Sports Nutrition: Mental Performance November/December 2017
by Steve Myers
INSIDER’s Take
• Several ingredients that enhance bioenergetics also help protect brain cells and communications. • Several dietary compounds boost production and activities of neurotransmitters and neurotrophins, such as BDNF, that improve neuronal structure and function.
• Much ingredient research on cognitive function is in the early stages and does not specifically address athletes and active consumers, but results can be translated to sports nutrition formulations.
Athletes and coaches often proclaim sports performance is 90 percent mental. Imagine trying to dribble around swarming defenders, keep up with Peyton Manning’s erratic audibles, watch both the soccer ball and the changing clues of Cristiano Ronaldo’s dancing hips in a big World Cup game, or desperately elude a mid-ice check sure to separate you from more than just the puck. These take quick thinking and processing to make the right moves.
Doug Kalman, Ph.D., a nutrition researcher and a sports nutritionist, said the athletes and teams he works with are tuning in to the influence of cognition on performance, as well as the role nutrition plays in cognitive health. “The message rings home,” he said. “More and more individual athletes and the team coaches are asking for meal plans and nutritional guidance not only to make sure they have optimal glycogen stores and are stimulating muscle protein synthesis, but are also supporting the brain and nervous system.”
The mind games in sports nutrition involves not just how the brain functions, especially under stress, but also how it recovers from the rigors of exercise.
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Sports Nutrition: Mental Performance November/December 2017
First, the brain needs energy. While relatively small in weight, the brain consumes almost 20 percent of the body’s energy. Several ingredients established in the energy category have merit in the growing cognitive area of sports nutrition.
Creatine, part of the first fuel source used during exercise/activity, helps replenish the body’s energy molecule, adenosine triphosphate (ATP), in anaerobic conditions. It may be useful in helping protect the brain during low-oxygen conditions that can compromise cognitive health and function.
Researchers have noted creatine supplementation has been associated with improving symptoms in neurological conditions marked by energy impairment.1 They studied creatine monohydrate and placebo in healthy young adults under acute oxygen deprivation, finding supplementation restored hypoxia- induced cognitive performance and attention capacity while increasing corticomotor excitability (motor function). Researchers hypothesized the supplement augments creatine and energy in brain cells.
Carnitine shuttles fatty acids into the mitochondria to fuel production of ATP and energy, and its derivative acetyl-L-carnitine (ALCAR) helps the brain recover from lack of oxygen.2 However, it accumulates in lower amounts in the brain than in other areas of the body, such as the muscles, and ALCAR transport through the finicky blood-brain barrier may rely on protein kinase c (PKC). Still, when it reaches the brain, carnitine has shown neuroprotective properties by increasing the levels of neurotrophins, special protein responsible for the survival and function of neurons (brain cells).3
Carnitine is also a precursor to acetylcholine, a neurotransmitter acting on motor neurons that control the muscles, but may also impact autonomic nervous system (ANS) functions, such as “fight-or-flight” response, as well as central nervous system (CNS) functions, including attention, learning, memory and motivation.
Choline also facilitates energy production from fats (from the liver) and is required for normal brain development. When ALCAR breaks down in the brain, its byproduct, acetyl-COA, combines with choline to make acetylcholine.
Citicoline, or cytidine diphosphate choline (CDP), is a source of not only choline but also cytidine, a nucleoside molecule found in DNA and RNA, and a modulator of transmitter glutamate in neurons and glial (neuronal support) cells.
Early human studies confirmed citicoline supplementation (as Cognizin®, from Kyowa Hakko) increased both acetylcholine and phosphatidylcholine synthesis in the brains of both young and old subjects.4
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Sports Nutrition: Mental Performance November/December 2017
More recently, a team from McLean Hospital and Harvard Medical School found Cognizin improves bioenergetics (phosphocreatine and ATP) and protects phospholipids in the brain.5 And, human research has shown Cognizin taken for one month in healthy adolescent males improved attention and psychomotor speed while reducing impulsivity.6
The enzyme acetylcholinesterase (AChE) breaks down acetylcholine, and AChE inhibitors have become pharmaceutical tools to increase acetylcholine levels, and increase neuronal transport and cognitive function.
