Exploring nootropic opportunities in sports nutrition.
Athletes and visitors to the Ted Stevens Sport Services Center at the Olympic Training Center (OTC) in Colorado Springs will find a state-of-the-art sports-medicine assessment facility, a team of world-class strength and conditioning coaches-even a high-altitude training center and teaching kitchen where Olympians can learn how to feed for peak performance.
But they’ll also find, located appropriately in the center’s Sport Sciences wing, a psychophysiology training space designed to monitor athletes’ brain and body responses while resting and under competitive simulation. For, as U.S. Olympic Committee sport psychologist and psychophysiologist Lindsay Thornton, points out, “Every change in the physiological state is accompanied by an appropriate change in the mental or emotional state, conscious or unconscious, and, conversely, every change in the mental or emotional state, conscious or unconscious, is accompanied by an appropriate change in the physiological state.”
In other words, brain and body are one. And, as Karen Hecht, PhD, scientific affairs manager, AstaReal Inc. (Burlington, NJ), notes, the very presence of the psychophysiology space at the OTC “shows that no less an august body than the U.S. Olympic Committee has dedicated a facility and program to studying how mental fitness impacts physical fitness and athletic achievement.”
Sports nutrition products are increasingly dedicating space in their formulations for ingredients-called nootropics-that link the mental and the physical, too, boosting cognitive function in such a way that athletic performance also improves. And the more we learn about the relationship between brain and body, the more exciting the prospects for these ingredients seem.
Though it would be difficult to find precise data on the strength of nootropic sports performance products-that’s how nascent the category is- “the number of cognitive-support supplements aimed toward athletes and fitness enthusiasts certainly seems to be growing, with abundant opportunities,” Hecht says.
Perhaps that’s because the convergence of several trends points the category toward success. “First,” says Elyse N. Lovett, MBA, MS, marketing manager, Kyowa Hakko U.S.A. Inc. (New York City), “good science on ingredients showing the correlations between sports and brain health has started to emerge. Second, consumers have started demanding products with brain health aspects to get that competitive edge. And third, manufacturers need to differentiate themselves in the crowded sports nutrition supplement space.”
As the audience for sports nutrition has expanded beyond its core focus on muscle mass and competition, the category has drawn what Kim Colletti, MBA, global cognition product manager, Kemin Human Nutrition and Health (Des Moines, IA), calls “active-lifestyle users, including key groups like on-the-go business professionals, working mothers, and outdoor enthusiasts.” This broader base, she says, “is looking for a wide range of benefits from sports products, including improvements in mental and physical performance.”
It is worth noting that this connection is hardly a new development. “Stimulants and other ingredients with cognitive benefits have been used in sports nutrition for many years,” Colletti points out. “The traditional sports-nutrition consumer welcomed the inclusion of nootropics long before they were even termed as such.” But, she says, “Now the expansion of the category to the active-lifestyle consumer has resulted in the emergence of nootropics as a category within the sports-nutrition market.”
Meanwhile, the nootropics field has been going through its own evolution. “For the last 20 years, ‘cognitive function’ products were more or less focused on aging baby boomers, tied to the hopes that they could help slow or prevent cognitive decline,” observes James Komorowski, MS, CNS, chief science officer, Nutrition 21 LLC (Purchase, NY). “Today’s nootropics are more closely targeted at Millennials, as the demographic is on a constant search to increase its number of productive hours in a day, whether for work, school, sports, or just daily life.”
Get Your Game On
And to the extent that Millennials are the central spectators of and participants in the world of eSports, or competitive video gaming, they deserve top billing for encouraging nootropic sports nutrition’s growth.
“Without question,” says Tim Ziegenfuss, PhD, CSCS, FISSN, CEO, Center for Applied Health Sciences (Stow, OH), “the gamer market has the biggest potential and most relevance” for driving nootropics’ future in sports formulations. The global audience for competitive gaming approaches 140 million, he notes, and elite eSports “athletes” now earn college scholarships.
