Flavanol deficiency linked to age-related memory loss in clinical trial, experts contest results

31 May 2023 --- Flavanol deficiency may drive age-related memory loss according to a team of US-based researchers. After conducting a three-year clinical trial, the team found that replenishing flavanols in deficient adults over 60 improved performance on tests designed to detect memory loss due to normal aging. However, experts point to limitations.

In the first year of the study, participants who reported consuming a poorer diet with lower baseline flavanol levels improved their memory scores by an average of 16% compared to their memory at baseline. This was an increase of 10.5% compared to the placebo group. 

However, considering all study participants, memory improvement was not statistically significant. 

“The improvement among study participants with low-flavanol diets was substantial and raises the possibility of using flavanol-rich diets or supplements to improve cognitive function in older adults,” says the study’s co-author, Adam Brickman, Ph.D., professor of neuropsychology at Columbia University, US. 

Although experts applaud the extensive and rigorous study, they question its outcomes. 

“The trial result was negative for all three years. In other words, there is no evidence that a diet rich in flavanols protects from memory loss,” states Naveed Sattar, professor of metabolic medicine at the University of Glasgow, UK.  

One mug of tea, six squares of dark chocolate and a couple of servings of berries/apples would together provide about 500 mg of flavanols.“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 we 100% know to protect against many illnesses – eat better, walk more, sleep well and have traditional risk factors tested and, if needed, improved.”

Study set-up  
In the study, published in Proceedings of the National Academy of Sciences, 3,562 healthy older adults were randomly assigned to receive a daily flavanol supplement or placebo for three years. The active supplement contained 500 mg of cocoa flavanols, including 80 mg of epicatechins, which adults are advised to obtain from food. 

All participants filled out a survey to assess the quality of their diet, including foods known to be high in flavanols. The researchers also assessed participants’ short-term memory through web-based activities in their homes. These tests were repeated each year of the study. 

In addition, over a third of participants supplied urine samples to ensure the research team could measure a biomarker for dietary flavanol levels and determine whether these corresponded to performance on the cognitive tests. 

The study builds on previous research that links age-related memory loss to changes in the dentate gyrus in the brain’s hippocampus – vital for learning new memories – showing that flavanols improved function in this part of the brain. 

Co-author Scott Small, MD, professor of Neurology at Columbia University, US, comments that flavanols do not affect people who don’t have a flavanol deficiency.

However, “Our study, which relies on biomarkers of flavanol consumption, can be used as a template by other researchers to identify additional, necessary nutrients.” 

“Relevance of findings are overstated”  
Dr. Carl Hodgetts, senior lecturer of cognitive neuroscience at the University of London, UK, warns that while the initial results from this study are interesting, “the relevance of these findings to the hippocampus and aging-related diseases like dementia are somewhat overstated in the paper.”

“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.” 

Previous research showed that flavanols improved the function of the dentate gyrus in the brain’s hippocampus, which is vital for learning new memories. Hodgetts notes that a “wider range of tasks would be more informative in determining the specific neurobiological effects of flavanol on the hippocampal system” as the word recall task used in the study is unlikely to be intensely dependent on the hippocampus.

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

Maintaining a high-quality diet   
Experts note that people should obtain sufficient flavanols from a balanced diet that includes a variety of fruit and vegetables.  

Professor Aedin Cassidy, chair in Nutrition and Preventive Medicine at the Institute for Global Food Security in Belfast, Northern Ireland, explains that simple additions to the diet, like flavanols, can contribute to maintaining brain health. 

“The dose required for these improvements in brain health is readily achievable – for example, one mug of tea, six squares of dark chocolate, a couple of servings of berries or apples would provide about 500 mg of flavanols.”

Dr. Ian Johnson at the Quadram Institute, UK, adds that the study’s results emphasize the role of nutrition in the maintenance of the aging brain. 

“They suggest the importance of maintaining a high-quality diet, rich in familiar sources of flavanols such as apples, grapes, other berries and tea. In circumstances where this is difficult, dietary supplements may be a practical solution, though further studies are probably needed to explore this approach in depth.” 

A clinical trial is needed to restore levels in adults with severe deficiency to confirm flavanols’ effect on the brain.Next steps 
It’s not clear whether boosting dietary flavanol levels might also reduce the risk of progressive conditions such as dementia, as the study wasn’t set up to answer this question, adds Dr. Rosa Sancho, head of research at the Alzheimer’s Research UK. 

“Dementia is caused by complex diseases, like Alzheimer’s, 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.”

“We cannot yet definitively conclude that low dietary intake of flavanols alone causes poor memory performance because we did not conduct the opposite experiment: depleting flavanol in people who are not deficient,” notes Small. He adds that such an experiment might be considered unethical. 

Small explains that a clinical trial is needed to restore levels in adults with severe deficiency to confirm flavanols’ effect on the brain. 

Though there is a significant amount of variability in age-related memory decline, he concludes that it occurs in nearly everyone. 

“If some of this variance is partly due to differences in dietary consumption of flavanols, then we would see an even more dramatic improvement in memory in people who replenish dietary flavanols when they’re in their 40s and 50s.”

By Jolanda van Hal