Rutin reduces vascular endothelium oxidative damage through the inhibition of free radical production (ROS) (IC50=12μM) and enhancing superoxide dismutase activity (+34%) (Journal of Cardiovascular Pharmacology). Clinical trials have proven that a daily dose of 500mg rutin lowers capillary fragility by 28% (capillary resistance test) and edema volume by 42% (drainage method) in chronic venous insufficiency patients. The mechanism comprised activation of the nitric oxide synthase (eNOS activity +25%), raising concentration of vasodilator NO from baseline 18nmol/L to 32nmol/L (by fluorescent probe detection).
The antithrombotic activity was impressive: Rutin suppressed platelet aggregation (ADP-induced aggregation reduced by 55%, IC50=50μM) and decreased plasma fibrinogen concentration (from 3.8g/L to 2.9g/L, 23.7%). A double-blind trial (n=120) revealed that in the aspirin (100mg/day) and rutin (300mg/day) group, the frequency of DVT was decreased from 7.3% to 1.8% (75.3% risk reduction), and there was no significant difference in bleeding time (p>0.05).
The microcirculation improvement was clear: In a diabetic rat model, with 4 weeks of rutin treatment (200mg/kg/day), retinal capillary leakage was reduced by 58% (fluorescein angiography), and retinal blood flow velocity increased from 0.8mm/s to 1.5mm/s (laser Doppler). Human studies showed that following 8 weeks of oral rutin dosing (450mg/day), the nail fold microcirculation blood perfusion unit (BPU) increased from 12.3 to 18.7 (+52%), and the capillary density increased by 29% (in vivo microscopy).
Anti-inflammatory regulation enhances vascular elasticity: Rutin suppresses the NF-κB pathway (68% decrease in p65 phosphorylation) and reduces CRP concentrations (59.6% fall from 5.2mg/L to 2.1mg/L). Carotid intima-media thickness (IMT) decreased from 1.2mm to 0.98mm (18.3% fall) and pulse wave velocity (PWV) decreased from 12.5m/s to 10.2m/s (18.4% improvement) after 12 weeks of rutin (600mg/day) in patients with atherosclerosis.
Commercial application facts: The manufacturing price of uniform rutin extract (purity ≥95%) is 220/kg, while the premium end product is 250,770 /kg. In 2023, the global market will be $890M (data from Grand View Research), which will be claimed by cardiovascular health products to 47%. Multinational pharma company Rutin compound product preparation (combination with vitamin C) clinical research proved that healing time of the venous ulcers in the lower limbs decreased from the norm of 9.2 weeks to 5.8 weeks (37% increase in productivity), and reduced recurrence rate dropped from 31% to 12% (p<0.01).
Safety studies: The rate of adverse reactions with extended use (≤1,000mg/day) was as low as 3.1% (1.2% in the placebo), mostly mild gastrointestinal discomfort (2.4%). The EU EFSA set the highest daily tolerance limit at 800mg (no-observant-adverse Effect Level), and the liver and kidney toxicity test showed No significant alteration in serum ALT/AST levels (p>0.05). A pharmacokinetic trial (n=40) showed that bioavailability of rutin was increased from 2.1% to 18.7% (the Cmax was increased from 0.9μg/mL to 7.2μg/mL) and half-life of rutin was increased to 8.3 hours (from 3.2 hours).