(+)-Epicatechin

TUESDAY, May 30, 2023 -- You'll likely lose some of your memory and thinking abilities as you age, but nutrients called flavanols might help thwart that decline, a new study suggests. Not getting enough flavanols -- natural compounds found in fruits, vegetables and even chocolate -- could be driving that age-related memory loss, researchers say. This research is the pinnacle of 15 years of work showing that flavanols seem to benefit the dentate gyrus, an area within the brain’s hippocampus that is critical to memory. “This is the first time we can conclude that flavanols are acting as a nutrient for the aging brain,” said Dr. Scott Small , a professor of neurology and director of the Alzheimer’s Disease Research Center at Columbia University College of Physicians and Surgeons. “We show in this study, because we had biomarkers of flavanols, that if you're relatively deficient in your flavanols, that seems to be driving your age-related memory decline.” This study was funded by the U.S. National Institutes of Health and Mars Edge, a subsidiary of the candy company. It’s possible that just as babies need certain nutrients for their developing brains, the aging brain also requires specific nutrients for optimal health, Small said. Now that people live longer, scientists are looking into a series of recommendations of nutrients that are beneficial for the aging body and brain, he noted. “I'd like to believe that this is one of the first studies that is beginning to establish that dietary recommendation,” Small said. Besides berries and dark chocolate, other flavanol-containing foods include apples -- particularly the peels -- grapes, citrus fruits, cocoa and green tea. Good vegetable sources of flavanols are onions, hot peppers, kale, broccoli, rutabagas and spinach, according to the U.S. Department of Agriculture. “I believe that you could consume enough flavanols to prevent yourself from being deficient,” Small said. However, he urged people not to focus on getting this nutrient through chocolate. “There’s no way you can eat enough chocolate to have this benefit. In fact, if you tried, you would die first,” Small said. Prior research in mice found that a particular substance in flavanols called epicatechin enhanced the growth of neurons and blood vessels, improving memory. In humans, a small study linked the dentate gyrus to cognitive, or mental, aging. A larger trial found that flavanols improved memory, having the greatest impact on people who had a poor-quality diet to start. To study this further, researchers randomly assigned 3,500 healthy older adults to receive either a placebo or a daily flavanol supplement in pill form. The supplements contained 500 mg of flavanols, including 80 mg of epicatechins (an amount that's recommended you get from food). Participants answered questions about their diet, and then did web-based activities to assess short-term memory that involved the hippocampus, repeating them after years one, two and three. More than one-third of participants also supplied urine samples, so that researchers could measure a biomarker for dietary flavanol levels. No one was severely flavanol-deficient, although those with mild deficiency benefited from flavanol supplements, researchers said. Researchers also found that memory scores improved just slightly for the entire group taking the supplements, possibly because most already had flavanol-rich diets. Yet those who reported having a poor diet and who had lower baseline levels of flavanols had memory scores improve by an average of about 11% compared to those on the placebo at the end of the first year. Their memory improved 16% from baseline. They sustained the one-year improvement for at least two more years. However, flavanols only improved memory governed by the hippocampus and not other areas of the brain, the researchers noted. Emma Laing is director of dietetics at the University of Georgia and a national spokesperson for the Academy of Nutrition and Dietetics. She said flavanols are one of several sub-classifications of flavonoids, naturally occurring bioactive compounds linked to human health. “Consuming foods high in flavanols has been shown in research studies to benefit health and reduce the risk for chronic diseases involving the brain, heart and other organs,” said Laing, who was not involved in this study. These nutrients give foods like peaches and apples their bright colors, Laing said. She noted that the role of flavanols on neurological health is an exciting, ongoing area of research with a lot left to learn. “Intentionally adding flavanol-rich foods to your eating pattern is a relatively simple lifestyle change that you could make to support your health. Many foods naturally contain these compounds, so aiming to add one or more servings of flavanol-rich foods per week would be a realistic place to start,” Laing said. Lang also recommended eating nutrient-dense foods, getting enough sleep, exercising, staying well-hydrated and avoiding alcohol as ways to reduce the risk of chronic disease and improve overall health. Because of the study's design, Small said it can't definitively conclude that low dietary intake of flavanols alone causes poor memory, only that there's an association. The study was published in the journal Proceedings of the National Academy of Sciences . Sources Scott Small, MD, professor, neurology, and director, Alzheimer’s Disease Research Center, Columbia University College of Physicians and Surgeons, New York City Emma Laing, PhD, RDN, national spokesperson, Academy of Nutrition and Dietetics, and director of dietetics, University of Georgia, Athens Proceedings of the National Academy of Sciences , May 29, 2023 Posted May 2023

