Missed ZZZ’s, More Disease?

As bleary-eyed college students in exam week will attest, lack of sleep impairs mood, performance, and judgment. They might guess, however, that the fast food and candy gobbled down during an all-nighter are far worse for bodily health than are the lost hours of slumber. After all, scientists have long been preaching that too many

Big Macs and too few workouts are bad for you, but they have yet to demonstrate any definitive health costs of chronic sleep loss.

Bolstered by new evidence, however, some scientists are suggesting that poor sleep habits are as important as poor nutrition and physical inactivity in the development of chronic illness. They say that this country’s sleep debt may be contributing to its current epidemics of obesity, diabetes, and cardiovascular disease.

People in the United States sleep an average of 7.0 hours on weeknights, 1.5 hour less than they did a century ago, according to the National Sleep Foundation in Washington, D.C. One-third of the population sleeps 6.5 or fewer hours, far less than the 8 hours that many sleep specialists recommend.

Several recent studies report that reducing sleep to 6.5 or fewer hours for successive nights causes potentially harmful metabolic, hormonal, and immune changes, at least in test volunteers in the sleep lab. “All of the changes are what you find in normal aging,” says sleep researcher Eve Van Cauter of the University of Chicago.

It’s still too early for doctors to start prescribing sleep to ward off age-related disease. Scientists agree that the findings are preliminary and that larger experiments are needed. If the story bears out, however, U.S. sleep habits may be having enormous public health consequences.

Dieter’s nightmare

Early sleep-loss research focused on military personnel, rescue workers, shift workers, and others for whom on-the-job wakefulness is crucial. These studies examined the performance declines that occur with extended periods of total sleep loss.

Investigating the relationship between health and the pattern of partial sleep deprivation that the average American faces is a much newer research endeavor. Van Cauter and her colleagues helped launch the field with a surprising 1999 study that showed that sleep deficits of several hours a night can impair the body’s processing of the sugar glucose.

The study reported that 11 healthy, lean young men showed signs of insulin resistance after several nights of sleep restriction. Insulin resistance, a condition in which the body handles glucose poorly because cells respond inefficiently to insulin, is a precursor to type II diabetes.

Experimenters carefully controlled the men’s sleep time, food intake, and exercise during their 2-week stay in the sleep lab. During the sleep-restriction phase of the experiment, the men were kept awake by minimally stressful activities, such as watching television, joking with the staff, and playing games, Van Cauter says.

The restraints imposed in the study, which permitted only 4 hours of sleep a night for 6 nights, were more severe than most people in the United States experience. The study also excluded women. So, the scientists next compared 13 men and women who habitually slept 6.5 hours or less per night at home with 14 men and women who regularly slept about 8 hours. On the weekends, the short sleepers slept extra hours, indicating that their weekday patterns resulted from social constraints rather than biological constitution, Van Cauter notes.

Researchers verified the test volunteers’ sleep patterns at home for a week and then brought them into the lab for a glucose-tolerance test. The short sleepers showed 50 percent more insulin resistance than the others did (SN: 7/14/01, p. 31: Available to subscribers at Does lack of sleep lead to diabetes?.).

Short sleep may accelerate the onset of diabetes, Van Cauter speculates. “If you are predisposed to diabetes, and you might become diabetic at 55, are you becoming diabetic at 45?” she asks.

In further experiments, sleep-deprived test volunteers showed other hormonal changes that promote weight gain. Men who were held to 4 hours a night had markedly reduced 24-hour leptin concentrations compared with when they were fully rested, Van Cauter’s research team reported at the 2001 Association of Professional Sleep Societies meeting in Chicago. Leptin is a hormone that signals satiety and regulates energy balance; mice that lack leptin overeat and become morbidly obese.

Van Cauter reported that although the men’s food intake was adequate, the dip in leptin they exhibited was equivalent to that seen in people underfed by 1,000 calories a day for 3 days. In other words, the leptin signal was telling the men’s bodies that they were short nearly a pound’s worth of calories. That misleading signal might cue the body to slow metabolism, increase fat deposition, and overstimulate appetite.

