Thrombolytic Effects of Nattokinase In Vivo in a Carrageenan-Induced Rat Thrombosis Model

This animal study evaluated the in vivo thrombolytic activity of nattokinase in a carrageenan-induced rat tail thrombosis model, comparing high-dose nattokinase against a positive control (vermis kinase) and saline, measuring fibrin degradation products (FDP) and D-dimer as markers of thrombolysis.

High-dose nattokinase produced partial thrombolysis with FDP and D-dimer levels comparable to the positive control and significantly higher than saline — demonstrating in vivo fibrinolytic activity in a validated rodent thrombosis model.

The carrageenan-induced thrombosis model is a standard pharmacological validation tool for fibrinolytic agents. However, it uses a highly artificial route of thrombus induction (subcutaneous carrageenan injection to the tail) that differs mechanistically from spontaneous coronary or cerebral thrombosis. The model is also typically conducted with parenteral rather than oral drug administration, bypassing the oral bioavailability question that remains central to nattokinase’s clinical potential.

The consistent pattern across nattokinase animal studies — fibrinolytic activity demonstrated in multiple model systems — establishes that nattokinase has real biochemical activity. The persistent gap is human clinical translation: whether oral administration achieves therapeutically relevant systemic concentrations, whether the fibrinolytic effect persists in the presence of human plasma proteases and endogenous inhibitors, and whether there is cardiovascular outcome benefit in humans.

We rate the evidence limited. A rat thrombosis model study demonstrating nattokinase’s in vivo fibrinolytic activity — adding to the basic science evidence base for nattokinase but not advancing the clinical translation questions that remain unanswered.