May 29, 2023

expert reaction to dietary flavanols and memory loss in older adults

A study published in PNAS looks at dietary flavanols and hippocampal-dependent memory in older adults.

This Roundup accompanied an SMC Briefing.

Dr Ian Johnson, Emeritus Fellow, Quadram Institute, said:

“This large and rigorously conducted study adds strong support to previous evidence showing the importance of diet as a factor supporting cognitive health in later life. It demonstrates that older adults consuming lower levels of food-borne flavanols scored less well in tests of hippocampal memory function than individuals consuming higher levels, and that their performance scores were significantly improved by daily supplementation with flavanols derived from cocoa.  Importantly, the estimates of flavonoid intake in the study group were validated by means of urine analysis to provide an objective measure of consumption. These results emphasise the role of nutrition in the maintenance of the ageing brain, and in particular they suggest the importance of maintaining a high-quality diet, rich in everyday sources of flavanols such as apples, grapes, other berries, and tea.  In circumstances where this is difficult, the use of dietary supplements may be a practical solution, though further studies are probably needed to explore this approach in depth.”

Dr Carl Hodgetts, Senior Lecturer of Cognitive Neuroscience, Royal Holloway, University of London, said:

“Understanding how our brains age, and how we might protect them from this process, is a crucial question that has global implications, especially in the fight against dementia. This is particularly relevant when it comes to the part of our brain known as the hippocampus, which plays a significant role in our memory and is often linked to Alzheimer’s disease.

“This is an interesting study that starts to address such questions, but we cannot conclude that flavanol supplements affect hippocampal function. Firstly, no direct brain-related measures were taken using tools like MRI. It will be important to conduct further studies where such interventions are combined with MRI to examine whether cognitive improvements are also associated with changes in the structure of the hippocampus.

“Second, the word recall task used is also unlikely to be strongly dependent on the hippocampus. The hippocampus is involved in a range of functions, especially those requiring memory for spatial and temporal relationships, like spatial navigation or autobiographical memory. A wider range of tasks would be more informative in determining the specific neurobiological effects of flavanol on the hippocampal system.

“Lastly, it’s crucial to remember that other parts of the brain, such as the prefrontal cortex, also play significant roles in tasks like word list learning. These areas help us organise our memory through strategies like sorting elements based on their meaning.

“In summary, while the initial results from this study are interesting, the relevance of these findings to the hippocampus and ageing-related diseases like dementia are somewhat overstated in the paper.”

Prof Tara Spires-Jones, President of the British Neuroscience Association, UK Dementia Research Institute Group Leader, and Deputy Director of the Centre for Discovery Brain Sciences at the University of Edinburgh said:

“This large, well-conducted study found an association between healthy diet including flavanol consumption and better memory in older adults.  Scientists conducted a randomized clinical trial of taking a flavanol supplement.

“This trial did not meet its primary endpoint (meaning the trial failed) although in a subset of people who had low diet quality and flavanol consumption at baseline, there was a benefit to memory. Other studies have found that flavanols, found in foods like tea, apples, cocoa, and berries, may be protecting the brain through boosting formation of synapses, the connections between neurons. 

“Together, this study and data from the wider field supports the idea that taking care of ourselves as we age, including healthy diet and exercise, protects our brains.”

Prof Naveed Sattar, Professor of Metabolic Medicine, University of Glasgow, said:

“It is great to see a randomised trial in this space with decent numbers.  The key result is in fact the trial result which was clearly negative at all 3 years. In other words, there is NO evidence that a diet rich in flavanols protects from memory loss. 

“The rest of the paper is observational and creates the illusion of benefit but it is of little value.  People should not rush to such drinks or diets but rather keep doing the things that we 100% know protect against many illnesses – eat better (and fewer calories if overweight), walk a little more and sleep well and have traditional risk factors tested and, if needed, improved.”

Prof Aedin Cassidy, Chair in Nutrition & Preventative Medicine and Director for Interdisciplinary Research, Institute for Global Food Security, Queen’s University Belfast (QUB), said:

“This is a really important study showing that dose of flavonoids called flavanols, present in tea, cocoa, apples, berries is key for improving memory in the ageing brain. Although we have animal experiments and short term human studies showing that flavanols improve cognitive function, this is the first long term 3 year intervention trial showing that dietary flavanols can restore memory in older adults whose general diet was of poor quality (including low intakes of flavanols). Supplementing with flavanols reversed the lower memory in the participants who had low diet quality after 1 year of intake and this was sustained throughout the 3 year intervention period. So when habitual diets are not as healthy as they could be we now have evidence that simple additions to the diet like flavanols can contribute to maintain brain health as we age. The dose required for these improvements in brain health are readily achievable – for example 1 mug of tea, 6 squares of dark chocolate, a couple of serving of berries/apples would together provide about 500mg of flavanols).”

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

“I’m afraid that the results obtained do not support the claim that flavanols improve memory function. Even in the group who initially had low flavanol consumption, those taking a flavanol supplement for years had about the same memory function as those taking placebo and any differences were well within chance expectation. The authors do claim that a couple of results are statistically significant but in my view this because the analyses have been performed incorrectly. If anything, this study shows that flavanol supplements do not have any major effect on memory function. The study fails to provide evidence that increasing flavanol intake is beneficial and there is no need for anybody to contemplate changing their diet in the light of its findings.”

Dr Davide Bruno, reader in psychology at Liverpool John Moores University, said:

“This is a good and convincing piece of work.  But it’s important to make the distinction between age-related memory loss and dementia.  While the primary sign of Alzheimer’s disease is loss of episodic memory, age-related memory loss is common for everyone.

“This study does not suggest that increasing flavanols intake will prevent Alzheimer’s disease, but it’s worth noting that mitigating the effects of cognitive aging may actually postpone the emergence of dementia – so flavanols could play a part. 

“However, the effects on memory appear to be modest, and limited to those individuals with a lower quality diet at the start of the study”.

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:

“This study explored whether boosting levels of certain plant-based substances in our diet could help protect against age-related memory and thinking decline. After three years, it found a small improvement in memory test scores among participants who originally had lower dietary levels of flavanols, a result that will need to be followed up in further studies to confirm whether replenishing flavanol intake can boost memory for these people. 

“It’s far from clear whether boosting dietary flavanol levels might also reduce the risk of progressive conditions like dementia, and the study wasn’t set up to answer this question. Dementia is caused by complex diseases, like Alzheimer’s, which are separate from age-related memory decline, and seem to develop through very different biological mechanisms. More research will be needed to understand whether the effects seen in this study have any impact on long-term risk of dementia.”

“People should be able to get enough flavanols from a balanced diet that includes a variety of fruit and vegetables. While we do not yet know for sure whether flavanols specifically influence risk of conditions like dementia, we do know that things like staying mentally sharp, keeping socially connected, and keeping our heart healthy – including by eating a balanced diet – are important for looking after our long-term brain health.”

‘Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption’ by Adam M. Brickman et al. was published in PNAS at 8pm UK time Monday 29 May 2023.

DOI: https://doi.org/10.1073/pnas.2216932120

Declared interests

Prof Cassidy: ‘I work in the flavonoid field and currently have funding from the USHBC (US Highbush blueberry council).’

Prof Sattar: No COI

Prof Spires-Jones: I have no conflicts with the study

Prof Curtis: I have no conflict of interest to declare.

Prof Johnson: I have previously advised the food industry on the physiological effects of flavanols.

For all other experts, no reply to our request for DOIs was received.