Researchers from Rush University Medical Center, Brigham and Women's Hospital and Harvard Medical School have discovered that caffeine works by thwarting one of two interacting physiological systems that govern the human sleep-wake cycle. The researchers, who report their findings in the May issue of the journal SLEEP, propose a novel regimen, consisting of frequent low doses of caffeine, to help shift workers, medical residents, truck drivers, and others who need to stay awake get a bigger boost from their tea or coffee.
"I hate to say it, but most of the population is using caffeine the wrong way by drinking a few mugs of coffee or tea in the morning, or three cups from their Starbuck's grande on the way to work. This means that caffeine levels in the brain will be falling as the day goes on. Unfortunately, the physiological process they need to counteract is not a major player until the latter half of the day," said James Wyatt, PhD, sleep researcher at Rush University Medical Center and lead author on the study.
Though many studies have measured caffeine's sleep-averting effects, most do not take into account that sleep is governed by two opposing but interacting processes. The circadian system promotes sleep rhythmically--an internal clock releases melatonin and other hormones in a cyclical fashion. In contrast, the homeostatic system drives sleep appetitively--it builds the longer one is awake. If the two drives worked together, the drive for sleep would be overwhelming. As it turns out, they oppose one another.
Caffeine is thought to block the receptor for adenosine, a critical chemical messenger involved in the homeostatic drive for sleep. If that were true, then caffeine would be most effective if it were administered in parallel with growing pressure from the sleep homeostatic system, and also with accumulating adenosine.
To test their hypothesis, the scientists studied 16 male subjects in private suites, free of time cues, for 29 days. Instead of keeping to a 24-hour day, researchers scheduled the subjects to live on a 42.85–hour day (28.57-hour wake episodes), simulating the duration of extended wakefulness commonly encountered by doctors, and military and emergency services personnel. The extended day was also designed to disrupt the subjects' circadian system while maximizing the effects of the homeostatic push for sleep.
Following a randomized, double-blind protocol, subjects received either one caffeine pill, containing 0.3 mg per kilogram of body weight, roughly the equivalent of two ounces of coffee, or an identical-looking placebo. They took the pills upon waking and then once every hour. The goal of the steady dosing was to progressively build up caffeine levels in a way that would coincide with--and ultimately, counteract--the progressive push of the homeostatic system, which grows stronger the longer a subject stays awake.
The strategy worked. Subjects who took the low-dose caffeine performed better on cognitive tests. They also exhibited fewer accidental sleep onsets, or microsleeps. EEG tests showed that placebo subjects were unintentionally asleep 1.57 percent of the time during the scheduled wake episodes, compared with 0.32 percent for those receiving caffeine. Despite their enhanced wakefulness, the caffeine-taking subjects reported feeling sleepier than their placebo counterparts, suggesting that the wake-promoting effects of caffeine do not replace the restorative effects gained through sleep.
"Our results highlight the impairments in cognition that accompany all work schedules that lie outside the usual 9 to 5 workday. In addition, they reveal an entirely new way to use caffeine to maintain alertness and performance in the face of sleep loss," said Wyatt. As the researchers hypothesized, the behavioral differences between the groups appear to be due to caffeine's effects on the homeostatic rather than circadian system. Wyatt and his colleagues suggest that shift workers, medical residents, truck drivers, and others who need to stay alert consider taking frequent low doses of caffeine. "While there is no perfect substitute for sleep, our results point the way toward a much better method for using caffeine in order to maintain optimal vigilance and attention, particularly when someone has to remain awake longer than the traditional 16-hour wake episode," said Wyatt.
Founded in 1978 by Rosalind Cartwright, PhD, the Sleep Disorders Center at Rush was the first such center in Illinois and the first in the region to receive accreditation from the American Academy of Sleep Medicine (then the American Sleep Disorders Association). Since that time, the doctors of the center have treated more than 16,000 patients. To inquire about hours or to request an appointment, call 312-942-5440.
Rush University Medical Center is an academic medical center that encompasses the 729-bed Presbyterian-St. Luke's Hospital (including Rush Children's Hospital), the 79-bed Johnston R. Bowman Health Center and Rush University. Rush University, with more than 1,270 students, is home to one of the first medical schools in the Midwest, one of the nation's top-ranked nursing colleges, as well as graduate programs in allied health and the basic sciences. Rush is noted for bringing together clinical care and research to address major health problems, including arthritis and orthopedic disorders, cancer, heart disease, mental illness neurological disorders and diseases associated with aging.