Nattokinase
A fibrin-dissolving enzyme produced by Bacillus subtilis during fermentation of natto (Japanese soybeans), studied for its blood-thinning, clot-dissolving, and blood pressure-lowering effects.
At a Glance
- Best known for
- Fibrinolytic: breaks down fibrin and supports clot dissolution, Reduces blood pressure modestly in RCTs, Reduces platelet aggregation and blood viscosity
- Evidence
- Preliminary
- Typical dose
- 2,000 FU (100 mg) daily
- Type
- Compound
What is Nattokinase?
Nattokinase is an enzyme discovered in 1987 by Japanese researcher Hiroyuki Sumi in natto, a sticky, pungent food made by fermenting soybeans with Bacillus subtilis var. natto that has been eaten in Japan for over a thousand years. Sumi found that natto placed on a fibrin plate dissolved it rapidly, and named the responsible protease 'nattokinase' (though it is not technically a kinase). Supplement-grade nattokinase is produced by bacterial fermentation and purified, so it contains no vitamin K2 or soy protein unless specified, and it is standardized in fibrinolytic units (FU). Interest centers on its ability to break down fibrin, the protein mesh of blood clots.
Known Health Benefits
How It Works
Nattokinase degrades fibrin directly, cleaving the cross-linked protein that forms the scaffold of blood clots, and also degrades fibrinogen. It enhances the body's own clot-dissolving system by increasing tissue plasminogen activator (tPA) and inactivating plasminogen activator inhibitor-1 (PAI-1), the main brake on fibrinolysis. In human studies a single dose increased fibrin degradation products and prolonged clotting times within hours, and it reduces factor VIII and platelet aggregation. Its blood pressure effect is attributed to inhibition of angiotensin-converting enzyme and reduced plasma renin. Animal studies suggest it reduces arterial wall thickening and may degrade amyloid fibrils, but these findings have not been confirmed in humans.
What Research Says
Evidence is mostly from small trials and mechanistic studies. A 2008 Korean double-blind RCT in 86 people with prehypertension or stage 1 hypertension found 2,000 FU daily for 8 weeks lowered systolic pressure by about 5.5 mmHg and diastolic by 2.8 mmHg versus placebo. A 2015 study in 12 healthy men showed a single 2,000 FU dose increased markers of fibrinolysis and anticoagulation over 2–8 hours. A 2016 North American RCT in 79 hypertensive adults found a diastolic reduction mainly in men. A 2009 open-label study reported reduced fibrinogen and factor VII with 8 weeks of use. A 2022 Chinese observational study in over 1,000 people reported reduced carotid plaque with high-dose nattokinase (10,800 FU daily) over a year, but it lacked a placebo group. By contrast, a well-designed 2021 US RCT (NAPS) of 265 adults found 2,000 FU daily for 3 years had no effect on carotid artery thickening or stiffness. Long-term outcome data for preventing thrombosis or stroke do not exist. The enzyme's biological activity is real; clinical benefit remains unproven.
Active Compounds
Nattokinase (subtilisin NAT), a 275-amino-acid serine protease; activity measured in fibrinolytic units (FU)
Forms & Bioavailability
Nattokinase is a protein and was once assumed to be fully digested, but human studies detect intact enzyme in plasma within hours of oral dosing, and its effects on clotting markers confirm systemic activity. Absorption appears to occur across the intestinal wall, possibly aided by its resistance to acid and pepsin. Enteric coating may improve delivery. It should be taken on an empty stomach so it is not consumed by digesting food protein. Activity (FU) is a more useful measure than milligrams.
Dosage Guidance
| Use Case | Dosage |
|---|---|
| Blood pressure support | 2,000 FU (100 mg) daily |
| Circulation / fibrinolytic support | 2,000 FU 1–2x daily on empty stomach |
| Higher-dose protocols (plaque) | Up to 10,800 FU daily |
| Travel / long-haul flights (traditional use) | 2,000 FU before and during flight |
| Natto (food) | 50 g natto daily |
Always consult a healthcare provider for personalized dosing.
Natural Food Sources
- Natto (fermented soybeans) — roughly 50 g provides a substantial dose of enzyme plus vitamin K2
- Not found in other foods; supplements are produced by fermentation
Potential Side Effects
Bleeding or bruising; stomach upset; headache; rare allergic reactions; case reports of cerebellar hemorrhage with concurrent aspirin
Who Should Avoid It
- Anticoagulant or antiplatelet therapy (warfarin, DOACs, aspirin, clopidogrel) without medical supervision
- Bleeding disorders, peptic ulcer, recent hemorrhagic stroke, or intracranial aneurysm
- Surgery or dental procedures (stop at least 2 weeks before)
- Pregnancy and breastfeeding (no safety data; bleeding risk)
- Severe low blood pressure
- Soy allergy (check whether the product contains soy residues)
Pregnancy & Lactation
Avoid. There are no safety data for nattokinase in pregnancy or breastfeeding, and its anticoagulant effect could increase bleeding risk during delivery and in the postpartum period. Natto as a food is safe in pregnancy.
Known Drug Interactions
Additive bleeding risk with warfarin, DOACs (apixaban, rivaroxaban), heparin, aspirin, clopidogrel, NSAIDs, fish oil, vitamin E, and ginkgo; may add to antihypertensives; natto (the food) is high in vitamin K and counteracts warfarin, whereas purified nattokinase does not
Evidence Classification
Based on in vitro studies, animal models, pilot trials, or traditional use documentation. Clinical evidence is limited.
Frequently Asked Questions
Can nattokinase replace blood thinners?
No. Prescription anticoagulants have decades of trial evidence proving they prevent strokes and clots at known, monitored doses. Nattokinase has mechanistic studies and small trials showing it affects clotting markers, but no trials showing it prevents strokes, heart attacks, or DVT. Replacing a prescribed anticoagulant with it could be life-threatening. Adding it to one increases bleeding risk and should be discussed with your prescriber.
Does it dissolve arterial plaque?
Animal studies and an uncontrolled Chinese study of high doses suggested reduced carotid plaque, but the best-designed trial (3 years, placebo-controlled, 2,000 FU) found no effect on carotid thickening. Claims that nattokinase 'cleans out arteries' are not supported by controlled evidence.
Is natto as good as a supplement?
Natto provides nattokinase along with vitamin K2 (MK-7), protein, and probiotics, and population studies in Japan link natto intake with lower cardiovascular mortality. However, its vitamin K content makes it unsuitable for people on warfarin, and the enzyme dose per serving is variable. Purified supplements isolate the enzyme without the vitamin K.
Why is it dosed in FU rather than milligrams?
FU (fibrinolytic units) measure how much fibrin the enzyme actually dissolves, which is what matters; milligrams of powder say nothing about activity. A typical capsule is 100 mg providing 2,000 FU. Look for the FU figure on the label.
References
- A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet. Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H. Experientia (1987)View study
- Effects of nattokinase on blood pressure: a randomized, controlled trial. Kim JY, Gum SN, Paik JK, et al.. Hypertens Res (2008)View study
- A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Kurosawa Y, Nirengi S, Homma T, et al.. Sci Rep (2015)View study
- Nattokinase. Examine.comView study
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This entry is for educational purposes only. It is not medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement regimen, especially if you take medications or have health conditions.