Hermetica Superfood Encyclopedia
The Short Answer
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.
CategoryNamed Bioactive Compounds
GroupCompound
Evidence LevelModerate
Primary Keywordisoquercetin benefits
Synergy Pairings3
Isoquercetin (Quercetin-3-O-glucoside) — botanical close-up
Health Benefits
Origin & History
Natural habitat
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.
“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.”Traditional Medicine
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.
Preparation & Dosage
Traditional preparation
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.
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."}
How It Works
Mechanism of Action
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.
Clinical Evidence
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.
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.
Synergy Stack
Hermetica Formulation Heuristic
Also Known As
Quercetin-3-O-glucosideQuercetin 3-glucosideQuercetin glucosideQ3GIsoquercitrinHirsutrinQuercetin-3-β-D-glucoside3-O-β-D-glucopyranosyl quercetin
Frequently Asked Questions
What is the difference between isoquercetin and regular quercetin?
Isoquercetin is quercetin bound to glucose, making it significantly more water-soluble and bioavailable than quercetin aglycone. Studies show isoquercetin achieves 20-fold higher plasma levels compared to regular quercetin supplementation.
What dose of isoquercetin was used in sickle cell disease studies?
The phase 2 trial in sickle cell disease patients used specific dosing protocols that reduced thromboinflammation markers. However, the exact dosage and duration details require consultation of the full study protocol (PMID: 38157227).
Can isoquercetin help prevent blood clots?
Clinical studies in advanced cancer patients show isoquercetin improves coagulation markers and may reduce thrombosis risk. However, it should not replace prescribed anticoagulant medications and requires medical supervision for clot prevention.
Is isoquercetin safe to take with blood thinners?
Isoquercetin may enhance anticoagulant effects due to its impact on coagulation pathways. Patients taking warfarin, heparin, or other blood thinners should consult healthcare providers and may require INR monitoring.
What foods contain natural isoquercetin?
Isoquercetin occurs naturally in onions (particularly red varieties), apples with skin, and certain berries. However, dietary sources provide much lower concentrations than standardized supplements used in clinical research.
How does isoquercetin work differently in cancer patients versus sickle cell disease patients?
In cancer patients, isoquercetin targets extracellular protein disulfide isomerase (PDI) to reduce thrombosis risk and improve coagulation markers, addressing cancer-associated hypercoagulability. In sickle cell disease, isoquercetin reduces thromboinflammation markers, though a phase 2 trial showed it did not significantly reduce P-selectin levels as a primary outcome. These different mechanisms reflect how the compound's anti-inflammatory and anticoagulant properties address distinct pathophysiological processes in each condition.
What does the clinical evidence tell us about isoquercetin's effectiveness for thrombosis prevention?
Isoquercetin shows promise in reducing thrombosis risk through multiple mechanisms: it decreases platelet aggregation, reduces tissue factor expression, and improves coagulation markers in advanced cancer patients. However, evidence in sickle cell disease is more limited—while it reduced thromboinflammation markers in a phase 2 trial (n=46), it did not achieve statistical significance on the primary outcome of P-selectin reduction. Overall, evidence is strongest for thrombosis prevention in cancer-related hypercoagulability rather than sickle cell disease.
Should people taking isoquercetin be monitored for any specific blood markers?
Patients taking isoquercetin for thrombosis prevention may benefit from monitoring coagulation markers (such as P-selectin, tissue factor, and platelet aggregation parameters) to assess therapeutic response. Those with cancer or sickle cell disease should have baseline and periodic coagulation testing, especially if combining isoquercetin with anticoagulant medications, to ensure safe and effective management. Regular monitoring is particularly important given that clinical trials have used these biomarkers to evaluate isoquercetin's efficacy.
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