Sleep Loss Affects More than the Brain

by Rabiya S. Tuma

September, 2006

Researchers have known that too little sleep affects mental performance. Now they are finding that sleep loss affects a whole lot more, including the immune system, cardiovascular health, and even hunger regulation.

Epidemiologic studies around the world show that time spent in sleep is linked to all causes of death and to conditions that include cardiovascular risk, hypertension, diabetes, and stroke, says David Dinges, a sleep researcher at the University of Pennsylvania School of Medicine in Philadelphia. “The risk goes up when you sleep below seven hours or above eight, especially below seven,” he says.

Several large studies have been designed to look at the impact of sleep disturbance on physical health, including the Sleep Heart Health Study, a multicenter study implemented by the National Heart, Lung, and Blood Institute at the National Institutes of Health. After compiling the complete health history of more than 1,000 volunteers and obtaining basic information such as weight and blood pressure, the researchers fitted each participant with equipment that enabled the researchers to measure electrical currents in the brain, oxygen saturation in their breath, and chest and body movement.

Because different stages of sleep are associated with different electrical patterns as measured by electroencephalogram (EEG), the researchers could see who slept soundly and who had broken sleep. Eyal Shahar of the University of Minnesota, one of the Sleep Heart Health Study leaders, found that people who had severe sleep apnea, in which they stop breathing for a short period of time repeatedly during the night, were 42 percent more likely to have heart problems and 58 percent more likely to suffer a stroke than participants who did not have the disorder.

In a separate study, scientists found that patients treated for sleep apnea had a lower risk of heart attack and stroke, and were less likely to require bypass surgery than those who had untreated sleep apnea of a similar severity. Although neither of these studies shows definitively that cardiovascular problems are caused by sleep apnea or disrupted sleep, the data suggest that there is an important interaction between the two processes.

Immune System Link

To find out what links sleep and cardiovascular problems, scientists are watching what happens to healthy people after sleep deprivation, Dinges says. “In some individuals there is a clear increase in inflammatory markers” after a week of getting only four or five hours of sleep per night, he says. Proinflammatory cytokines, including interleukin-6, become elevated in response to sleep loss. These cytokines likely trigger a chain of other inflammatory proteins, such as C-reactive protein, which is a marker for cardiovascular inflammation and risk.

The relationship between sleep, cytokines, and immune system function is not simple, however. In 1994, Dinges found that after sleep deprivation, young adults produced an abnormally high number of white blood cells, as if they were fighting an infection, although no pathogen was present. Such a strong response could lead to an increase in proinflammatory cytokines.

On the other hand, Eve van Cauter, a professor of medicine at the University of Chicago, and colleagues found that young men who were sleep-deprived produced a less robust response to an influenza vaccination than did those who were fully rested. Even after ten nights of adequate sleep following the immunization, the effect was still visible, suggesting that some aspect of the immune response was compromised significantly.

Metabolic Effects

Studies in healthy adults have also shown a strong correlation between sleep and body mass index. In 2004, Shahrad Taheri, Emmanuel Mignot, and colleagues at Stanford University showed that people who slept fewer than eight hours had an increased body mass index in proportion to their decreased sleep, as well as altered levels of hormones that regulate metabolism and hunger. Specifically, volunteers who typically slept five hours per night had a 15 percent reduction in leptin, a hormone that suppresses appetite, and a 15 percent increase in ghrelin, a hormone that stimulates appetite.

In other words, people who slept less tended to feel hungrier than those who slept 8 hours. In one experiment, which van Cauter reported in June at the annual sleep research meeting, men consumed 26 percent more calories during periods of extended wakefulness when they got only five hours of sleep per night than they did during recovery periods in which they were allowed to sleep between 10 and 12 hours per night.

Researchers calculate that the 15 percent change in leptin could lead to about 500 extra calories per day, significantly more than the body consumes by staying awake. “After several days that could lead to some serious weight gain,” says Kristen Knutson, a postdoctoral fellow in van Cauter’s group.

The research group also reported at the June meeting that sleep quality had an impact on metabolic hormones. They brought nine healthy young adults into the sleep lab for five nights. The first two nights, the volunteers were allowed to sleep normally, but during the following three nights the researchers played intermittent loud noises so that the volunteers experienced “microarousals.”

With these interruptions, the volunteers never reached the deep sleep stages that are characterized by slow wave activity on an EEG monitor. Sleep fragmentation and suppression of slow-wave sleep reduced insulin sensitivity in these volunteers. Because insulin resistance is considered a prediabetic condition, the work hints at how sleep disorders might increase a person’s risk of developing type 2 diabetes, which has been shown previously to correlate with chronic sleep loss in epidemiological studies.

Perchance to Think

In addition to these physiological changes, scientists find dramatic alterations in cognition after people are either completely deprived of sleep or have several nights with less sleep than normal. When volunteers used a computer task that requires constant attention, Dinges’s group saw a steady decline in performance among subjects who slept less. The deficits increased as the number of nights of sleep loss accumulated: people who have short sleep for a couple of weeks can be as impaired cognitively as someone who has been awake for two or three days straight, but they do not know it, Dinges says.

In a separate study, the team found that, after 36 hours of complete sleep deprivation, those who were asked to work on the task for a longer period of time performed worse than those similarly sleep-deprived who worked on it for less time.

“Even though this is something that people say happens to them in the real world, and is sort of obvious, it has rarely been studied or documented,” Dinges says. Remarkably, those who worked harder also spent more time in slow-wave sleep during the recovery period. That observation supports the notion that the brain’s requirement for slow-wave sleep is proportional to brain use during waking hours, which researchers refer to as a use-dependent requirement for sleep (see “A Model of Sleep’s Role in the Brain”).

Scientists used to say that sleep was of, by, and for the brain, but recent findings suggest otherwise. Sleep may have initially evolved to take care of the brain, but many other systems now appear to rely on it for regulation and stabilization.

“Sleep is not just one thing,” Knutson says. “For a long time people thought that you get sleepy and maybe your brain is not there. But that’s not it. It affects the whole body.”