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.

Allium Flavonols: Health Benefits, Molecular Targets, and Bioavailability

“…Cardiovascular disease (CVD) is the leading cause of deaths worldwide. A number of recent meta-analyses of prospective cohort studies have indicated that individuals with the highest flavonoid intakes have lower relative risk of mortality from CVD and all-causes compared with that of individuals with the lowest intakes [111][112][113]. Several studies evidenced the beneficial effects of Allium flavonols on the cardiovascular system via their regulatory effects on platelet aggregation [83,84,96], atherogenesis [78], thrombotic activities [79], endothelial function [81], hypertension [77,82], lipid metabolism [77], and oxidative stress [42] (Table 3).…”

Flavonoids and Mitochondria: Activation of Cytoprotective Pathways?

“…Indeed, it has been demonstrated that flavonoids, i.e., suppress the expression of pro-inflammatory mediators (NF-κβ cascade), have vasodilator activity, improve vascular endothelial function, protect cells against insulin resistance, regulate proliferation, and suppress neuroinflammation by reducing cytokine release [19][20][21][22][23][24][25][26]. As shown in many studies, the consumption of flavonoid-rich foods significantly decreases the possibility of cardiovascular disease development [11,[27][28][29]. A recent meta-analysis demonstrated that dietary intake of anthocyanins reduced the risk of coronary heart disease and cardiovascular disease mortality [30].…”

Preventive Role of Diet Interventions and Dietary Factors in Type 2 Diabetes Mellitus: An Umbrella Review

“…Four [ 35 , 36 , 37 , 38 ] and one [ 39 ] SRMA found that high intake of magnesium and flavonoid significantly decreased the risk of T2DM with pooled RRs ranging from 0.77 (95% CI: 0.72, 0.84) to 0.83 (95% CI: 0.80, 0.86) for high intake and pooled RR of 0.89 (95% CI: 0.82, 0.96) for dose response analysis ( Figure 3 A,B). However, one SRMA that assessed the effect of flavan-3-osl, a subclass of dietary flavonoid did not find the significant benefit of this subclass for the prevention of T2DM [ 40 ]. According to n-3PUFA, results from all three SRMAs did not show the significant benefit of a high intake of n-3 PUFA in prevention of T2DM [ 41 , 42 , 43 ].…”

“…In contrast, Mediterranean (n = 4) and DASH diet showed protective effects on T2DM with the pooled RRs ranging from 0.77 (95% CI: 0.66, 0.89) [47] analysis ( Figure 3A,B). However, one SRMA that assessed the effect of flavan-3-osl, a subclass of dietary flavonoid did not find the significant benefit of this subclass for the prevention of T2DM [40]. According to n-3PUFA, results from all three SRMAs did not show the significant benefit of a high intake of n-3 PUFA in prevention of T2DM [41][42][43].…”