Brain health targets: stress, sleep, healthy aging, esports, and more: Page 2 of 2

May 11, 2020

Staying Sharp with Age
While energy and focus are areas of cognitive health that present newer opportunities for dietary supplements among younger demographics, older adults are an important population because their brain health needs are more urgent. Taking dietary supplements to maintain brain health against age-related decline and to support facets of cognitive health such as memory can have an important impact on a person’s quality of life.

“Baby boomers have become the primary age group for cognitive products,” says Lisa Riedell, senior director of marketing, Alfasigma USA Inc. (Covington, LA). “They want to maintain a high quality of life for as long as possible. Maintaining cognitive acuity, including memory and performance, is critical for this age group.”

Kyowa’s Cognizin citicoline has been studied for its effects on memory in aging adults for some time now. A 1996 study, for example, found that supplementation with citicoline improved verbal memory in subjects between the ages of 50 and 85. The randomized, double-blind, placebo-controlled, parallel-group-design clinical study found that compared to placebo, supplementation only improved delayed recall related to logical memory for the subjects with relatively inefficient memories. These subjects were then recruited for a crossover study in which a higher dosage of citicoline was clearly associated with improved immediate and delayed logical memory.12

A more recent animal study on Cognizin found a potential synergistic benefit with omega-3 fatty acid docosahexaenoic acid (DHA), an important active component of fish oil, which many older consumers already take to support cardiovascular health.13 Phospholipids, structural components of cellular membranes, play an important role as precursors to signaling pathways that modulate neuronal membrane function. Phosphatidylcholine is the most abundant cellular phospholipid, and citicoline along with DHA is an essential intermediate in the synthesis of phosphatidylcholine. In the study, mice with brain ischemia were treated with a combination of Cognizin citicoline and DHA, or each alone. Results showed that the combination significantly improved learning and memory ability compared to the ingredients independently.

Polyphenol-rich extracts derived from grapes and blueberries have a growing library of evidence supporting their use in cognitive health formulations. Given their fruit origin, they also have a functional advantage for use in foods and beverages as well as recognition by consumers.

In a study published in Biological Sciences, 215 healthy subjects between the ages of 60 and 70 years of age were randomized to receive either 600 mg per day of a polyphenol-rich extract from grape and blueberry (Cerebelle from Diana Food; Hasbrouck Heights, NJ) or placebo for six months.14 Subjects were given a CANTAB Paired Associates Learning (PAL) test, a visuospatial learning and episodic memory test, as well as a Verbal Recognition Memory (VRM) and Spatial Span (SSP) working memory test, at baseline and 24 weeks.

There were no significant changes in primary outcomes in the placebo and experimental group, but subjects taking the extract did see significant improvements in VRM-free recall compared to baseline and placebo group. Researchers then stratified subjects into four quartiles based on cognitive performance at baseline. Results showed that the quartile with the lowest performance at baseline experienced the most significant improvements in primary and secondary outcomes, compared to placebo.

A study of a different polyphenol-rich extract ingredient from grape and blueberry (Memophenol from Activ’Inside; Beychac-et-Caillau, France) published in Antioxidants also saw positive results.15 In the study, 30 healthy students were randomized to consume either 600 mg of Memophenol or a placebo. Ninety minutes after intake, cognitive assessments were conducted for one hour. These assessments included Serial Three Subtraction task (STS), Rapid Visual Information Processing task (RVIP), and subjective ratings using Visual Analogue Scale (VAS).

Results showed that consumption of Memophenol was associated with a 2.5-fold increase in STS variation net scores, compared to placebo. The STS task requires participants to count quickly and accurately backwards in threes from a given random starting number between 800 and 999 presented on a screen. The task aims to evaluate subjects’ working memory and attention levels. A serial seven subtraction task was also performed but showed no significant improvements.

Healthy Aging
Healthy aging as a category represents a more holistic approach to combatting age-related decline, within which cognitive health is an important factor. It represents a major opportunity for manufacturers as well. For example, Natural Alternatives International (NAI; Carlsbad, CA) recently introduced a slow-release version of its patented beta-alanine ingredient CarnoSyn, called SR CarnoSyn. The new slow-release version focuses primarily on the healthy aging market rather than the sports nutrition space, a market in which the original CarnoSyn ingredient is already well known.16

The amino acid beta-alanine supports the synthesis of muscle carnosine in the body, which acts as a buffer against lactic acid to delay the onset of muscle fatigue. Carnosine levels decline as people age; therefore supplementation reduces the risk of sarcopenia. As an antioxidant, beta-alanine also helps fight glycation. Glycation leads to the accumulation of advanced glycation endpoints, which damage brain cells and function.

Ingredients touting mitochondrial health benefits are a big part of the healthy aging space. “Through the body’s regulation of healthy mitochondria and the removal of dysfunctional mitochondria, brain activities such as memory and learning may be improved,” says Shoji Matsukawa, vice president of Mitsubishi Gas Chemical, manufacturer of BioPQQ, a branded pyrroloquinoline quinone ingredient. “Importantly, the healthiness of mitochondria can affect not only brain functions but so many other functions as well, especially associated with aging, so it is important to have consumers conscious of the importance of mitochondrial health.”

