Brain Boosters

Some nutritional supplements provide real food for thought

On his third consecutive evening of air combat, a military pilot closes in on the night’s quarry, a suspected Taliban fuel depot in Afghanistan. Fatigued, his alertness flagging, the pilot throws some chewing gum into his mouth. Laced with caffeine, it’s the cockpit alternative to a cup of coffee.

Brain: rosendo/istockphoto, adapted by E. Feliciano; cup: piovesempre/istockphoto

SWITCH TEST | Used to assess some cognitive impacts of food supplements, this test asks participants to hit a computer key when either of two combinations appears on-screen. Screens refresh once a second for five minutes, and target combinations may switch during the task. The example here prompts participants to respond when they see a letter and an even number (but only if green) or a number and vowel (but only if orange). L-theanine-rich tea boosted scores on this task, which measures one aspect of attention: the ability to plan and execute decisions. Source: E. De Bruin/Unilever

This pilot would probably suspect that the gum is just a perk-me-up. But several caffeinated military rations — including this relatively new one — do more than stave off sleepiness. Emerging data indicate that these rations boost not only attention but also cognitive performance, features that do not necessarily climb in lockstep.

The U.S. Department of Defense has been investigating such supplements to improve the ability of U.S. armed forces to maintain sustained periods of intense vigilance and focus, explains Harris Lieberman, a psychologist at the Army Research Institute of Environmental Medicine in Natick, Mass. Another hope, he notes: These dietary aids might minimize the risk of “friendly fire.”

Army researchers at the institute, including Lieberman, are at the forefront of a small but growing cadre of investigators exploring how to boost what they call mental energy. This rather fuzzy phrase embraces wakefulness, but also includes mood, motivation and the capacity to perform key mental tasks.

Increasing mental energy is important for those enervated because of a lack of sleep or for those whose jobs, like those of fighter pilots, require vigilance even in the face of sleep deprivation. Compounds that keep you awake, it turns out, can also boost other aspects of mental performance. Improved cognition is emerging as a quantifiable side benefit of many of these substances — in some cases, even for those folks who aren’t sleepy to begin with. 

But the data can be hard to interpret, primarily because no test exists to directly measure mental energy, explains Patrick O’Connor of the University of Georgia in Athens. It must be inferred from other indicators. Still, it is fair to view fatigue and mental energy as anchoring opposite poles of a common spectrum, he says.

Similarly, caffeine anchors the stimulatory end of a spectrum of natural products exhibiting promise in hiking or sustaining cognitive aspects of mental energy. Others include L-theanine in tea, guarana, cocoa constituents and ginseng.

Learning how these compounds work, at what doses and under what circumstances, is important, argues O’Connor, because “mental energy underlies everything in our lives.” It’s key, he says, to achieving goals at home and work — and even to the success of the economy.

Perky brews

More data has emerged on caffeine’s role in promoting mental energy than on any other dietary constituent. The stimulant blocks the activity of adenosine, a molecule that slows heart rate and induces drowsiness. Caffeine perks people up, Lieberman says, “by blocking something that normally slows you down.”

At the Experimental Biology 2010 meeting in April in Anaheim, Calif., he described how, some 25 years ago, his team found that as little as 32 milligrams of caffeine — equivalent to what’s in a 12-ounce can of cola or less than a cup of regular coffee — improved attentiveness for auditory and visual cues.

People had thought that any improved performance from caffeine might be limited to people who were tired. Here, though, the young men in the study were well rested, suggesting broader benefits.

Lieberman’s more recent work has tested caffeine’s effects on tasks especially relevant to the military. For instance, a study conducted during the training of 68 Navy SEALs assayed the effects of caffeine after 72 hours of sleep deprivation and round-the-clock exposure to cold and other stressors. The men were taking part in a weeklong test of endurance known as Hell Week.

Not surprisingly, the exhausted trainees didn’t do nearly as well on tests of vigilance and other measures of cognitive performance three days into Hell Week as they had before the training marathon began. But those who got between 100 and 300 milligrams of caffeine an hour before a battery of mental tests made fewer mistakes and responded more quickly.