A separate, ongoing study is examining sleep restriction and hunger. When held to 4 hours of sleep, volunteers reported being hungrier than when they had adequate slumber, Van Cauter says. The sleep-deprived people overwhelmingly asked for candy, starchy foods, and salty snacks such as potato chips. “There were no cravings for fruits and vegetables,” she quips.

Animal studies also suggest that partial sleep deprivation leads to hormonal and metabolic changes. In one experiment, rats that normally sleep 8 to 10 hours a day were restricted to 4 hours of daily sleep for a week, mirroring Van Cauter’s studies in people. During that time, the rats showed increased concentrations of stress hormones and an altered hormonal response to stressful situations, such as being confined in a small space.

Initially, such changes may help the body cope with lack of sleep, says Peter Meerlo of the University of Groningen in the Netherlands, who reported the results in the May Journal of Neuroendocrinology. If stress hormones are chronically altered, however, sleep deprivation may have adverse health effects, Meerlo speculates.

Inflammatory ideas

Modest sleep deprivation may also be associated with low-grade inflammation, which can lead to a host of cardiovascular problems, according to Alexandros N. Vgontzas of the Pennsylvania State University College of Medicine in Hershey.

Trying to mimic the modest chronic sleep loss that many people in the United States endure, Vgontzas and colleagues deprived 25 healthy young men and women of just 2 hours of sleep per night for a week. The scientists measured blood concentrations of immune-system molecules called cytokines, which are normally secreted during inflammation and infection.

After a week of sleeping 6 hours per night, the test volunteers had higher blood concentrations of the cytokine IL-6, than they did in their pre-deprivation state. Furthermore, the men, but not the women, had increased concentrations of the cytokine TNF-a. Increased cytokines may reflect pervasive inflammatory action, the researchers speculated last June in San Francisco at the annual meeting of the Endocrine Society.

Unremitting low-grade inflammation can damage the inner walls of the arteries, which sometimes leads to vessel narrowing, high blood pressure, stroke, and heart disease.

Also, cytokines have been associated with insulin resistance, diabetes, and obesity.

Cytokines cause fatigue. By overproducing cytokines, a person’s body is probably trying to say, “Go to sleep,” Vgontzas says. Test participants fell asleep faster and slept more deeply when they were sleep deprived, demonstrating that their bodies were trying to compensate for the reduced sleep time, he adds. However, the more efficient sleep didn’t thwart the cytokine response, which lasted the entire week. The volunteers were also sleepier and performed more poorly on an alertness test at the week’s end than at the beginning of the experiment.

“There are some researchers, even in the sleep area, that say that these extra couple of hours of sleep are not important,” Vgontzas concludes. “Our data say that 6 hours is not good for healthy, young people.”

In a separate study, sleep of 4 hours a night for 10 nights was also associated with increased concentrations of C-reactive protein, another key inflammation mediator. Boosts in C-reactive protein might have a negative effect on health, says David F. Dinges of the University of Pennsylvania School of Medicine in Philadelphia, a researcher on the study.

Currently, the evidence linking increases in inflammatory molecules and cardiovascular disease is stronger for C-reactive protein than for the cytokines, adds Dinges’ collaborator Janet Mullington of Beth Israel Deaconess Medical Center in Boston.

A recent epidemiological study also showed a direct association between short sleep and heart disease. After controlling for other factors, researchers found that men who slept 5 hours or less a night had twice as many heart attacks as men who slept 8 hours, report Japanese scientists in the July Occupational and Environmental Medicine.

Obstructive sleep apnea, a condition marked by temporary pauses in breathing during sleep, is a natural model of chronic sleep loss because people with the condition repeatedly wake up through the night. Several recent studies have linked sleep apnea to elevated blood concentrations of IL-6, TNF-a, and C-reactive protein and to high blood pressure, cardiovascular problems, and stroke. However, it’s hard to tease out whether these effects result from lack of oxygen due to the apnea, loss of sleep, or both, says sleep-apnea researcher Virend K. Somers of the Mayo Clinic in Rochester, Minn.

Virtue or indulgence?

Some scientists remain skeptical that sleeping 8 hours should be the next great health virtue. They say that getting from the current evidence to a firm link between sleep loss and disease requires a giant leap of faith.

