Nattokinase
Nattokinase
TL;DR
Nattokinase is a fibrinolytic enzyme from fermented soy that modestly lowers blood pressure and fibrinogen in small trials. Promising but under-powered, and it carries genuine bleeding risk with anticoagulants.
Ideal For
- Adults with mildly elevated blood pressure not on anticoagulants
- People interested in circulation support who can stop two weeks before surgery
Avoid If
- You take warfarin, DOACs, aspirin or clopidogrel
- You have a bleeding disorder or active peptic ulcer
- You are within two weeks of scheduled surgery
- You are pregnant or breastfeeding
- You have a soy allergy
Frequently Asked Questions
What is nattokinase?
What does the evidence show?
What dose is used?
Does it prevent blood clots?
What are the safety concerns?
Does it contain vitamin K2?
Overview
Nattokinase is a serine protease isolated from natto, a Japanese fermented soybean food. It degrades fibrin directly and also raises endogenous fibrinolytic activity by inactivating plasminogen activator inhibitor-1. Human evidence consists mostly of small Japanese, Korean and Chinese trials lasting 8 to 26 weeks. Meta-analyses of these report average reductions of roughly 3 to 6 mmHg systolic blood pressure, small declines in fibrinogen, factor VII and factor VIII, and in one longer trial a slowing of carotid plaque progression. Trial quality is the limiting factor: sample sizes are typically under 100, blinding is inconsistent, and most studies come from a narrow geographic and commercial base. No cardiovascular outcome trial exists. Dosing is expressed in fibrinolytic units (FU) rather than milligrams, and 2000 FU daily is the most commonly studied dose.
How It Works
- Directly cleaves fibrin, the protein scaffold of clots
- Inactivates plasminogen activator inhibitor-1, increasing endogenous tPA activity
- Lowers circulating fibrinogen, factor VII and factor VIII in small trials
- May inhibit ACE weakly, contributing to modest blood pressure reduction
Benefits & Outcomes
Fibrinogen Reduction
Plausible but under-evidenced. Never a substitute for prescribed anticoagulation.
Platelet Aggregation Reduction
Nattokinase has plausible fibrinolytic activity but far too little human outcome data to recommend it.
Venous Return
Nattokinase has fibrinolytic activity with no venous insufficiency outcome data.
Health Concerns Addressed
Elevated Blood Pressure
Small reductions in two short trials, no effect in a 3-year trial; a bleeding risk with blood thinners and aspirin.
Deep Vein Thrombosis
Fibrinolytic activity in a test tube does not equal clot prevention in a person. No DVT outcome trials, no dose standard, no monitoring — and a fatal downside if used as a substitute.
Supporting Research11 studies
The effects of nattokinase supplementation on collagen-epinephrine closure time, prothrombin time and activated partial thromboplastin time in nondiabetic and hypercholesterolemic subjects
Yoo HJ, Kim M, Kim M +4 more
nattokinase supplementation was associated with prolonged C-EPI CT and aPTT
Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial
Liu M, Xu Z, Wang Z +4 more
the combined NK and RYR supplementation is safe and more effective than separately
Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds
Chang YY, Liu JS, Lai SL +2 more
nattokinase may increase risk of intracerebral hemorrhage
Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis
Elahi MM, Choi CH, Konda S +1 more
we strongly discourage its use for this purpose
A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles
A single-dose of 2,000 FU nattokinase potentiated thrombolysis and anti-coagulation profiles in healthy male subjects.
Nattokinase atherothrombotic prevention study: a randomized controlled trial
Hodis HN, Mack WJ, Meiselman HJ
Nattokinase did not change carotid intima-media thickness progression or coagulation markers versus placebo over one year.
Nattokinase supplementation and cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials
Li X, Long J, Gao Q +1 more
Nattokinase reduced total cholesterol, LDL and systolic blood pressure modestly across randomised trials.
Effects of nattokinase on blood pressure: a randomized, controlled trial
Kim JY, Gum SN, Paik JK
Nattokinase lowered systolic blood pressure by 5.6 mmHg versus placebo in pre-hypertensive adults.
Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor: a randomized, double-blind, placebo-controlled, multicenter North American clinical trial
Jensen GS, Lenninger M, Ero MP +1 more
Nattokinase lowered blood pressure in men and reduced von Willebrand factor over eight weeks.
Nattokinase: an updated critical review on challenges and perspectives
Selvarajan E, Bhatnagar N
Oral bioavailability and interaction with anticoagulants remain poorly characterised.
Clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia
Ren NN, Chen HJ, Li Y +1 more
Nattokinase reduced carotid plaque size and improved lipids in a lower-quality Chinese trial.
Safety Information
Potential Side Effects
Generally mild: GI upset, headache. The meaningful risk is bleeding, and case reports of cerebellar haemorrhage exist when combined with antiplatelet therapy.
Contraindications
Anticoagulant or antiplatelet therapy, bleeding disorders, imminent surgery, pregnancy.
Drug Interactions
- Warfarin and DOACs: additive bleeding risk
- Aspirin, clopidogrel and NSAIDs: additive bleeding risk
- Antihypertensives: possible additive blood pressure lowering
Pregnancy & Breastfeeding
Pregnancy: Likely unsafe
Breastfeeding: Not enough evidence to judge
Dosage Guidelines
Dosage Used in Studies
Consult healthcare provider
Dosing by Goal
| Goal | Dose | Notes |
|---|---|---|
| Typical | 2000 FU (about 100 mg) once daily | |
| Range | 1000-4000 FU daily in trials | |
| Duration | Studies ran 8-26 weeks | |
| Notes | Dose by fibrinolytic units, not milligrams; milligram labels are not comparable across brands |
Forms Compared
Enteric-coated capsules
Preferred; protects the enzyme from gastric acid
Standardised FU capsules
Look for 2000 FU per serving, the trial dose
Natto (the food)
Provides the enzyme plus vitamin K2 MK-7, which opposes warfarin
Nattokinase with serrapeptase blends
No added evidence; complicates dosing
Food & Timing
On an empty stomach or before bed is conventional, though no trial has compared timing directly.
Medical Disclaimer
The information provided on this website is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any supplement regimen.
Individual results may vary. The statements on this website have not been evaluated by the Food and Drug Administration. Products and information are not intended to diagnose, treat, cure, or prevent any disease.