Cognitive Support R&D: The Intersection of Nutrition, Neuroscience, and Systems Biology 

Researchers are exploring brain physiology, neuroimaging, and the connections between cognition and adjacent health areas like stress, sleep, the gut microbiome, heart health, metabolism, and overall health and nutritional status. This new systems biology approach, once considered very forward-thinking, is now a definitive part of today’s research landscape in cognitive support nutraceuticals. 

Trends in R&D  

The field of cognitive support nutrition is becoming more mechanistic and biomarker-driven, noted Shaheen Majeed, global CEO and managing director of Sabinsa. The company recently evaluated Sabroxy Oroxylum indicum for its role in increasing brain-derived neurotrophic factor (BDNF), “which is critical for neuronal survival and synapse formation.”¹

“Researchers have examined BDNF as a biomarker in nutritional research, but changes in circulating BDNF should be considered alongside other outcomes measured in a study,” said Maggie McNamara, vice president of global marketing at Saanroo. A 2024 study on the company’s Levagen PEA ingredient found supplementation increased serum BDNF alongside improvements on the Paired Associates Learning test.²

The trend toward “structural whole-body outcomes tied to long-term brain resilience,” and evidence of lasting physiological support is phasing out studies on more short-term stimulation, said Mark LeDoux, chairman and CEO of Natural Alternatives International, Inc. The most definitive development of the category in recent years has been “the growing body of clinical research linking specific nutrients to measurable brain tissue and structural outcomes,” and not just subjective measures, he added. 

Researchers are moving past asking whether a nutrient improves cognitive test scores and instead asking which specific biological mechanism it modifies. 

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Emerging studies on iron’s role in the synthesis of neurotransmitters is generating interest in its role on mood, stress, and cognitive function, noted Vincent Hackel, president of SloIron. “Under iron deficiency, dopamine in the prefrontal cortex may be reduced, which can directly impair the ability to regulate attention, sustain focus, and perform complex cognitive tasks. In a review of 14 different human studies, evidence showed that iron supplementation may improve attention and concentration.”³

In a 2026 clinical study, researchers gave 365 older adults at elevated dementia risk 2 grams of DHA daily for 24 months, achieving targeted increases in cerebrospinal fluid DHA. “These findings address a critical uncertainty that has limited interpretation of prior omega-3 prevention trials,” the authors wrote. “We demonstrate that high-dose supplementation achieves robust CNS target engagement even in individuals with chronically low omega-3 intake.”⁴

B vitamins may do more than previously understood to support brain health. While they’ve been known to reduce homocysteine and slow cognitive decline, a recent study that followed up on the VITACOG trial used untargeted metabolomics to determine that B-vitamin treatment produced a unique metabolic signature that altered brain energy metabolism and neurotransmission.⁵

Thomas Druke, senior marketing and business development manager at Balchem, noted how new science is expanding understanding of choline’s role in cognitive health, beyond fetal development. It is a precursor for acetylcholine, helping “coordinate the response of neuronal networks and transmit messages from the brain to the muscles, facilitating essential cognitive functions like memory and muscle control.” In a study by Balchem and University of Vermont researchers, choline supplementation improved working memory-related brain activation and functional connectivity in post-menopausal women, measured by fMRI.⁶

“We used to think of creatine purely in terms of muscle strength, and now we understand it has a role in supporting cognition under stress and in demanding conditions,” noted Brittany Johnson, PhD, RDN, business development director at FutureCeuticals. ⁷

Broadly, the category is moving beyond subjective questionnaires and incorporating validated cognitive assessments. “The Rosell Institute for Microbiome and Probiotics (RIMAP) by Lallemand is investing in research and development in this particular field,” said Karine Lasfargue, product manager at Lallemand Health Solutions, pointing to a recent clinical study (pending publication) on the supplier’s Cerebiome which examined attention-related cognitive measures. “Preliminary findings showed improvements in reaction time and processing speed in healthy young adults, extending the conversation around psychobiotics beyond mood and stress support into the realm of cognitive performance.”⁸

Finished products and multi-ingredient supplements also appear more often in clinical studies, as researchers recognize the value of complementary mechanisms of action. “We’re seeing more thought put into why ingredients are combined, rather than simply how many can fit into a formula. Multi-ingredient products make sense when each component has a defined role,” said McNamara. 

