Is it safe and appropriate for a healthy adult aged 18–65 without bleeding risk factors to take nattokinase (natto kinase) for cardiovascular risk reduction, and what dose is recommended?

Nattokinase for Cardiovascular Risk Reduction

Nattokinase is not recommended for cardiovascular risk reduction in healthy adults, as it lacks support from major cardiovascular guidelines and has no established role in evidence-based primary prevention strategies.

Absence from Evidence-Based Guidelines

None of the major cardiovascular prevention guidelines—including the 2024 AHA/ASA stroke prevention guideline 1, 2024 ESC hypertension guidelines 1, 2024 ESC chronic coronary syndromes guidelines 1, or 2024 Diabetes Care cardiovascular disease management standards 1—mention nattokinase as a recommended intervention for cardiovascular risk reduction. These guidelines consistently emphasize Life's Essential 8 components (diet, physical activity, healthy weight, sleep, tobacco avoidance, and management of blood lipids, glucose, and blood pressure) as the foundation for primary prevention 1.

Established Primary Prevention Strategies Take Priority

For healthy adults aged 18-65 without bleeding risk factors, evidence-based cardiovascular risk reduction should focus on:

• Mediterranean diet for adults at high or intermediate CVD risk (Class I, Level B-R recommendation) 1
• Blood pressure screening every 3-5 years for adults 18-39 years, yearly for those >40 years 1
• Traditional risk factor screening every 4-6 years in adults 20-79 years 1
• DASH diet for blood pressure management when indicated 1
• Aspirin only considered for primary prevention in those with diabetes and additional major risk factors, after careful discussion of bleeding risks 1

Limited and Conflicting Evidence for Nattokinase

While research studies suggest potential mechanisms of action, the evidence base is insufficient for clinical recommendation:

• A 2023 meta-analysis of 6 RCTs (546 participants) showed nattokinase reduced systolic BP by 3.45 mmHg and diastolic BP by 2.32 mmHg, but had inconsistent effects on lipids depending on dosage 2
• Low-dose nattokinase actually increased total cholesterol (MD = 5.27) and LDL cholesterol (MD = 6.49) while decreasing HDL cholesterol (MD = -2.76) 2
• A 2009 study showed reductions in fibrinogen (9%), factor VII (14%), and factor VIII (17%) in healthy volunteers, but this was an open-label, self-controlled trial without placebo comparison 3
• Pharmacokinetic data from a small pilot study (n=11) showed peak serum levels at 13.3 hours post-dose, but bioavailability and clinical significance remain unknown 4

Critical Safety Concerns

The fibrinolytic and antithrombotic properties of nattokinase create theoretical bleeding risks that have not been adequately studied:

• Nattokinase decreases multiple coagulation factors (fibrinogen, factor VII, factor VIII) 3
• No large-scale safety trials have evaluated bleeding complications, particularly in combination with antiplatelet agents or anticoagulants
• The 2023 meta-analysis noted "no notable adverse events" but studies were small and short-term (typically 2 months) 2
• Unlike guideline-recommended interventions (Mediterranean diet, DASH diet, exercise), nattokinase lacks established safety profiles in diverse populations

Comparison to Evidence-Based Supplements

The 2024 AHA/ASA stroke prevention guideline explicitly evaluated dietary supplements and found:

• No benefit (Class 3) for vitamin C, vitamin E, selenium, antioxidants, calcium, calcium with vitamin D, and multivitamins for stroke reduction 1
• No benefit (Class 3) for long-chain fatty acids for stroke reduction 1
• Folic acid and B-complex vitamins have uncertain benefit (Class 2b) 1

Nattokinase has even less evidence than these supplements that received "no benefit" recommendations.

Practical Clinical Approach

For a healthy adult aged 18-65 seeking cardiovascular risk reduction:

1. Calculate baseline cardiovascular risk using validated tools (ASCVD risk calculator for those with risk factors) 1
2. Implement proven lifestyle interventions first: Mediterranean diet 1, regular physical activity, tobacco avoidance, healthy weight maintenance 1
3. Screen and manage traditional risk factors: blood pressure, lipids, glucose 1
4. Reserve pharmacologic interventions for those meeting guideline-based thresholds (e.g., BP ≥140/90 mmHg for most adults, or ≥130/80 mmHg for those with 10-year ASCVD risk ≥10%) 1
5. Avoid unproven supplements that lack guideline support and may carry unknown risks

Bottom Line

Nattokinase cannot be recommended for cardiovascular risk reduction in healthy adults because it is absent from all major cardiovascular prevention guidelines, has limited and conflicting clinical trial data, poses theoretical bleeding risks that have not been adequately studied, and diverts attention from proven interventions with robust evidence bases. Healthy adults should focus on guideline-recommended lifestyle modifications and evidence-based medical therapies when indicated, rather than experimental supplements with uncertain benefit-risk profiles 1.