What are the benefits of nattokinase for an adult patient with a history of cardiovascular disease?

Nattokinase for Cardiovascular Disease: Evidence-Based Assessment

Based on the highest quality evidence available, nattokinase supplementation cannot be recommended for adults with cardiovascular disease, as the largest and most rigorous long-term trial demonstrated no benefit on atherosclerosis progression, blood pressure, or cardiovascular biomarkers. 1

Critical Evidence from the Definitive Trial

The Nattokinase Atherothrombotic Prevention Study provides the strongest evidence against nattokinase use:

• 265 participants followed for a median of 3 years in a double-blinded, randomized controlled trial using 2,000 fibrinolytic units daily 1
• No effect on subclinical atherosclerosis progression measured by carotid intima-media thickness (CIMT) or carotid arterial stiffness (CAS) 1
• No effect on blood pressure, despite claims of antihypertensive properties 1
• No effect on any laboratory parameters including metabolic factors, blood rheology, coagulation factors, fibrinolysis markers, inflammatory markers, or cellular activation markers 1

This trial directly contradicts the theoretical benefits and supersedes smaller, shorter-duration studies.

Why Smaller Studies Are Misleading

Short-term studies showed modest effects that did not translate to meaningful outcomes:

• A 2023 meta-analysis of 6 studies (546 participants) found nattokinase reduced systolic blood pressure by 3.45 mmHg and diastolic by 2.32 mmHg 2
• However, these reductions are clinically insignificant compared to established antihypertensive therapies that reduce cardiovascular events and mortality 3
• Low-dose nattokinase actually worsened lipid profiles, increasing total cholesterol by 5.27 mg/dL and LDL cholesterol by 6.49 mg/dL 2

Coagulation factor reductions lack clinical validation:

• A 2009 study showed 9-17% reductions in fibrinogen, factor VII, and factor VIII after 2 months 4
• No evidence exists that these laboratory changes translate to reduced thrombotic events, stroke, or myocardial infarction 4, 1
• The 3-year atherothrombotic prevention trial found no clinical benefit despite these theoretical mechanisms 1

Established Cardiovascular Therapies That Actually Work

For adults with cardiovascular disease, prioritize evidence-based interventions:

Blood Pressure Management

• ACE inhibitors or ARBs reduce heart failure risk by approximately 50% and are recommended for all patients with atherosclerotic vascular disease, diabetes, or hypertension 3
• Beta-blockers improve survival in patients with prior myocardial infarction or heart failure 3
• Target blood pressure <130/80 mmHg for patients with diabetes and cardiovascular disease 3

Lipid Management

• Statins are the cornerstone of lipid therapy, with proven reduction in cardiovascular events and mortality 3
• Treat lipid disorders according to contemporary guidelines for all high-risk patients 3

Antiplatelet and Anticoagulation

• Aspirin reduces myocardial infarctions in patients with established cardiovascular disease 3
• Antiplatelet drugs reduce cardiac events after revascularization procedures 3

Omega-3 Fatty Acids (Not Nattokinase)

• 1 gram EPA+DHA daily significantly reduces cardiovascular events and mortality in patients with documented coronary heart disease 3, 5
• Consuming fatty fish at least twice weekly provides foundational cardiovascular protection 3, 5
• Unlike nattokinase, omega-3 fatty acids have robust evidence from multiple large trials showing mortality benefit 3

Critical Pitfalls to Avoid

Do not substitute nattokinase for proven therapies:

• Patients may delay or avoid ACE inhibitors, statins, or antiplatelet agents in favor of nattokinase, increasing their cardiovascular risk 3
• The 3-year null trial demonstrates that nattokinase provides no cardiovascular protection despite widespread marketing claims 1

Recognize the limitations of surrogate endpoints:

• Reductions in coagulation factors or modest blood pressure changes do not equal reduced morbidity or mortality 4, 1
• Only interventions proven to reduce cardiovascular events, heart failure hospitalizations, or death should be recommended 3

Pharmacokinetic data does not establish efficacy:

• While nattokinase is detectable in serum with peak levels at 13.3 hours post-dose, this merely confirms absorption, not clinical benefit 6

Safety Considerations

• No significant adverse events were reported in clinical trials 2, 4, 1
• However, safety without efficacy is insufficient justification for use in cardiovascular disease 1

Alternative Evidence-Based Supplement

If patients insist on supplementation beyond standard therapy:

• Omega-3 fatty acids (EPA+DHA) 1 gram daily have proven cardiovascular mortality benefit in patients with coronary heart disease 3, 5
• This recommendation is supported by the American Heart Association and multiple randomized controlled trials 3
• Omega-3s provide additional benefits including reduced arrhythmias, decreased thrombosis risk, improved endothelial function, and reduced inflammatory responses 3