Modest but promising findings from small human trials and preclinical work reveal a growing interest in healthy aging and neuroprotection, alongside short-term focus and alertness. There is also an increasing attention to ingredients or combination formulas that act through broader biological systems including mitochondrial function, microcirculation, oxidative stress and the gut-brain axis.
Below a look at some of the most recent science, with results often shaped by dose, ingredient standardization, study duration and participant characteristics.
Indena explores brain effects of gingko-phosphatidylserine combination
A pair of small randomized clinical trials suggests that a supplement combining standardized Ginkgo biloba extract and phosphatidylserine may offer modest benefits for stress, mood and some aspects of cognitive performance.
The product tested was GBP (Virtiva Plus, supplied by Indena S.p.A., Milan, Italy) a standardized formula combining Ginkgo biloba extract and phosphatidylserine-containing sunflower-derived lecithin.
In the first study, healthy adults between the ages of 25 to 55 who took 480 mg/day showed signs of improvement in delayed verbal memory and some reaction-time measures compared with placebo, both after a single dose and after four weeks of supplementation. In the second, four weeks both doses (240 mg/day and 480 mg/day) moderately stressed adults between the ages of 50 to 70 significantly reduced perceived stress and anxiety and improved well-being, energy, emotional health and overall mood though cognitive results in were mixed.
“The formula demonstrated promising preliminary evidence on emotional balance and cognitive performance, possibly linked to neuroprotective properties, likely mediated through enhanced microcirculation and central nervous system support,” the researchers wrote in the journal Food, Science & Nutrition. “Thus, microcirculation, defined as blood flow through the smallest vessels, is essential for optimal brain function. Its impairment is linked to cognitive decline, while its maintenance supports memory, attention and general cognitive performance.”
Nestlé study reports increased motivation from taurine-B vitamin blend
A Nestlé Health Science-funded study evaluated the effects of a targeted blend of taurine with vitamins B6, B9 and B12 in 44 adults between the ages of 25 and 40, reporting improved performance on effort-based tasks designed to measure motivation.
“A key finding of our study is that the active group showed superior performance in incentivized trials, as well as non-incentivized trials, highlighting the effectiveness of the supplementation in enhancing motivation and cognitive stamina,” the researchers wrote in Frontiers in Nutrition. “The findings reveal a notable improvement in the active group compared to the placebo, with an average performance increase of +12% in incentivized trials, which compares well to existing interventional data.”
Mechanistically, the study linked the formulation to glutathione biology. Preclinical work in astrocytes suggested taurine could help raise glutathione production and protect mitochondria from oxidative stress but only when folate status was adequate. In the human trial, supplementation significantly increased blood levels of taurine, vitamin B6 and folate, while baseline testing suggested inadequacies in taurine and folate were relatively common in the study population.
The researchers called for larger and longer trials to determine whether the benefits extend to broader populations, including those with low energy, higher stress burden or greater nutritional insufficiency.
OmniActive study explores no-crash performance of Alpinia galanga
An OmniActive Health Technologies-funded study suggests that its EnXtra Alpinia galanga extract may help support alertness and reduce fatigue in sleep-restricted adults, either on its own or in combination with caffeine, with the botanical appearing to offer a more sustained effect profile than caffeine alone.
In a randomized, double-blind, placebo-controlled trial conducted in two stages—an acute crossover phase and a 28-day parallel supplementation phase—researchers compared the EnXtra, caffeine, the combination and placebo in habitual caffeine consumers between the ages of 18 and 40.
“A. galanga extract demonstrated improvements in certain measures of alertness and subjective fatigue compared with placebo in sleep-restricted adults,” the researchers wrote in Dove Medical Press. “When combined with caffeine, the extract was associated with improvements in early alertness responses and appeared to maintain performance at later time points compared with caffeine alone.
They added that while findings suggest potential cognitive benefits, the results should be interpreted with caution due to the study’s small sample size, short intervention duration, and exploratory analyses across multiple endpoints.
Metabolite may increase brain performance better than caffeine
A preclinical study suggests that paraxanthine, the main metabolite of caffeine, may offer stronger cognitive benefits than caffeine, at least in an animal model of learning and memory.
In the study, a team of researchers led by Ingenious Ingredients, compared low- and high-dose paraxanthine with high-dose caffeine in young and aged rats, assessing spatial learning alongside a panel of brain biomarkers linked to neurotransmission, neuroprotection and oxidative stress.
“Our study provides novel evidence that paraxanthine and caffeine supplementation can enhance learning and memory in both young and old animals, with particularly pronounced effects observed in young animals receiving high-dose paraxanthine,” they wrote in the journal Experimental Brain Research. “Additionally, paraxanthine may boost cognitive function across age groups by increasing BDNF levels.”
