For consumers, taking cognitive health supplements means feeling less wired, being more mindful and getting through life with a positive mood.
The demand for well-rounded cognitive health supplements is real. In the European Commission’s Eurobarometer on mental health, 46% of EU respondents reported an emotional or psychosocial difficulty (such as anxiety or low mood).1
These demands and wishes fall into three categories: adaptogens, nootropics and mood ingredients. On the shelf, the three are often blurred:
- Adaptogens help the body respond to and recover from stress, largely by influencing the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system.
- Nootropics support cognitive functions such as memory, attention and learning.
- Mood ingredients support emotional well-being, often through serotonergic and dopaminergic signalling.
Similarly, in practice, the biology overlaps. For example, chronic stress raises cortisol, which can suppress brain-derived neurotrophic factor (BDNF), a protein central to learning and memory.
Ingredients that act on more than one of these pathways are ideal for formulators.
Stress resilience: supporting the body’s response
Under threat, the HPA axis releases cortisol and the sympathetic nervous system takes over. When this state never switches off, people feel tense and tired.
Two markers track it: cortisol and heart rate variability (HRV), which reflects how well the body restores balance.
CALMaluma is a patented extract of Caralluma fimbriata, an edible succulent traditionally consumed in India.
In an 8-week randomised, double-blind, placebo-controlled trial of 97 adults with mild to moderate self-reported anxiety, 500 mg of CALMaluma taken twice daily significantly reduced anxiety and perceived stress more than placebo at weeks 4 and 8.
Moreover, salivary cortisol levels in male participants decreased, which the authors suggest indicates an effect on the HPA axis.2
Levagen+ is palmitoylethanolamide (PEA), a fatty acid amide produced naturally in our bodies in response to stress and injury.
PEA has been shown to work alongside the endocannabinoid system to regulate stress responses.
In a crossover trial with 16 female university students with elevated perceived stress, 600 mg/day of Levagen+ for 6 weeks significantly increased SDNN, a heart rate variability marker of autonomic resilience, objectively demonstrating PEA’s potential to regulate stress and pressure.3
Saanroo’s Levagen+ pairs PEA with LipiSperse delivery technology to double PEA plasma levels (standard PEA is poorly absorbed).4
Moreover, at a dose as low as 350 mg/day, Levagen+ has established a robust track record (18-plus published clinical studies) of helping adults to fall asleep faster and wake feeling more alert.5
ActivAMP is an extract of Gynostemma pentaphyllum (jiaogulan), a climbing vine used in East Asian traditions as a tonic and often described as an adaptogen.
In laboratory studies, its dammarane saponins, including damulins A and B, activate AMP-activated protein kinase (AMPK), the cell’s energy sensor under metabolic stress.
In a 12-week randomised, double-blind, placebo-controlled trial of 100 healthy adults, 450 mg/day increased VO2 max and improved perceived exertion and fatigue ratings compared with a placebo, which the authors interpreted as greater resistance to physical and mental fatigue.6
A separate 8-week trial with a different G. pentaphyllum leaf extract in 72 chronically stressed adults lowered trait anxiety by 16.8% more than a placebo — a finding worth testing with ActivAMP itself.7
Cognitive performance: the BDNF connection
Current research focuses on the brain’s own maintenance systems rather than on short-acting stimulants.
BDNF supports neuronal growth and synaptic plasticity, which underpin learning and memory. Stress and inflammation tend to lower BDNF, which is why stress and “brain fog” often appear together.
Levagen+ also shows nootropic effects. In a 6-week, randomised, double-blind crossover trial of 39 healthy young adults, 700 mg/day significantly increased serum BDNF compared with a placebo.
On a paired-associates learning test, participants also made significantly fewer memory errors.8
HydroCurc is a cold-water-dispersible turmeric (Curcuma longa) extract.
Standard curcumin is poorly absorbed; in a human pharmacokinetic study, HydroCurc delivered significantly higher plasma curcuminoid levels than an equivalent standard curcumin extract.9
In a 6-week randomised, placebo-controlled trial in 155 healthy adults, 500 mg of HydroCurc taken with 18 mg of iron raised serum BDNF by 26% (ending 35% higher than with iron alone). Iron alone did not, so the pairing suits women’s cognitive formulas.10
Mood: saffron’s evidence base
Saffron, the stigma of Crocus sativus L., has been used for emotional well-being since antiquity. Its main bioactives, crocins and safranal, are thought to support mood by influencing the reuptake of serotonin, dopamine and noradrenaline.