For these high-stakes competitors, “optimizing brain ‘flow’ during a game of Call of Duty might make the difference between getting recruited by a top team like Optic Gaming or getting trounced by a seven-year-old with cheat codes,” Ziegenfuss says. “I mean, have you seen the number of buttons and joysticks some of these controllers have nowadays? And don’t even get me started on the virtual reality headsets.”
Of course, Millennials staring at video screens are hardly the only targets for nootropic formulations. All sports “require tremendous focus and intense concentration,” Hecht says. “Team sports and sports such as tennis often require the player to instantly assess the situation and immediately anticipate what will happen next and how to react to win. And singular performance sports such as gymnastics and golf also require the ability to focus intently.”
Do nootropics help them do all that? They do, says Komorowski. “A few of the major benefits associated with nootropic supplements are enhanced mental acuity, faster processing times, and improved focus. As any athlete will tell you, focus is what helps push them through their last trying sets of a workout or the final minutes of a long game.” Additionally, athletes appreciate that focus and mental acuity help them avoid injury. “More efficient multitasking also benefits performance by helping athletes save energy,” Komorowski adds.
Add their purported effects on mood, motivation, cognitive flexibility, and anxiety and nootropics are naturals for inclusion in sports formulations. “Think of it this way,” says Komorowski: “Athletes are already consuming sports nutrition pre-workout to pump their energy levels and improve performance during exercise, as well as post-workout supplements to support muscle growth and recovery. So, it’s a logical progression that they’d look to a nootropic supplement to help improve their overall performance, which really does stem from their ability to focus and think clearly during workouts.”
All About Timing
Some might wonder, though, if anything sets a sports nootropic apart from ingredients that mainstream consumers have tapped for mental sharpening. And, Hector Lopez, MD, CSCS, FAAPMR, FISSN, CEO and cofounder, Supplement Safety Solutions (Bedford, MA), and CMO, Center for Applied Health Sciences, says the main difference boils down to timing, onset of action, and degree of impact.
“Orthodox” nootropics support brain health on a more chronic basis, Lopez explains, “impacting various types of memory and executive function over extended periods by supporting the structural health of neurons, bioenergetics, and modulating neuro-inflammatory pathways.” Examples run from marine long-chain omega-3 fatty acids, phosphatidylserine, and curcumin to anthocyanins and flavanoids, phytocannabinoids like CBD-even creatine.
A nootropic intended to heighten physical performance, by contrast, works acutely-“within one to three hours,” Lopez says-on the neurochemical bases of reaction time, focus, perceived energy, cognitive flexibility, and processing speed. Think caffeine, citicoline, rhodiola, ashwagandha, and L-alpha-glycerylphosphorylcholine (alpha-GPC).
Understanding just how sports-oriented nootropics alter the brain’s neurochemistry continues to occupy scientists. But, says Mark J.S. Miller, PhD, MBA, FACN, CNS, principal, Kaiviti Consulting LLC (Dallas), the mechanisms of action seem to follow certain themes.
Most common is a strong antioxidant action. “This is important,” Miller says, “because the vascular endothelial production of nitric oxide is subject to oxidative degradation, and this can compromise local blood flow.” By neutralizing the free radicals that degrade nitric oxide, nootropics improve vasodilation, increase blood flow, and let nutrients travel to the brain and muscle cells that need them. “This is part of the explanation for the acute benefits of astaxanthin and other carotenoids, grapeseed extract, and N-acetyl cysteine,” Miller says.
Similarly, dietary nitrate helps maintain optimal blood flow to the brain and muscles because a bacterial enzyme in saliva converts it to nitrite, which can then be converted on demand to nitric oxide. “So, supplementation with nitrate-usually via beets or spinach-is associated with improved aerobic and anaerobic performance, and improved mental functions,” Miller says.
Some supplements actually replenish neurotransmitters that are “consumed” during the mind–muscle communications that underlie sports and exercise, Miller continues. And not surprisingly, scientists are eyeing the microbiome for clues as to how it may affect cognitive and physical performance. “Research in this area, especially with gut–brain interactions achieving increasing clarity, is progressing at a frenzy,” Miller says. “Here we can link the old knowledge of diet to sports performance with a new twist-our microbial friends that make up the community that we call ‘us.’”
