Nattokinase: Cardiovascular Health, Blood Pressure & Fibrinolysis — Evidence Review
⚡ 60-Second Summary
Nattokinase is a serine protease enzyme extracted from natto (Japanese fermented soybean dish). Unlike most proteins that are digested and inactivated in the gut, nattokinase retains enzymatic activity after oral administration. It directly degrades fibrin (the protein mesh that forms blood clots), inhibits PAI-1 (the primary endogenous clot-inhibitor inhibitor), and reduces blood viscosity — producing fibrinolytic and antiplatelet effects.
Best-evidenced uses: Blood pressure reduction (multiple RCTs show ~5–7 mmHg systolic reduction); fibrinolytic activity (reduced fibrin degradation products, improved blood viscosity); prevention of deep vein thrombosis (small RCTs in high-risk patients); cardiovascular risk factor improvement. NOT a substitute for prescription anticoagulants in established thrombosis.
CRITICAL safety note: Nattokinase has clinically significant fibrinolytic and antiplatelet activity. The interaction with anticoagulants (warfarin, heparin, direct oral anticoagulants — DOACs) and antiplatelet drugs can cause serious or life-threatening bleeding. This is not a theoretical concern — it is the most important safety issue for this supplement. Never combine with anticoagulants without hematologist consultation.
What is Nattokinase?
Nattokinase cleaves fibrin at specific arginine and lysine residues, dissolving existing clots and reducing clot formation. It also inhibits PAI-1 (plasminogen activator inhibitor-1), enhancing tissue plasminogen activator (tPA) activity — the body's endogenous clot-dissolving system. Nattokinase has ACE-inhibitory activity that partially explains its blood pressure-lowering effect. Oral bioavailability is improved by taking on an empty stomach.
Natto is a traditional Japanese food consumed for centuries, with historical association with cardiovascular longevity in Japan's health statistics. Nattokinase as a purified enzyme supplement was first studied by Hiroyuki Sumi (who discovered it accidentally in the mid-1980s). Multiple Japanese and some Western clinical trials have established cardiovascular evidence. It is particularly popular in Japan as a cardiovascular supplement.
Evidence-based benefits
1. Blood pressure reduction
Multiple RCTs (200 mg/day nattokinase, 8–12 weeks) show significant systolic BP reduction of ~5–7 mmHg and diastolic of ~3–4 mmHg. ACE inhibitory activity is proposed as the primary mechanism.
2. Fibrinolytic activity
Multiple human studies show nattokinase reduces fibrin degradation products and improves blood viscosity. Small RCT in pre-hypertensive adults showed reduced plasma fibrinogen.
3. Cardiovascular risk factors
Some RCTs show improved total cholesterol, triglycerides, and arterial stiffness with nattokinase. Evidence is promising but smaller than for more established cardiovascular supplements.
Supplement forms compared
| Form | Typical dose / Bioavailability | Best for | Notes |
|---|---|---|---|
| Nattokinase (2,000 FU per capsule) | 100–200 mg/day (2,000–4,000 FU) | Blood pressure, fibrinolytic, cardiovascular | Standard supplement form. FU = Fibrinolytic Units. Take on empty stomach. |
| Natto (food) | Variable FU | Traditional cardiovascular diet | 2–3 tablespoons natto provides significant nattokinase; also high in vitamin K2. |
| Nattokinase + serrapeptase combinations | Varies | Enhanced systemic fibrinolytic | Combining proteolytic enzymes; less studied than nattokinase alone. |
How much should you take?
- Blood pressure: 2,000 FU/day (100 mg) — studied dose in most RCTs
- Thrombosis prevention: 2,000–4,000 FU/day
- Take on empty stomach or 30 minutes before meals
SERIOUS INTERACTION WARNING: Do not combine with warfarin, heparin, aspirin/clopidogrel, or other blood thinners without hematologist supervision. The fibrinolytic activity is additive with anticoagulants and can cause dangerous bleeding. Discontinue at least 7 days before surgery. Never use to treat existing deep vein thrombosis or pulmonary embolism without medical supervision.
