Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies

Gowri Raman*, Esther E. Avendano, Siyu Chen, Jiaqi Wang, Julia Matson, Bridget Gayer, Janet A. Novotny, Aedín Cassidy

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

61 Citations (Scopus)
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Background: Although available data suggest that some dietary flavan-3-ol sources reduce cardiometabolic risk, to our knowledge no review has systematically synthesized their specific contribution. 

Objective: We aimed to examine, for the first time, if there is consistent evidence that higher flavan-3-ol intake, irrespective of dietary source, reduces cardiometabolic risk. 

Methods: MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau abstracts were searched for prospective cohorts and randomized controlled trials (RCTs) published from 1946 to March 2019 on flavan-3-ol intake and cardiovascular disease (CVD) risk. Random-effects models meta-analysis was used. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach assessed the strength of evidence. 

Results: Of 15 prospective cohorts (23 publications), 4 found highest compared with lowest habitual intakes of flavan-3-ols were associated with a 13% reduction in risk of CVD mortality and 2 found a 19% reduction in risk of chronic heart disease (CHD) incidence. Highest compared with lowest habitual intakes of monomers were associated with a reduction in risk of type 2 diabetes mellitus (T2DM) (n = 5) and stroke (n = 4) (10% and 18%, respectively). No association was found for hypertension. Of 156 RCTs, flavan-3-ol intervention resulted in significant improvements in acute/chronic flow-mediated dilation (FMD), systolic (SBP) and diastolic blood pressure (DBP), total cholesterol (TC), LDL and HDL cholesterol, triglycerides (TGs), hemoglobin A1c (HbA1c), and homeostasis model assessment of insulin resistance (HOMA-IR). All analyses, except HbA1c, were associated with moderate/high heterogeneity. When analyses were limited to good methodological quality studies, improvements in TC, HDL cholesterol, SBP, DBP, HOMA-IR, and acute/chronic FMD remained significant. In GRADE evaluations, there was moderate evidence in cohort studies that flavan-3-ol and monomer intakes were associated with reduced risk of CVD mortality, CHD, stroke, and T2DM, whereas RCTs reported improved TC, HDL cholesterol, SBP, and HOMA-IR. 

Conclusions: Available evidence supports a beneficial effect of flavan-3-ol intake on cardiometabolic outcomes, but there was considerable heterogeneity in the meta-analysis. Future research should focus on an integrated intake/biomarker approach in cohorts and high-quality dose-response RCTs. Th

Original languageEnglish
Pages (from-to)1067-1078
Number of pages12
JournalAmerican Journal of Clinical Nutrition
Issue number5
Early online date26 Aug 2019
Publication statusPublished - 01 Nov 2019

Bibliographical note

Funding Information:
Supported by International Life Sciences Institute North America.

Publisher Copyright:
Copyright © American Society for Nutrition 2019.

Copyright 2019 Elsevier B.V., All rights reserved.


  • blood pressure
  • cardiovascular
  • diabetes
  • flavan-3-ols
  • flavonoids

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics


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