Increased consumption of flavanols—compounds that occur naturally in fruit and vegetables—can increase mental agility, according to new research by scientists at the University of Birmingham, U.K., and the University of Illinois at Urbana Champaign. The study results showed that the brains of healthy adults recovered faster from a mild vascular challenge and performed better on complex tests if the participants were given a cocoa drink containing high levels of flavanols beforehand.

“Our results showed a clear benefit for the participants taking the flavanol-enriched drink—but only when the task became sufficiently complicated,” commented Catarina Rendeiro, PhD, lecturer in nutritional sciences at the University of Birmingham’s School of Sport, Exercise, and Rehabilitation Sciences. “We can link this with our results on improved blood oxygenation—if you’re being challenged more, your brain needs improved blood oxygen levels to manage that challenge. It also further suggests that flavanols might be particularly beneficial during cognitively demanding tasks.”

The researchers say the study is the first to link the cognitive effects of flavanols with brain blood oxygenation in young, healthy subjects, and that the results could have clinical implications, if dietary flavanols could help to speed repair after mild brain injury and disease, or prevent decline in those at risk. Reporting on their findings in Scientific Reports, Rendeiro and colleagues concluded, “ … if the acute benefits demonstrated in the present study were to be sustained by continued intake of flavanol-rich foods (e.g., grapes, apples, cocoa, berries, tea), this may be particularly beneficial for populations at higher risk.” Their paper is titled, “Dietary flavanols improve cerebral cortical oxygenation and cognition in healthy adults.”

Flavanols are a sub-group of plant flavonoids, and are present in cocoa, grapes, apples, tea, berries, and other foods. “Flavanols are small molecules found in many fruits and vegetables, and cocoa, too,” Rendeiro said. “They give fruits and vegetables their bright colors, and they are known to benefit vascular function.” Flavanols are also known to have a beneficial effect on cardiovascular health—with positive effects on endothelial function linked to increased bioavailability of nitric oxide (NO)—but their effects on brain health are not well understood.

University of Birmingham lecturer in nutritional sciences Catarina Rendeiro, PhD, found that cocoa flavanols improve brain oxygenation and cognition in healthy adults. [Photo courtesy Catarina Rendeiro]

While some evidence does suggest that flavanol-rich diets protect against cognitive aging, the mechanisms remain elusive, the team noted. “Another emerging line of research further suggests that this class of plant-derived compounds may protect against cognitive decline in aging and cognitive resilience to neuropsychiatric disorders and stress,” they continued. “Yet, the extent to which increases in circulatory levels of NO by flavanols can translate into benefits in the brain vasculature, and effectively influence cognitive performance in humans, is poorly understood.”

“We wanted to know whether flavanols also benefit the brain vasculature, and whether that could have a positive impact on cognitive function,” Rendeiro said. For the reported study, 18 healthy, nonsmoking male participants aged 18–40 years underwent a procedure to challenge the brain’s blood circulation, which involves breathing 5% carbon dioxide—about 100 times the normal concentration in air—to produce an effect called hypercapnia. This is a standard method for challenging brain vasculature to determine how well it responds, explained co-author Gabriele Gratten, PhD, psychology professor at the University of Illinois at Urbana-Champaign Gratton. The body typically reacts by increasing blood flow to the brain. “This brings in more oxygen and also allows the brain to eliminate more carbon dioxide,” he said.

Non-invasive near-infrared spectroscopy, a technique that uses light to capture changes in blood oxygenation levels, was used to track the increases in brain oxygenation in the frontal cortex in response to this carbon dioxide challenge. “This allows you to measure how well the brain defends itself from the excess carbon dioxide,” added psychology professor Monica Fabiani, PhD, also at the University of Illinois at Urbana-Champaign.

Each participant underwent the test before and after drinking a cocoa drink on two occasions, and on one of those occasions, the drink was enriched with flavanols. Following the carbon dioxide test, the participants were also asked to complete a number of progressively complex cognitive tests. “To measure the cognitive effects of flavanols, we employed tasks with escalating levels of difficulty, which could inform us of the level at which the cognitive benefits of flavanols may emerge,” the scientists wrote.

The results showed that the participants who had taken the flavanol-enriched drink had the highest blood oxygenation in response to hypercapnia, with oxygenation reaching up to three times higher than in participants drinking the non-flavanol-enriched drink. These elevated levels were also achieved faster than increases in participants who drank the non-enriched cocoa. “The levels of maximal oxygenation were more than three times higher in the high-flavanol cocoa versus the low-flavanol cocoa, and the oxygenation response was about one minute faster,” Rendeiro said.

The team suggested the findings on brain oxygenation could have clinical implications. “In physiological, real-world conditions, flavanol-induced faster vascular reactivity may help recovery from injuries such as mild brain injury or stroke, conditions that are also associated with impaired cerebrovascular reactivity to CO2,” they wrote.

With their colleagues, University of Illinois psychology professors Gabriele Gratton, PhD, left, and Monica Fabiani, PhD, found evidence that ingesting flavanols can positively influence neurovascular health and brain function. [Photo by L. Brian Stauffer]
In the cognitive tests, the researchers found significant differences in the speed and accuracy with which volunteers completed the higher complexity tasks, with volunteers who had taken the flavanol-enriched drink performing the tasks 11% faster on average. The benefits of flavanols were only evident for these more difficult tests, however. There was no measurable difference in performance on easier tasks.

“Our results showed a clear benefit for the participants taking the flavanol-enriched drink—but only when the task became sufficiently complicated,” Rendeiro said. “We can link this with our results on improved blood oxygenation—if you’re being challenged more, your brain needs improved blood oxygen levels to manage that challenge. It also further suggests that flavanols might be particularly beneficial during cognitively demanding tasks.” The team suggested that future work should focus on using difficult-graded cognitive challenges when assessing the efficacy of dietary flavonoids on human cognitive function.

Importantly, there was a small group of participants who did not benefit at all from the flavanol-enriched drink in terms of blood oxygenation levels, and who also did not derive any cognitive benefit. “Although most people benefited from flavanol intake, there was a small group that did not,” Rendeiro said. This group was shown to have high initial levels of brain oxygenation responses to start with, which were not increased further by drinking the enriched cocoa. “ … only individuals who benefited from flavanol intake during hypercapnia experienced cognitive benefits, suggesting that these effects are likely linked,” the investigators wrote. “This is the first time that such a relationship between hemodynamic and cognitive benefits of flavanols has been shown in a young healthy sample after a single dose of flavanols.”

This finding may indicate that some individuals, that perhaps those who are already very fit, have little room for further improvement,” explained Rendeiro. “While we did not assess the fitness of the participants in the present study, one possible explanation for the differential responses observed between sub-groups was that flavanols may have improved the cerebrovascular reactivity of less fit individuals to levels similar to those of potentially highly fit individuals,” the authors wrote. “Future work should formally address this hypothesis, which may have significant translational implications.”

The authors suggest their findings have important future implications for the potential use of dietary strategies containing plant-derived flavanols, for boosting blood oxygenation and cognitive performance both in healthy people, and in those who might be at higher risk, such as smokers, people with hypertension, or diabetes, or to help people recover from brain injury and disease.

Diets rich in dietary flavanols might be particularly beneficial when executive function becomes more limited, for example, in older adults or people at higher risk for cognitive decline, they suggested. “Future work should focus on systematically employing difficulty-graded cognitive challenges when assessing the efficacy of dietary flavonoids on human cognitive function,” they wrote. “Most importantly, our data can potentially open new avenues for precision-medicine research with regard to understanding individual responses to flavanol intake and helping to identify populations that might benefit the most from interventions.”

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