Dietary Supplementation of Fermented Soybean, Natto, Suppresses Intimal Thickening and Modulates the Lysis of Mural Thrombi After Endothelial Injury in Rat Femoral Artery

This rat model study fed natto dietary supplementation to rats and then induced femoral artery endothelial injury, measuring intimal thickening at follow-up and characterizing mural thrombus resolution compared with controls.

Rats receiving dietary natto supplementation showed reduced intimal thickening after vascular injury and accelerated lysis of mural thrombi compared with controls. The investigators attributed these effects to nattokinase’s fibrinolytic activity and hypothesized additional mechanisms involving isoflavone content of the fermented soy product.

Animal studies demonstrating vascular benefits of natto in rodent injury models are relevant as mechanistic hypothesis generators, but face significant translational barriers. Nattokinase’s pharmacokinetics after oral ingestion in humans — particularly whether enzymatic activity survives gastric and intestinal digestion intact, reaches systemic circulation, and achieves concentrations relevant to in vivo fibrinolysis — remain incompletely established. The rat femoral injury model is not an analog of spontaneous coronary atherosclerosis in humans.

There is no randomized controlled trial evidence demonstrating cardiovascular event reduction from natto or nattokinase supplementation. The animal literature provides hypothesis-generating data for a compound that has not undergone rigorous clinical outcome testing.

We rate the evidence limited. A rat model study demonstrating reduced intimal thickening and enhanced thrombolysis with dietary natto — mechanistically interesting but far from clinical applicability without human pharmacokinetic and outcome data.