Several species of sage (Salvia), including common sage (S. officinalis) and Greek sage (S. fruticosa), also inhibit AChE, according to in vitro and animal research.7,8,9 Phenolic diterpenes, carnosic acid, quercetin and rosmarinic acid are among the sage constituents responsible for AChE inhibition.
Sage also appears to support neurotrophins, including BDNF (brain-derived neurotropic factor), which has been a popular cognitive health research target due to its role in the survival, growth and differentiation of neurons and synapses (junctions between neurons that enable signaling). A 2017 research review highlighted rosmarinic acid’s ability to increase BDNF, especially in the hippocampus, while the flavonoids quercetin and luteolin boost BDNF and other important neurotrophins, including nerve growth factor (NGF); carnosic acid also increases NGF.10
Spearmint (Mentha spicata) leaves also contain rosmarinic acid, as well as numerous other active phenolic compounds. A proprietary extract of selectively bred spearmint leaves (as Neumentix™, from Kemin Foods) contains more than 50 such phenolic constituents, including salvianolic, lithospermic and caftaric acids, as well as higher levels of rosmarinic acid than found in commercial spearmint.11
One 2015 study looking at the antioxidant, anti-inflammatory and anti-AChE activity of Neumentix in healthy adults with memory impairment found supplementation improved the overall quality of working memory as well as spatial working memory accuracy, compared to placebo.12 Within the supplemented subjects, there was a significant dose response effect in the higher-dose group (900 mg/d) compared to the lower-dose group (600 mg/d) for both benefits. Researchers further noted the higher-dose group reported falling asleep easier and faster than the placebo group.
Most recently, research presented at the International Society for Sports Nutrition (ISSN) annual conference in Phoenix, June 2017, demonstrated the nootropic (“smart drug”) benefits of Neumentix (900 mg/d) translated to improved active reaction time in recreationally active adults undertaking Makoto Arena II testing—a unique device linking cognitive function to active performance using stationary, lateral and multi-directional testing involving both hands and/or feet.13
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Sports Nutrition: Mental Performance November/December 2017
Other botanicals have demonstrated cognitive-function benefits, including influence over BDNF levels.
Ashwagandha (Withania somnifera), a botanical popular in India’s Ayurveda system of traditional medicine, has been used as an adaptogen for thousands of years, and its roots contain steroidal lactones called withanolides and several alkaloids, such as withanine, somniferine and tropine. Research has shown ashwagandha can increase levels of BDNF and glial fibrillary acidic protein (GFAP), which affects neuronal and synaptic activities related to learning and memory.14
A full spectrum ashwagandha root extract (as KSM-66®, from Ixoreal Biomed) may improve both immediate and general memory, as well as executive function, attention and processing speed in people with MCI.15 A 2014 crossover study found healthy male adults taking a root and leaf extract of ashwagandha (as Sensoril®, from Natreon) had improved cognitive and psychomotor performance, including reaction times, compared to placebo.16
Whole coffee fruit (Coffea Arabica) is loaded with phytonutrients, including quercetin, chlorogenic acids and caffeic acids. Early research on whole coffee fruit extract (as NeuroFactor™ made from Coffeeberry®, both from Futureceuticals) indicated supplementation in healthy adult subjects increased BDNF levels by 1,443 percent, compared to an increase of 31 percent in subjects taking either grapeseed extract powder or green coffee caffeine powder.17 The researchers noted the rise in BDNF levels was not due to the amount of polyphenols or caffeine in NeuroFactor, but more likely due to its overall profile of procyanodins and polyphenols.
In this study, those taking the placebo (silica dioxide) had an unexpected decrease in BDNF levels, so researchers conducted a follow-up study, also in healthy subjects, to confirm the beneficial increase of BDNF. In the second study, NeuroFactor was compared to only a cup of brewed coffee and a placebo— this time, an empty gelatin capsule.18 Once again, NeuroFactor was associated with a significant increase in plasma BDNF levels compared to coffee and placebo; researchers further noted NeuroFactor raised BDNF levels in serum exosomes, extracellular vesicles that may function as messengers between different cells and tissues.
