Nattokinase is a serine protease enzyme isolated from natto, a traditional Japanese food made by fermenting soybeans with the bacterium Bacillus subtilis. A review reports intact nattokinase in the serum of healthy people after a single 2,000 FU capsule, although EFSA said the supplied data could not show whether active nattokinase is absorbed. It has been a subject of growing scientific interest for its effects on blood coagulation and fibrin breakdown [1][4].
The core claim behind nattokinase supplements is that the enzyme can degrade fibrin, the protein mesh that forms the structural backbone of blood clots, and may also upregulate the body’s own clot-dissolving pathways.[1] Human trials investigating these effects exist, though most are small and short-term. This article explains what nattokinase is, how it is proposed to work, what the current evidence suggests, and the genuine safety considerations anyone considering it should know.
Key Takeaways
- Nattokinase is a serine protease enzyme from fermented soybeans that degrades fibrin directly and may upregulate the body’s own plasminogen activators, producing measurable fibrinolytic effects in humans.
- Small randomized trials have reported modest blood pressure changes and fibrinolytic marker shifts, but a 3-year trial in 265 healthy adults found no effect on blood pressure or artery thickening, and trials with hard clinical outcomes (heart attack, stroke) have not been completed [5][6][7][8].
- It carries a real drug interaction risk with anticoagulants and antiplatelets (including warfarin, aspirin, clopidogrel, and direct oral anticoagulants) and should never be combined with these without physician guidance.
- Nattokinase should be stopped at least one week before surgery due to its antiplatelet and fibrinolytic activity.
- The FDA has not evaluated nattokinase as a treatment for any disease; it is sold as a dietary supplement, and quality varies across brands: look for third-party tested products with standardized FU activity.
Where Nattokinase Comes From
Natto is a centuries-old Japanese fermented food produced by inoculating cooked soybeans with Bacillus subtilis and allowing them to ferment at warm temperatures for roughly 24 hours. The result is a sticky, pungent food with a distinct flavor profile that remains a staple in Japanese cuisine, particularly eaten at breakfast.
During fermentation, Bacillus subtilis secretes a variety of enzymes into the substrate.[3] A particularly potent fibrinolytic enzyme was identified within natto and named nattokinase [9]though it is technically classified as a subtilisin-type serine protease, not a kinase in the biochemical sense. The enzyme can be extracted, purified, and concentrated into supplement form, typically standardized in fibrinolytic activity units (FUs) per capsule.
Whole natto contains nattokinase alongside vitamin K2 (menaquinone-7), soy isoflavones, and other bioactive compounds. Nattokinase supplements are usually designed to isolate the enzyme while removing vitamin K2, which matters clinically because vitamin K2 has opposing effects on coagulation relative to the enzyme itself.
The Proposed Mechanism: How Nattokinase May Work
Nattokinase is thought to exert its fibrinolytic effects through two complementary pathways. First, the enzyme can directly cleave fibrin: the insoluble protein polymer that cross-links to form a clot’s structural scaffold. In laboratory clot-lysis tests nattokinase dissolved whole blood clots, but dissolving existing clots has not been shown in people [10][11].
Research note: EFSA used a rat no-effect level of 1,000 mg/kg body weight per day against a 100 mg/day maximum intake (1.43 mg/kg for a 70-kg person) and judged the margin of exposure of 700 sufficient [4].
Second, in lab and animal work nattokinase appears to raise tissue plasminogen activator (tPA) activity, although a 3-year trial in 265 healthy adults found no effect on tPA antigen [11][12][2][8]. These are the body’s own enzymes responsible for converting plasminogen into plasmin, which is the primary fibrinolytic agent the body uses to break down clots naturally. By amplifying this pathway, nattokinase may produce fibrinolytic effects that extend beyond what its own direct enzymatic action accounts for.
