Flavonoids

1. What This Class of Substances Is

Flavonoids are secondary plant compounds with a phenolic structure. They include subgroups such as flavanols (e.g., in cocoa), flavonols (e.g., quercetin), anthocyanins (e.g., in berries), flavones, and isoflavones. These compounds are often present in glycosidic form and are metabolised by gut microbiota after ingestion. Their bioavailability varies widely: some, such as epicatechin from cocoa, achieve measurable plasma levels, while others, like curcumin, are barely absorbed. Natural sources include fruit, vegetables, tea, spices, and extracts such as grape seed or pine bark extract.

The effects in humans are difficult to measure because flavonoids undergo complex metabolism. Laboratory and animal studies often demonstrate direct antioxidant or anti-inflammatory effects, which in the human body may be overshadowed by metabolites, interactions with the microbiome, or systemic regulatory mechanisms. Controlled studies therefore typically use biomarkers (e.g., endothelial function, inflammatory parameters) or clinical endpoints (e.g., blood pressure, insulin resistance). The applicability of in vitro results is limited.

2. Which Materials Are Included

All substances in the database for which this mechanism of action is described—ordered by the extent of human testing. The numbers represent studies per type of investigation.

3. How Robust the Evidence Is

Cocoa flavanols, quercetin, and anthocyanins are the best supported by over 100 controlled human studies. Green tea (EGCG), turmeric (curcumin), and milk thistle (silymarin) follow with 10–14 controlled studies. Substances such as humic acid complexes, frankincense, or astaxanthin show almost exclusively laboratory or animal data. The level of evidence often correlates with the availability of standardised extracts and research funding, not necessarily with biological relevance.

Flavonoids share fundamental mechanisms of action, such as radical-scavenging properties, modulation of enzymes (e.g., COX, LOX), or signalling pathways (e.g., NF-κB). Extrapolating findings is plausible when substances form similar metabolites (e.g., methylated or sulphated derivatives) or target the same structures. However, pharmacokinetics, tissue penetration, and interactions with the microbiome differ. For example: quercetin and epicatechin both affect vascular function, but with varying potency and duration.

4. Key Human Studies

• 1 Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomised, controlled, double-blind, crossover intervention study (2011) — Cocoa flavanols
• 2 Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol da (2008) — Cocoa flavanols
• 3 Flavonoid-rich dark chocolate improves endothelial function and increases plasma epicatechin concentrations in healthy adults (2004) — Cocoa flavanols
• 4 Effects of Quercetin on Blood Pressure: A Systematic Review and Meta-Analysis of Randomised Controlled Trials (2016) — Quercetin
• 5 Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food-Grade Lecithin (2019) — Quercetin
• 6 Acute intake of quercetin from onion skin extract does not influence postprandial blood pressure and endothelial function in overweight-to-obese adults (2017) — Quercetin
• 7 Enhanced task-related brain activation and resting perfusion in healthy older adults following chronic blueberry supplementation (2017) — Anthocyanins (berries)
• 8 Anthocyanins in the Management of Metabolic Syndrome: A Pharmacological and Biopharmaceutical Review (2018) — Anthocyanins (berries)
• 9 Blackberry Consumption Increases Fat Oxidation and Improves Insulin Sensitivity in Overweight and Obese Males (2018) — Anthocyanins (berries)
• 10 Dietary Factors and Supplements Influencing Prostate-Specific Antigen (PSA) Concentrations in Men with Prostate Cancer and Increased Cancer Risk: An Evidence Review (2020) — Green tea and EGCG
• 11 The combined effect of green tea and α-glucosyl hesperidin in preventing obesity: a randomised, placebo-controlled clinical trial (2021) — Green tea and EGCG
• 12 Efficacy and safety of dietary polyphenols in rheumatoid arthritis: A systematic review and meta-analysis of 47 randomised controlled trials (2023) — Green tea and EGCG
• 13 Further Evidence of Benefits to Mood and Working Memory from Lipidated Curcumin in Healthy Older People: A 12-Week, Double-Blind, Placebo-Controlled Trial (2020) — Turmeric and curcumin
• 14 Polyphenol Intervention Ameliorates Non-Alcoholic Fatty Liver Disease: An Updated Comprehensive Systematic Review (2024) — Turmeric and curcumin
• 15 Effects of Dietary Components on Mast Cells: Potential Use as Nutraceuticals for Allergies? (2023) — Turmeric and curcumin
• 16 Milk thistle (Silybum marianum): A concise overview of its chemistry, pharmacological, and nutraceutical uses in liver diseases (2018) — Milk thistle (silymarin)
• 17 Topical silymarin administration for the prevention of acute radiodermatitis in breast cancer patients: A randomised, double-blind, placebo-controlled clinical trial (2019) — Milk thistle (silymarin)
• 18 Silibinin and SARS-CoV-2: Dual targeting of host cytokine storm and viral replication machinery for clinical management of COVID-19 patients (2020) — Milk thistle (silymarin)
• 19 Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double-blind, randomised, placebo-controlled trial examining metabolic parameters (2009) — Grape seed extract (OPC)
• 20 Pleiotropic benefits of monomeric and oligomeric flavanols on vascular health: a randomised, controlled clinical pilot study (2011) — Grape seed extract (OPC)
• 21 The effect of red grape seed extract on serum paraoxonase activity in patients with mild to moderate hyperlipidaemia (2016) — Grape seed extract (OPC)
• 22 Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence (2013) — Resveratrol
• 23 A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination (2015) — Resveratrol
• 24 A placebo-controlled, pseudo-randomised, crossover trial of botanical agents for Gulf War Illness: Resveratrol (Polygonum cuspidatum), luteolin, and other compounds (2021) — Resveratrol

5. Open Questions

• Standardisation: Which extract qualities (e.g., degree of oligomerisation in cocoa flavanols) are critical for reproducible effects?
• Dose-response: Are there clinically relevant dose thresholds for less studied compounds (e.g., humic acid complexes)?
• Combinations: How do flavonoids interact with other polyphenols or micronutrients (e.g., vitamin C) in vivo?
• Long-term effects: What chronic effects do flavonoids exhibit with regular intake over years?
• Microbiome: How do individual gut bacteria influence the metabolism and efficacy of specific flavonoids?
• Target groups: Which patient groups (e.g., those with a predisposition to inflammation) benefit most from specific flavonoids?

See also the Gap List covering all substances. This page is recalculated with each harvest.