Regardless of the mechanistic specifics, Miller says, “There is a triad at play” in the relationship among nutrition, the brain, and the body. At its apex are nutrients and natural products that can improve sports performance and brain function. “More recently,” he adds, “there has been growing evidence that exercise itself can improve brain function and suppress the cognitive decline that occurs with aging and disease.”
He adds that, while fewer ingredients have currently been studied to see how they can simultaneously effectuate “improved exercise and brain performance with supplementation,” the number of those potential ingredients is growing. “Undoubtedly, some of the research that will fill this gap will come in the elderly population, where preservation of cognitive function is being linked to exercise, mitochondrial health, and limiting oxidative stress,” Miller says. “Linking that research to athletes and their trainers will be the hurdle.”
Hartley Pond, senior vice president, technical sales, FutureCeuticals (Momence, IL), would agree. Among the most compelling studies he has seen on the brain–body connection have been those involving elderly patients with mild cognitive impairment (MCI), which he describes as “a constellation of symptoms, from loss of short-term memory, loss of executive function, loss of motor control, and typically shrinkage of and lesions on the hippocampus.”
In one such study,1 a randomized controlled trial conducted at the University of British Columbia, researchers assigned women with a median age of 75 and probably MCI to a walking program, a walking and weightlifting program, or no program at all. After a year, the researchers found that the control had lost hippocampal volume, developed further hippocampal lesions, and performed worse in a cognitive assay than at baseline. The walking-only group fared better than the control, Pond says, but “continued to decline in terms of cognitive function, hippocampal volume, and the number of lesions on the hippocampus.” But the subjects in the weightlifting and walking group saw their hippocampal shrinkage plateau, cognitive performance increase 18%, and number of lesions fall.
“This was all possibly correlated to increases in levels of BDNF,” or brain-derived neurotrophic factor, Pond says, which is a myokine protein that muscles release during exercise and that crosses the blood–brain barrier to effect improvements in cognitive function. And while we know that exercise-as well as fasting-triggers BDNF’s release, Pond notes that his company’s whole coffee fruit extract (trade named Neurofactor) also stimulates BDNF production.
The company has three clinical trials underway, one of which looks specifically at the extract’s effects on subjects with MCI, and it’s eagerly awaiting the results over the first half of 2018. “We’ve shown increases in BDNF,” Pond says, “and now we’re looking at functionality with MCI.”
The importance of such testing can’t be stressed enough when it comes to establishing nootropic sports formulations’ legitimacy, for both regulators and consumers will demand proof of products’ effectiveness. As Hecht puts it, “Continual research-credible human clinicals to show mechanism of action, results that may be expected, and validation of these results-needs to be performed and disseminated to the media. To create the pull effect-where the target consumers seek these products out-will take time and effort.” But as any athlete can attest, time and effort pay off.
Here are some branded nootropic ingredients that researchers are putting to the test, and formulators are putting to use:
Arginine. One branded ingredient (Nitrosigine from Nutrition 21) is a novel complex of arginine and silicon stabilized with inositol, and Nutrition 21 has carried out clinical studies demonstrating its “significant effect on cognitive acuity, including processing speed and executive functioning,” Komorowski says.
One study2 published in late 2016 showed that a 1,500-mg dose significantly improved subjects’ performance on cognitive tests (specifically, the Trail Making Test) requiring mental flexibility, processing speed, and executive functioning, says Komorowski. A previous clinical study suggested that the ingredient’s mechanism of action might be through increased nitric oxide levels, and thus increased blood flow carrying nutrients and glucose to the body and brain, he says.
Spearmint. A branded water-soluble extract of spearmint leaves selectively bred for their high phenolic content (Neumentix Phenolic complex K110-42 from Kemin Human Nutrition and Health) has been the focus of earlier studies examining its effects on cognitive performance and working memory in older adults, as well as its potential antioxidant, neuroprotective, cholinergic, and neurotrophic mechanistic benefits, Colletti says.
