Cocoa extract improves memory in older adults with flavanol-poor diet

A large 3-year study of >3,500 older adults finds that flavanol-rich cocoa extract restores memory in participants with low-quality diet or low habitual flavanol consumption.

Flavanols are bioactive compounds commonly found in tea, apples, berries, grapes, cocoa, and other fruits and vegetables. Dietary intervention studies demonstrate that flavanol consumption can play a role in attenuating cognitive ageing in animals and humans by improving hippocampal-dependent memory via increased angiogenesis and regional perfusion. [Nat Neurosci 2014;17:1798-1803; J Neurosci 2007;27:5869-5878]

To confirm these observations, the researchers focused on one of the arms of the COSMOS study (COcoa Supplement and Multivitamin Outcomes Study), in which either a flavanol-containing cocoa extract (500 mg of cocoa flavanols, including 80 mg of (–)-epicatechin) or placebo was given daily to 3,562 generally healthy older adults (mean age, 71 years; women, 66.9 percent). The primary prespecified endpoint was improvement in hippocampal-dependent memory across all participants at year 1. [Proc Natl Acad Sci U S A 2023;doi:10.1073/pnas.2216932120]

“In our primary analysis, participants in both the flavanol and placebo groups showed a typical learning [practice] effect, but no treatment differences were observed, with a similar magnitude of improvement across both groups,” reported the researchers. However, flavanol intervention significantly (p=0.011) improved hippocampal-dependent memory in participants in the lowest tertile of habitual diet quality (ie, diet quality ranging from the US average to slightly below average), but not among those in the medium or highest tertile. Participants in the lowest tertile of diet quality also had poorer memory performance at baseline.

In addition, researchers stratified study participants into tertiles according to habitual flavanol consumption, as estimated by urinary concentrations of 5-(3’,4’-dihydroxyphenyl)-γ-valerolactone metabolite (gVLM) at study baseline. Like diet quality, baseline gVLM levels selectively correlated with hippocampal-dependent memory, and the group with relatively lower gVLM levels exhibited worse baseline memory. At the same time, hippocampal-dependent memory was significantly improved with the dietary flavanol intervention (p=0.006) in the lowest gVLM tertile. “The degree of improvement was associated with the magnitude of increase in gVLM urine concentrations after adjusting for treatment group, age, sex, and education [p=0.009],” noted the researchers.

“Participants in the low tertile showed an increase in gVLM levels after 1 year of flavanol intervention, while those in the highest tertile, who at baseline were above the population mean, did not,” pointed out the researchers. “The presence of a ‘ceiling effect’ is a common observation in the context of nutrient intake.”

Flavanol-associated restoration of memory, which was observed among participants in the lower tertile of habitual diet quality and in the subset of participants with lower habitual flavanol consumption, was apparent after 12 months of dietary intervention and appeared to be sustained over 3 years of follow-up.

“Our findings suggest that flavanol consumption might be considered in future dietary recommendations, perhaps together with the flavanol biomarker, specifically geared towards preventing flavanol depletion and improving brain health in later life,” concluded the researchers.