In 1987, a Japanese researcher working at a laboratory in Chicago made an observation that would quietly reshape interest in food-derived enzymes and cardiovascular health. Dr. Hiroyuki Sumi, then studying natural thrombolytic compounds at the University of Chicago Medical School, placed a small amount of natto, a traditional Japanese fermented soybean food, onto a laboratory fibrin clot. What happened next became one of the more cited origin stories in functional food research.
The enzyme Sumi identified and named nattokinase is a serine protease produced by Bacillus subtilis natto during fermentation. It degrades fibrin directly and appears to upregulate the body’s own plasminogen activators, giving it measurable fibrinolytic activity in laboratory and human settings.[1] This article traces the history of that discovery, explains the proposed mechanism in plain terms, and is honest about where the evidence is strong and where it remains preliminary.
Key Takeaways
- Dr. Hiroyuki Sumi discovered nattokinase in 1987 while testing natto on a laboratory fibrin clot, observing rapid dissolution at body temperature.
- Nattokinase is a serine protease produced by Bacillus subtilis natto fermentation; it breaks down fibrin directly and upregulates the body’s own plasminogen activators.
- Small human trials have reported modest and mixed effects on coagulation markers and blood pressure [6][7], but long-term cardiovascular outcomes data does not yet exist.
- Nattokinase must not be combined with warfarin, heparin, aspirin, clopidogrel, or other anticoagulants or antiplatelets without physician supervision due to serious bleeding risk.
- The FDA has not evaluated nattokinase for treating, curing, or preventing any disease; this article is informational, not medical advice.
Who Was Dr. Hiroyuki Sumi?
Dr. Hiroyuki Sumi was a Japanese biochemist with a research focus on thrombolytic, clot-dissolving, enzymes. During the 1980s, he was associated with the University of Chicago Medical School, where he was investigating naturally occurring substances capable of breaking down fibrin, the protein that forms the structural mesh of blood clots. His work sat at the intersection of enzymology and cardiovascular biology, fields that were drawing significant interest as researchers sought alternatives or complements to pharmaceutical thrombolytics.
Sumi brought to this work a familiarity with natto, a fermented soybean preparation long consumed in Japan, particularly in the Kanto and Tohoku regions. Natto has a distinctive sticky texture and strong flavor produced by Bacillus subtilis natto fermentation, and it had been part of the Japanese diet for centuries. Sumi’s insight was to ask whether the fermentation process itself might produce enzymes with biological activity beyond nutrition: a question that turned out to have a concrete answer.
The 1987 Discovery: An Observation in the Lab
The discovery is often described as partially accidental, in the tradition of many productive scientific observations. According to accounts Sumi himself gave in subsequent interviews and publications, he placed natto directly onto a laboratory fibrin clot and left it at body temperature (37°C). According to those accounts, the clot dissolved: a rate he described as far exceeding what other food-derived substances he had tested had produced. The effect was striking enough that Sumi named the responsible enzyme ‘nattokinase,’ using the ‘-kinase’ suffix loosely to describe its thrombus-dissolving activity, though technically it functions as a protease rather than a true kinase.
Research note: In rats with an acetic-acid-induced carotid artery clot, nattokinase restored 62.0% of arterial blood flow on a molar basis, versus 15.8% for plasmin and 0% for elastase [12].
Sumi’s initial publication in 1987 described the enzyme’s fibrinolytic activity and its extraction from natto. This work established the foundational characterization: nattokinase is a serine protease, meaning it uses a serine residue at its active site to cleave peptide bonds, with a characteristic molecular weight. It acts on fibrin directly and also appears to stimulate the body’s intrinsic fibrinolytic system by promoting plasminogen activators. The 1987 paper gave researchers a reproducible starting point, and the subsequent decades brought increasing interest in whether laboratory fibrinolysis translated to meaningful human health effects.
Why Natto? The Role of Bacillus subtilis Fermentation
Natto is produced by fermenting cooked soybeans with Bacillus subtilis natto, a bacterial strain that has been used in Japanese food preparation for over a thousand years. The fermentation process does more than preserve the soybeans: it generates a range of enzymes and bioactive compounds as metabolic byproducts of bacterial activity. Nattokinase is one such byproduct: the bacteria produce it as part of their own biochemical processes, and it accumulates in significant concentrations in the finished food.
Other fermented foods also contain proteolytic enzymes, but nattokinase from B. subtilis natto has strong fibrin-degrading activity in lab tests, although heating a nattokinase solution to 70 degrees C or higher deactivated it in one lab study, and EFSA said the supplied data could not show whether active nattokinase is absorbed [3][4]. Sumi’s work helped explain why populations with high natto consumption had drawn epidemiological attention in Japan, though establishing causation from dietary patterns to cardiovascular outcomes remains methodologically difficult and was not something the 1987 discovery claimed to do.
