Intervention Summary
Quercetin is a flavonoid polyphenol with dual anti-inflammatory and metal-chelating properties. Inhibits NF-kB p65 and IL-8 signaling pathways. Chelates transition metals (Cu2+, Fe2+/Fe3+) to reduce Fenton-mediated oxidative damage. Gut bacteria metabolize quercetin into bioactive phenolic acids, creating a bidirectional interaction between supplementation and microbiome ecology.
Evidence
- Inflammation: RCTs demonstrate reduced CRP and TNF-alpha with quercetin 500-1000mg/day in metabolic syndrome and inflammatory conditions
- Cardiovascular: Reduces blood pressure (meta-analysis: -3.0 mmHg systolic), LDL oxidation, and endothelial dysfunction
- Immune function: Reduces upper respiratory infection incidence and severity in athletes under physical stress
- Microbiome interaction: Quercetin glycosides are hydrolyzed by gut bacterial beta-glucosidases; aglycone is further metabolized to 3,4-dihydroxyphenylacetic acid by Eubacterium and Clostridium species
Mechanism
- NF-kB inhibition: Quercetin blocks IKK-mediated phosphorylation of IkB-alpha, preventing NF-kB p65 nuclear translocation and downstream inflammatory gene expression
- Metal chelation: Binds Cu2+ and Fe2+/Fe3+ at the catechol and carbonyl groups, reducing free metal availability for Fenton reactions and pathogen metal acquisition
- Microbiota modulation: Acts as a prebiotic-like substrate for beneficial bacteria; increases Bifidobacterium and Lactobacillus while reducing Enterobacteriaceae in animal models
- Mast cell stabilization: Inhibits histamine release from mast cells, relevant to conditions with mast cell activation
Clinical Context
Quercetin has poor oral bioavailability (~2%) unless formulated with absorption enhancers (bromelain, vitamin C, phytosomal delivery). Typical dose: 500-1000mg/day in divided doses. The metal-chelating property makes it particularly relevant in conditions where transition metal excess drives pathology. Safe and well-tolerated; rare reports of headache at high doses.