Coffee fruit is low in caffeine, and researchers concluded its benefits to BDNF were not caffeine-related. However, caffeine has demonstrated effects on fatigue signaling in the brain and associated improvements to focus and cognitive performance.19
Caffeine, naturally occurring in coffee, tea and other botanicals, occupies CNS receptors that would otherwise take up adenosine left over from the breakdown of ATP during energy release. As adenosine fills the receptors, the brain signals fatigue, so caffeine staves off fatigue messaging, resulting in alertness and perceived energy.
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Sports Nutrition: Mental Performance November/December 2017
Theacrine, also found in coffee and tea, is a purine alkaloid molecularly similar to caffeine but not considered as addictive.20 In 2016, exercise nutrition scientists published study results suggesting supplementation with theacrine (as Teacrine®, from Compound Solutions) at both 200 mg/d and 400 mg/d in healthy subjects increased energy, focus and concentration.21 Only the lower dose was associated with motivation and willingness to train; there were no adverse effects on resting heart rate.
Still, caffeine has been found safe in low and moderate doses, as evidenced by research in male and female cyclists who had no adverse effects on respiratory or heart rate following caffeine supplementation.22
Several studies have looked at combinations of caffeine and theanine, an amino acid in tea, on cognitive function, with some researchers noting no difference in blood pressure or heart rate between the various treatment protocols.23
A 2008 crossover study looked at acute cognitive and mood effects of 250 mg theanine and 150 mg caffeine, both combined and isolate, compared to placebo.24 Caffeine alone was associated with faster reaction time, better visual information processing and fatigue inhibition; theanine increased headache ratings. The combination of the two led to faster simple reaction times and numeric working memory reaction time, as well as improved sentence verification accuracy.
Another 2008 study reported caffeine alone boosted alertness, but when combined with theanine improv, in addition to reducing distraction tendencies.25
Kalman, who is a co-editor of the Journal of the International Society of Sports Nutrition (JISSN), noted newer research has demonstrated these two ingredients can enhance mental function, reaction time, alertness, while also having synergy beyond caffeine alone. “Products that combine these two ingredients in the studied doses have real world utility on the sporting field, not only in the lab,” he suggested.
Several other studies comparing various dose levels of caffeine and theanine, combined against placebo, have confirmed the combo improved alertness, attention, accuracy and overall cognitive performance, in addition to reducing fatigue and overall tiredness.26,27,28,29 A 2015 study found caffeine had a vasoconstrictive effect, compared to placebo, but combining theanine with caffeine—at levels and ratios equivalent to one or two cups of tea—improved cerebral blood flow, reversing the vasoconstrictive effects of caffeine.30
Nitric oxide (NO) is a key compound in the body that promotes vasodilation and improved circulation, but it also may help limit mild cognitive impairment (MCI) by preserving endothelial function.31
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Sports Nutrition: Mental Performance November/December 2017
Arginine is a precursor to NO and is used primarily as a pre-workout ingredient for better “pump” or swelling of muscles.
However, research published in 2016 noted an inositol-stabilized arginine silicate ingredient (as Nitrosigine®, from Nutrition 21) helped healthy male subjects better perform complex cognitive tasks— widely used Trail Making test (TMT)—involving mental flexibility, processing speed and executive functioning.32 The researchers credited Nitrosigine’s reported ability to enhance blood levels of arginine, thereby increasing NO production.33
Traumatic brain injury (TBI)—concussions tend to be mild to moderate TBIs—results in tissue damage and reduced cerebral blood flow. Long chain omega-3s, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are crucial for brain development and maintaining neuronal tissue membrane fluidity—DHA is the most abundant polyunsaturated fat in the brain and is highly concentrated in brain phospholipids. And, omega-3s produce resovlins that improve blood flow.34
In addition to generally supporting anti-inflammatory signaling in the body, omega-3s also counter oxidative stress, including lipid peroxidation and nucleic acid and protein oxidation in the brain.35 Further, omega-3s have been found to promote several aspects of cognitive recovery from TBI, including neurotransmitter release and restoration of synaptic activity.36
From a study of EPA and DHA supplementation in young adults, researchers reported subjects had better cognitive performance, but worked less after taking EPA, compared to baseline, while there were no improvements to time or accuracy in performance after DHA supplementation.37
A 2014 review of research on omega-3s and cognitive performance found EPA and DHA supplementation improved memory and psychomotor speed; however, other cognitive performance parameters were not consistently reported across several randomized controlled trials (RCTs).38 The reviewers called the evidence on cognitive performance preliminary and noted the trials tended to be small.
