Affiliate disclosure: Some links in this article are affiliate links. We may earn a commission at no additional cost to you.

Medical disclaimer: This article reviews research on nattokinase, a fibrinolytic enzyme derived from fermented soybeans. It is not medical advice, diagnosis, or treatment. Not medical advice. Consult a qualified healthcare professional before changing your diet, supplement regimen, or any cardiovascular health management plan — particularly if you take anticoagulant or antiplatelet medication.

What the decision actually looks like

You have heard that natto is good for the heart, or that nattokinase supplements may support healthy blood pressure. You want to know whether there is trial data, what the effect sizes look like, and whether this is something worth taking seriously.

The honest position: nattokinase sits in the middle tier of supplement evidence. It has more human RCT data than most plant-derived supplements, but the trials are short, the populations are specific, and no long-term event study has been completed. The blood pressure signal is real enough to understand precisely — which means understanding both where it holds and where it stops.

Where nattokinase comes from

Natto is fermented soybeans, a traditional Japanese food with a centuries-long history in the Kanto region, particularly in Ibaraki and Chiba prefectures. The fermentation is driven by Bacillus subtilis natto, a bacterium that breaks down soy protein and generates a range of bioactive compounds, including vitamin K2 (menaquinone-7) and the enzyme that concerns us here.

Nattokinase (NK) is a serine protease first isolated and characterized by Japanese researcher Hiroyuki Sumi at the Chicago Medical School in 1987. Sumi’s original observation was that a natto extract dissolved a fibrin clot placed in a laboratory dish — an in vitro result that opened a sustained line of research.

The supplement form is an extracted and concentrated version of the enzyme, standardized in Fibrinolytic Units (FU). It is distinct from eating natto, which also delivers vitamin K2, isoflavones, and dietary fiber, but in quantities and enzymatic activity that vary with preparation and commercial source. Studies on natto-as-food and studies on nattokinase supplements are measuring different exposures and should not be conflated.

How the enzyme works: the mechanism

Nattokinase is a fibrinolytic enzyme — it breaks down fibrin, the protein network that forms clots. Two proposed pathways:

• Direct fibrinolysis: cleaving fibrin directly, in a manner analogous to plasmin (the body’s native fibrin-dissolving enzyme)
• Plasminogen activator stimulation: upregulating endogenous fibrinolysis by increasing tissue plasminogen activator (tPA) activity and reducing plasminogen activator inhibitor-1 (PAI-1)

Both mechanisms have been demonstrated in vitro and in animal models. The translation to human outcomes is more complicated. Nattokinase is a protein, and dietary proteins face degradation in the gastrointestinal tract. Whether and how much enzymatically active nattokinase crosses the gut wall and reaches systemic circulation is debated. Some human trials have measured circulating fibrinolysis markers and found changes; others have not.

The blood pressure mechanism appears to involve separate pathways. Proposed mechanisms include ACE-inhibitory peptides generated during fermentation and direct effects on vascular smooth muscle. The pathway has not been fully characterized under controlled trial conditions, and the blood pressure reduction observed in trials may be partly independent of fibrinolytic activity.

The RCT evidence on blood pressure

The most methodologically useful human trial to date is Kim et al. 2008 (Hypertension Research, vol. 31, pp. 1583–1588; PubMed 18971533). Design:

• Subjects: 86 adults aged 20–80 with pre-hypertension or stage 1 hypertension (systolic 130–159 mmHg at baseline)
• Intervention: 2,000 FU nattokinase per day for 8 weeks versus placebo
• Primary outcomes: systolic and diastolic blood pressure

Summary of results:

Outcome	Nattokinase group	Placebo group	Net difference
Systolic BP change	approximately −5.5 mmHg	approximately −2.5 mmHg	approximately −3 mmHg
Diastolic BP change	approximately −3 mmHg	approximately −1 mmHg	approximately −2 mmHg

The differences were statistically significant for both systolic and diastolic pressure. A net systolic reduction of approximately 3 mmHg versus placebo is clinically meaningful at the population level — sufficient to shift cardiovascular risk in a meaningful direction across a large group — though modest compared to first-line antihypertensive medications, which typically produce 8–15 mmHg reductions at standard doses.

A 2018 review of multiple nattokinase blood pressure RCTs pooled results from eight trials and reported a net systolic reduction of approximately 3–5 mmHg across studies, broadly consistent with the Kim et al. result. The review noted significant heterogeneity across trials — different doses, populations, and baseline blood pressure levels — which limits how firmly to hold the pooled estimate.

What the RCT literature supports: at 2,000–4,000 FU/day over 8–12 weeks, nattokinase is associated with modest reductions in systolic blood pressure in adults with elevated baseline blood pressure. This is a replicable signal across multiple independent trials.

What the RCT literature does not support: any claim that nattokinase produces the effect sizes of antihypertensive drugs, generates durable cardiovascular outcomes, or benefits adults with normal baseline blood pressure. No long-term event trial (stroke, myocardial infarction, cardiovascular death) has been completed with nattokinase.

The fibrinolysis evidence

The fibrinolysis data is more preliminary than the blood pressure data.