One task asked SEALs to scan for faint images that appeared for a couple of seconds on a computer monitor. Trainees who got no caffeine scored an average of 7.9 correct hits out of 20, while those given caffeine averaged between 10.6 and 12.2 correct responses. Caffeine recipients also had nearly 30 percent shorter response times. Scores on several other tasks, including a test of marksmanship, were unaffected.

Other scientists have been exploring caffeine’s impacts on the brain. Andrew Smith of Cardiff University in Wales, for instance, asked 118 students to watch a computer screen where three-digit numbers appeared at a rate of 100 per minute. When two consecutive numbers matched, participants were to note it with a keystroke. Before the tests, 84 students were given chewing gum; roughly half (41) got gum laced with 40 milligrams of caffeine.

Students reported feeling substantially more alert after chewing the caffeinated gum. They also performed better on some tests, including the one in which they had to identify repeated numbers. Those given caffeine were 4.4 percent faster than those who worked gum-free and 4 percent faster than noncaffeinated-gum chewers. The stimulant also appeared to speed up people’s ability to learn new information, Smith reported in the April 2009 Human Psychopharmacology.

Tea’s bonus

Tea, which people worldwide drink more of than any other beverage except water, is a major dietary source of caffeine. Unlike coffee, it contains another potentially powerful ingredient for brain activity: L-theanine, an amino acid that can alter alpha brain wave rhythms, inducing wakeful relaxation.

In 2008 in Nutrition Reviews, Janet Bryan of the University of South Australia in Adelaide observed that alpha wave activity has been linked to “increased performance under stress and improved learning and concentration” and reduced anxiety. L-theanine seems to enhance caffeine’s mental benefits, she noted.

Unilever, which owns Lipton, is actively investigating L-theanine’s effects. Neither caffeine nor tea’s caffeine-theanine combo augment performance on all types of mental tests, says Eveline De Bruin, a cognitive neuro­scientist with Unilever’s R&D facility in Vlaardingen, the Netherlands. The biggest impacts, she says, are in enhancing what’s known as executive function — the ability to perform complex tasks that rely on planning or decision making.

For instance, in an upcoming issue of Appetite, De Bruin’s team reports that tea brings boosts in executive function that increase with dose. On each day of a two-day study, 26 volunteers drank either strong tea or a tealike placebo before testing. One test asked participants to listen to rules on how to respond to sounds or images on a computer screen — and the rules changed every few seconds during each five-minute session. The men and women responded correctly in the auditory test almost twice as often (around 15 to 20 percent of the time versus 8 or 9 percent) after drinking tea rather than the placebo. Participants were also marginally — but reliably — more accurate after tea on a test that looked at the ability to plan and execute decisions (see “Switch test”).

While Unilever has demonstrated that tea enriched with triple the normal amount of L-theanine improves attention, De Bruin says Lipton has no plans to market such a product. “It is an interesting idea,” she concedes, “but at present Lipton is proud of producing an all-natural leaf-tea product that is unmodified yet capable of noticeably improving attention and alertness.”

Sweet paradox

Thinking, calculating, planning, learning, remembering — such mental tasks consume plenty of energy. Because glucose, better known as blood sugar, fuels body and brain, it might seem that a good dose of something sweet would be just what Mother Nature ordered to kick-start your neural hardware. Yet people with diabetes and high blood sugar levels can suffer from cognitive impairments.

Studies have begun probing this seeming contradiction. Two papers in August in Psychopharmacology, for instance,report a boost in mental performance when healthy people down a drink fortified with at least 50 grams of glucose (about 10 teaspoons worth) following a 12-hour overnight fast.

Christine Gagnon of the University of Quebec at Montreal and colleagues showed that in 44 people age 60 and up, drinking the glucose 15 minutes before the start of testing led to better scores on some tests than did the sugar-free alternative. Those on a sugar rush performed faster and accrued fewer errors when asked to quickly read a color name or name the color of words (even if a color word, such as green, appeared in a different color, say red). Glucose appeared especially beneficial in tasks that required switching and dividing attention, the researchers observed.

Among 90 undergrads, a sugary drink improved immediate recall of words, not faces, compared with a sugar-free one, reported a team led by Lauren Owen of the Brain Sciences Institute at the Swinburne University of Technology in Melbourne, Australia. Recall of large numbers that had appeared in earlier math calculations also improved.

