Management of Atherosclerosis Progress and Hyperlipidemia With Nattokinase: A Clinical Study With 1,062 Participants

This is the largest human study of nattokinase for cardiovascular benefit, and it gives the supplement its most substantial — though still qualified — support.

Over 12 months in more than 1,000 participants, high-dose nattokinase (10,800 fibrinolytic units daily) was associated with improved lipid profiles and reduced carotid intima-media thickness and plaque size. Notably, lower doses were ineffective, and benefits appeared amplified by exercise and by co-administration of aspirin or vitamin K2. The dose-dependence at least suggests a real effect rather than noise.

The limitations are substantial. This was a retrospective study, not a randomized controlled trial — meaning it cannot rule out that healthier or more motivated patients drove the apparent benefit — and it relied on a surrogate (artery thickness) rather than clinical events. The very high dose required also raises questions about real-world applicability and bleeding risk.

We rate the evidence moderate, leaning cautious. It is the best nattokinase evidence available, which is itself telling: a large but non-randomized study using surrogate endpoints. The supplement remains unproven for preventing heart attacks or strokes, and its anticoagulant activity warrants medical guidance.