Cardiology · Medical Literature
Dietary intakes of anthocyanins and cardiometabolic health: a systematic review and meta-analysis of randomized trials and prospective cohort studies in healthy participants.
Abstract
Meta-analyses support anthocyanins' cardiometabolic benefits in heterogeneous populations (including diseased), but efficacy in healthy participants remains unknown. Across prospective cohorts, and randomized controlled trials (RCTs; ≥50 mg/d anthocyanins), we assessed impacts on surrogate cardiometabolic biomarkers and clinical endpoints. Database searches (PubMed, Cochrane Central, Commonwealth Agricultural Bureau, and Web of Science) identified publications (1946-September 2024) that reported anthocyanin intake (or data, from which anthocyanin intake could be calculated), and cardiovascular disease (CVD) risk or cardiometabolic biomarkers. Random-effects meta-analysis and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) assessment followed. Across 18 cohorts in 27 publications, highest compared with lowest habitual anthocyanin intake showed a risk reduction of 26% CVD incidence (4 studies), 18% myocardial infarction (MI, 5 studies), 11% type 2 diabetes mellitus (T2DM, 8 studies), 9% CVD mortality (10 studies), and 8% hypertension risk (6 studies). GRADE identified moderate evidence for CVD/MI. Stroke risk was unaffected. Across 65 RCTs, chronic anthocyanins (≥1 d) improved flow-mediated dilation (FMD) (net change: 1.41%; 95% confidence interval: 0.90%, 1.91%), acute anthocyanins (≤1 d) improved FMD (1.50%; 1.16%, 1.84%), and insulin concentrations (-2.24 pmol/L; -4.22, -0.27). GRADE identified strong evidence for acute FMD and moderate for chronic FMD. Lipids, blood pressure, glucose, and homeostatic model assessment for insulin resistance were unaffected. In the subanalysis, by anthocyanin type, cyanidin improved chronic FMD (1.62%; 1.21%, 2.04%), whereas delphinidin improved acute FMD (1.69%; 1.20%, 2.18%), chronic FMD (1.59%; 1.21%, 2.04%), chronic pulse wave velocity (-0.33; -0.62, -0.05), insulin (-2.32 pmol/L; -4.39, -0.26), and triglycerides (-0.10 mmol/L; -0.17, -0.03). Higher anthocyanin intake lowers CVD, MI, hypertension, and T2DM risk in cohorts, whereas RCTs show that dietarily achievable anthocyanin intakes (as low as 50 mg/d) improve atherosclerosis and metabolic syndrome biomarkers in healthy participants. These findings provide comprehensive unifying evidence that supports the inclusion of anthocyanins within evidence-based nutrition guidelines for CVD prevention. This review was registered at PROSPERO database as CRD420251015416.
Clinical relevance
In healthy, disease-free individuals, does higher dietary anthocyanin intake — assessed via prospective cohort studies and RCTs using ≥50 mg/day — reduce CVD risk and improve surrogate cardiometabolic biomarkers? __SNAPSHOT__ {"studyDesign":"Systematic review and meta-analysis of prospective cohort studies and randomized controlled trials (RCTs)","setting":"Multi-database search (PubMed, Cochrane Central, Commonwealth Agricultural Bureau, Web of Science); publications from 1946 to September 2024; international scope","sampleSize":"Cohort arm: 18 cohorts across 27 publications; RCT arm: 65 RCTs; individual participant counts not reported in available abstract","population":"Healthy, disease-free adults; cohort studies assessed habitual dietary anthocyanin intake; RCTs required ≥50 mg/day anthocyanin intervention dose","intervention":"Higher habitual anthocyanin intake (cohorts: highest vs. lowest category); anthocyanin-rich foods or supplements ≥50 mg/day, administered both acutely (≤1 day) and chronically (≥1 day) in RCTs","comparator":"Lowest habitual anthocyanin intake category (cohorts); placebo or control (RCTs)","primaryOutcome":"CVD incidence, MI, T2DM, CVD mortality, hypertension risk (cohort studies); flow-mediated dilation (FMD), lipids, blood pressure, glucose, insulin, and other cardiometabolic biomarkers (RCTs)","followUp":"Not reported (varied across included cohort studies and RCTs)","fundingSource":"Not reported in available abstract or excerpts"}
Key findings
COHORT STUDIES: Across 18 prospective cohort studies (27 publications), highest versus lowest habitual anthocyanin intake was associated with the following risk reductions: 26% lower CVD incidence (4 studies), 18% lower MI risk (5 studies), 11% lower T2DM risk (8 studies), 9% lower CVD mortality (10 studies), and 8% lower hypertension risk (6 studies). GRADE rated evidence as moderate for CVD incidence and MI. No significant association was found for stroke risk. Absolute risk differences, confidence intervals, and p-values for cohort outcomes were not reported in the available abstract. RCTs — VASCULAR FUNCTION: Across 65 RCTs, chronic anthocyanin intake (≥1 day) improved FMD by a net change of +1.41% (95% CI: 0.90%, 1.91%); acute anthocyanin intake (≤1 day) improved FMD by +1.50% (95% CI: 1.16%, 1.84%). GRADE rated evidence as strong for acute FMD and moderate for chronic FMD. RCTs — INSULIN: Acute anthocyanin intake was associated with a reduction in insulin concentrations of −2.24 pmol/L (95% CI: −4.22, −0.27 pmol/L). RCTs — ANTHOCYANIN SUBTYPE ANALYSES: In subgroup analyses by anthocyanin type, cyanidin improved chronic FMD (+1.62%; 95% CI: 1.21%, 2.04%); delphinidin improved acute FMD (+1.69%; 95% CI: 1.20%, 2.18%), chronic FMD (+1.59%; 95% CI: 1.21%, 2.04%), pulse wave velocity (−0.33; 95% CI: −0.62, −0.05), insulin (−2.32 pmol/L; 95% CI: −4.39, −0.26), and triglycerides (−0.10 mmol/L; 95% CI: −0.17, −0.03). RCTs — NULL FINDINGS (BIAS-RESTRICTED SENSITIVITY ANALYSIS): In sensitivity analyses restricted to low-risk-of-bias RCTs (≥3 low-bias studies per outcome), no significant difference was observed for BMI, body fat, body weight, DBP, glucose, HbA1c, HOMA-IR, HDL cholesterol, hsCRP, LDL cholesterol, TNF-α, SBP, total cholesterol, triglycerides, or waist circumference. NNT/NNH: Not calculable from available data.
