Flavonoids

Flavonoids are a large subclass of plant polyphenols with a 15-carbon benzo-γ-pyrone backbone, spanning six subfamilies: flavonols (quercetin, kaempferol; onions, kale), flavan-3-ols (catechins, epicatechins; tea, cocoa), anthocyanins (berries, red cabbage), flavanones (naringenin; citrus), flavones (luteolin, apigenin; herbs), and isoflavones (genistein; soy). Key mechanisms: scavenging reactive oxygen species, inhibiting NF-κB inflammatory signalling, activating Nrf2, and — for flavan-3-ols — raising nitric-oxide bioavailability to improve endothelial function. Observational evidence consistently links higher intake to lower cardiovascular and all-cause mortality: a dose-response meta-analysis of 39 cohorts (1.5 million individuals; Micek et al., 2021) found inverse associations with cardiovascular disease risk, strongest for anthocyanins and flavan-3-ols. A 2025 UK Biobank analysis (Parmenter, Cassidy et al.) found subclass diversity — not quantity alone — associated with 6–20% lower risk of all-cause mortality, CVD, type 2 diabetes, and neurodegenerative disease. RCT evidence is limited: COSMOS (Sesso, Manson et al., 2022) tested 500 mg/day cocoa flavanols in 21,442 older US adults; total cardiovascular events were not significantly reduced, but cardiovascular death fell 27%. COSMOS-Mind (Baker et al., 2022) found no cognitive benefit over three years. Bioavailability varies markedly by subclass and individual (partly gut-microbiome-dependent); isolated supplementation has not replicated benefits observed with whole-food dietary patterns.