The enzyme survives the gastrointestinal environment well enough to retain activity: a practical requirement for any orally consumed enzyme intended to act systemically. Research since Sumi’s initial work has examined absorption, stability at various pH levels, and whether nattokinase intact or in fragments reaches the bloodstream. A review reports that intact nattokinase was detected in the serum of healthy people after a single 2,000 FU dose, but EFSA said the supplied data could not show whether active nattokinase or any functional metabolite is absorbed [1][4].
The Proposed Mechanism: How Nattokinase Works
Nattokinase works through at least two complementary pathways. First, it acts directly on fibrin by cleaving specific peptide bonds within the fibrin mesh, physically breaking down clot material. Second, it appears to upregulate tissue plasminogen activator (t-PA) and urokinase, enzymes the body naturally uses to dissolve clots, while also degrading plasminogen activator inhibitor type 1 (PAI-1), a molecule that otherwise suppresses fibrinolysis. The net effect is both a direct fibrinolytic action and an amplification of the body’s own clot-clearing machinery.
As a serine protease, nattokinase shares structural and mechanistic features with other enzymes in this class, including plasmin and the bacterial enzyme subtilisin from which it derives. Its substrate specificity, the molecular ‘targets’ it prefers to cleave, makes it relatively selective for fibrin over other plasma proteins, though it is not perfectly selective. This selectivity is relevant to both its potential utility and its safety profile.
Researchers have also examined nattokinase’s effects on platelet aggregation and blood viscosity. Some small human trials have reported modest reductions in blood pressure (a 2023 meta-analysis of a few small trials found about 3.45 mmHg systolic and 2.32 mmHg diastolic), but results are mixed: one trial found only a diastolic fall, and a 3-year trial in 265 healthy adults found no effect on blood pressure. In a single-dose study in healthy young men, coagulation changes stayed within the normal range [5][6][7][8]. Because these trials are generally small, short in duration, and vary in dosing protocol, the findings are suggestive rather than definitive. The FDA has not approved nattokinase for treating, preventing, or curing any disease.
From Discovery to Supplement: The Decades After 1987
Sumi’s 1987 finding generated a body of follow-on research spanning in vitro studies, animal models, and eventually small randomized human trials. The enzyme was extracted, purified, and eventually produced at scale for dietary supplement use. Standardization became an important consideration: nattokinase activity is measured in Fibrinolytic Units (FU) or nattokinase units (NKU), and products on the market vary considerably in their stated potency.[2]
Regulators have reviewed nattokinase, but a listing or licence is not proof that it works
Assessed one branded ingredient
EFSA assessed the novel food NSK-SD at a proposed maximum of 100 mg per day. Using a rat no-effect level, it judged the margin of exposure of 700 sufficient.
Human studies were not enough
The human studies supplied were too low-powered and inconsistent to conclude on safety of the ingredient.
Listed, not approved
FDA's New Dietary Ingredient notification list includes nattokinase products. That is a listing, and a review of blood thinner alternatives notes nattokinase is not FDA-approved.
Licensed for general support only
One licence authorises only general cardiovascular support, and its label says not to use with products that affect blood coagulation.
Regulatory status tells you about safety review and labelling, not about benefit.
EFSA's opinion covers one branded ingredient, not every nattokinase product. Source: European Food Safety Authority (EFSA NDA Panel) 2016; U.S. Food and Drug Administration 2026; Muric et al., Biomolecules 2024; Health Canada 2026.
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Interest in nattokinase grew notably in Western markets during the 1990s and 2000s as consumers sought alternatives and adjuncts to pharmaceutical cardiovascular interventions. This commercialization ran ahead of the clinical evidence base: a pattern common in the supplement industry. The honest picture is that nattokinase has demonstrated real fibrinolytic activity in rigorous in vitro and ex vivo models, and some small human trials have shown statistically significant blood pressure changes (not seen in a 3-year trial of 265 healthy adults) and shifts in coagulation markers, but the trials are small [7][8] and the long-term cardiovascular outcomes data that would satisfy regulatory or clinical practice standards does not yet exist.
Sumi continued contributing to nattokinase research and became a prominent advocate for natto’s health properties in Japan. His original discovery gave the field a credible biochemical foundation, and that foundation remains the basis for ongoing investigation into nattokinase’s therapeutic potential.
