Plant flavanols reverse age-related memory decline

27 October 2014

Plant flavanols, a range of compounds found in certain plants such as cocoa beans, can reverse age-related memory decline in healthy older adults, according to a study led by Columbia University Medical Center (CUMC).

The study, published in Nature Neuroscience, provides the first direct evidence that one component of age-related memory decline in humans is caused by changes in a specific region of the brain and that this form of memory decline can be improved by a dietary intervention.

The cocoa used in the research was specially prepared by food company Mars using a proprietary process to extract flavanols from cocoa beans. The company also partly supported the research. Most methods of processing cocoa remove much of the flavanols found in the raw plant because they have a bitter taste.

Flavanols (different chemical structure from flavonols) are found in many plants including tea, and certain fruits, vegetables and spices and also wine. They all have antioxidant properties, which are thought to provide health benefits in limited quantities. The chemical compounds range in complexity from the relatively simple molecule of cinnamic acid (characteristic compound in cinnamon) up to complex tannins. Previous studies have shown that consumption of fruit, vegetables and especially wine produce a high level of flavonol in blood plasma [1].

Previous work, including by the laboratory of senior author Scott A. Small, MD, had shown that changes in a specific part of the brain—the dentate gyrus — are associated with age-related memory decline. Until now, however, the evidence in humans showed only a correlational link, not a causal one. To see if the dentate gyrus is the source of age-related memory decline in humans, Dr. Small and his colleagues tested whether compounds called cocoa flavanols can improve the function of this brain region and improve memory. Flavanols extracted from cocoa beans had previously been found to improve neuronal connections in the dentate gyrus of mice.

In the CUMC study, 37 healthy volunteers, ages 50 to 69, were randomized to receive either a high-flavanol diet (900 mg of flavanols a day) or a low-flavanol diet (10 mg of flavanols a day) for three months. Brain imaging and memory tests were administered to each participant before and after the study. The brain imaging measured blood volume in the dentate gyrus, a measure of metabolism, and the memory test involved a 20-minute pattern-recognition exercise designed to evaluate a type of memory controlled by the dentate gyrus.

“When we imaged our research subjects’ brains, we found noticeable improvements in the function of the dentate gyrus in those who consumed the high-cocoa-flavanol drink,” said lead author Adam M. Brickman, PhD, associate professor of neuropsychology at the Taub Institute.

The high-flavanol group also performed significantly better on the memory test. “If a participant had the memory of a typical 60-year-old at the beginning of the study, after three months that person on average had the memory of a typical 30- or 40-year-old,” said Dr. Small. He cautioned, however, that the findings need to be replicated in a larger study — which he and his team plan to do.

The precise formulation used in the CUMC study has also been shown to improve cardiovascular health. Brigham and Women’s Hospital in Boston recently announced an NIH-funded study of 18,000 men and women to see whether flavanols can help prevent heart attacks and strokes.

The researchers point out that the product used in the study is not the same as chocolate, and they caution against an increase in chocolate consumption in an attempt to gain this effect.

Two innovations by the investigators made the study possible. One was a new information-processing tool that allows the imaging data to be presented in a single, three-dimensional snapshot, rather than in numerous individual slices. The tool was developed in Dr. Small’s lab by Usman A. Khan, an MD-PhD student in the lab, and Frank A. Provenzano, a biomedical engineering graduate student at Columbia. The other innovation was a modification to a classic neuropsychological test, allowing the researchers to evaluate memory function specifically localized to the dentate gyrus. The revised test was developed by Drs. Brickman and Small.

Besides flavanols, exercise has been shown in previous studies, including those of Dr Small, to improve memory and dentate gyrus function in younger people. In the current study, the researchers were unable to assess whether exercise had an effect on memory or on dentate gyrus activity. “Since we didn’t reach the intended VO2max (maximal oxygen uptake) target,” said Dr. Small, “we couldn’t evaluate whether exercise was beneficial in this context. This is not to say that exercise is not beneficial for cognition. It may be that older people need more intense exercise to reach VO2max levels that have therapeutic effects.”

About age-related memory decline

As people age, they typically show some decline in cognitive abilities, including learning and remembering such things as the names of new acquaintances or where one parked the car or placed one’s keys. This normal age-related memory decline starts in early adulthood but usually does not have any noticeable impact on quality of life until people reach their fifties or sixties. Age-related memory decline is different from the often-devastating memory impairment that occurs with Alzheimer’s, in which a disease process damages and destroys neurons in various parts of the brain, including the memory circuits.


1. Ruidavets J, et al. Catechin in the Mediterranean diet: vegetable, fruit or wine?. Atherosclerosis 153 (1): 107–17. doi:10.1016/S0021-9150(00)00377-4.


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