Beyond fibrinolysis, nattokinase has shown antiplatelet activity in rabbit and rat plasma tests, not in verified human trials, meaning it may reduce [13][14] the tendency of platelets to aggregate and adhere. This dual mechanism, breaking down existing fibrin while also reducing new clot formation, underpins most of the cardiovascular interest in the enzyme. It also underpins the drug interaction risks discussed later in this article.
What Human Research Has Examined
Human trials on nattokinase have measured several outcomes: plasma fibrinolytic activity markers (such as D-dimer and euglobulin clot lysis time), blood pressure, and in some cases lipid profiles. Results across small randomized controlled trials have shown that nattokinase supplementation can produce measurable fibrinolytic effects in human plasma, consistent with the proposed mechanism.
Some trials have reported modest blood pressure reductions in adults with elevated pressure: a maker-funded trial in 86 adults reported falls in both systolic and diastolic pressure, while a 2016 trial in 79 adults found only a diastolic fall. A 3-year trial in 265 healthy adults found no effect on blood pressure [5][6][8].[2] The magnitude of these reductions has generally been modest rather than dramatic, and the trials are short in duration, typically ranging from four to eight weeks, with participant counts often in the range of dozens rather than hundreds.
It is important to be direct about what this evidence base does and does not support. The studies confirm that nattokinase has biological activity in humans and can shift measurable markers in meaningful directions. What they do not establish is whether these surrogate marker changes translate into reduced rates of heart attack, stroke, deep vein thrombosis, or other hard clinical endpoints. Larger, longer-term trials with clinical outcomes have not been completed. The existing research is promising but should be interpreted cautiously.
Safety Profile and Drug Interactions
Nattokinase carries a possible drug interaction risk that must be understood before anyone considers using it; human interaction data are lacking, but a Health Canada licence says not to use it with products that affect blood coagulation [15][16][17]. Because the enzyme has genuine fibrinolytic and antiplatelet activity, combining it with anticoagulant or antiplatelet medications may add to bleeding risk [15][18]. Medications in this category include warfarin, heparin and low-molecular-weight heparins, aspirin, clopidogrel (Plavix), apixaban (Eliquis), rivaroxaban (Xarelto), and dabigatran (Pradaxa), among others. Anyone taking any of these medications should not add nattokinase without direct guidance from the prescribing physician.
Case reports describe a cerebellar hemorrhage in a patient also taking aspirin and a fatal hemoperitoneum in a patient taking no anticoagulant (causation unproven) [18][19].
Nattokinase should also be discontinued at least one week before any surgical or dental procedure. The fibrinolytic and antiplatelet activity that makes the enzyme pharmacologically interesting in a cardiovascular context becomes a bleeding liability in a surgical setting where clot formation is necessary for wound healing and hemostasis.
Beyond drug interactions, nattokinase is derived from soybeans and is therefore a concern for individuals with soy allergies. People with bleeding disorders, those who have recently experienced a stroke (particularly hemorrhagic stroke), or those with active ulcer disease should approach it with caution and physician consultation. Pregnant or breastfeeding individuals should avoid it due to the absence of safety data in those populations.
Regulatory Status and What It Means
In the United States, nattokinase is sold as a dietary supplement, not a drug. This regulatory category means that the FDA has not evaluated nattokinase for the purpose of treating, curing, or preventing any disease. Manufacturers are permitted to make structure-function claims, statements about how a substance may affect normal body structure or function, but are prohibited from claiming that it treats or prevents specific diseases.
This distinction matters practically. It means that supplement manufacturers are not required to demonstrate efficacy or safety to the FDA’s drug standard before selling nattokinase. It also means that quality control, potency, and purity vary across brands. When comparing products, looking for third-party testing certifications (such as USP, NSF International, or ConsumerLab) and standardized fibrinolytic activity units (FUs) on the label provides at least some assurance of what is actually in the capsule.
This is not a statement against the enzyme’s biological plausibility: the research supporting its mechanism is real. It is simply an accurate description of the regulatory landscape and what consumers should understand about the difference between a supplement with promising preliminary evidence and a clinically validated pharmaceutical.
