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
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 .
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
“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
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
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.
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