Notably, high-dose paraxanthine produced the largest gains overall, suggesting the caffeine metabolite may have a more potent effect on memory-related performance than caffeine. While preclinical, the authors noted that the work strengthens the case for paraxanthine as a next-generation nootropic ingredient, particularly given its reported lower toxicity and lower anxiogenic potential compared to caffeine.
Single-dose creatine may support cognition in sleep deprivation
A single dose of creatine may help blunt some of the cognitive fallout associated with short-term sleep deprivation.
Researchers from the German Institute of Neuroscience and Medicine (INM-2) administered either creatine monohydrate at 0.2 g/kg or placebo to 29 healthy adults during 21 hours of wakefulness, tracking performance across a battery of logic, numerical, language, memory and vigilance tasks.
“Our results show that administration of a dose of 0.2 g/kg creatine reduces, to a modest extent, the deterioration in cognitive performance during sleep deprivation,” they wrote in the journal Nutrients. “Although the effect is weak, an improvement of up to 12% is still observed.”
Notably, the response did not appear uniform across groups, with findings indicating that female participants showed more pronounced benefits than males in several domains, including logic, vigilance and processing speed, while some subgroup analyses also suggested advantages in vegetarians. The research also noted that effects were less pronounced than with a high dose of 0.35 g/kg and that further research to determine the specific dosage for different population groups.
Breastmilk prebiotic may improve metabolism and boost cognition for older adults
Dietary supplementation with the human milk oligosaccharide (HMO) 2′-fucosyllactose boosted the growth of Bifidobacterium in the guts of older adults and improved a range of metabolic measures, according to findings reported by Stanford University and Abbott Nutrition.
Data from the Rejuvenating the Aging Microbiota with Prebiotics (RAMP) study found that six weeks of supplementation with 5 g/day of 2′-fucosyllactose (2′-FL) improved levels of HDL cholesterol, insulin levels and FGF21, a hormone that plays a crucial role in regulating metabolism, energy expenditure and insulin sensitivity.
Writing in Cell Reports Medicine, the researchers noted that not all of the participants responded to the prebiotic treatment. Interestingly, the Bifidobacterium responders were also found to have improved performance on a cognitive test compared to non-responders, a result the study called “speculative”.
“These results demonstrate a potential impact of 2′-FL supplementation on cognitive function in human adults,” wrote the researchers, led by Stanford’s Dr. Justin Sonnenburg. “Previous work has shown that 2′-FL levels in breast milk are positively associated with cognitive development in human infants, and 2′-FL supplementation influences vagus-nerve-mediated memory adaptations in adult rodents.”
Review supports omega-3 supplementation for cognitive health
A review of the literature on the effects of omega-3 supplementation on cognitive decline revealed modest but consistent improvements in Mini Mental State Examination scores among 26,881 participants aged 40 years or older.
The team of Portuguese researchers indicated results “are unlikely to be due to chance alone and represent a genuine therapeutic effect.” They also suggested a threshold effect rather than a dose-response relationship.
“These findings support n3-PUFA supplementation as a complementary approach to lifestyle-based strategies for cognitive health, including diet, physical activity, sleep optimization and cognitive training,” they wrote in the journal Nutrients.
Commenting on the study, Dr. Kaitlin Roke, director of scientific communication and outreach at The Global Organization for EPA and DHA Omega-3s (GOED), said that most people consume little to no omega-3 EPA and DHA in their diets and that encouraging increased intake through supplementation or diet across life stages could support brain and mental health.
She also noted that the lack of the lack of consistency across studies on omega-3s and brain health compromises the ability to make clear recommendations.
“This review addressed that issue by focusing specifically on the MMSE, enabling direct comparisons across studies,” Dr. Roke said. “Future research could build on this approach by continuing to use standardized assessments, which would improve comparability and strengthen the evidence base.”
‘Longevity vitamin’ ergothioneine could protect the aging brain
A study from ergothioneine supplier Blue California suggests that supplementation with its ErgoActive ingredient leads to dose-dependent improvements in subjective memory and sleep in healthy older adults.
“This publication reflects years of investment in building the scientific foundation for ergothioneine,” said Dr. Linda May-Zhang, vice president of science & innovation at Blue California and co-author on the study. “These findings offer clinical evidence that ergothioneine supports neurocognitive and physiological resilience in aging humans and provide a strong foundation for future studies in populations with lower ergothioneine status or greater risk for age-related decline.”
Blue California, the first to produce L-ergothioneine via fermentation, launched its ErgoActive ingredient in 2015 as an alternative to chemical synthesis and mushroom extraction and received FDA Generally Recognized as Safe (GRAS) status in 2019.
