Cohort study links flavonol intake to Alzheimer's risk

By Nikki Hancocks

- Last updated on GMT

Getty | Artemidovna
Getty | Artemidovna

Related tags Flavonoid Cognitive function Cognitive health Alzheimer's disease

Higher flavonol intake could help lower the risk of Alzheimer's dementia by up to 48%, according to a prospective cohort study of 921 older adults from Rush University in Chicago.

The study, published in Neurology​, found that, after adjusting for genetic, demographic, and lifestyle factors, people who consumed the highest dietary intake of flavonols were 48% less like to develop Alzheimer's dementia than people with the least intake. 

Flavonols are a sub group of of flavonoids - a group of phytochemicals found in plant pigments - known to have anti-inflammatory properties that have the potential to protect against cellular damage due to oxidative stress and sustained inflammation.

According to the authors, earlier research has looked at antioxidants and Alzheimer's risk​, but no studies have researched whether dietary intake of flavonoid subclasses is associated with Alzheimer's dementia.


In this study, Holland and colleagues followed 921 people with no dementia at baseline who participated in the Rush Memory and Ageing Project,​ an ongoing community-based, prospective cohort.

Over a mean follow-up of 6.1 years, 220 participants developed Alzheimer's dementia. Clinical diagnoses of Alzheimer's and other dementias were based on Neurologic and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria.

The average age of the sample was 81, and 75% were female. Each year, participants had annual neurologic evaluations and completed a modified version of the Harvard Food Frequency Questionnaire, which asked about the frequency of eating or drinking 144 food items in the previous 12 months.

The researchers multiplied intake frequency by each food's bioactive contents, looking at four flavonols - kaempferol (kale, beans, tea, spinach, and broccoli), quercetin, myricetin (tea, wine, kale, oranges, and tomatoes), and isorhamnetin (pears, olive oil, wine, and tomato sauce) - and total flavonol (the sum of the four individual flavonols). 

Participants were grouped into quintiles based on how much flavonol was in their diet. The lowest quintile consumed 5.3 mg per day on average; the highest had 15.3 mg per day.

People with the highest intake of total flavonols had higher levels of education and more participation in physical and cognitive activities. In models adjusted for age, sex, education, APOE​ ɛ4, and cognitive and physical activity, people in the highest versus lowest quintiles of total flavonol intake had a 48% lower rate of developing Alzheimer's dementia (HR 0.52, 95% CI 0.33–0.84).

People in the highest versus lowest quintile of isorhamnetin intake had a 38% reduced rate of incident Alzheimer's dementia. Similarly, highest versus lowest kaempferol intake showed a 51% lower rate, and highest versus lowest myricetin intake was tied to a 38% reduced rate. Quercetin was not associated with Alzheimer's dementia.

As in all observational studies, participants selected their own diets. Food frequency was self-reported and subject to recall bias, and the study findings may not apply to other populations. It's also possible that dietary changes in participants with subclinical Alzheimer's may have biased the results, the team noted.

Expert reaction 

In response to the research, many experts have argued the research only shows the benefits of a diet rich in vegetables, fruit, tea, beans, lentils and olive oil, as opposed to flavonols specifically.

Dr Ada Garcia, Lecturer in Public Health Nutrition, University of Glasgow, points out that when the authors considered the effect of consuming other nutrients such as omega-3, vitamin E, folate and lutein, which have similar actions to flavonols, then the protective effect of flavonoids was no longer present. T

She also points out that the study relies on participants memory to report what foods were consumed over a period of time which is particulary difficult in elderly participants.

She adds: “Following a ‘healthful diet pattern’ which includes a variety of foods such fruits, vegetables, oily fish, seeds, nuts, legumes  is known to be a good approach to chronic disease prevention rather than focusing on particular nutrients. This is important because the general public might interpret this study wrongly and think about the term “antioxidant” as a magic pill that will prevent the onset of dementia. It is important to remember that consuming isolated flavonols or extracts of flavonol rich foods, for example tea extracts, will not work on isolation to reduce risk of disease but high doses can also have negative effects on health.”

Dr James Pickett, head of research, Alzheimer’s Society, agrees that the study does not provide evidence of a causal effect. He says: “Our researchers are currently looking at a specific flavonol called Epicatchin to understand exactly which components are responsible for slowing the build-up of toxic proteins. This will help fill in the missing pieces of the puzzle as to whether flavonols have any protective effects against Alzheimer’s.

“In the meantime, we can say for sure that eating a balanced diet, with lots of fruit and vegetables, and getting enough exercise is a proven way to reduce your risk of dementia.”

Dr Ana Rodriguez-Mateos, Lecturer in Nutritional Sciences, Kings College London, argues that this study actually shows that foods containing flavonols as well as other phytochemicals and bioactives provide a health benefit, rather than the flavonols alone.

“The intake of flavonols in this study is very low, between 5 and 15 mg/day. A big limitation of this study is that they did not report associations with other flavonoids and phytochemicals present in the same foods as flavonols. This is particularly important because flavonols tend to be present in foods in much lower amounts than other phytochemicals. For example, tea is very abundant in other flavonoids and phytochemicals, such as thearubigins, theaflavins and flavanols, while red wine is very rich in other flavonoids such as anthocyanins and flavanols.  Olive oil is very rich in phenolic compounds such as tyrosols.  In comparison, the amount of flavonols in such foods are tiny.

“The estimated flavonoid intake in the UK for example is typically between 500-1000 mg of flavonoids/day, and existing meta-analysis of clinical studies investigating the efficacy of flavonols have used typically amounts of flavonols between 100 to 700 mg/day. It looks more feasible that the effects observed here are related to the consumption of foods containing flavonols and to other phytochemicals and bioactives present in such foods than to the flavonols themselves.”

Ms Catherine Collins, NHS Dietitian, adds: “No matter how good the assessment of fruit and vegetables intake, absolute dietary intakes of phytochemicals can’t be evaluated in absolute terms. Plant based foods are subject to natural variations depending on location of growth and variety of fruit or vegetable grown, time of harvesting and duration of storage. Current phytochemical analysis – which does not include every plant-based food we eat – can only define an average value in a particular food at the time of food analysis. They also don’t compensate for any changes associated with cooking method or the effect within the meal matrix on the bio-availability of that phytochemical. 

“The predicted presence of a flavonoid in a food does not automatically mean we will derive benefit from its presence – even if it has an antioxidant potential in laboratory testing. For this reason, the USDA ceased publication of its database on the anti-oxidant properties of food (ORAC potential) so that misinterpreting the data or extrapolating results to human health benefits could not be made.

“In summary, this study appears to show that higher intakes of fruit and vegetables may confer some degree of prevention against Alzheimer’s disease in a higher risk, elderly population. The study didn’t address whether fruit and vegetable intake conferred direct benefit or represented changes in diet and lifestyle as the individual adjusted to their progressive Alzheimer’s disease (reverse causality)

“Finally, it isn’t helpful to infer that specific flavonols found naturally in fruits and vegetables conferred benefit, given the wide natural variation in these foodstuffs and differences in their digestion, absorption and metabolism between individuals. However, it does add to the wide body of research that confirms longstanding health benefits of just eating more fruits and vegetables.”

Source: Neurology

Holland. T., et al

"Dietary flavonols and risk of Alzheimer dementia" 


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