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

Abstract

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. This review was registered at www.crd.york.ac.uk/PROSPERO/ as CRD42018035782.

Keywords: blood pressure; cardiovascular; diabetes; flavan-3-ols; flavonoids.

FIGURE 1

Study flow diagram depicting the review process. CAB, Commonwealth Agricultural Bureau; RCT, randomized controlled trial.

FIGURE 2

The effect of flavan-3-ols on cardiometabolic health outcomes from prospective cohort studies. Data reported are RRs and 95% CIs for a fully adjusted random-effects meta-analysis model for each outcome. *Hypertension outcome included men and women subpopulations from the same cohort from 1 article that reported total flavan-3-ol intake and blood pressure. CHD, chronic heart disease; CVD, cardiovascular disease.

FIGURE 3

The effect of flavan-3-ols on cardiometabolic risk biomarkers from RCTs. Data estimates are from meta-analysis of the net change and 95% CI for each outcome. DBP, diastolic blood pressure; FBG, fasting blood glucose; FMD, flow-mediated dilation; HbA1c, hemoglobin A1c; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; RCT, randomized controlled trial; SBP, systolic blood pressure; TC, total cholesterol; TG, triglyceride.