Washington-Battlefields once quieted down after dark, but no longer. Night vision technology, refined over the past two decades, lets wars rage around the clock. "Modern warfare pushes the limits of human performance," noted Col David Penetar, PhD, of the US Army Research Institute of Environmental Medicine in Natick, Mass. Sleep disruption, coupled with heavy physical demands, he said, may impair critical decision-making and other cognitive skills.

The role of caffeine in countering such decrements and new ways to deliver this drug were the focus of a 2-day meeting at the National Academy of Sciences (NAS) last month. Speakers addressed the Committee on Military Nutrition Research of the NAS Food and Nutrition Board, which will advise the US Department of Defense on applying research findings. Caffeine studies also hold implications for civilian life, for physicians on call, pilots, truckers, rescue workers, and perhaps even for the sleep-deprived general public.

SLEEP IS BEST, BUT...

"Caffeine is no substitute for adequate sleep," Penetar stressed. Troops, he said, need to be educated about their need for sleep and ways to foster it. They also need equipment and work-rest schedules designed to minimize errors and cross-training so that activities can continue while some people rest. But extended duty hours in military operations, he said, may warrant pharmacological interventions to sustain the performance of mental tasks.

The maximal zone of vulnerability, according to James Wyatt, PhD, of Harvard Medical School, occurs when sleep loss intersects with the disrupted biological rhythms that accompany transmeridian travel and night work. In recent US military action in the Persian Gulf, for example, troops newly deployed from the United States, still experiencing jet lag, were needed for night missions. An individual's ability to obtain sleep and the quality of that sleep, both related to the timing of sleep, he said, also affect the degree of neurobehavioral impairment.

[The cover of Asleep at the Throttle, a brochure about fatigue prepared for military pilots by John A. Caldwell, PhD, director of Sustained Operations Research at the US Army Aeromedical Research Laboratory at Fort Rucker, Ala. The brochure offers hints for avoiding fatigue and staying awake and alert. Credit: John D. Sowell]

In studies under way in the time isolation laboratory at Brigham and Women's Hospital in Boston, Wyatt and colleagues use a month-long protocol to simulate military operations. They put subjects on variable-length days, shift their bedtimes and wake times, and give them capsules containing either caffeine or placebo several times during each wake episode. The researchers will assess the drug's efficacy as a possible fatigue countermeasure and its optimal time of administration.

In studies at Walter Reed Army Institute of Research (WRAIR) in Silver Spring, Md, Mary Kautz, PhD, and colleagues gave subjects 150 mg, 300 mg, or 600 mg of caffeine after 48 hours of sleep deprivation and tested them during the next 12 hours. (The amount of caffeine in an average cup of coffee is 100 mg.) The 600-mg dose improved cognitive performance, objective alertness, and self-ratings of mood to the same extent that 20 mg of amphetamine had been shown to do in a comparable study. The caffeine caused fewer adverse effects. The findings suggest, Kautz said, that caffeine may help postpone sleep up to 12 hours. WRAIR researchers plan similar studies to evaluate the nonamphetamine drug modafinil as a fatigue countermeasure in healthy subjects. Modafinil was approved by the Food and Drug Administration (FDA) in 1998 to improve wakefulness in people with narcolepsy.

HELP IN THE FIELD

Under field conditions, coffee and cola drinks, from which Americans typically get their caffeine, may be scarce. Even water may be in short supply. Pill-aversive troops, it's believed, may spurn caffeine tablets.

Chewing may be a viable alternative to brewing. Garry Kamimori, PhD, also of WRAIR, showed a standard-size stick of Stay Alert gum containing 50 mg of caffeine. Two sticks are the equivalent of an ordinary cup of coffee. "Chew out" data (a measure of caffeine extraction) from the gum's manufacturer, Amurol Confections Co, Yorkville, Ill, shows that 80% of the caffeine in the gum is absorbed in 5 minutes, Kamimori said, and provides a quicker cognitive response than the same dosage of caffeine in beverage form. The gum, he noted, is easy to use and portable, requires no fluids, and comes in an easily titratable dose. It also reportedly is formulated to withstand temperatures from below freezing to about 120°F-without sticking to its wrapper. Studies at WRAIR scheduled to start in April, Kamimori said, will assess the impact of 1, 2, and 4 sticks of gum on vigilance tasks around the clock, in rested and sleep-deprived subjects. The gum, already commercially available, comes in five-stick packs in mocha and mint flavors.

Other research focuses on performance-enhancing foods. Scientists at the Department of Defense Soldier Center of Excellence (SCOE) in Natick have created what they say is the first caffeine-supplemented food bar. Developing this product, still in pilot testing, "was a food technologist's nightmare," said Jack Briggs, senior food technologist at SCOE. Caffeine's bitterness and lingering taste, he said, are hard to conceal. Moreover, only FDA-approved food
constituents are permitted in military rations. Food items must taste good enough to ensure consumption, provide complete nutrition, and have a 3-year shelf life, in contrast to about 6 months for civilian products.

To formulate their food bar, Briggs and colleagues mixed mocha chocolate flavoring with almond butter, almond pieces, currants, vegetable oil, and other ingredients. Their test bars contain 100 mg to 600 mg of caffeine, the equivalent of one to six cups of coffee. The bars also total 370 calories, providing the energy density needed in times of high physical activity. The SCOE scientists also are investigating other possible performance enhancers, including tyrosine, creatinine, glutamine, choline, and antioxidants.

Even in sustained operations, scheduled naps may reduce the need for pharmacological interventions, said Michael Bonnet, PhD, of Wright State University School of Medicine in Dayton, Ohio. "Sleep may be viewed as a drug that increases alertness," he said. He has conducted a series of studies of napping for 2, 4, or 8 hours prior to 64 hours of sleep loss, with and without caffeine. The studies show that a nap prior to sleep loss improves alertness, he said. A daytime nap followed by two cups of coffee restores nighttime alertness to daytime baseline levels.

The Committee on Military Nutrition Research expects to publish its review later this year.

Caffeine Tactics for Physicians on Call

House officers perform better and stay more alert if they take a 2-hour nap after 2 PM on the day before a night shift and then stay up all night with the aid of caffeine, according to Michael Bonnet, PhD, of Wright State University School of Medicine in Dayton, Ohio.

Normal young adults, particularly those with a chronic sleep debt, he said, fall asleep easily in the daytime in a sleep-conducive environment, that is, a quiet, dark room where they are protected from interruptions. Bonnet's research suggests, he said, that 200 mg of caffeine (two cups of coffee) at 1 AM preserves alertness through the night. Another 200 mg at 7 AM helps alertness the following day.

Napping on night duty, even if one's workload permits, may harm rather than help alertness, Bonnet said. Sleep-deprived people sink quickly into deep sleep. When awakened abruptly, they often experience sleep inertia, or mental fogginess.