“BioPQQ has been proven to activate mitochondrial biogenesis—a process critical to healthy cell activity in which clusters of mitochondria divide and multiply,” explains Matsukawa. “As we get older, mitochondrial function begins to decline, leading to the deterioration of brain health as well as the heart and other vital organs. But by reenergizing the mitochondria, BioPQQ can fuel cellular activity, providing more efficient energy production.”17

Another ingredient that supports mitochondrial health and, in turn, cognitive health, is MitoCarn from Alfasigma USA Inc. The ingredient is an acetyl-L-carnitine (ALC) form of L-carnitine. “As nerve growth factors in the brain decline, so do acetyl-L-carnitine and acetylcholine levels,” explains Alfasigma’s Riedell. “As a result, mitochondria tend to lose their efficiency. This loss of efficiency contributes to common complaints related to aging, including loss of memory, learning, recall, and cognition.”

MitoCarn, says Riedell, penetrates the blood/brain barrier to deliver nutrients directly to the brain. “The molecules may help to increase healthy blood flow and support wide-ranging functions that contribute to healthy cognition, including help with managing oxidative damage, support of mitochondrial function, and maintaining healthy neurotransmitter activity,” she continues. “MitoCarn may also help to minimize cellular waste during the ATP process. Antioxidants are critical in helping to reduce damage caused by free radicals or reactive oxygen species and other toxic residue byproducts.”

  1. Hasell CF et al. “The effects of L-theanine, caffeine and their combination on cognition and mood.” Biological Physiology, vol. 77, no. 2 (2008): 113-122
  2. Rogers PJ et al. “Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together.” Psychopharmacology, vol. 194, no. 4 (2008): 569-577
  3. Dimpfel W et al. “Zynamite (Mangifera indica leaf extract) and caffeine act in a synergistic manner on electrophysiological parameters of rat central nervous system.” Food and Nutrition Sciences, vol. 9 (2018): 502–518
  4. George A. et al. “Efficacy and safety of Eurycoma longifolia water extract plus multivitamins on quality of life, mood and stress: a randomized placebo-controlled and parallel study.” Food & Nutrition Research, vol. 62 (2018): 1374
  5. Yoto A et al “Effects of L-theanine or caffeine intake on changes in blood pressure under physical and psychological stresses.” Journal of Physiological Anthropology, vol. 31, no. 1 (2012): 28
  6. Hidese S et al. “Effects of L-theanine administration on stress-related symptoms and cognitive functions in healthy adults: A randomized controlled trial.” Nutrients, vol. 11, no. 10 (2019): 2362
  7. Krawiec S. “Positioning cognitive health ingredients toward gamers and e-sports athletes, a SupplySide West 2019 report.” Nutritional Outlook. Published November 4, 2019.
  8. Ostfeld I et al. “Effect of spearmint extract containing rosmarinic acid on physical and executive functioning after a tactical operation.” Journal of Special Operations Medicine, vol. 18 (2018), no. 4: 94-98
  9. Falcone PH et al. “Efficacy of a nootropic spearmint extract on reactive agility: a randomized, double-blind, placebo-controlled, parallel trial.” Journal of the International Society of Sports Nutrition, vol. 15, no. 58 (2018)
  10. Tartar JL et al. “A prospective study evaluating the effects of a nutritional supplement intervention on cognition, mood states, and mental performance in video gamers.” Nutrients, vol. 11, no. 10 (2019): 2326
  11. McGlade E et al. “The effect of citicoline supplementation on motor speed and attention in adolescent males.” Journal of Attention Disorders, vol. 23, no. 2 (2019): 121-134
  12. Spiers PA et al. “Citicoline improves verbal memory in aging.” Archives of Neurology, vol. 53, no. 5 (1996): 441-448
  13. Nakazaki E et al. “Combined citicoline and docosahexaenoic acid treatment improves cognitive dysfunction following transient brain ischemia.” Journal of Pharmacological Sciences, vol. 139, no. 4 (2019): 319-324
  14. Bensalem J et al. “Polyphenols from grape and blueberry improve episodic memory in healthy elderly with lower level of memory performance: A bicentric double-blind, randomized, placebo-controlled clinical study.” The Journals of Gerontology, vol. 74, no. 7 (2019): 996-1007
  15. Philip P et al. “Acute intake of a grape and blueberry polyphenol-rich extract ameliorates cognitive performance in healthy young adults during a sustained cognitive effort.” Antioxidants, vol. 8, no. 12 (2019): 650
  16. Grebow J. “Could a new, sustained-release version of CarnoSyn beta-alanine be the next big ingredient in healthy aging? SupplySide West 2019 report.” Nutritional Outlook. Published online on October 28, 2019.
  17. Saihara K et al. “Pyrroloquinoline quinone, a redox-active o-quinone, stimulates mitochondrial biogenesis by activating the SIRT1PGC-1alpha signaling pathway.” Biochemistry, vol. 56 (2017): 6615−6625