Doses given in each study were high and would be ill-advised for people with trouble controlling their blood sugar, such as those with diabetes or metabolic syndrome. But David Benton of Swansea University in Wales has shown there may be a way to get the benefits of a glucose burst without overdoing sugary drinks. At the experimental biology meeting, he presented data indicating that for mental performance, it’s actually better to deliver glucose parsimoniously. He does it by giving subjects foods containing carbohydrates that digest slowly.

In an early study, Benton’s team gave cereals, breakfast bars or biscuits with roughly equal calories to 106 undergraduate women. The main difference between the meals was their glycemic index — how quickly the carbs break down into glucose.

Thirty minutes later and at regular intervals thereafter, the women took memory tests. Those who got the low-glycemic breakfast performed progressively better than those eating the rapidly digested meals. The difference was most dramatic for a later testing, 3.5 hours after breakfast, Benton says.

His group ran a similar test in rats, feeding them either quickly or slowly digested carbs. The rodents exhibited a similar improvement in learning when they got the slowly digested chow.

In a follow-up test, Benton’s group administered breakfast to kids in an elementary school class for four weeks. Kids got a meal with high-glycemic carbs on one-third of the days, low-glycemic foods on another third, and carbs that broke down at an intermediate rate on the remaining days.

On various days throughout the trial, hidden cameras recorded the 19 children while they were supposed to be working independently on a reading or math assignment. The behavior of each child was recorded over a 30-minute period and scientists later logged what the youngster had been doing: working, looking around the room, talking to others, fidgeting, acting out or moving around the room. On days when the kids had eaten the low-glycemic breakfast, they were much more likely to remain on task — 26 percent of the time versus 18 percent or less on the other days.

The kids also took simple memory tests and played with a video game that was rigged to be frustratingly difficult to master. On days they had eaten the slow-to-digest breakfast, kids exhibited more initial patience with the game. Their recall was also better — “about 10 percent better,” Benton says. It’s a small difference, he acknowledges. “But if your child came home with 10 percent better scores on a test, would it matter to you? Most parents would say yes.”

Herbal therapies

Tea and coffee aren’t the only natural stimulant-laced plant extracts to show energizing as well as brain-boosting attributes. There’s also guarana. Seeds of this Amazonian plant are an especially potent source of caffeine, which can constitute 5 percent of dried extracts. But guarana may have more than caffeine going for it.

At the experimental biology meeting, David Kennedy of Northumbria University in Newcastle upon Tyne, England, described cognitive benefits in young adults given small amounts of guarana — more benefits than when those volunteers received high doses. Indeed, Kennedy noted, guarana amounts needed to boost test scores and mood contained just 4 to 9 milligrams of caffeine. “That’s only about a tenth as much as you’d find in a cup of coffee,” Kennedy points out. “So guarana was doing something that wasn’t attributable to its caffeine” — although his team doesn’t yet know what.

He and colleagues have also been investigating other natural products that might elevate energy, attention and mental performance. Among these: Chinese ginseng (Panax ginseng). Young adults scored better on a battery of mental tests — including serial subtraction of numbers in their heads — and exhibited less mental fatigue after getting this herbal supplement rather than a placebo.

How Chinese ginseng may improve performance is unknown, but Kennedy suspects the effect might have to do with ginseng’s ability to moderate blood sugar levels. At least at the 200-milligram dose used by his group, this supplement caused a drop in blood-glucose levels one hour after consumption.

Researchers report that American ginseng (P. quinquefolius) also shows promise. Compared with a placebo, all doses improved some aspect of cognition, Swinburne’s Andrew Scholey and colleagues report in October in Psychopharmacology. One difference: This herbal supplement had no effect on blood glucose.

The Northumbria researchers are also exploring the idea that some natural products bolster brain function by affecting blood flow. For instance, if they dilate vessels, the products might allow more fuel — glucose — in to power brain activities. Kennedy and colleagues tested the idea by giving 30 students a cup of cocoa on three mornings. Each day’s formulation contained a different amount — 46, 520 or 994 milligrams per serving — of cocoa flavanols, natural agents that have antioxidant and sometimes heart-healthy properties.

The cocoa packages used in the study were prepared by Mars, a candy company that has been exploring health attributes of some chocolate products.

