A particular taste may directly signal the brain to wake up

A new study reveals that the astringent sensation from flavanols, compounds found in foods like cocoa and berries, can directly stimulate brain activity and enhance memory in mice. The research, published in Current Research in Food Science, suggests this sensory signal functions as a mild stressor that triggers a state of heightened alertness and improved cognitive function without the compounds needing to be absorbed into the bloodstream.

Flavanols are a group of natural compounds abundant in plant-based foods such as cocoa, red wine, tea, and various berries. Past research has associated their consumption with several health benefits, including improved memory and cognitive skills. A significant puzzle, however, has been their poor bioavailability, which means only a very small fraction of ingested flavanols actually enters the circulatory system. This left a gap in understanding how these compounds could exert such noticeable effects on the brain.

To investigate this question, a research team led by Yasuyuki Fujii and Professor Naomi Osakabe from the Shibaura Institute of Technology in Japan proposed a different mechanism. They hypothesized that the physical sensation of astringency, the dry, puckering feeling flavanols cause in the mouth, might itself be the trigger.

“We hypothesized that this taste serves as a stimulus, transmitting signals directly to the central nervous system,” explained Fujii, suggesting that sensory nerves could be activating the brain and producing physiological responses.

The researchers conducted a series of experiments on mice to test this idea. In the first part of the study, they orally administered a flavanol solution to one group of mice, while a control group received only distilled water. They then observed the animals’ spontaneous behavior in an open arena. The mice that received flavanols traveled a greater distance, spent more time exploring the center of the arena, and exhibited more behaviors associated with wakefulness, like grooming and rearing, compared to the control group.

To assess the impact on memory, the team used a novel object recognition test. Mice were first allowed to familiarize themselves with two identical objects in an enclosure. Later, one object was replaced with a new, unfamiliar one. The researchers found that mice given flavanols spent substantially more time exploring the new object. This preference for novelty is a standard indicator of recognition memory, suggesting that the flavanol administration had enhanced the mice’s ability to learn and remember.

The team then looked for physiological signs of a stress response, which can be linked to heightened alertness. They collected urine from the mice over a 24-hour period and measured the levels of catecholamines, a class of hormones that includes adrenaline and noradrenaline. The results showed that mice given a higher dose of flavanols had significantly elevated levels of these hormones in their urine. This indicated an activation of the sympathetic nervous system, the network responsible for the body’s “fight-or-flight” response.

Probing deeper into the brain, the scientists examined the hypothalamus, a region central to regulating the body’s stress response. Using a technique that visualizes gene activity in tissue slices, they looked for markers of neural activation. Thirty minutes after the mice received flavanols, there was a significant increase in the activity of a gene that produces corticotropin-releasing hormone, a key initiator of the body’s stress cascade. This finding provided direct evidence that flavanol intake was stimulating a stress-response pathway in the brain.

The most direct evidence for the study’s hypothesis came from a technique called mass spectrometry imaging, which allowed the researchers to create a map of specific chemicals within the brain.

Immediately after the mice consumed the flavanols, the images showed a sharp increase in the neurotransmitter noradrenaline within a small but important brainstem region called the locus coeruleus. This area acts as a primary source of noradrenaline for much of the brain and plays a major role in regulating arousal, attention, and memory. Levels of related chemicals, including dopamine, were also elevated in other brain areas.

In a final experiment, the researchers analyzed gene expression for the enzymes responsible for producing these neurotransmitters. They found that immediately after flavanol administration, the genetic instructions for building noradrenaline and dopamine synthesis machinery were more active in the locus coeruleus. This suggests the brain was not only releasing these chemicals but also ramping up its capacity to produce more of them in response to the astringent stimulus.

Taken together, the results paint a picture of how astringency can affect the brain. The sensation appears to act as a mild, beneficial stressor, similar to physical exercise. This sensory input activates the locus coeruleus, which then bathes the brain in noradrenaline, increasing alertness, sharpening attention, and improving memory consolidation.

“Stress responses elicited by flavanols in this study are similar to those elicited by physical exercise,” remarked Fujii. He adds that moderate intake of these compounds, despite their low absorption, “can improve the health and quality of life.”

This study was conducted in mice, and further research is needed to confirm if the same mechanisms apply to humans. The precise way in which the digestive tract senses astringency and transmits that signal to the brain also remains an area for future investigation.

The researchers suggest that specific sensory receptors may be involved in detecting the chemical properties of flavanols, initiating the entire neural cascade. Understanding these sensory-to-brain pathways could open new avenues for developing foods designed to support cognitive health through their sensory properties.

The study, “Astringent flavanol fires the locus-noradrenergic system, regulating neurobehavior and autonomic nerves,” was authored by Yasuyuki Fujii, Shu Taira, Keisuke Shinoda, Yuki Yamato, Kazuki Sakata, Orie Muta, Yuta Osada, Ashiyu Ono, Toshiya Matsushita, Mizuki Azumi, Hitomi Shikano, Keiko Abe, Vittorio Calabrese, and Naomi Osakabe.