Astringent, Sharper Mind: Flavanols Trigger Brain Activity for Memory and Stress Response

The beneficial effects of dietary flavanols can be attributed to their ability to activate brain and stress responses 

Flavanols are plant-derived compounds known for their astringent taste , exhibiting pro- or antioxidant properties depending on the environment. Due to poor bioavailability, the mechanism of their health promotion activity remains unclear. A new study has determined  the mechanism of action of dietary flavanols via the brain-gut axis.  A single oral intake of flavanols stimulated brain regions involved in memory and sleep-wake regulation, and increased sympathetic nervous activity, a stress response. These findings may lead to future applications, such as the development of next-generation foods.

Astringency is a dry, puckering, rough, or sandpapery sensation in the mouth causedplant-derived polyphenols. Polyphenols, including flavanols, are well known for risk reduction in cardiovascular diseases. Flavanols, found abundantly in cocoa, red wine, and berries, are associated with improved memory and cognition, as well as protection against neuronal damage. Despite these benefits, flavanols have poor bioavailability—the fraction that actually enters the bloodstream after ingestion. This has left an important knowledge gap: how can flavanols influence brain function and the nervous system when so little of them is absorbed? 

In response to this challenge, a research team led by Dr. Yasuyuki Fujii and Professor Naomi Osakabe from Shibaura Institute of Technology, Japan, investigated how flavanols affect the nervous system through sensory stimulation. The study, made available online on September 11, 2025, and published in Volume 11 of the journal Current Research in Food Science, tested the hypothesis that the astringent taste of flavanols may act as a direct signal to the brain. “Flavanols exhibit an astringent taste. We hypothesized that this taste serves as a stimulus, transmitting signals directly to the central nervous system (comprising the brain and spinal cord). As a result, it is thought that flavanol stimulation is transmitted via sensory nerves to activate the brain, subsequently inducing physiological responses in the periphery through the sympathetic nervous system. ” explains Dr. Fujii. 

The researchers conducted experiments in 10-week-old mice, administering flavanols orally at doses of 25 mg/kg or 50 mg/kg body weight, while control mice received only distilled water. Behavioral tests showed that flavanol-fed mice exhibited greater motor activity, exploratory behavior, and improved learning and memory compared to controls. Flavanols enhanced neurotransmitter activity across several brain regions. Dopamine and its precursor levodopa, norepinephrine and its metabolite normetanephrine were elevated in the locus coeruleus–noradrenaline network immediately after the administration. These chemicals regulate motivation, attention, stress response, and arousal. Furthermore, enzymes critical for noradrenaline synthesis (tyrosine hydroxylase and dopamine-β-hydroxylase) and transport (vesicular monoamine transporter 2) were upregulated, strengthening the signaling capacity of the noradrenergic system.

In addition, biochemical analysis revealed higher urinary levels of catecholamines—hormones released during stress—as well as increased activity in the hypothalamic paraventricular nucleus (PVN), a brain region central to stress regulation. Flavanol administration also boosted the expression of c-Fos (a key transcription factor) and corticotropin-releasing hormone in the PVN. 

Taken together, these results demonstrate that flavanol intake can trigger wide-ranging physiological responses resembling those induced by exercise—functioning as a moderate stressor that activates the central nervous system and enhances attention, arousal, and memory. “Stress responses elicited by flavanols in this study are similar to those elicited by physical exercise. Thus, moderate intake of flavanols, despite their poor bioavailability, can improve the health and quality of life,” remarks Dr. Fujii.

These findings have potential implications in the field of sensory nutrition. In particular, next-generation foods can be developed based on the sensory properties, physiological effects, and palatability of foods. 

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Authors

About Dr. Yasuyuki Fujii from SIT, Japan

Dr. Yasuyuki Fujii is a researcher at the Shibaura Institute of Technology, Japan. He is a postdoctoral researcher in the SIT Research Laboratories, working under the supervision of Professor Naomi Osakabe at the Department of Bioscience and Engineering. His research focuses on the biological and physiological effects of flavanols. He is the recipient of several awards, including the Arimoto Prize from SIT and the Ikushi Award from the Japan Society for the Promotion of Science. He has published his studies in several peer-reviewed journals, including Biomolecules, Neuroscience Letter, , and Food Bioscience.

Funding Information

This work was supported by JSPS KAKENHI (Grant Number 23H02166).