Vitamin E tocotrienols ‘emerging as promising neuroprotective agents’
Tocotrienols, a form of vitamin E found in tocotrienol-rich fraction (TRF) from palm oil, are emerging as promising neuroprotective agents due to their antioxidant, anti-inflammatory and immune-enhancing properties.
Despite limited human trials, they show potential in supporting brain health and mitigating neurodegenerative changes associated with aging. Current research highlights the need for further studies, particularly human clinical trials, to fully understand the therapeutic potential and pharmacokinetics of tocotrienols compared to the more widely studied tocopherols.
The study called for future research to explore synergistic effects between tocotrienols and tocopherols and consider population-specific trials.
L-theanine may be neuroprotective in sleep deprivation
Research conducted by Anhui University of Chinese Medicine and Anhui Agricultural University indicated that L-theanine, an amino acid from green tea, may offer neuroprotective benefits against sleep deprivation-induced damage by reducing NADPH oxidase 4 (NOX4) and protecting brain mitochondria.
The study focused on ferroptosis, a form of cell death linked to iron-dependent lipid reactive oxygen species, in the hippocampus.
Findings showed that L-theanine improved learning and memory in sleep-deprived mice, while a selective NOX4 inhibitor, GLX351322, reversed these benefits, highlighting L-theanine’s potential against cognitive deficits related to oxidative stress and suggesting further human studies.
Review backs neuroprotective effects of Bacopa monnieri
Researchers at Poznan University of Medical Sciences in Poland, evaluated the current evidence on the efficacy and safety of Bacopa monnieri, a perennial, creeping herb which grows predominantly in the Southeastern regions of Asia. It has been used traditionally in Ayurveda to improve memory and aid sleep, with a number of clinical trials demonstrating its potential benefits.
Bacopa monnieri contains 52 bioactive compounds including bacosides A and B, polyphenols, flavonoids, terpenoids and proteins. Bacosides, its main active compounds, are thought to be largely responsible for potential effects. Research suggests these active compounds have a wide variety of antioxidant, antibacterial and anti-inflammatory properties. Its antioxidant effects are thought to preserve brain function by neutralizing reactive oxidant species and reducing oxidative stress.
“This wide spectrum of properties makes Bacopa monnieri a compelling subject for further investigation into its systemic health benefits,” the researchers wrote. “[However], there are a number of important limitations that need to be taken into account when interpreting [study] results.”
The review highlighted that differences in extraction methods, the source of the plant material, culture conditions and type of standardized active compounds used affect the reproducibility and comparability of the results. It also underscored the need for more studies to confirm these effects, particularly in neurological diseases, and highlights challenges with bioavailability and standardization of extracts.
Green tea may protect the aging brain
A new study links higher green tea consumption to fewer cerebral white matter lesions, suggesting that it could contribute to preventing cognitive decline in some populations.
Writing in the journal npj Science in Food, a team of Japanese researchers investigated the associations between green tea or coffee intake with various measures associated with structural integrity of the brain among over 8,000 community-dwelling adults.
“Given that cerebral white matter lesions are closely related to vascular dementia and AD, our findings indicate that drinking green tea, especially three or more glasses per day, may help prevent dementia,” they reported. “Nevertheless, further prospective longitudinal studies and basic research are needed to validate our results.”
At the intersection of genetics, caffeine and cognition
Variations in people’s genetic makeup could explain the variations in their cognitive response to habitual caffeine consumption.
According to a paper published in the Journal of Psychopharmacology, research on caffeine and cognitive performance remains controversial, and this in part could be due to the CYP1A2, AHR and ADORA2A genes.
“As nutrigenetics science has advanced, some of the variability in study results has been attributed to common genetic variations, specifically single nucleotide polymorphisms (SNPs), which are associated with caffeine metabolism and response,” wrote researchers from the Faculty of Sport, Allied Health and Performance Science at St Mary’s University Twickenham in London.
“Research suggests that variants in the Adenosine Receptor A2a (ADORA2A) gene may influence an individual’s response to caffeine, leading to caffeine-induced anxiety and insomnia. Moreover, variants in the Cytochrome P450 1A2 (CYP1A2) and Aryl Hydrocarbon Receptor (AHR) genes are associated with variability in caffeine metabolism.”
Key takeaways
- The category is shifting from broad “brain boost” claims toward more targeted support for cognitive resilience, healthy aging and neuroprotection.
- Multi-ingredient and caffeine-combo formulations are being studied more seriously.
- The strongest themes in recent research are mitochondrial support, oxidative stress, microcirculation, sleep-related cognition and the gut-brain axis.
- Evidence is mixed: Some ingredients show encouraging human data, while others are still supported mainly by preclinical findings or small exploratory trials.
- Benefits appear highly dependent on dose, ingredient standardization, study length and participant profile.
- Large, well-controlled human trials are still needed before many nootropic claims can be considered robust.