“Some people don’t have time to sleep, or they’d rather watch television. Should we condemn them before the evidence is in?” asks Daniel F. Kripke of the University of California, San Diego. Kripke argues that telling people that they’ll get sick if they don’t sleep enough may, ironically, worry them into insomnia.

Kripke and his colleagues published results in February that, on the surface, contradict the idea that more sleep is good for you (SN: 3/16/02, p. 173: Available to subscribers at Eight hours of sleep may not be so great.). During a large epidemiological study lasting 6 years, people were more likely to die if they initially reported sleeping 7.5 hours or more a night than if they reported sleeping 5.5 to 7.5 hours a night. The researchers took into account such factors as age, weight, diagnosed illness, and medication use.

The amount that the average person in the United States sleeps per night, about 7 hours, is consistent with good health, Kripke concludes. “People who are saying you should sleep more don’t have the evidence,” he adds.

Anything more than 7 hours is optional sleep, which can be taken for relaxation and indulgence but is not necessary for good health, agrees sleep scientist Jim A. Horne of Loughborough University in England.

Vgontzas disagrees. Underlying depression and sickness probably explain the apparent association between sleeping 8 or more hours and increased mortality in Kripke’s study, he says.

However, neither Horne nor Kripke is swayed by the studies that show physiological changes in sleep-deprived subjects in the lab. The changes are probably real, they agree, but may not be meaningful–either because they’re not severe enough to cause long-term health effects or because they’re artifacts of the experimental situation.

The immune system probably does crank up and go on red alert when a person is awake longer, Horne explains. After all, a body is more likely to come across pathogens when it’s up and about. But there’s no evidence that this activity undermines health, he says.

The argument that people are evolutionarily programmed to sleep 8 or 9 hours a night doesn’t hold up, at least in European history, Horne adds. Hundreds of years ago, people worked 14- or 15-hour days and were lucky to get 6 hours of sleep at night, he says. Moreover, their sleep patterns were different than those of modern slumberers (SN: 9/25/99, p. 205: https://www.sciencenews.org/sn_arc99/9_25_99/bob2.htm). In England, people went to bed an hour after sundown, got up a few hours later for a midnight meal, and then slept a few more hours until sunup, Horne says. People are probably designed to sleep 6 or 7 hours at night and take a short afternoon nap, he suggests.

Bleary picture

Research on sleep deprivation and health is still in its infancy, Van Cauter admits.

Nevertheless, she maintains that 8 or more hours of sleep a night is optimal.

“To suggest to people that you can maintain average sleep time of 6 hours and get on the road and drive your truck is criminal,” she asserts. It’s too early to say whether sleep loss causes disease, but sleeping certainly hinders performance and diminishes safety, she says.

There’s no reason to believe that sleeping more than 8 hours could be harmful or that insomnia could be good for you, Vgontzas adds.

“My general appraisal of the literature is, in terms of more or less normal variations in sleep amount and effects on health, we really don’t know,” reflects sleep specialist Alan Rechtschaffen of the University of Chicago. There’s a consensus that the extreme–below 6 hours a night–isn’t advisable, he says. Beyond that, distinguishing the health effects, if any, of 6 versus 7 versus 8 hours of sleep is going to take large, well-controlled studies that follow people over long periods.

Optimal sleep also probably varies with age and gender, says Vgontzas.

So, as to whether millions of cases of obesity, diabetes, and cardiovascular disease could be prevented if people in the United States were simply to increase their sleep from 7 to 8 hours a night, the issue hasn’t been put to bed. But the early data are at least provocative.

“We have all the dots or a lot of the dots, and it looks like there’s a picture there, but the science that actually connects those dots hasn’t been done yet,” Dinges says.

Sleep disorders, such as sleep apnea, that were once seen as mere nuisances are now recognized by the community of sleep researchers as serious health concerns. The data suggest that even young, healthy people should give more consideration to sleep.

Of all the health prescriptions out there, it may be easier to convince people to change their sleep habits than to make other lifestyle changes.

After all, in a time when we are constantly told to eat more broccoli, eat less chocolate, and do more push-ups, wouldn’t it be nice if hitting the snooze button were just what the doctor ordered?

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