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expert reaction to study looking at flavonols and Alzheimer’s disease

Research, published in the journal Neurology, reports that the antioxidant flavonol may be linked to lower risk of Alzheimer’s.

 

Dr Ada Garcia, Lecturer in Public Health Nutrition, University of Glasgow, said:

“This study shows that when elderly people, in particular females, self-reported to eat foods that contained about 15mg of favonols in their diet (for comparison a cup of black tea will provide that amount) then their risk for developing Alzheimer’s over a period of 6 years was reduced by about 44 percent. However, 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. These types of studies are informative but need to be consider carefully before making public health recommendations. They rely on participants memory to report what foods were consumed over a period of time, this is in particular difficult in elderly participants because reduction in cognitive function is a normal process of ageing.

“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.”

 

Prof Bart De Strooper, Director, UK Dementia Research Institute, said:

“The relationship between food and health always draws a lot of attention from the public. This new study suggests that specific components in fruit, vegetables and tea are protective against Alzheimer’s Dementia. For studies of this sort we must however not forget that it only describes an association which was observed in a small group of individuals. Association does not demonstrate that there is a real biological or causal link. To give confidence in this observation it must first be repeated in other groups. Many studies in the past have shown however that such observations do not replicate well. So, in general one should be careful not to overstate the importance of such findings.”

 

Dr Adrian Ivinson, Director, UK Dementia Research Institute, said:

“We’ve long known that there are links between what we eat and our health. This new study suggests tea could be added the equation and shows that the general health benefits may extend to brain health. However, it only describes an association, so further work is needed to see if there are true biological links. But Alzheimer’s disease is exceptionally complex. Whilst diet may help stack the odds in our favour, we need to do discovery research to understand the disease and from there develop ways of preventing or slowing it.”

 

Dr James Pickett, Head of Research, Alzheimer’s Society, said:

“Early-stage research in mice does show flavonols might reduce the build-up of toxic proteins in the brain we know are involved in Alzheimer’s. This new study in people isn’t definitive about whether flavonols can lower dementia risk, and it definitely doesn’t provide enough evidence to say that drinking tea, and eating food rich in flavonols, will ward off dementia. But the study results do suggest we should keep investigating the potential of flavonols. 

“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, said:

“This research reports an association between flavonols and lower risk of Alzheimer’s disease. To estimate flavonol intake in this population, researchers used a type of food questionnaire which is not the best tool to measure food intake, as it relies on what people remembered they ate over a year.

“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.”

 

Prof Tara Spires-Jones, UK Dementia Research Institute Programme Lead and Deputy Director, Centre for Discovery Brain Sciences, University of Edinburgh, said:

“This paper by Dr Holland and colleagues provides more evidence that a healthy diet rich in vegetables is associated with a reduced risk of Alzheimer’s disease. Scientists followed over 900 people for up to 12 years and found that people who reported they ate a diet rich in flavonols (found in vegetables including onions, kale, broccoli, and spinach) were less likely to develop Alzheimer’s disease than people who ate lower levels of these compounds.  This study was well conducted and looked at a large number of people.  As the authors point out, one limitation is this study relied on people reporting their food intake and there could be errors in their recall.  Another limitation to keep in mind is that although it was carefully controlled, this type of observational study cannot prove that the higher intake of flavonols caused the reduced risk of dementia. There could be an unrelated factor that was related to diet that the scientists did not know about that could have influenced disease risk.”

 

Prof Gunter Kuhnle, Professor of Nutrition and Food Science, University of Reading, said:

“There are a lot of misunderstandings regarding flavonols and flavonoids. First of all, they do not act as antioxidants in the human body. This was believed decades ago due to their chemical structure, but a better understanding of their metabolism has shown that once they are taken up by the body, they can no longer act as antioxidant. Secondly, they are a huge class of compounds and all of them are likely to act different – but because they are found in many fruits and vegetables, their intake is often just a marker for a diet rich in fruits and vegetables.

“Flavonols are a subgroup of flavonoids that are found in many fruits and vegetables. They are found for example in onions (125 mg/100 g – about 250 mg in an onion) or berries (42 mg/100 g in elderberry). They’re also found in tea – a cup of tea contains about 20 mg– although depending on how it is made, it can be anywhere between 2 and 40. In the UK, people consume about 30 mg per day – which is higher than the average intake of about 20 mg per day in Europe.

“This is an observational study where flavonol intake was estimated based on the diet reported by participants. Especially for compounds such as flavanols, where food content is very variable and depends on preparation and processing, it is virtually impossible to estimate intake accurately and reliably. The study found a rather modest beneficial effect for total flavonols and most individual compounds – and only a substantial reduction in risk for a one group of flavonols – Kaempferol. These compounds are found in particular in herbs and spices and some cabbages – but variability in food content in these foods is huge and it is therefore difficult to derive any recommendation from this. They’re also found to a small extent in tea. Interestingly, the mean kaemperfol intake in the UK is about 8 mg per day – higher than the highest intake in the study.

“The mode of action of flavonols is not known, and it is likely that the observed associations are simply due to a dietary pattern rich in specific foods and vegetables. A risk reduction of almost 50% iS of course impressive, but there are currently no data that suggest that flavonols as a compound could have such an effect. It is important to keep in mind that the study participants did not consume flavonols, but foods that contained flavonols – and many other compounds as well and it might be that these compounds are much more relevant. For example: tea contains kaempferol – the one compound that has been shown to be associated with a reduced risk. However, tea also contains flavan-3-ols – compounds for which there considerably more and better data to suggest a beneficial effect on cognitive function.