Practice implications
This is the first systematic review and meta-analysis to integrate both prospective cohort and RCT evidence specifically in healthy, disease-free populations to evaluate anthocyanin intake and cardiometabolic outcomes. The cohort data provide moderate-certainty evidence that higher habitual anthocyanin intake is associated with lower risks of CVD incidence and MI, with smaller associations for T2DM, CVD mortality, and hypertension. However, as observational associations, these cannot establish causality and are subject to residual confounding from other dietary and lifestyle factors. The RCT data demonstrate consistent and relatively robust improvements in endothelial function (FMD), supported by strong-to-moderate GRADE evidence, and modest effects on insulin and — in delphinidin-specific subanalyses — arterial stiffness and triglycerides. Critically, when analyses were restricted to low-risk-of-bias RCTs only, no significant effects were demonstrated on any traditional cardiometabolic biomarkers including blood pressure, lipids, glucose, HbA1c, HOMA-IR, or inflammatory markers. This is a clinically important finding that tempers overinterpretation of the overall (higher-bias) pooled results. The populations best represented are healthy adults consuming anthocyanin-rich diets or ≥50 mg/day supplemental anthocyanins; populations with established cardiometabolic disease, older adults, specific ethnic groups, and those with low dietary anthocyanin exposures are not adequately characterized by this review. The clinical magnitude of a ~1.4–1.5% absolute FMD improvement is consistent with prior estimates suggesting meaningful CVD risk reduction at the population level, though its translation to individual clinical outcomes requires confirmation. An optimal dose, anthocyanin type, food source, and duration of intake to achieve clinically significant benefit remain undefined. Practice should not change on the basis of this review alone; rather, findings should inform the design of adequately powered, longer-duration RCTs. Only the abstract and select article excerpts were available for review; full methodology and supplemental data were not independently assessed. __LIMITATIONS__ Surrogate endpoints only in the RCT arm: no RCT-level data on hard clinical outcomes (MI, stroke, CVD death) in this review.,When restricted to low-risk-of-bias RCTs, effects on all traditional cardiometabolic biomarkers (blood pressure, lipids, glucose, HOMA-IR, hsCRP) were null — suggesting that positive findings in the full pooled RCT analysis are largely driven by higher-bias studies.,High proportion of low-quality RCTs: 48% of blood pressure trials and 46% of HDL trials were classified as low quality.,Only 65 RCTs included (vs. 156 in the parallel flavan-3-ol meta-analysis by same group), limiting sensitivity analyses for dose, duration, and dietary form.,In 50 of 65 RCTs, anthocyanin content was estimated via a standardized method rather than independently quantified — introducing exposure measurement uncertainty.,Cohort analyses used highest-vs.-lowest intake categories, which may introduce bias when anthocyanin intake distributions vary substantially across cohorts.,Dietary anthocyanin assessments in cohort studies relied on food frequency questionnaires or diet records — subject to measurement error and residual dietary confounding.,Considerable heterogeneity in CVD incidence cohort results, attributable to differences in anthocyanin intake ranges and follow-up duration.,Presence of other bioactive compounds (flavonoids, phenolic acids) co-occurring in anthocyanin-rich foods may confound observed effects in both cohorts and RCTs.,Small average RCT sample sizes limit power to detect modest effects on metabolic outcomes.,Funding source not reported in available text; potential industry relationships of individual study authors cannot be assessed from this summary alone.,Only the abstract and published excerpts were reviewed; full methodological detail was unavailable. __BOTTOM_LINE_CATEGORY__ potentially_practice_informing __BOTTOM_LINE__ In healthy, disease-free individuals, higher habitual anthocyanin intake is associated with moderate-certainty reductions in CVD incidence and MI risk (18–26%) in cohort studies, and with consistent improvements in endothelial function (FMD ~+1.4–1.5%) in RCTs graded as strong-to-moderate evidence. However, when RCT analyses are restricted to low-risk-of-bias studies, no significant effects on blood pressure, lipids, glucose, or insulin resistance are demonstrated, substantially limiting the mechanistic conclusions that can be drawn. Clinicians may reasonably encourage anthocyanin-rich dietary patterns as part of a heart-healthy diet, but current evidence is insufficient to support specific anthocyanin supplementation targets or to modify practice beyond general dietary guidance.