Trial reportProceedings of the National Academy of Sciences of the United States of America2023
Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04582617 (COSMOS Web), which is not on this map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
COSMOS Web: Investigating the Effects of Cocoa Flavanol on Cognition Assessed Online
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- The role of cocoa flavanols in modulating peripheral and cerebral microvascular function in healthy individuals and populations at-risk of cardiovascular disease: a systematic review.Nutrition journal · 2025Pooled it
- Acute pre-exercise oral intake of cacao polyphenols attenuates central fatigue development during sustained low-intensity ankle dorsiflexion exercise in healthy young male adults.Physiological reports · 2026Trial
- Effects of daily multivitamin-multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial.Nature medicine · 2026Trial
- Dietary flavanols preserve upper- and lower-limb endothelial function during sitting in high- and low-fit young healthy males.The Journal of physiology · 2026Trial
- Long-Term Effect of Cocoa Extract Supplementation on Incident Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Trial
- The Impact of Cocoa Flavanols in Modulating Resting Cerebral Blood Flow During Prolonged Sitting in Healthy Young and Older Adults.Nutrients · 2025Trial
- Effects of cocoa extract supplementation and multivitamin/multimineral supplements on self-reported fractures in the Cocoa Supplement and Multivitamins Outcomes Study randomized clinical trial.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Trial
- Effect of cocoa extract supplementation on cognitive function: results from the clinic subcohort of the COSMOS trial.The American journal of clinical nutrition · 2024Trial
- Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial.The American journal of clinical nutrition · 2023Trial
- Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption.Proceedings of the National Academy of Sciences of the United States of America · 2023Trial
- Dietary Polyphenols as Modulators of Redox Signalling: From the Antioxidant-Pro-Oxidant Continuum to Clinical Translation (2015-2025).Current issues in molecular biology · 2026Review
- Adhering to dietary guidelines does not yield flavanol intake levels associated with beneficial cardiovascular effects.Food & function · 2026Article
- Development of a Sensory Evaluation Method for Polyphenols via Analysis of Chemical Structure and Organoleptic Properties: A Pilot Study.Foods (Basel, Switzerland) · 2026Article
- The Mitochondrial Guardian α-Amyrin Mitigates Alzheimer's Disease Pathology via Modulation of the DLK-SARM1-ULK1 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting the Gut Microbiota: Mechanistic Investigation of Polyphenol Modulation of the Gut-Brain Axis in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Flavonoids for gastrointestinal tract local and associated systemic effects: A review of clinical trials and future perspectives.Journal of advanced research · 2025Review
- The gut microbiome connects nutrition and human health.Nature reviews. Gastroenterology & hepatology · 2025Review
- Nutrition: A non-negligible factor in the pathogenesis and treatment of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Astringent flavanol fires the locus-noradrenergic system, regulating neurobehavior and autonomic nerves.Current research in food science · 2025Article
- A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor.Open medicine (Warsaw, Poland) · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Dietary flavanols are food constituents found in certain fruits and vegetables that have been linked to cognitive aging. Previous studies suggested that consumption of dietary flavanols might specifically be associated with the hippocampal-dependent memory component of cognitive aging and that memory benefits of a flavanol intervention might depend on habitual diet quality. Here, we tested these hypotheses in the context of a large-scale study of 3,562 older adults, who were randomly assigned to a 3-y intervention of cocoa extract (500 mg of cocoa flavanols per day) or a placebo [(COcoa Supplement and Multivitamin Outcomes Study) COSMOS-Web, NCT04582617]. Using the alternative Healthy Eating Index in all participants and a urine-based biomarker of flavanol intake in a subset of participants [n = 1,361], we show that habitual flavanol consumption and diet quality at baseline are positively and selectively correlated with hippocampal-dependent memory. While the prespecified primary end point testing for an intervention-related improvement in memory in all participants after 1 y was not statistically significant, the flavanol intervention restored memory among participants in lower tertiles of habitual diet quality or habitual flavanol consumption. Increases in the flavanol biomarker over the course of the trial were associated with improving memory. Collectively, our results allow dietary flavanols to be considered in the context of a depletion-repletion paradigm and suggest that low flavanol consumption can act as a driver of the hippocampal-dependent component of cognitive aging.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.