Safety, Interactions, and Honest Caveats
Because nattokinase has genuine fibrinolytic and antiplatelet activity, it carries real interaction risks that should not be minimized by framing it as simply a food-derived supplement. Combining nattokinase with anticoagulants (warfarin, heparin, direct oral anticoagulants) or antiplatelet medications such as aspirin or clopidogrel without physician supervision creates a meaningful risk of excess bleeding. Direct human interaction data are lacking, but this is more than theory: a case report describes a cerebellar hemorrhage in a patient taking aspirin who added nattokinase, and the Health Canada licence for a nattokinase capsule says not to use it with products that affect blood coagulation [9][10][11].
Anyone scheduled for surgery or a procedure should discontinue nattokinase at least one week in advance, consistent with the general guidance applied to supplements with anticoagulant or antiplatelet activity. People with bleeding disorders, a history of hemorrhagic stroke, or active bleeding should not use nattokinase. Pregnant or breastfeeding individuals should consult a physician before use, as human safety data in these populations is not available. As with any supplement, the absence of FDA approval for treating disease means product quality and dosing vary: selecting products from manufacturers with third-party testing and transparent FU labeling is advisable.
🛒 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
The evidence supporting nattokinase’s human health benefits comes primarily from small, short-duration trials, and the FDA has not approved it for any medical use; this article is informational only and does not constitute medical advice. Nattokinase has meaningful fibrinolytic and antiplatelet activity and must not be used alongside anticoagulants or antiplatelet medications without physician supervision, and it should be discontinued at least one week before any surgical or invasive procedure.
Frequently Asked Questions
When exactly did Dr. Sumi discover nattokinase?
Dr. Hiroyuki Sumi published his initial findings on nattokinase in 1987. The discovery followed laboratory experiments in which he placed natto on a fibrin clot and observed dissolution within approximately 18 hours at body temperature, leading him to identify and name the responsible enzyme.
What does nattokinase actually do in the body?
Nattokinase is a serine protease that cleaves fibrin directly, breaking down the protein mesh of blood clots. It also appears to upregulate tissue plasminogen activator and urokinase while degrading plasminogen activator inhibitor type 1, amplifying the body’s own fibrinolytic system. These mechanisms have been characterized in laboratory and some human studies, though clinical outcomes evidence remains limited.
Is nattokinase the same as eating natto?
Nattokinase is an enzyme found in natto, the fermented soybean food, and is also available as a concentrated dietary supplement measured in Fibrinolytic Units or nattokinase units. Eating natto provides nattokinase alongside other nutrients and compounds in the whole food, while supplements deliver isolated enzyme at standardized (though variable) potencies. The two are related but not interchangeable from a dosing perspective.
Can I take nattokinase with my blood thinner?
No, not without physician supervision. Nattokinase has real fibrinolytic and antiplatelet activity, and combining it with anticoagulants such as warfarin or heparin, or antiplatelet agents such as aspirin or clopidogrel, significantly increases the risk of bleeding. Consult your prescribing physician before adding nattokinase to any regimen that includes these medications.
Has nattokinase been approved by the FDA for any condition?
No. The FDA has not evaluated nattokinase for treating, curing, or preventing any disease. It is sold as a dietary supplement in the United States, not as a drug. Supplement manufacturers are not permitted to make disease treatment claims, and the clinical evidence base, while suggestive, does not meet the standard required for pharmaceutical approval.
Why is the discovery called a 'breakthrough' if the evidence is still limited?
Sumi’s 1987 work was a genuine scientific contribution because it identified and characterized a specific enzyme with measurable fibrinolytic activity derived from a widely consumed traditional food. That characterization gave researchers a reproducible target for study. Calling the human health evidence ‘limited’ is accurate (small, short-term trials are not the same as large randomized controlled trials) but it does not diminish the biochemical validity of the original discovery, which has been consistently replicated.
References
- Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. International Journal of Molecular Sciences (2017). PMID 28264497
- Nattokinase: production and application. Applied Microbiology and Biotechnology (2014). PMID 25348469
- Chieko Yatagai et al. Nattokinase-Promoted Tissue Plasminogen Activator Release from Human Cells. Pathophysiology of Haemostasis and Thrombosis (2007). PMID 19996631
- 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
- Li X et al. Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Reviews in cardiovascular medicine (2023). PMID 39076715
- 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
- Hodis HN et al. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clinical hemorheology and microcirculation (2021). PMID 33843667
- Yuko Kurosawa et al. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Scientific Reports (2015). PMID 26109079
- Chen H et al. Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases. Biomarker insights (2018). PMID 30013308
- 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
- Health Canada Licensed Natural Health Product NPN 80089299: Nattokinase 100 mg. Health Canada (2026). source
- Fujita M et al. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat. Biological & pharmaceutical bulletin (1995). PMID 8593442
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.
