Clinical Study on the Effect of Nattokinase on Carotid Artery Atherosclerosis and Hyperlipidemia

This Chinese RCT enrolled 82 patients with carotid artery atherosclerosis and hyperlipidemia and compared nattokinase (a serine protease derived from fermented soybeans with fibrinolytic and potential anti-atherogenic properties) against simvastatin over a 26-week treatment period, with carotid plaque size and lipid levels as outcomes.

Nattokinase significantly reduced carotid plaque size by 36.6% versus 11.5% in the simvastatin group — a striking difference. Nattokinase also modestly lowered total cholesterol and LDL-C and uniquely increased HDL-C.

These results require cautious interpretation. The plaque measurement method (ultrasound plaque size) is operator-dependent and not standardized to established IVUS or MRI protocols. The sample size is small. The simvastatin dose used (likely not high-intensity given the era and context) may not represent optimal statin therapy. The claimed plaque regression magnitude substantially exceeds that observed with any proven intervention — including high-dose statins with PCSK9 inhibitors — raising methodological concerns about measurement reliability.

Nattokinase has a theoretical mechanistic basis in fibrinolysis and anti-inflammatory effects. It is commercially available as a supplement and increasingly studied. However, its evidence base consists primarily of small, often poorly controlled trials, and it has not been evaluated in large cardiovascular outcomes trials. These results are intriguing but insufficient to support clinical recommendations.

We rate the evidence limited. A small RCT with implausibly large plaque regression claims for nattokinase — exploratory data requiring replication with standardized imaging methods and outcomes data.