Several small trials have measured circulating fibrinolysis markers — D-dimer, PAI-1, tPA activity — after nattokinase supplementation at 2,000–4,000 FU/day. A number of these trials, including work published in Annals of Nutrition and Metabolism and similar journals in the 2010s, reported changes consistent with increased fibrinolytic activity: elevated tPA and reduced PAI-1 in healthy subjects over 8–12 weeks.

The methodological limitations are more serious at this evidence level:

• These are surrogate endpoints, not clot events. The clinical meaning of modest marker changes in healthy adults is unclear.
• Trial populations are typically small (20–60 subjects), follow-up is short, and baseline fibrinolysis status varies.
• No trial has randomized people to nattokinase and measured actual thromboembolic outcomes as a primary endpoint.

For anyone asking whether nattokinase has meaningful fibrinolytic effects in humans: the marker-level evidence suggests some activity at typical supplement doses, but whether this affects real clotting risk — in either a protective or a potentially problematic direction for anticoagulation-sensitive patients — is not established by the current trial record.

Drug interactions and who should not take this

This section is the most clinically important for most readers.

Because nattokinase has demonstrated fibrinolytic and potentially antiplatelet-like activity, combining it with anticoagulant or antiplatelet drugs is a meaningful concern. Specific issues:

• Warfarin (Coumadin): case reports in the clinical literature document elevated INR when nattokinase is added to warfarin therapy. This combination is generally flagged as contraindicated in clinical guidance, not merely cautioned.
• Aspirin, clopidogrel, and related antiplatelet agents: additive effect is plausible on mechanistic grounds; trial data on the interaction is limited, but combination use is consistently flagged in clinical references.
• Direct oral anticoagulants (rivaroxaban, apixaban, dabigatran): no direct interaction trial data, but the theoretical concern parallels the warfarin risk.
• NSAIDs taken regularly: mild antiplatelet overlap; lower concern than anticoagulants, but worth noting.

Populations where a physician consultation is required before considering nattokinase:

• Anyone currently taking anticoagulants or antiplatelet medication
• Anyone with a bleeding disorder, recent surgery, or upcoming procedure
• Anyone with a history of hemorrhagic stroke or active bleeding risk
• Pregnant or breastfeeding women (no safety data)

For patients on warfarin or a direct oral anticoagulant, nattokinase is not a benign add-on supplement. This interaction is the primary safety flag for this enzyme and needs to be discussed with the prescribing clinician.

Dose and form

Study doses cluster at 2,000–4,000 FU per day. Consumer supplements are typically sold in 100–200 mg capsules standardized to approximately 2,000 FU per capsule. There is no trial evidence supporting benefit above 4,000 FU/day, and no clear dose-response advantage between 2,000 and 4,000 FU from the blood pressure RCTs.

Two practical considerations on form:

• Enteric-coated capsules are marketed on the basis of protecting the enzyme from gastric acid. Some fibrinolysis marker data supports modestly better outcomes with enteric coating; the evidence is not definitive, but the theoretical rationale is sound.
• Vitamin K2: nattokinase supplements do not contain meaningful amounts of vitamin K2. If MK-7 is also a goal — which it may be for individuals interested in natto’s other proposed effects on arterial calcification markers — a separate MK-7 supplement or eating natto food is needed. Some combination products exist; check labels to confirm both components and doses.

How to source nattokinase supplements

iHerb carries several nattokinase products with certificates of analysis, including Doctor’s Best Nattokinase (2,000 FU) and NOW Foods Nattokinase — both mid-range, established products at the dose tier supported by trial data.

Amazon US has wider selection at comparable prices. The practical filter when shopping either platform: look for a stated FU standardization on the label (not milligrams alone), a current certificate of analysis from the brand, and mid-range pricing. Products priced below approximately $15 for a 60-day supply often do not carry reliable FU documentation.

Expect to pay $20–35 for a 60–90 day supply at 2,000 FU/day from mainstream retailers in 2026.

If you prefer the food source rather than the supplement, natto is available frozen from Japanese grocery stores and online specialty retailers. For context on natto as a food, the fermentation profile, and probiotic considerations, see our best Japanese probiotics and gut health guide.

What the evidence actually supports

At 2,000–4,000 FU/day over 8–12 weeks, nattokinase is associated with modest reductions in systolic blood pressure — roughly 3–5 mmHg net versus placebo — in adults with elevated baseline blood pressure. This is one of the more replicable blood pressure signals in the plant-derived supplement category, supported by at least one methodologically solid small RCT and several smaller confirming trials.

The fibrinolytic mechanism has human biomarker evidence, but no clinical outcome data exists. The drug interaction profile — particularly with warfarin and other anticoagulants — is the most important practical consideration for most adults evaluating this supplement.

For an adult with modestly elevated blood pressure who is not on anticoagulant medication and has already addressed the foundational variables (sodium intake, exercise, sleep quality), a 12-week trial at 2,000 FU/day is a calibrated approach worth discussing with their physician. The blood pressure effect, if it materializes, will be modest — not transformative — but is consistent with the trial record.

For anyone already managing cardiovascular conditions with prescription medication, that conversation with a clinician is not optional before adding nattokinase.

---

See also: Best Japanese probiotics and gut health supplements, NMN vs NR: what human trials actually show, 5 Japanese longevity habits backed by research.