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 new dietary regime consisting of frequent low doses of caffeine, to help shift workers, medical residents, truck drivers, and others who need to stay awake to get a bigger boost from their tea or coffee.
"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, 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, say the researchers.
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, free of a timetable, 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, military and emergency services personnel.
The extended day was also designed to disrupt the subjects' circadian system while maximising the effects of the homeostatic push for sleep.
Following a randomised, 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 on waking up 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," said the scientists, who claim their 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 per cent of the time during the scheduled wake episodes, compared with 0.32 per cent 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 reveal an entirely new way to use caffeine to maintain alertness and performance in the face of sleep loss," said Wyatt.