Cardiovascular disease remains the leading cause of death worldwide, with atherosclerosis and elevated lipids at its core. For decades, statins have been the gold-standard therapy for lowering LDL cholesterol and stabilizing atherosclerotic plaque. But what if a naturally derived enzyme could offer comparable benefits and even outperform statins in certain aspects of plaque regression? This is precisely what new clinical evidence suggests.
What Is Nattokinase?
Nattokinase is a serine protease enzyme extracted from natto, a traditional Japanese fermented soybean dish. It’s best known for its fibrinolytic (clot-busting) activity, but preclinical and clinical research indicates it may also influence lipid metabolism and atherosclerotic processes through multiple pathways including enhanced lipoprotein lipase activity and modulation of cholesterol metabolism.
Research Findings
One pivotal clinical trial directly compared nattokinase to a statin regimen in patients with carotid atherosclerosis and hyperlipidemia. In this randomized, head-to-head study, researchers enrolled 82 participants and assigned them to:
- Nattokinase Group: 6,000 FU/day of oral nattokinase
- Statin Group: 20 mg/day simvastatin for 26 weeks.
Key Results
Plaque Regression
- Both nattokinase and statin therapy significantly reduced carotid intima-media thickness (IMT) and plaque size compared to baseline.
- Remarkably, nattokinase produced a 36.6% reduction in carotid plaque area, while statin treatment showed only an 11.5% change over the same period — suggesting a superior effect of nattokinase on plaque regression in this cohort.
Lipid Profile Improvements
- Both therapies significantly lowered total cholesterol (TC), LDL-C, and triglycerides (TG).
- While statin therapy achieved a greater absolute reduction in TC, LDL-C, and TG, nattokinase also produced meaningful improvements and was the only therapy to significantly raise HDL-C.
Distinct Mechanisms
Interestingly, the lipid-lowering effect in the nattokinase group did not correlate statistically with the degree of plaque regression. This suggests nattokinase might influence atherosclerosis through additional, lipid-independent mechanisms such as enhanced fibrinolysis, anti-inflammatory effects, and improved microcirculation, distinct from the cholesterol-centric action of statins.
Summary
- Comparable Lipid-Lowering Effects
- Although statins achieved stronger absolute LDL-C reductions in this study, nattokinase still produced significant improvements across key lipid parameters, including TC, LDL-C, TG, and HDL-C. Raising HDL-C in particular is a challenge for many therapies, yet this was observed with nattokinase — an effect not seen with statin therapy in the same study.
- Superior Plaque Regression
- The dramatically greater reduction in plaque area with nattokinase, over three times greater than statins in this trial, raises questions about whether targeting fibrin and plaque matrix stability provides advantages beyond lipid lowering alone.
- Mechanistic Complementarity
- Statins primarily exert benefit via HMG-CoA reductase inhibition, lowering circulating LDL and reducing lipid deposition. Nattokinase’s efficacy appears to involve fibrinolytic activity, plaque matrix modulation, and possibly lipid metabolism pathways, offering a complementary approach.