Astaxanthin, a carotenoid found in red/pink-colored marine animals and commonly sourced from the microalgae Haematococcus pluvialis, improves antioxidant status in the brain and decreases phospholipid peroxidation.39
Based on astaxanthin’s antioxidant properties and the known oxidative stress challenges to cognitive health and function, researchers studied the effects of an astaxanthin-rich extract of H. pluvialis on cognitive function in healthy middle-aged and elderly subjects.40 They noted no significant differences between the high- and low-dose astaxanthin groups and the placebo group on most of the CogHealth
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Sports Nutrition: Mental Performance November/December 2017 tests for accuracy and response time. However, the high-dose group showed significant improvements in response time and accuracy for one task, with additional “trends” in improvements in three other tasks, compared to low-dose and placebo.
Two months of supplementation with astaxanthin, in combination with Bacopa monnieri, phosphatidylserine and vitamin E (as Illumina®, from Cristalfarma), was shown to counter cognitive impairment and improve memory in subjects with MCI, compared to baseline performance, but the researchers called the study exploratory, noting no control arm.41
The challenge in formulating dietary supplements for cognitive benefits related to sports nutrition and active consumers is the early stage of research on most ingredients.
“I hope to see researchers continue to examine how to support the brain and nervous system as a means to further support and enhance how an athlete performs,” Kalman said. “This has real world application not only in athletes, but also in those who are tactical athletes (Military and select police) and can further lead to potential interventions for enhancing brain health past the game, match or event.”
While some studies specifically target healthy, active adults and physical performance endpoints, many studies involve older populations and those with neurological conditions or diseases. Still, the mechanisms of action highlighted across these research publications suggest potential benefits and can provide insights on how various ingredients can help brands meet growing consumer demand for cognitive benefits for exercise and competition.
References
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7. Kennedy DO et al. “Effects of cholinesterase inhibiting sage (Salvia officinalis) on mood, anxiety and performance on a psychological stressor battery.” Neuropsychopharmacology. 2006;31(4):845–852. 8. Scholey AB et al. “An extract of Salvia (sage) with anticholinesterase properties improves memory and attention in healthy older volunteers.” Psychopharmacology (Berl). 2008;198(1):127–139. 9. Senol FS et al. “Evaluation of cholinesterase inhibitory and antioxidant activities of wild and cultivated samples of sage (Salvia fruticosa) by activity-guided fractionation.” J Med Food. 2011;14(11):1476–1483. 10. Lopresti LL. “Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective Effects.” Drugs R D. 2017 Mar;17(1):53–64. 11. Cirlini M et al. “Phenolic and Volatile Composition of a Dry Spearmint (Mentha spicata L.) Extract.” Molecules. 2016;21(8):1007. 12. Fonseca B et al. “Effects of a distinct phenolic complex on working memory performance in healthy men and women with age-associated memory impairment (P7.105).” Neurology. 2015 April;84(14S):P7.105. 13. Falcone P et al. “Chronic supplementation with a natural nootropic spearmint extract improves active reaction performance in young, healthy individuals.” JISSN. 2017 June;14(Suppl 2):31. 14. Konar A et al. “Protective Role of Ashwagandha Leaf Extract and Its Component Withanone on Scopolamine-Induced Changes in the Brain and Brain-Derived Cells.” PLoS One. 2011;6(11): e27265. 15. Choudhary D et al. “Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions.” J Diet Suppl. 2017 Nov 2;14(6):599-612. 16. Pingali U et al. “Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants.” Pharmacognosy Res. 2014 Jan-Mar;6(1):12–18. 17. Reyes-Izquierdo T et al. “Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects.” Br J Nutr. 2013 Aug 28;110(3):420-5. 