Both higher-dose formulations, especially the middle one, improved performance during mentally challenging tests involving math and the visual processing of information, the scientists report. At the same time, the college students receiving the middle dose reported a reduction in mental fatigue. Maximum benefits showed up two hours into testing, which roughly corresponds to the expected peaks in concentrations of flavanols in the blood and in blood flow to the brain, Kennedy’s team reported in the October Journal of Psychopharmacology.

Buyer beware

The concept of mental energy is hardly new; recognition of it, on some level, dates back to Aristotle. But only during the last two decades has a steady trickle of studies begun quantifying how various dietary constituents battle fatigue and the fuzzy thinking that may accompany it.

The food industry has paid rapt attention to study findings (and, as is the case with Unilever and Mars, has even helped pay for some of the research). Indeed, O’Connor observes, hundreds of new products claim to boost mental energy. And their appeal is understandable since mental energy helps motivate people not only to work but also to stick with it when the going gets hard.

“Unfortunately,” he adds, product claims “rarely are supported by compelling, unbiased scientific evidence.”

Michael Falk and colleagues at the Life Sciences Research Organization in Bethesda, Md., recently conducted a major review of supplements and ingredients (other than caffeine) that purport to boost attentiveness and mental performance in people. The researchers identified 265 research reports in the scientific literature that met certain criteria.

Falk’s team focused on 35 dietary constituents or factors, such as meal timing and the number of calories consumed. Promising data exist for ginkgo, ginseng, glucose and a few others, Falk says. But overall, his team concluded, for most “insufficient evidence is available to evaluate mental energy claims.”

Much of the problem may reflect how the testing was conducted, he points out. For about three-fourths of the substances, there were no more than 10 qualifying studies; for more than half, there were five or fewer, the team reported in the December 2010 Nutrition Reviews. And for any given nutrient, Falk notes, different trials often applied different tests to assess mood, motivation and mental prowess — which made comparisons difficult.

Many of the reports also tested very different populations (young adults in some, the elderly in others), had different criteria for whether subjects were healthy, and failed to establish baseline measures of mood and mental proficiency before administering a potential brain booster. Further complicating the picture: “You’re looking at what are relatively small effects and hard to measure,” he says. “And these are against a background of high methodological and statistical noise.” Such variations “undermine our ability to make strong conclusions.”

But Falk suspects that may change fairly soon. Researchers have been investigating what to measure and how to do it. And they’ve determined that agents with promise don’t always point to common benefits. Some may aid memory. Others may sharpen mental focus or speed up reaction times. Still others might make decision making easier.

When scientists begin standardizing tests, “I’m betting they’ll come out with stronger, more narrowly focused and more [scientifically] supportable conclusions,” Falk says. Findings that he says should point to whom these dietary supplements will benefit — and under which real-world conditions.

On the mental menu
Recent work suggests dietary substances such as caffeine and glucose may boost mental skills. Evidence for others (“Emerging substances”) is preliminary.

Increases visual and auditory vigilance; speeds reaction times, improves accuracy and limits false positives on vigilance tasks; and increases learning and short-term memory on computer tests that require keystroke responses.

Increases speed and accuracy of pattern recognition that switches arbitrarily over time, increases relaxation, boosts accuracy of processing of rapidly delivered visual information and reduces susceptibility to distracting information during memory tests. May improve aspects of cognitive performance when delivered with caffeine, as in tea.

Enhances memory of recent words or images, increases verbal fluency, improves pace of some types of serial subtraction, speeds decision times, enhances facial recognition and, among children, limits vulnerability to distraction when working alone.

Increases alertness and the ability to recall words and images at a later point in time.

Emerging substances
Ginkgo biloba
Improves pattern recognition and sustained attention, enhances delayed recall and memory of faces, and improves pace of serial subtraction and executive decision making.

Chinese ginseng
Enhances speed of recall, improves performance on simple arithmetic tasks and decreases false alarms on tests that require rapid processing of visual information.

Cocoa flavanols Increase processing of rapid visual information and improve the ability to count backward (though have led to more errors in some serial subtractions).

Janet Raloff is the Editor, Digital of Science News Explores, a daily online magazine for middle school students. She started at Science News in 1977 as the environment and policy writer, specializing in toxicology. To her never-ending surprise, her daughter became a toxicologist.