Safety and side effects
Common side effects
- Bleeding risk — the most important concern; additive with anticoagulants
- GI upset (uncommon)
- Possible allergy in soy-allergic individuals (processed from soybean ferment)
Serious risks
The main safety concern is bleeding risk from additive fibrinolytic effects with anticoagulants. This is a significant real-world risk that warrants explicit discussion with any healthcare provider prescribing blood thinners. Nattokinase should generally not be used in people on anticoagulant therapy.
Drug and nutrient interactions
- Warfarin, heparin, DOACs (rivaroxaban, apixaban) — CONTRAINDICATED without hematologist consultation; additive bleeding risk can be severe
- Antiplatelet drugs (aspirin, clopidogrel, ticagrelor) — additive antiplatelet and fibrinolytic effect; significant bleeding risk
- NSAIDs — additive antiplatelet effects; avoid regular combined use
Check our free interaction checker for additional combinations.
Who might benefit — and who should use caution
| Most likely to benefit | Use with caution or seek guidance |
|---|---|
| People with cardiovascular risk and elevated blood pressure seeking evidence-based adjunct support | People on any anticoagulant or antiplatelet therapy — serious bleeding risk; do not combine without hematologist consultation |
| Individuals with high fibrinogen or hypercoagulable state (confirmed by physician) | People scheduled for surgery within 7–10 days — stop nattokinase; significant fibrinolytic activity |
| Those interested in evidence-based cardiovascular protection beyond diet and exercise | People with GI ulcers or active bleeding — absolutely avoid |
| Adults concerned about blood viscosity and cardiovascular aging |
Frequently asked questions
How does nattokinase lower blood pressure?
Nattokinase has ACE-inhibitory activity — reducing angiotensin II production and its vasoconstrictive effects. This is the same mechanism as ACE inhibitor medications (lisinopril, enalapril), though nattokinase is much weaker. Multiple RCTs confirm 5–7 mmHg systolic BP reduction. The fibrinolytic effects on blood viscosity may also contribute to reduced peripheral resistance.
Is nattokinase safe to take if I'm on blood thinners?
No — or only with hematologist supervision. Nattokinase directly degrades fibrin and inhibits PAI-1, producing significant fibrinolytic activity that is additive with anticoagulants (warfarin, DOACs) and antiplatelet drugs. The combination can cause serious bleeding including intracranial hemorrhage. If you are on blood thinners for any reason, do not take nattokinase without explicit clearance from the prescribing physician.
Can nattokinase prevent blood clots?
Nattokinase has demonstrated fibrinolytic and antiplatelet activity that reduces clot formation. Small RCTs in high-risk patients show reduced DVT incidence with nattokinase supplementation. However, it is not a substitute for prescribed anticoagulants in people with established clotting conditions (atrial fibrillation, mechanical heart valves, DVT history). Always work with your cardiologist or hematologist for clotting disorder management.
What is a Fibrinolytic Unit (FU)?
FU (Fibrinolytic Units) measures nattokinase's clot-dissolving enzymatic activity. The standard reference enzyme activity is calibrated against urokinase. Most clinical trials use 2,000 FU/day. Supplements typically provide 2,000 FU per capsule. Always use FU-based dosing rather than mg alone, since enzyme potency varies by product.
Is nattokinase from natto the same as nattokinase supplements?
Yes — nattokinase is purified from Bacillus subtilis var. natto fermented soybeans, the same organism used to make traditional natto food. Natto itself contains nattokinase alongside vitamin K2 (MK-7), which also has cardiovascular benefits. The supplement is purified enzyme; natto is the whole fermented food with multiple bioactives.
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Disclaimer: This information is for educational purposes only and should not replace medical advice. Always consult a qualified healthcare provider before starting any supplement, especially if you have a medical condition, are pregnant, or take prescription medications. These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.