18. Reyes-Izquierdo T et al. “Stimulatory Effect of Whole Coffee Fruit Concentrate Powder on Plasma Levels of Total and Exosomal Brain-Derived Neurotrophic Factor in Healthy Subjects: An Acute Within-Subject Clinical Study.” Food and Nutr Sci. 2013 Sept;4(9):984-990. 19. McLellan TM et al. “A review of caffeine's effects on cognitive, physical and occupational performance.” Neurosci Biobehav Rev. 2016 Dec;71:294-312. 20. Taylor L et al. “Safety of TeaCrine®, a non-habituating, naturally-occurring purine alkaloid over eight weeks of continuous use.” JISSN. 2016 Sept;13:2. 21. Zeigenfuss TN et al. “A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine®) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters.” J Diet Suppl. 2016 May;10:1-15. 22. Talanian JL and Spriet LL. “Low and moderate doses of caffeine late in exercise improve performance in trained cyclists.” App Physiol Nutr Metab. 2016;41(8):850-855. 23. Giesbrecht T et al. “The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness.” Nutr Neurosci. 2010 Dec;13(6):283-90. 24. Haskell CF et al. “The effects of L-theanine, caffeine and their combination on cognition and mood.” Biol Psychol. 2008 Feb;77(2):113-22. 25. Owen GN et al. “The combined effects of L-theanine and caffeine on cognitive performance and mood.” Nutr Neurosci. 2008 Aug;11(4):193-8. 26. Kelly SP et al. “L-theanine and caffeine in combination affect human cognition as evidenced by oscillatory alpha-band activity and attention task performance.” J Nutr. 2008 Aug;138(8):1572S-1577S.
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27. Einother SJ et al. “L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness.” Appetite. 2010 Apr;54(2):406-9. 28. Foxe JJ et al. “Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task.” Neuropharmacology. 2012 Jun;62(7):2320-7. 29. Kahathuduwa CN et al. “Acute effects of theanine, caffeine and theanine-caffeine combination on attention.” Nutr Neurosci. 2017 Jul;20(6):369-377. 30. Dodd FL et al. “A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood.” Psychopharmacology (Berl). 2015;232(14):2563–2576. 31. Austin SA et al. “Endothelial nitric oxide modulates expression and processing of amyloid precursor protein.” Circ Res. 2010 Dec 10;107(12):1498–1502. 32. Kalman D et al. “Randomized Prospective Double-Blind Studies to Evaluate the Cognitive Effects of Inositol- Stabilized Arginine Silicate in Healthy Physically Active Adults.” Nutrients. 2016 Nov;8(11):736. 33. Kalman D et al. “A clinical evaluation to determine the safety, pharmacokinetics, and pharmacodynamics of an inositol-stabilized arginine silicate dietary supplement in healthy adult males.” Clin Pharmacol. 2015 Oct 7;7:103-9. 34. Massaro M et al. “Basic mechanisms behind the effects of n-3 fatty acids on cardiovascular disease.” Prostaglandins Leukot Essent Fatty Acids. 2008 Sep-Nov;79(3-5):109-15. 35. Michael-Titus AT. “Omega-3 fatty acids and neurological injury.” Prostaglandins Leukot Essent Fatty Acids. 2007 Nov-Dec;77(5-6):295-300. 36. Wu A et al. “The salutary effects of DHA dietary supplementation on cognition, neuroplasticity, and membrane homeostasis after brain trauma.” J Neurotrauma. 2011 Oct;28(10):2113-22. 37. Bauer I et al. “Omega-3 supplementation improves cognition and modifies brain activation in young adults.” Hum Psychopharmacol. 2014 Mar;29(2):133-44. 38. Muldoon MF et al. “Long-chain Omega-3 Fatty Acids and Optimization of Cognitive Performance.” Mil Med. 2014 Nov; 179(11 0): 95–105. 39. Nakagawa K et al. “Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes.” Br J Nutr. 2011 Jun;105(11):1563-71. 40. Katagiri M et al. “Effects of astaxanthin-rich Haematococcus pluvialis extract on cognitive function: a randomised, double-blind, placebo-controlled study.” J Clin Biochem Nutr. 2012 Sep;51(2):102–107. 41. Zanotta D et al. “Cognitive effects of a dietary supplement made from extract of Bacopa monnieri, astaxanthin, phosphatidylserine, and vitamin E in subjects with mild cognitive impairment: a noncomparative, exploratory clinical study.” Neuropsychiatr Dis Treat. 2014;10:225–230.
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