The industry can improve how it communicates the science, noted Steve Fink, vice president of marketing at PLT Health Solutions. “The quality of evidence and the way it is communicated remain uneven. Too often, a finished product borrows the reputation of an ingredient without matching the studied material, dose, population, or duration. A long list of references is not the same thing as evidence for the article of commerce.” 

Published evidence is only as strong as a product’s ingredient identity, standardization, batch consistency, safety, and traceability, he added. “Better standards will come from greater transparency around all of these details, not simply from making stronger claims.” 

“Having strong science isn’t enough if it’s locked in academic journals,” said Sébastien Bornet, vice president of global sales and marketing at Horphag Research. “We work hard to make the research accessible by translating complex technical data into understandable language for a variety of audiences.” 

It can be especially compelling to support traditional medicinal plants with modern research, extraction methods, and standardization, noted Blake Haynes, public relations and communications manager at Stratum Nutrition. “Sage has a long history of use associated with memory and cognition, while modern research continues to investigate mechanisms related to neurotransmitter activity, oxidative balance, and inflammatory signaling,” positioning it for both acute benefits and healthy aging products.  

“One of the most important steps the industry can take is to place greater emphasis on research conducted on the specific ingredient being marketed, rather than relying exclusively on generalized research about an ingredient category or botanical species,” Haynes said. 

New Waves in Nootropics

Cal Bewicke, CEO of Ethical Naturals, Inc., noted crossover between mood/stress and cognitive performance benefits; AlphaWave L-theanine, for instance, has been clinically studied for effects on selective attention and inhibitory control, sustained attention, and working performance. People feel overstimulated, creating major opportunities for products that can create relaxation without the associated drowsiness in addition to conventional cognitive benefits, he said.⁹

“Botanicals that influence neuroplasticity, neural communication, neurotransmitter activity, and the stress response are particularly relevant,” said Majeed. 

Across a variety of ingredients, Sabinsa has used in vitro models and neuroimaging to examine effects such as BDNF increase, nerve impulse transmission, lipid peroxidation in neurons, dendritic growth, dopamine modulation, and GABAergic and cholinergic pathways, he noted. 

Kemin has been researching green tea and spearmint extracts from plants selectively bred from high-polyphenol varieties, offering benefits such as focus, working memory, mental speed, and decision-making with none of the sleep effects associated with caffeine or other nootropics, noted Samantha Maci, global technical services lead. 

Systems Biology 

“The body does not organize itself by supplement categories,” noted McNamara. A finding related to sleep benefits, for instance, can give researchers a reason to examine related effects on stress, mood, cognition, and more. 

“Chronic stress can affect memory, decision-making, sleep, digestion, cardiovascular health, immune function, and hormonal balance,” Majeed noted, driving interest in a more systems-oriented approach. Complementary pathways to target include the microbiome, metabolic function, stress responses, neurotransmitter activity, and BDNF production. “The result is a shift toward formulations designed around multiple aspects of resilience.” 

“This systems-based perspective is helping broaden the category beyond the idea of simply taking something for memory,” said Haynes. In the case of sage, studies have highlighted several complementary pathways, including acetylcholinesterase inhibition, cholinergic activity, and brain-related antioxidant and inflammatory pathways, he said. “The future will likely involve combining targeted ingredient science with a broader understanding of interconnected systems that contribute to cognitive health.”  

Michael Anthonovage, vice president of product development and innovation at Vitaquest, noted that FTC’s emphasis on competent and reliable scientific evidence (CARSE) is important to consider on top of FDA’s structure/function claim regulations. CARSE stresses gold-standard randomized studies, and “appropriate populations, validated endpoints, adequate study duration, clinically meaningful results, and consideration of the totality of evidence.” Research on formulations and their systemic effects, not just individual components, holds claims up to regulatory scrutiny. 

The plethora of pathways through which the gut and brain interact continue to garner scientific intrigue, noted Lasfargue, and the field is moving beyond established work on mood and stress response to more performance-aligned cognitive processes. The appeal of “psychobiotics” is that, rather than influencing solely on neurotransmitter pathways, they affect broader biological systems involved in stress or cognition. 

The gut comes into play in unexpected ways, according to Brian Zapp, director of marketing at Applied Food Sciences, who noted a recent study by AFS on MycoThrive Lion’s Mane that found the ingredient significantly increased Faecalibacterium prausnitzii in addition to cognitive improvements over 45 days. “That does not establish that the change in the microbiome caused the cognitive response, but it gives us a much clearer biological picture of how lion’s mane works.” 