New human clinical trial3 data show that supplementation with the extract supports cognition and enhances physical performance in young, healthy individuals. In the randomized, double-blind, placebo-controlled trial, 142 healthy, recreationally active men and women approximately 27 years old supplemented with either 900 mg of the ingredient or a placebo for 90 days, with testing on days 0, 7, 30, and 90. Physical performance assessments used a 360-degree mobility device called the Makoto Arena II; cognitive measures came from a computerized cognitive-test battery.
Researchers found that subjects taking the supplement had significantly higher sustained attention scores after 30 days-scores still present at day 90. They also displayed significantly improved physical choice reaction performance as early as day 7, and improvements in the number of “hits” on the mobility device at day 30, which persisted throughout the study.
“The results suggest that the extract may benefit overall physical performance by supporting cognitive performance in a sports setting,” Colletti says. “These findings build on earlier work showing benefits in working memory, another executive function in the brain, and further emphasize the uniqueness of this special ingredient.”
Citicoline. A branded form of citicoline (Cognizin from Kyowa Hakko USA) has built a reputation for its effects on focus, attention, and mental recall, says Lovett. “It increases phosphatidylcholine,” she adds, “which is critical for healthy brain function.” A 2015 study4 deployed the Finger Tap and Ruff 2&7 tests to show that the ingredient produced an increase in motor speed and attention, respectively, in adolescent males after 298 days of supplementation.
Theacrine. Theacrine, a purine alkaloid found naturally in certain coffee, tea, and cacao-like botanical species, resembles the chemical structure of caffeine, but it has “very different physiological effects,” says Lopez, whose company has a branded form (TeaCrine from Compound Solutions; Carlsbad, CA).
For example, both caffeine and theacrine inhibit adenosine activity via two specific receptors, and it’s this inhibition, Lopez says, that sets off the biochemical processes that prevent the perception of fatigue and increase the attention, focus, and alertness that athletes prize. But, theacrine is a direct dopamine D1 and D2 receptor agonist, he adds, while caffeine is not. These agonist actions help theacrine increase the dopamine signaling associated with attention, movement control, motor performance, task initiation and completion, motivation, mood, and learning.
Caffeine is also what’s known as an orthosteric adenosine inhibitor, meaning it directly blocks the receptor sites. Meanwhile, theacrine “is likely to act as an indirect, allosteric modulator of these receptors,” Lopez continues, “contributing to differences in habituation.”
So, while caffeine habituation can set in after as few as five days of consumption, “a significant attribute of theacrine is the lack of habituation, or the decrease in response known as tachyphylaxis,” Lopez says. An eight-week study5 involving 60 subjects who took 200 mg and 300 mg of theacrine showed no signs of the rapid tachyphylaxis typically associated with caffeine and other nootropics.
Astaxanthin. Natural astaxanthin is a carotenoid derived from the algae Haemotococcus pluvialis. A recent study designed to induce the fatigue and stress of daily life-and of athletic training-put a branded form (AstaReal astaxanthin from AstaReal) to the test.
In the double-blind, placebo-controlled trial,6 subjects consumed either 12 mg/day of the astaxanthin supplement or a placebo for eight weeks. To test mental function, the participants performed a battery of timed calculations (i.e., the Uchida-Kraepelin test) to evaluate concentration and mental clarity; physical challenges were performed using a bicycle ergometer. The researchers then measured individuals’ subjective and objective perceptions of fatigue both before and after the stressor tests.
Visual Analogue Scale (VAS) analysis showed a significant reduction in perceived symptoms of mental and physical fatigue with supplementation compared to the placebo. “These included improvements in cognitive acuity, concentration, motivation, and mood,” Hecht notes. Subjects also reported reduced feelings of body heaviness and irritation. And while the placebo group displayed an increase in errors during the second half of the test, such an increase “was almost nonexistent” in the astaxanthin group. Supplementation also significantly lowered levels of salivary cortisol, a stress biomarker.
Says Hecht, “The study is believed to be the first clinical trial demonstrating that a nutraceutical ingredient has properties effective against both physical and mental fatigue.”