes our oil and tops off our fluids, so we operate at peak function. Good sleep is absolutely essential to good health.

In our modern society, there's almost an anti-sleep ethic. There is still this perception in people's minds that sleep is a null state because nothing much seems to be happening except for dreaming. So, there's a perception that sleep can be dispensed with without any effect.

Blame it on Thomas Edison. He insisted that three hours of sleep was all he needed. So people assume that if they sleep three hours, just like Edison, they can be geniuses, too. Nothing could be further from the truth.

We need to look more deeply into what is healthy sleep. And what is it about sleep that makes us healthy. The MacArthur Foundation is playing a major role in focusing the attention of scientists on just these questions, encouraging us to synthesize the findings of sleep research into a bigger and more whole picture of what sleep is and why it is so important to health.

Melatonin - Hype or Cure?

Melatonin is a natural substance in the human body. It's a hormone made by the pineal gland, a tiny pine-cone-shaped organ located deep within the brain. Melatonin's secretion is controlled by the light-dark cycle. As dusk falls, melatonin begins to be secreted. The secretion tapers off towards dawn.

Melatonin doesn't cause sleep, but it seems to initiate changes throughout the body that make it ready for sleep. Scientific studies generally agree that taking commercially prepared melatonin during times when the body is not producing any of its own (for example, during the day) can cause drowsiness and encourage sleep. So, it can be helpful to people who have trouble falling asleep.

Melatonin may also help older adults, whose hormone production has slowed as a natural consequence of aging.

However, melatonin isn't likely to help people who fall asleep easily but then wake up halfway through the night and can't get back to sleep again - the group that comprises the majority of insomniacs.(2)

- National Sleep Foundation

Did You Know...

The average adult American gets six hours and fifty-seven minutes of sleep a night during the workweek, while experts say the average need is eight hours. The average adult gets more sleep on the weekend: seven hours and thirty-one minutes a night.

64 percent of Americans get less than the recommended eight hours of sleep a night during the workweek, even though 98 percent agree sleep is as important to their health as nutrition and exercise; 83 percent agree that one can be successful and still get enough sleep.

37 percent of adults report being so sleepy during the day that it interferes with their activities.

- 1998 Omnibus Sleep in America Poll, The National Sleep Foundation
Contact: (202) 347-3471 (www.sleepfoundation.org)

Cytokines: The 'Stuff' of Sleep

Sleep researchers are learning what it is about sleep that promotes health and cures sickness and they are finding answers on the molecular level, in studies of cytokines.

Our bodies have at least 30 different cytokines. Most of them work in association with lymphocytes - white blood cells. They are intimately involved in orchestrating production of antibodies and activating immune cells that kill bacteria.

James Krueger, PhD, of Washington State University, and his colleagues began studying the sleep-related properties of cytokines years ago when they discovered a bacterial product in the brain. They knew bacteria stimulate cytokine production, so they looked for cytokines in the brain - a search many thought fruitless since it was assumed that cytokines were never produced there.

The first sleep-inducing brain cytokine Krueger's team found was interleukin-1, an immune response modifier. The team then learned that, in laboratory animals, sleep deprivation raised the levels of interleukin-1 in the brain. Here was a clear connection between cytokines and sleep.

Can lack of sleep make you sick?

Actually, short-term deprivation may enhance the immune system response. Studies have shown that sleep deprivation affects the body in different ways, depending on whether the deprivation is short term or long term: short-term sleep loss is linked with increases in the number of circulating white blood cells, natural killer cells, and immune response modifiers, indicating that the immune system may be "revving up" to meet the challenge of sleep deprivation.(6)

And research carried out by Bernard Bergmann and colleagues at the University of Chicago showed that short term sleep loss actually reduces the size of tumors in laboratory rats.(1)

Long-term sleep deprivation, however, can have lethal results, as shown in studies with laboratory rats.(4) Human experimentation has yet to demonstrate an increased incidence of infection, largely because most studies use healthy young volunteers in unchallenging environmental conditions and short deprivation periods.