Affron is a saffron extract standardised to 3.5% Lepticrosalides — the compounds responsible for its activity — that combines the longstanding use of saffron for mood regulation with science-backed studies.
In a three-arm, randomised, double-blind, placebo-controlled trial with 128 healthy adults reporting occasional stress, 28 mg/day of Affron for 4 weeks improved mood and symptoms of stress and anxiety.11
Another trial with 55 adults who reported poor sleep found that 14 mg of Affron twice a day for 28 days significantly improved insomnia severity index scores, sleep quality and restorative sleep.
Affron also showed an increasing trend in alertness upon waking and in evening melatonin levels.12
Applications: formulating across the three areas
Because stress, cognition and mood are linked, these ingredients combine well.
- Daytime calm and focus: CALMaluma with Levagen+ to target both the stress response and BDNF-related cognition.
- Active resilience: ActivAMP for formulas that target physical and mental fatigue and stress.
- Mood and sleep: Affron with Levagen+, both studied for sleep quality, in evening formulas.
- Women’s cognitive health: HydroCurc with iron, a combination shown to raise BDNF.
Format matters too: Levagen+ and HydroCurc are cold-water-dispersible, whereas CALMaluma is a heat-stable, water-soluble powder, so all three suit RTD’s, gummies and capsules.
Quality is the other test: saffron is among the most adulterated botanicals, so branded, standardised extracts backed by human trials provide firmer grounds for claims.
Supporting everyday well-being, responsibly
The consumers driving this category are rarely in crisis. They are managing persistent pressure and want daily support that leaves them calmer, sharper and more like themselves.
Supplements are not a substitute for professional care and responsible brands make that clear.
CALMaluma, ActivAMP, Levagen+, HydroCurc and Affron each deliver benefits measured in human trials across different aspects of the stress, cognition and mood picture.
References
- https://europa.eu/eurobarometer/surveys/detail/3032.
- G. Kell, et al., “A Randomised Placebo-Controlled Clinical Trial on the Efficacy of Caralluma fimbriata Supplement for Reducing Anxiety and Stress in Healthy Adults Over Eight Weeks,” Journal of Affective Disorders 246, 619–626 (2019).
- S.K. Deb, et al., “The Effects of Formulated Palmitoylethanolamide Supplementation on Indicators of Stress and Heart Rate Variability in Female University Students: A Randomised Cross-Over Trial,” Frontiers in Nutrition 12, 1586409 (2025).
- https://nutraceuticals.imedpub.com/articles/increased-absorption-of-palmitoylethanolamide-using-a-novel-dispersion-technology-system-lipisperse.php?aid=26738.
- A. Rao, et al., “Palmitoylethanolamide for Sleep Disturbance. A Double-Blind, Randomised, Placebo-Controlled Interventional Study,” Sleep Science and Practice 5(1), 12 (2021).
- P.H. Nguyen, et al., “New Dammarane-Type Glucosides as Potential Activators of AMP-Activated Protein Kinase (AMPK) from Gynostemma pentaphyllum,” Bioorganic & Medicinal Chemistry 19(21), 6254–6260 (2011).
- E.K. Choi, et al., “Supplementation with Extract of Gynostemma pentaphyllum Leaves Reduces Anxiety in Healthy Subjects with Chronic Psychological Stress: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial,” Phytomedicine 52, 198-205 (2019).
- N. Kim, et al., “Formulated Palmitoylethanolamide Supplementation Improves Parameters of Cognitive Function and BDNF Levels in Young, Healthy Adults: A Randomised Cross-Over Trial,” Nutrients 16(4), 489 (2024).
- D. Briskey, et al., “Increased Bioavailability of Curcumin Using a Novel Dispersion Technology System (LipiSperse®),” European Journal of Nutrition 58(5), 2087–2097 (2019).
- H. Tiekou Lorinczova, et al., “Coadministration of Iron and a Bioavailable Curcumin Supplement Increases Serum BDNF Levels in Healthy Adults,” Antioxidants 9(8), 645 (2020).
- G. Kell, et al., “Affron® A Novel Saffron Extract (Crocus sativus L.) Improves Mood in Healthy Adults Over 4 Weeks in a Double-Blind, Parallel, Randomized, Placebo-Controlled Clinical Trial,” Complementary Therapies in Medicine 33, 58–64 (2017).
- A.L. Lopresti, et al., “Effects of Saffron on Sleep Quality in Healthy Adults with Self-Reported Poor Sleep: A Randomized, Double-Blind, Placebo-Controlled Trial,” Journal of Clinical Sleep Medicine 16(6), 937–947 (2020).