Age-related memory loss is likely caused, in part, by lack of flavanols -- nutrients found in certain fruits and vegetables -- according to a large study in older adults. A large-scale study led by researchers at Columbia and Brigham and Women's Hospital/Harvard is the first to establish that a diet low in flavanols -- nutrients found in certain fruits and vegetables -- drives age-related memory loss. The study found that flavanol intake among older adults tracks with scores on tests designed to detect memory loss due to normal aging and that replenishing these bioactive dietary components in mildly flavanol-deficient adults over age 60 improves performance on these tests. "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 Adam Brickman, PhD, professor of neuropsychology at Columbia University Vagelos College of Physicians and Surgeons and co-leader of the study. The finding also supports the emerging idea that the aging brain requires specific nutrients for optimal health, just as the developing brain requires specific nutrients for proper development. "The identification of nutrients critical for the proper development of an infant's nervous system was a crowning achievement of 20th century nutrition science," says the study's senior author, Scott Small, MD, the Boris and Rose Katz Professor of Neurology at Columbia University Vagelos College of Physicians and Surgeons. "In this century, as we are living longer research is starting to reveal that different nutrients are needed to fortify our aging minds. Our study, which relies on biomarkers of flavanol consumption, can be used as a template by other researchers to identify additional, necessary nutrients." Age-related memory loss linked to changes in hippocampus The current study builds on over 15 years of research in Small's lab linking age-related memory loss to changes in the dentate gyrus, a specific area within the brain's hippocampus -- a region that is vital for learning new memories -- and showing that flavanols improved function in this brain region. Additional research, in mice, found that flavanols -- particularly a bioactive substance in flavanols called epicatechin -- improved memory by enhancing the growth of neurons and blood vessels and in the hippocampus. Next, Small's team tested flavanol supplements in people. One small study confirmed that the dentate gyrus is linked to cognitive aging. A second, larger trial showed that flavanols improved memory by acting selectively on this brain region and had the most impact on those starting out with a poor-quality diet. In the new study, the Columbia team collaborated with researchers at Brigham and Women's Hospital studying the effects of flavanols and multivitamins in COSMOS (COcoa Supplements and Multivitamin Outcomes Study). The current study, COSMOS-Web, was designed to test the impact of flavanols in a much larger group and explore whether flavanol deficiency drives cognitive aging in this area of the brain. Study methods More than 3,500 healthy older adults were randomly assigned to receive a daily flavanol supplement (in pill form) or placebo pill for three years. The active supplement contained 500 mg of flavanols, including 80 mg epicatechins, an amount that adults are advised to get from food. At the beginning of the study, all participants completed a survey that assessed the quality of their diet, including foods known to be high in flavanols. Participants then performed a series of web-based activities in their own homes, designed and validated by Brickman, to assess the types of short-term memory governed by the hippocampus. The tests were repeated after years one, two, and three. Most of the participants identified themselves as non-Hispanic and white. More than a third of the participants also supplied urine samples that allowed researchers to measure a biomarker for dietary flavanol levels, developed by co-study authors at Reading University in the UK, before and during the study. The biomarker gave the researchers a more precise way to determine if flavanol levels corresponded to performance on the cognitive tests and ensure that participants were sticking to their assigned regimen (compliance was high throughout the study). Flavanol levels varied moderately, though no participants were severely flavanol-deficient. People with mild flavanol deficiency benefited from flavanol supplement Memory scores improved only slightly for the entire group taking the daily flavanol supplement, most of whom were already eating a healthy diet with plenty of flavanols. But at the end of the first year of taking the flavanol supplement, participants who reported consuming a poorer diet and had lower baseline levels of flavanols saw their memory scores increase by an average of 10.5% compared to placebo and 16% compared to their memory at baseline. Annual cognitive testing showed the improvement observed at one year was sustained for at least two more years. The results strongly suggest that flavanol deficiency is a driver of age-related memory loss, the researchers say, because flavanol consumption correlated with memory scores and flavanol supplements improved memory in flavanol-deficient adults. The findings of the new study are consistent with those of a recent study, which found that flavanol supplements did not improve memory in a group of people with a range of baseline flavanol levels. The previous study did not look at the effects of flavanol supplements on people with low and high flavanol levels separately. "What both studies show is that flavanols have no effect on people who don't have a flavanol deficiency," Small says. It's also possible that the memory tests used in the previous study did not assess memory processes in the area of the hippocampus affected by flavanols. In the new study, flavanols only improved memory processes governed by the hippocampus and did not improve memory mediated by other areas of the brain. Next steps "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," Small says, adding that such an experiment might be considered unethical. The next step needed to confirm flavanols' effect on the brain, Small says, is a clinical trial to restore flavanol levels in adults with severe flavanol deficiency. "Age-related memory decline is thought to occur sooner or later in nearly everyone, though there is a great amount of variability," says Small. "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."