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Antioxidant Flavonols Associated With Slower Memory Decline

A woman stirring a salad with leafy greans which contain flavonols.
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Consuming food and beverages containing flavonols might help to slow the rate of cognitive decline, researchers from Rush University suggest. 

Food and brain health

We know that a healthy diet, rich in fruits and vegetables, legumes and less fat can help to protect us against diseases such as heart disease, cancer and diabetes. A direct relationship also exists between the foods we eat and the health of our brain – the most complex organ of the body. A poor diet can have adverse effects on cognitive function and is linked to the development of neurodegenerative conditions such as Alzheimer’s disease (AD). The late Professor Martha Clare Morris, a nutritional epidemiologist and director of Rush University’s Institute for Healthy Aging, is considered one of the “pioneers” of this research space.

In 2015, Morris published the MIND diet study, which calls for the consumption of leafy greens, vegetables, seafood and whole grains – staples of the Mediterranean diet – to protect brain health and cognition. Now, a new study led by Dr. Thomas Holland, assistant professor at the Rush Institute for Health Aging and former mentee of Morris, takes this work a step further, exploring associations between the bioactives found in food products – like flavonols – and cognition. The research is published in Neurology.

Flavonols – what you need to know

Flavonols are a type of flavonoid, a group of phytochemicals that are found in plants. The compounds can be extracted from cocoa, tea, apples and other plant-based food and beverages, and growing research suggests that the consumption of flavonols can have positive effects on human health. The average flavanol intake for an adult individual in the US is between 16–20 mg per day.

What mechanisms underly the health benefits of flavonols? “Through various biochemical reactions, free radicals and reactive oxygen species can cause cellular – and eventually – organ-level damage,” says Holland. This damage is known as oxidative stress. “When we ingest foods that contain antioxidants like flavonols or vitamin E, those antioxidants act as reducing agents and essentially ‘destroy’ those free radicals and prevent further cellular damage.” Flavonols are also known to have anti-inflammatory properties. “Dietary intake of foods that contain nutrients and bioactives with anti-inflammatory properties can potentially prevent the over-activation or continued response of inflammatory cells and thus avoid cellular damage,” Holland adds.

Flavonols and Alzheimer’s disease

In 2020, Holland and colleagues published a study of 921 participants from the Rush Memory and Aging (MAP) project. “This ongoing cohort was started in 1997 and is comprised of Chicago residents of retirement communities and senior public housing. They have no known dementia when they are recruited and undergo yearly clinical evaluations in-person, with detailed risk factor assessments and cognitive testing,” Holland describes.

From 2004, participants were asked to complete a comprehensive food frequency questionnaire during their annual in-person evaluations. Using this collection of data, the researchers concluded that a higher dietary intake of flavonols may be associated with a reduced risk of developing AD in their 2020 paper. The latest Neurology study is an extension of that work, exploring rates of cognitive decline (CD).

Higher flavanol consumption associated with reduced rate of cognitive decline

The participants had been followed for ~6.9 years, had an average baseline age of 81.4 years and were mostly white females. They were divided into five equal groups based on the amount of flavonols consumed in their diet – 5 mg per day on average. The highest group consumed 15 mg per day, which the researchers say is equivalent to one cup of dark leafy greens.

The team used a global cognition score that summarized 19 cognitive tests to determine rates of CD. “These 19 tests are standardized and allow for test/re-test reliability, but also a robust measure of cognition that can be consistent and trusted.”

The data was adjusted to account for age, sex, education, APOE ɛ4, caloric intake, participation in late-life cognitive activities and other variables that have the capability to impact cognition. “If we adjust for these parameters, we, in essence, remove them from the equation of investigating dietary flavonols association to CD (although it is impossible to remove entirely),” explains Holland.

The results show that the cognitive score of individuals with the highest intake of flavonols declined at a rate of 0.4 units per decade slower than those who had the lowest intake. The team then broke the flavonols down into four molecules belonging to the overall class – kaempferol, quercetin, myricetin and isorhamnetin, to look at how each individual flavanol was associated with cognitive decline.

Participants with the highest intake of kaempferol had a CD rate that was 0.4 units per decade slower than those in the lowest group, while a high intake of quercetin had a CD rate of 0.2 units per decade slower than those in the lowest group. High consumers of myricetin had a CD rate that was 0.3 units per decade slower than those in the lowest group. No associations were discovered between isorhamnetin and CD rates. 

Entire composition of food renders it beneficial

The researchers acknowledge that the study data suggests correlation, not causality. It is also a self-report methodology, which can impact the validity of results. “These types of studies are a very natural start to a very difficult research question,” says Holland. “They are important in that they allow us to glean insight into how foods, and the nutrients and bioactives found therein, have the potential to impact health. Thus, if we do find associations, we can start pursuing clinical trials to begin to answer the causality question.”

Behavioral intervention-type trials also pose their own unique barriers and proclivities that have to be considered. “In the end, we believe, and hope that others see, that the research we conduct is work worth doing on questions worth answering, with efforts toward improving every person’s overall health and well-being.”

Current treatment approaches for dementia are “sparse and specific” for a disease that is diverse and multi-faceted, Holland emphasizes. The researchers believe their work lends hope to those concerned about CD and AD, the “take-home” message being that they can take ownership of their health and modify their lifestyle – with a physician – to try and mitigate the detriment of CD.

“In the flavonoid realm, we initially want to confirm these findings through other prospective cohort studies, specifically a more diverse population wherein we can generalize our findings to the public at large,” Holland says when asked about the team’s next steps. “Thereafter, a clinical trial in which we could establish effect would be quite valuable and informative.” Determining how flavonols are metabolized in the body will also be an important learning process. 

Eat your fruits and vegetables, particularly dark leafy greens, and drink some tea every now and again. It is generally known that the vitamins and minerals found in these food items are important. But now we are understanding that it’s the entire composition of the food, inclusive of bioactives, like flavonols, that render these foods as beneficial,” Holland concludes.

Reference: Holland TM, Agarwal P, Wang Y, et al. Association of dietary intake of flavonols with changes in global cognition and several cognitive abilities. Neurology. 2022:10.1212/WNL.0000000000201541. doi: 10.1212/WNL.0000000000201541.

Dr. Thomas Holland was speaking to Molly Campbell, Senior Science Writer at Technology Networks.