Overall diet, fiber, microbial diversity, metabolic signaling, and stress responses exist on the gut-brain axis, said Skye Chilton, CEO of Nammex, reinforcing the importance of lifestyle fundamentals in how our brains function. “Mushrooms are relevant to this discussion not only because of their secondary metabolites, but also because they are foods containing beta-glucans, fiber, and other naturally-occurring compounds like ergothioneine.” 

“Emerging research on the gut-brain-cardiac axis makes clear that cognitive, cardiovascular, and metabolic outcomes share biological pathways, from the vagus nerve to gut-derived metabolites to systemic inflammation, which means treating ‘brain health’ as an isolated target is increasingly out of step with science,” said LeDoux. “Within a few years, ‘systems biology’ won’t be a niche talking point.”¹⁰

Bornet noted that endothelial function and nitric oxide production, traditional measures of heart health and cardiovascular endurance, also affect brain function. Recent research on Pycnogenol French Maritime Pine Bark extract shows that a supplement targeting these biological pathways has reduced hyperactivity and impulsivity in children with ADHD; improved overall cognitive function in healthy adults; and improved test scores and test-related anxiety in college students. “It has been shown that NO has beneficial effects on brain function. By regulating vascular smooth muscle relaxation, NO leads to increased blood flow, which ensures sufficient supply of oxygen to neuronal cells.”^11-14

Other processes on which brain health depends include cerebral blood flow, glucose regulation, inflammatory signaling, mitochondrial energy production, gastrointestinal physiology, and whole-body micronutrient status,” Anthonovage noted. “Systems biology should lead to more intelligent formulation, not simply longer Supplement Facts panels.” 

The eye-brain connection is another area of intrigue, said Maci. “The retina is neural tissue, and the eye and the brain share interconnected pathways,” raising questions about how carotenoids, which selectively accumulate in the eye and brain, support these systems.  

The findings are promising for the role lutein and zeaxanthin in cognitive development, starting from nutrition. Supplementation with FloraGLO lutein and zeaxanthin during pregnancy supported retinal development in infants, while supplementation in teens correlated with an improved ability to “focus on relevant information despite competing distractions, alongside enrichment of the macular pigment and reduced eye strain.”^15-16 

Longevity

Age-related cognitive impairment presents long preclinical windows, making nutrition an intuitive part of a broader early intervention strategy.

The 2025 U.S. POINTER study examined a multi-domain lifestyle intervention in over 2,000 older adults considered at risk of cognitive decline. Adherence to an intervention including regular exercise, the MIND diet, cognitive training, social engagement, and cardiovascular/health monitoring significantly improved global cognition measures over a 2-year window. The importance of this study, especially to the nutrition segment, is that participants’ cognitive function was healthy at baseline, despite genetic risk factors.¹⁷

Another study published in The Journal of Nutrition, Health & Aging in 2026 evaluated a plant-based ketogenic diet versus control in a population of people with early-to-mid-stage Alzheimer’s disease. Over the 6-month treatment window, the treatment group saw significantly greater improvements in Mini-Mental State Examination scores; significant differences in structural MRI indicative of slower neurodegenerative conditions; and metabolic-phenotype specific analysis which found that those with greater insulin resistance were better responders to the intervention.¹⁸

Anthonovage noted important directions for cognitive longevity research to follow, including: longer-duration trials; interventions that combine nutrition with lifestyle and exercise adjustments; measured correction of nutrient insufficiencies; the incorporation of inflammatory, metabolic, vascular, and neuronal injury biomarkers; and genetic, metabolomic, and microbiome-based approaches. 

“Cognitive health begins before cognitive decline,” he said. “The opportunity is to help consumers support cognitive performance and resilience throughout adulthood rather than waiting until something has been lost.” 

The Cocoa Supplement and Multivitamin Outcomes Study (COSMOS), fueled interest in the role of basic nutritional adequacy in cognitive aging, but studies showing vitamin and mineral benefits on cognition and episodic memory “should not be interpreted as demonstrating prevention of dementia,” he added.  