“In summary, this is an interesting study as it confirms the potentially beneficial effects of fruits and vegetables, but it is not suitable to change dietary recommendations.”

 

Ms Catherine Collins, NHS Dietitian, said:

“Flavonols are part of the flavonoid group of phytochemicals – naturally occuring plant substances that unlike vitamins and minerals aren’t essential for life but help support health. Phytochemicals contribute flavour and colour, with most being present in varying levels across a wide range of fruits and vegetables.

“This study predicted dietary intake of four phytochemicals derived from dietary questionnaire, and associated an increased intake of these four with a lower Alzheimer’s risk in a high risk group of people (ie those over 80 years old) – even when adjusted for medical conditions that would increase risk at this age.

“However, 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. This natural variation is well recognised in the literature1.  

“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 made2.

“The authors state that tea was a significant source of dietary quercetin intake. Quercetin in tea is highly variable depending on the type of tea consumed and the brewing method used. Injecting quercetin into mice bred to be at higher risk of Alzheimer’s seems to protect the mouse brain against the disease. The flavonoid quercetin ameliorates Alzheimer’s disease pathology and protects cognitive and emotional function in aged triple transgenic Alzheimer’s disease model mice, but current knowledge means we can’t say the public can ‘drink tea, prevent Alzheimer’s disease’ – even though we know that tea provides many healthful flavonoids3.

“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.”

1. http://scholar.google.co.uk/scholar_url?url=http://www.academia.edu/download/46163065/Databases_on_Food_Phytochemicals_and_The20160602-11683-mbn5n6.pdf&hl=en&sa=X&scisig=AAGBfm3G0XYf_6z45TqPg6qe1L_-nCOOxQ&nossl=1&oi=scholarr

2. https://jandonline.org/article/S2212-2672(13)00242-6/fulltext

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986534/

 

Dr Duane Mellor, Registered Dietitian and Senior Teaching Fellow, Aston Medical School, Aston University, said:

“This is an interesting study looking at an older population of adults to see if there is a link between dietary intake of flavonols and Alzheimer’s disease. The authors took an estimate of what people remembered that they ate over the last year and estimated how that might link to their intake of flavanols. This approach has a lot of assumptions, as people forget what they ate and they report eating foods, drinks or ingredients such as tea, olive oils, apples or broccoli and not kaemperfol or quercetin.

“Direct effect of flavonols has been questioned by other research which has shown that these compounds are very poorly absorbed, so although the authors describe these compounds as bioactives (something which has a biological effect on human bodies), it may not be that simple.

“What this study really seems to show, despite using statistics carefully, is that there is an association between a diet rich in vegetables, fruit, tea, beans, lentils and olive oil and a reduction in the risk of developing Alzheimer’s, rather than showing that this reduction in risk is associated with flavonols alone. So, perhaps this study adds to the evidence suggesting that a Mediterranean type diet may be the best diet to increase your chances of having a healthy and long life. It is best to focus on eating a variety of foods, rather than thinking about whether our diets contain enough kaemperfol or quercetin.”

 

Prof David Curtis, Honorary Professor, UCL Genetics Institute, said:

“The authors are right to be appropriately cautious about the findings of the study. It does seem that the risk of Alzheimer’s disease is lower in those who in general have a healthier lifestyle. However, it is extremely difficult to narrow down this effect to specific elements of the diet. They have had to apply complex statistical techniques to what is in fact a relatively small sample and the conclusions are critically dependant on whether these methods are valid. It would be premature to claim that specific dietary components can helpfully reduce Alzheimer’s risk.

“The advice remains that exercise and a healthy diet, rich in vegetables, probably reduces risk of Alzheimer’s disease along with other health problems. But on the basis of this study I would not be urging people to drink more tea or eat more kale. Dementia represents a huge public health problem and it is essential that adequate resources are directed towards following up promising findings such as this one.”

 

Dr James Connell, Research Manager at Alzheimer’s Research UK, said:

“Understanding how our behaviours affect our brain health is important, as there may be lifestyle factors we can change to help support healthy ageing.

“While this research highlights a possible link between flavonols, often found in tea and certain fruits and vegetables, and a lower dementia risk, it doesn’t tell us about cause and effect. This study relied on people self-reporting their eating habits, and this can lead to mistakes in reporting and a tendency to underestimate unhealthy behaviours.

“While we don’t know whether flavonols could have any particular effect on dementia risk, a balanced diet with plenty of fruits and vegetables can help to support a healthy brain. As well as a balanced diet, the best evidence suggests that controlling blood pressure and cholesterol, maintaining a healthy weight, not smoking, drinking within the recommended limits, and staying mentally and physically active can all help us to maintain a healthy brain as we age.”

 

Dietary flavonols and risk of Alzheimer dementia’ by Holland et al. was published in Neurology at 21:00 UK time on Wednesday 29 January. 

DOI: 10.1212/WNL.0000000000008981

 

Declared interests

Dr Ada Garcia: “No conflict of interest”

Dr Ana Rodriguez-Mateos: “No conflict of interest.”

Prof Tara Spires-Jones: “I have no conflicts with this study.”

Prof Gunter Kuhnle: “I conduct research into the associations between flavan-3-ols and health, which is funded by Mars.”

Ms Catherine Collins: “no conflict of interest declared”

Dr Daune Mellor: “No declarations of conflicts of interest.”

Prof David Curtis: “I have no conflict of interest.”

None others received.

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