Skip to main content

Flavonol Consumption Linked With Lower Risk of Alzheimer’s Dementia

February 06, 2020

Consuming more food and drink with the antioxidant flavonol is associated with a smaller chance of developing Alzheimer’s dementia years later, researchers reported in Neurology, the medical journal of the American Academy of Neurology. Flavonol is found in nearly all fruits and vegetables as well as tea.

A group of 921 people who did not have Alzheimer’s dementia, with an average age of 81, were followed for an average of 6 years, and filled out annual questionnaires on how often they ate certain foods. They were divided into 5 groups, based on the amount of flavonol in their diet.

The study found that people in the group with the highest amount of flavonol consumption were 48% less likely to later develop Alzheimer’s dementia than the people in the group with the lowest flavonol consumption amount, after adjusting for confounding factors. About 15% of the people in the highest consumption group developed the disease, compared with 30% of the lowest consumption group.

In this podcast, study author Thomas M. Holland, MD, of Rush University in Chicago, Illinois, discusses the findings of the study and their clinical implications.

Read the transcript:

My name is Thomas Holland. I am a faculty member of Rush University Medical Center and Rush University. My credentials are medical doctor.

What led myself and my colleagues to conduct this research was as my principal investigator and mentor, Martha Clare Morris, had published a manuscript finding an association between a dietary intake of various foods and Alzheimer's dementia, she followed that up with a paper looking at dark leafy greens and the nutrients found within.

From that point, we had a discussion on other components that are found in these foods, specifically bioactives. As we started to look at the bioactives that were found in leafy greens, that's where we developed the hypothesis of looking at flavonols and their association to Alzheimer's dementia.

As we were developing this process, we actually had to go to the NDSR [Nutrition Data System for Research] database, which is based on the USDA [United States Department of Agriculture] data, and determine, based on our food frequency questionnaire, what foods contained what flavonoids.

Flavonoids is a very broad category of bioactive and ours consisted of 5 subclasses. We developed our database and multiplied our intake data of each individual by the flavonoid content and from there, we ran our Cox proportional hazards model.

Our main findings were that in individuals that had the highest quintile of intake of total flavonols versus the lowest quintile, they had a 48% risk reduction in development of Alzheimer's dementia over time. Our cohort consisted of 921 participants. Of those 921, 220 developed Alzheimer's dementia over a follow‑up period of about 6 years.

I'm not necessarily surprised by the association in and of itself. I was quite pleasantly surprised by how strong the association was. Whenever we start looking at the breakdown of the constituents within the flavonol subclass—we're talking kaempferol, quercetin, isorhamnetin and myricetin—we started to see strong associations even for the constituents. Although quercetin was not statistically significant, it was highly suggestive.

The applications of these findings for clinical practice really indicate that the contents of the food that we eat does matter. Whenever we start thinking about our dietary intake and we say, well, leafy greens contain vitamin K, vitamin E, carotenoids, as well as these flavonols, we have to be cognizant that it would be quite difficult to get all of the diverse components of these foods in a supplement.

The clinical application is really to have a healthy balanced, very diverse diet, because that's going to be the best way to optimize nutrients in bioactive intake.

For expansion of this research, we're actually going to be investigating various outcomes with the flavonols being the independent intake and from that end, we'll be looking at microglia and how the activation is associated there.

We'll also be looking at genetic predisposition and metabolism of food, and beyond that, we're going to start investigating the other subclasses of flavonoids and the constituents found within.

I would like to add that these findings are very important in telling us what mechanisms are found within the food that make them healthy. From that end, we do also have to keep in mind that this research was a prospective cohort and that we are showing an association, but not showing a cause and effect.

From that end, for anybody that's really interested in delving further into prevention of Alzheimer's dementia or cognitive decline, we have to understand as our knowledge of the pathogenesis of Alzheimer's dementia expands, we recognize that it is quite multifactorial.

We should be preparing ourselves as best we can with multiple scientifically based tools to help stave off the progression with an eye toward the ultimate goal of prevention. Our toolbox should certainly be filled with as many diverse tools as the disease itself. Although diet is a strong factor, it is one component of a healthy lifestyle.

The lifestyle modifications that have shown to have an association with reduced risk or diminished cognitive decline are physical activity, socialization, cognitive‑stimulating activity, and getting good quality and quantity of sleep, as well as going to your primary care physician once a year for medical evaluation.

The mechanism that we understand as beneficial for flavonols and flavonoids as a group is their antioxidants and anti‑inflammatory properties. When we think about the cellular processes in the body, we know that reactive oxygen species as well as free radicals are going to be produced.

Therefore, having additional antioxidants there to essentially destroy the oxidative stress is important, as well as when we have these inflammatory reactions from the immune system, having something that can dampen the effect or inhibit it from continued activation that would lead to damage of normal cells, is important. 


Holland TM, MD, Agarwal P, Wang Y, et al. Dietary flavonols and risk of Alzheimer dementia. Neurology. 2020 January 29;[Epub ahead of print].

Study: antioxidant flavonol linked to lower risk of Alzheimer’s dementia [press release]. Minneapolis, Minnesota: American Academy of Neurology; January 24, 2020.

Thomas M. Holland, MD, is a physician scientist at Rush University Medical Center in the Rush Institute for Healthy Aging and a faculty member of Rush University, College of Health Sciences, Chicago, Illinois. Upon completion of his medical training, he joined Martha Clare Morris, ScD, as a postdoctoral fellow in the section of nutritional epidemiology, and is preparing his thesis for a master’s degree in clinical research. Dr. Holland is investigating the impact of lifestyle modifications on chronic diseases as we age. Specifically, he and his colleagues explore how diet and other lifestyle factors influence Alzheimer’s dementia, disease, and several cognitive abilities. Currently, Dr. Holland is assisting in several National Institutes of Health (NIH)-funded grants including Vitamin D and K measurements in brain tissue and the MIND diet clinical trial, focused on a dietary intervention for cognition. He was recently named the assistant trial director of the Chicago site of the US POINTER trial, and will be medical advisor for lifestyle modifications while serving on the safety and curriculum committees.

Back to Top