A 2025 study followed more than 125,000 people with an average starting age of 56 over nearly 12 years and found that high choline intake was associated with outperforming others on visual attention, fluid intelligence, and processing speed, noted Druke. “As a nutrient that is under-consumed by many worldwide, these findings open up promising opportunities for nutritional support throughout the lifespan.”¹⁹

Within the microbiome field, cognitive longevity research is dialed into “how microbial communities influence neuroinflammation, stress responses, and cognitive function across the lifespan,” Lasfargue noted. “There is also growing interest in understanding whether interventions that support attention, stress management, and cognitive performance earlier in adulthood may contribute to healthier aging trajectories.” These sorts of findings are challenging, however, due to the requisite timelines and robust methods needed, but the opportunity is “tremendous,” she said. 

Bewicke pointed to a recent review highlighting dietary antioxidants’ importance in neuroprotection, memory, attention, and overall brain function. Supplementation becomes more important with age due to the body’s diminishing ability to absorb and utilize antioxidants from the diet, he noted. For example, “vitamin C helps protect the brain from oxidative stress and plays a role in the synthesis and functioning of key neurotransmitters,” he said. “Another group of nutrients, polyphenols, play a key role in cognitive function … The evidentiary bar for long-term cognitive aging is much higher than the standard required to demonstrate an acute improvement.”²⁰

Extra care should be taken “particularly when we start using words like ‘prevention,’” said McNamara. Regulatory authorities scrutinize this market closely. Plenty of “scientifically interesting” findings can be generated on thinking, memory, reasoning skills, BDNF, cortisol, and more, but the context of a standard dietary supplement study doesn’t demonstrate the prevention of cognitive decline, she noted. To stay credible, industry must resist extrapolating even a 1- or 2-year study to a longer-term conclusion.

Language and research on supporting cognition for the long haul needs to be disciplined, Fink concurred. PLT’s botanical blend Nutricog, for instance, was studied for 120 days in aging adults. A “combination of performance outcomes and biomarker exploration points toward a more sophisticated way to study cognitive longevity without overreaching into disease claims.”²¹

Mushroom Spotlight 

As the mushroom segment matures and more well-characterized, standardized, and validated extracts come to market, there’s a stronger foundation to position them for condition-specific purposes like cognitive support. 

Overall, however, the mushroom segment is particularly saturated with borrowed science, noted Zapp, which is troubling given how complex their chemistry is. “Saying ‘Lion’s Mane has research’ is not enough. What part of the mushroom was used? How was it processed? What compounds are actually present? Can you measure them consistently from batch to batch?” 

With lion’s mane, beta-glucans are only part of the picture; proper characterization needs to include hericenones, hericenes, and ergosterol, measured by a published and validated method, to detect differences between biomass source, chemistry, and measurable composition, he said. “The standard we would like to see become normal is relatively simple: characterize the material, validate the analytical methods, conduct human research on the actual commercial ingredient whenever possible, use an appropriate dose and population, and communicate exactly what the study did and did not demonstrate,” Zapp said.  

Chilton concurred, noting just how materially different two ingredients from the same species can be. “Nammex is working with AOAC and other analytical experts to advance method-performance standards for Hericium erinaceus,” which will benefit all industry stakeholders by characterizing ingredients and ensuring consistency between materials used in a clinical study and those in the supply chain. 

Chilton also noted the importance of transparency in product labeling. “The mushroom and mycelium have different biochemical profiles; hericenones and other compounds have been studied in the mushroom, while erinacines occur in the mycelium. Advances in cultivation, analytical methods, and reference standards are helping the industry move beyond simply naming a species toward verifying the compounds actually present in specific fungal parts, and labeling them properly.” 

A new generation of highly purified mushroom ingredients is coming into the fold. Nammex now produces a lion’s mane mycelium ingredient standardized to 1% erinacine A through submerged liquid fermentation with no grain substrate needed. “This creates opportunities to formulate around a defined compound profile,” Chilton said.  

A December 2025 review summarized recent evidence on how ergothioneine, an antioxidant found in several mushroom species, supports systemic and neurological health. Unlike other antioxidants, it’s transported into cells via a specific transporter and supports broad activities including Nrf2 activation, suppression of several cytokines, mitochondrial preservation, and oxidative stress reduction, improving neuronal functions.²²

Reviews published in 2025 and 2026 highlight dozens of erinacines found in lion’s mane and their pharmacological, neurotrophic, neurogenic, and inflammatory-modulating activities, which promote neuronal signaling and neuroplasticity. These findings lay the groundwork for more developed health claims beyond the generic “memory and focus” positioning.^23-24 

References

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16.  https://nitesh_nut.rodpub.com/breaking-news/kemin-presents-clinical-findings-on-floraglo-lutein-in-children-and-adolescents/
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