Does nattokinase help reduce arterial plaque in patients with cardiovascular disease?

Nattokinase Does Not Reduce Arterial Plaque

Based on the highest quality evidence available, nattokinase supplementation does not reduce arterial plaque or slow atherosclerosis progression in patients with cardiovascular disease. The most definitive study—a 3-year randomized controlled trial—found no effect on carotid artery intima-media thickness or arterial stiffness 1.

Key Evidence Against Plaque Reduction

The nattokinase atherothrombotic prevention study provides the strongest evidence on this question 1:

• 265 participants followed for a median of 3 years with serial carotid ultrasound measurements every 6 months 1
• No significant difference in atherosclerosis progression between nattokinase (2,000 fibrinolytic units daily) and placebo 1
• No effect on carotid intima-media thickness (CIMT) or carotid arterial stiffness (CAS), the gold-standard measures of subclinical atherosclerosis 1
• No impact on blood pressure or metabolic parameters that might indirectly affect plaque 1

This was a well-designed, double-blinded trial with objective imaging endpoints—far superior to surrogate biomarker studies 1.

Contrast with Proven Plaque-Modifying Therapies

For context, omega-3 fatty acids (EPA+DHA) have demonstrated actual plaque regression in controlled trials 2:

• Omega-3 index ≥8.4% achieved regression of noncalcified coronary plaque in the HEARTS trial 2
• Patients with plaque regression had 4-fold fewer cardiac events (5% vs 22.3%, p<0.001) 2
• Triglyceride reduction correlated with plaque regression (r=0.135, p=0.036) in normotensive subjects 2

This demonstrates what genuine plaque modification looks like in clinical trials—something nattokinase failed to achieve 1.

Limited Cardiovascular Benefits of Nattokinase

While nattokinase does not reduce plaque, meta-analysis shows modest effects on other cardiovascular risk factors 3:

• Modest blood pressure reduction: systolic BP decreased by 3.45 mmHg and diastolic BP by 2.32 mmHg 3
• No consistent lipid-lowering effect: low-dose nattokinase actually increased total cholesterol and LDL cholesterol 3
• Slight increase in blood glucose (0.40 mg/dL) of unclear clinical significance 3

These effects are far less impressive than established therapies like statins, ACE inhibitors, or dual anti-thrombotic pathway inhibition 2.

Safety Profile

Nattokinase appears safe in clinical use 4:

• No adverse drug reactions or interactions reported in 153 patients with vascular diseases 4
• No bleeding complications when used alone or combined with anticoagulants under medical supervision 4
• Generally well-tolerated across multiple studies 3, 1

Clinical Bottom Line

Do not recommend nattokinase for arterial plaque reduction—it does not work for this indication. For patients seeking evidence-based plaque stabilization or regression, focus on proven therapies 2:

• High-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily) targeting LDL <70 mg/dL 5
• Aspirin 75-150 mg daily for antiplatelet effects 5
• ACE inhibitors (ramipril 10 mg or perindopril 8 mg daily) for plaque stabilization beyond blood pressure control 2, 5, 6
• Omega-3 fatty acids (EPA+DHA 2-4 grams daily) which have demonstrated actual plaque regression 2, 7
• Dual anti-thrombotic pathway inhibition (aspirin plus low-dose rivaroxaban 2.5 mg twice daily) for high-risk patients with polyvascular disease 2

Critical Pitfall to Avoid

Do not substitute nattokinase for proven cardiovascular therapies. While it may have theoretical fibrinolytic properties, the 3-year imaging study definitively shows no impact on atherosclerosis progression 1. Patients with cardiovascular disease require evidence-based medical therapy that reduces mortality and morbidity 2, 5.