Nattokinase vs. Eating Natto
A reasonable question is whether consuming whole natto provides the same benefits as taking a nattokinase supplement. Whole natto does contain nattokinase, and some research has used whole natto rather than isolated enzyme. However, whole natto also contains substantial amounts of vitamin K2 in the form of menaquinone-7 (MK-7). Vitamin K2 supports carboxylation of clotting factors and is directly antagonized by warfarin, so anyone on warfarin anticoagulation therapy faces a compounded drug-food interaction risk from whole natto that is more complex than from the isolated enzyme supplement (from which vitamin K2 is typically removed).
Nattokinase supplements offer a way to obtain the enzyme in a standardized dose without the accompanying vitamin K2 load, which is part of the reason the isolated supplement form is often preferred in research settings and by clinicians who are evaluating the enzyme’s specific fibrinolytic effects. That said, whole natto consumed as food in the context of a balanced diet is nutritionally valuable beyond its enzyme content and has a long history of safe dietary use in Japanese populations.
🛒 Where to Buy Nattokinase
- Doctor’s Best Nattokinase 2,000 FU
capsules, 100 mg NSK-SD per vcap (2,000 FU): Nattokinase from an established supplement brand; vegetarian capsules; 90 count - NOW Foods Nattokinase 100 mg
capsules, 100 mg per vcap (2,000 FU): Mainstream brand with third-party GMP-certified manufacturing; affordable entry-level option; 90 vcaps; widely available - Source Naturals Nattokinase 100 mg
capsules, 100 mg per tablet (2,000 FU): Long-established supplement brand; competitive pricing at 60 tablets; good for budget-conscious buyers familiar with the brand - Healthy Origins Nattokinase 2,000 FU
capsules, 100 mg per vcap (2,000 FU): Best cost-per-serving option on Amazon; 180 vcap bottle; uses NSK-SD ingredient; popular bulk buy for long-term users
As an Amazon Associate we earn from qualifying purchases. Nattokinase is sold on an enzymatic activity claim, and independent testing has repeatedly found bottles delivering well under their labelled potency. Check that the label states fibrinolytic units (FU) per capsule rather than milligrams alone, and prefer a brand that will supply a batch-specific certificate of analysis showing the measured FU result for that lot, since GMP certification alone does not verify it.
A Note on the Evidence
Most human trials on nattokinase are small, short-term, and measure surrogate markers rather than clinical outcomes like heart attack or stroke rates; the evidence is promising but not definitive. Anyone taking anticoagulants, antiplatelets, or blood pressure medications, or who has a bleeding disorder, upcoming surgery, soy allergy, or history of stroke should consult a physician before use: this article is informational only and does not constitute medical advice.
Frequently Asked Questions
What exactly does nattokinase do in the body?
Nattokinase is proposed to work through two pathways: directly cleaving fibrin, the structural protein in blood clots, and upregulating endogenous plasminogen activators like tissue plasminogen activator (tPA) that the body uses to dissolve clots naturally. In rabbit and rat plasma tests it reduced platelet aggregation, and fibrin breakdown markers rose in human studies [13][14][7].
Can I take nattokinase if I'm already on a blood thinner?
No, not without explicit guidance from your prescribing physician. Nattokinase has genuine fibrinolytic and antiplatelet activity that is additive with anticoagulant and antiplatelet medications including warfarin, heparin, aspirin, clopidogrel, apixaban, rivaroxaban, and dabigatran. Combining them may raise the risk of abnormal or dangerous bleeding; human interaction data are lacking [15].
Is nattokinase the same as eating natto?
Not exactly. Whole natto contains nattokinase but also substantial vitamin K2 (MK-7), which supports clotting factor production and complicates use in people on warfarin. Nattokinase supplements typically isolate the enzyme and remove vitamin K2, making the fibrinolytic effects more predictable and reducing the vitamin K2 interaction risk. Both contain the enzyme, but the overall biochemical profile differs.
