Isoquercetin (Quercetin-3-O-glucoside)

Isoquercetin (quercetin-3-O-glucoside) is a water-soluble flavonoid glycoside with superior bioavailability compared to quercetin aglycone. It demonstrates anti-thrombotic and anti-inflammatory properties by modulating coagulation pathways and reducing inflammatory markers.

Origin & History

Isoquercetin, also known as quercetin-3-O-glucoside, is a flavonoid glycoside belonging to the flavonol class that occurs naturally in onions, apples, and berries. It is typically extracted from plant sources through solvent extraction or enzymatic hydrolysis to isolate the glucoside form. This compound serves as a more bioavailable derivative of the aglycone quercetin.

Historical & Cultural Context

No specific historical or traditional medicine uses for isoquercetin (quercetin-3-O-glucoside) were identified in the available research sources. While the parent compound quercetin has been studied in modern contexts, traditional system references for the glucoside form are lacking.

Health Benefits

• Reduces thromboinflammation markers in sickle cell disease patients, though primary outcome (P-selectin) showed no significant change in phase 2 trial (n=46, PMID: 38157227)
• Improves coagulation markers and reduces thrombosis risk in advanced cancer patients by targeting extracellular protein disulfide isomerase (PDI) (PMID: 30652973)
• Decreases platelet aggregation and tissue factor expression based on secondary outcomes in clinical trials
• Shows potential anti-cancer effects through cooperative tumor growth suppression when combined with zafirlukast
• Demonstrates improved bioavailability compared to standard quercetin based on phase 1 pharmacokinetic studies (NCT01722669)

How It Works

Isoquercetin modulates thromboinflammatory pathways by reducing expression of adhesion molecules and coagulation factors. The compound undergoes hydrolysis by lactase phlorizin hydrolase in the small intestine, releasing bioactive quercetin that inhibits phospholipase A2 and cyclooxygenase enzymes. It also suppresses nuclear factor-κB (NF-κB) signaling, reducing production of pro-inflammatory cytokines and tissue factor expression.

Scientific Research

A phase 2 randomized controlled trial (NCT04514510) in 46 adults with sickle cell disease tested 1000 mg daily isoquercetin versus placebo for 28-35 days, showing improvements in secondary thromboinflammation biomarkers but not the primary outcome (PMID: 38157227). Additional clinical evidence includes a trial in advanced cancer patients demonstrating PDI inhibition and improved coagulation markers (NCT02195232, PMID: 30652973). Limited large-scale RCTs exist specifically for isoquercetin, though related quercetin meta-analyses show effects on blood pressure and insulin.

Clinical Summary

A phase 2 randomized controlled trial (n=46) in sickle cell disease patients found isoquercetin reduced thromboinflammation markers, though the primary endpoint of P-selectin reduction was not statistically significant. Clinical studies in advanced cancer patients demonstrated improvements in coagulation markers and reduced thrombosis risk through targeting extracellular protein disulfide isomerase. The evidence base remains limited with small sample sizes, requiring larger trials to establish definitive therapeutic benefits. Most studies focus on specific disease populations rather than healthy individuals.

Nutritional Profile

{"macronutrients": {"carbohydrates": "Not applicable", "proteins": "Not applicable", "fats": "Not applicable"}, "micronutrients": {"vitamins": "Not applicable", "minerals": "Not applicable"}, "bioactive_compounds": {"isoquercetin": "Concentration varies depending on source, typically found in amounts ranging from 0.1% to 0.5% in certain fruits and vegetables", "quercetin": "Isoquercetin is a glycoside form of quercetin, which is more bioavailable than quercetin itself"}, "bioavailability_notes": "Isoquercetin has higher bioavailability compared to quercetin aglycone due to its glycoside form, which enhances absorption in the human body."}

Preparation & Dosage

Clinically studied dose: 1000 mg once daily as oral capsules for 28-35 days, using pharmaceutical-grade isoquercetin. No standardized extract concentrations or alternative formulations were specified in available trials. Consult a healthcare provider before starting any new supplement.

Synergy & Pairings

Quercetin, Vitamin C, Bromelain, Zafirlukast, Rutin

Safety & Interactions

Isoquercetin appears well-tolerated in clinical trials with minimal reported adverse events at therapeutic doses. As a flavonoid, it may interact with anticoagulant medications like warfarin due to its effects on coagulation pathways, requiring monitoring of INR levels. Potential interactions exist with cytochrome P450 enzymes, particularly CYP3A4 and CYP2C9, affecting metabolism of certain medications. Safety during pregnancy and lactation has not been established, and use should be avoided without medical supervision.