Nattokinase Atherothrombotic Prevention Study: A Randomized Controlled Trial

This is the most rigorous test nattokinase has faced — a randomized controlled trial — and it is the one supplement enthusiasts least like to cite, because it came up empty.

Over the study period, nattokinase supplementation had no significant effect on the progression of subclinical atherosclerosis (carotid artery thickness), arterial stiffness, blood pressure, coagulation parameters, or inflammatory markers in healthy, low-risk individuals. None of the benefits suggested by the many small animal and observational studies materialized when tested properly.

This negative result is the appropriate counterweight to the enzyme’s promotional literature. The earlier rat thrombosis studies, the in vitro antioxidant work, and the uncontrolled observational reports all pointed one way; the randomized trial — the design built to defeat bias and placebo effect — pointed the other.

We rate the evidence strong as a trial, even though its clinical-significance score reflects a negative finding. For the central question of whether nattokinase slows atherosclerosis in people, this is the best evidence available, and the answer is no.