What does the research actually show about nattokinase and blood pressure?
Small randomized trials in humans have reported mixed results: one maker-funded trial in 86 adults found lower systolic and diastolic pressure, another in 79 adults found only a diastolic fall, and a 3-year trial in 265 healthy adults found no effect [5][6][8]. These findings are statistically meaningful in context but should be interpreted carefully given the small participant counts and short trial durations: most studies run four to eight weeks. Long-term blood pressure outcomes have not been established.
When should nattokinase be stopped before surgery?
Nattokinase should be discontinued at least one week before any surgical or dental procedure. Its fibrinolytic and antiplatelet activity impairs the normal clot formation that is necessary for wound healing and stopping surgical bleeding. This is a standard precaution that applies regardless of the type of procedure.
Is nattokinase FDA-approved for cardiovascular disease?
No. Nattokinase is classified as a dietary supplement in the United States, which means the FDA has not evaluated it for treating, curing, or preventing any disease, including cardiovascular disease. It cannot legally be marketed with disease treatment claims. The research supporting its mechanism is real but preliminary, and it does not meet the evidentiary standard required for drug approval.
References
- Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. International Journal of Molecular Sciences (2017). PMID 28264497
- Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Reviews in Cardiovascular Medicine (2023). PMID 39076715
- Nattokinase: production and application. Applied Microbiology and Biotechnology (2014). PMID 25348469
- European Food Safety Authority (EFSA NDA Panel) Safety of fermented soybean extract NSK-SD as a novel food pursuant to Regulation (EC) No 258/97. European Food Safety Authority (EFSA NDA Panel) (2016). source
- Kim JY et al. Effects of nattokinase on blood pressure: a randomized, controlled trial. Hypertension research : official journal of the Japanese Society of Hypertension (2008). PMID 18971533
- Jensen GS et al. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial. Integrated blood pressure control (2016). PMID 27785095
- Yuko Kurosawa et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Scientific Reports (2015). PMID 26109079
- Hodis HN et al. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clinical hemorheology and microcirculation (2021). PMID 33843667
- Japan Bio Science Laboratory (NSK-SD maker) About NSK-SD Nattokinase. Japan Bio Science Laboratory (NSK-SD maker) (2026). source
- Pinontoan R et al. Fibrinolytic characteristics of Bacillus subtilis G8 isolated from natto. Bioscience of microbiota, food and health (2021). PMID 34285859
- Tetsumei Urano et al. The Profibrinolytic Enzyme Subtilisin NAT Purified fromBacillus subtilis Cleaves and Inactivates Plasminogen Activator Inhibitor Type 1. Journal of Biological Chemistry (2001). PMID 11325965
- Hiroyuki Sumi et al. Natto Bacillus as an Oral Fibrinolytic Agent: Nattokinase Activity and the Ingestion Effect of Bacillus subtilis natto. Food Science and Technology Research (2004). doi:10.3136/fstr.10.17
- Ja‐Young Jang et al. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation. Laboratory Animal Research (2013). PMID 24396387
- Jae-Bum Kim et al. Evaluation of Nattokinase for Antithrombotic Effect and Pharmacological Efficacy by a Biological Test and Clinical Trial. KSBB Journal (2011). doi:10.7841/ksbbj.2011.26.5.393
- Chen H et al. Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases. Biomarker insights (2018). PMID 30013308
- Muric M et al. Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings. Biomolecules (2024). PMID 39199344
- Health Canada Licensed Natural Health Product NPN 80089299: Nattokinase 100 mg. Health Canada (2026). source
- Chang YY et al. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Internal medicine (Tokyo, Japan) (2008). PMID 18310985
- Lintu Ramachandran et al. Nattokinase-Associated Hemoperitoneum in an Elderly Woman. Cureus (2021). PMID 35003944
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Content is for informational purposes only and is not medical advice; consult a qualified healthcare provider before starting any supplement. As an Amazon Associate we earn from qualifying purchases.