Research by David Dinges and his colleagues at the University of Pennsylvania pushed human subjects as far as any study of sleep and the immune system has gone, depriving them of sleep for 64 hours. At that level of sleep deprivation, the researchers found that most of the immune responses increased, but when the subjects were allowed a period of recovery sleep, most of the increases were reversed.(3)

If you're sick, can sleeping make you better?

Fever and sleepiness have been hallmarks of illness throughout medical history. In fact, sleep is one of the oldest and most frequently prescribed "medicines."

Ten years ago, Linda Toth and Krueger inoculated laboratory rabbits with bacteria and recorded their sleep patterns for 48 hours. For the first 18-24 hours, the rabbits experienced a significant increase in deep, non-REM sleep, followed by a decrease. REM sleep was inhibited throughout the 48 hours. The researchers also noted that a rabbit's ability to survive the infection correlated with the amount of deep sleep it had during the first 12 hours.(11)

In humans, viral diseases are also linked with changes in sleep patterns. People at the early stages of HIV infection have increased amounts of deep sleep in the latter half of the night, but after AIDS develops, their sleep is disrupted and fragmented.(9) The link between infection and sleepiness appears also to involve cytokines. Infection is associated with a wide variety of immune response modifiers that are sleep-inducing.

The mechanism is not clearly known, but it may have to do with either increased nitric oxide in the brain, or increased levels of growth hormone-releasing hormone (GHRH), both of which induce sleepiness.(7)

The Research

1. Bergman, BM, Rechtschaffen A, et al. (1996) "Effect of extended sleep deprivation on tumor growth in rats," Am J Physiol 27:1460-4.

2. Czeisler, CA, Turek, FW (1997) "Is melatonin a treatment for insomnia and jet lag?" John Rachel Goldberg, Ed., National Sleep Foundation.

3. Dinges, DF, et al. (May 1994) "Leukocytosis and natural killer cell function parallel neurobe-havioral fatigue induced by 64 hours of sleep deprivation," J Clin Invest, 1930-39.

4. Everson, CA (November 1993) "Sustained sleep deprivation impairs host defense," Am J Physiol (265) 1148-54.

5. Hall, M, et al. (Jan-Feb 1998) "Sleep as a mediator of the stress-immune relationship," Psychosomatic Medicine, 48-51.

6. Krueger, JM, Majde JA (1994), "Microbial products and cytokines in sleep and fever regulation," Crit Rev. Immunol, 14:355-379.

7. Krueger, JM, Obal F (1997) "Sleep regulatory substances," in Sleep Science: Integrating Basic Research and Clinical Practice, Schwartz WJ (ed), Monogr Clin Neurosci, Basel: Karger, 15:175-94.

8. Leproult, R, et al. (1997) "Sleep loss results in an elevation of cortisol levels the next evening," Sleep, 20:865-870.

9. Norman, SE, et al. (1990) "Sleep disturbances in HIV-infected homosexual men," AIDS, 4:775-81.

10. Rechtschaffen, A, et al. (July 8, 1983) "Physiological correlates of prolonged sleep deprivation in rats," Science, 221:182-4.

11. Toth, LA, Krueger, JM (1988) "Alteration of sleep in rabbits by Staphylococcus aureus infection," Infect Immun, 1785-91.

12. Van Cauter, E, et al. (1998) "Alterations of circadian rhythmicity and sleep in aging: endocrine consequences," Hormone Research, 147-52.

13. Van Cauter, E, and Turek, FW (1995) "Endocrine and other biological rhythms," in Endocrinology, L.J. DeGroot, Ed., Philadelphia: W.B. Saunders.

14. Van Cauter, E, and Turek, FW, "Roles of sleep-wake and dark-light cycles in the control of endocrine, metabolic, cardiovascular and cognitive function," in Coping with the Environment: Handbook of Physiology Series, Bruce S. McEwen, Ed. in press.