The Science Behind Nattokinase.

Four decades of peer-reviewed research, summarized without spin. Every claim on this page is sourced from a published study. Read it. Pressure-test it. Then decide.

AT A GLANCE

40+

years since nattokinase's fibrinolytic activity was first characterized (Sumi, 1987).

1,062

participants in the largest published clinical trial of nattokinase (Chen, 2022).

6

randomized controlled trials pooled in the most recent meta-analysis (Li, 2023).

0

notable adverse events reported across the studies in that meta-analysis.

How it actually works.

Nattokinase is an enzyme isolated from nattō, the traditional Japanese fermented soybean. Its mechanism of action is unusual: it operates on the cardiovascular system through three distinct, well-characterized pathways.

01

Direct fibrin cleavage

Nattokinase is a serine protease that hydrolyzes fibrin — the structural protein that makes up blood clots — directly, without requiring activation by other enzymes.

02

Activates the body's own clot-clearing system

It potentiates endogenous fibrinolysis by raising plasmin activity and inactivating plasminogen activator inhibitor-1 (PAI-1), the brake on the body's natural clot-resolution pathway.

03

Reduces vascular pressure

Across randomized trials, supplementation has produced consistent, modest reductions in both systolic and diastolic blood pressure, with effects appearing within 8 weeks in most studies.

The studies, on the record.

Nattokinase is an enzyme isolated from nattō, the traditional Japanese fermented soybean. Its mechanism of action is unusual: it operates on the cardiovascular system through three distinct, well-characterized pathways.

Key findings from the study

“A significant reduction in the thickness of the carotid artery intima-media and the size of the carotid plaque was observed. The improvement rates ranged from 66.5 to 95.4%.”

Retrospective clinical study · 1,062 participants · 12 months · 10,800 FU/day

Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants

The largest published clinical study of nattokinase to date. At a daily dose of 10,800 FU over 12 months, the authors observed a significant reduction in carotid plaque size and intima-media thickness. The study also found that a lower dose of 3,600 FU produced no measurable effect — a finding the authors describe as a direct challenge to the commonly recommended dose of 2,000 FU.

Chen H, Chen J, Zhang F, et al. Front Cardiovasc Med. 2022;9:964977. doi:10.3389/fcvm.2022.964977
Read the full study on PubMed Central →
Key findings from the study

“Nattokinase supplementation significantly reduced systolic blood pressure (MD = −3.45, 95% CI: −4.37 to −2.18, p < 0.00001) and diastolic blood pressure (MD = −2.32, 95% CI: −2.72 to −1.92, p < 0.00001).”

Systematic review & meta-analysis · 6 RCTs · 546 participants

Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

A 2023 meta-analysis pooling six randomized controlled trials of nattokinase supplementation. Across 546 participants, the authors found statistically significant reductions in both systolic and diastolic blood pressure compared to placebo, with the conclusion that nattokinase “can be used as an effective adjunctive therapy for hypertension.” No notable adverse events were reported in any of the included studies.

Li X, Long J, Gao Q, et al. Rev Cardiovasc Med. 2023;24(8):234. doi:10.31083/j.rcm2408234
Read the full study on PubMed Central →
Key findings from the study

“A single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.”

Double-blind, placebo-controlled crossover · 12 healthy males · 2,000 FU single dose

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles

A randomized, double-blind, placebo-controlled crossover trial measuring the acute fibrinolytic response to a single oral dose. The authors reported significant elevations in D-dimer and fibrin/fibrinogen degradation products, alongside reductions in Factor VIII activity and prolongation of aPTT — all within normal physiological ranges. Evidence that even a single dose engages multiple coagulation pathways.

Kurosawa Y, Nirengi S, Homma T, et al. Sci Rep. 2015;5:11601. doi:10.1038/srep11601
Read the full study on PubMed Central →
Key findings from the study

“Oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.”

Open-label clinical trial · 45 subjects · 8 weeks

Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects

An open-label trial across three groups: healthy volunteers, patients with cardiovascular risk factors, and dialysis patients. After two months of nattokinase supplementation, fibrinogen, factor VII, and factor VIII — three established markers of cardiovascular risk — declined significantly across every group. No notable adverse events were observed in any subject.

Hsia CH, Shen MC, Lin JS, et al. Nutr Res. 2009;29(3):190–196. doi:10.1016/j.nutres.2009.01.009
Read the abstract on PubMed →

What the long record shows.

Tolerability

Across the six randomized trials in the 2023 meta-analysis (Li et al.), no notable adverse events were attributed to nattokinase supplementation. A 2021 post-market surveillance study in Nutrients (Gallelli et al.) supported the same conclusion in patients with vascular disease

Who should talk to a doctor first

Anyone taking prescription anticoagulant or antiplatelet medication (warfarin, apixaban, clopidogrel, aspirin), anyone with a bleeding disorder, pregnant or nursing women, and anyone scheduled for surgery within two weeks. Nattokinase is a supplement — it does not replace prescribed therapy.

The Science Behind Nattokinase.

Four decades of peer-reviewed research, summarized without spin. Every claim on this page is sourced from a published study. Read it. Pressure-test it. Then decide.

AT A GLANCE

40+

years since nattokinase's fibrinolytic activity was first characterized (Sumi, 1987).

1,062

participants in the largest published clinical trial of nattokinase (Chen, 2022).

6

randomized controlled trials pooled in the most recent meta-analysis (Li, 2023).

0

notable adverse events reported across the studies in that meta-analysis.

How it actually works.

Nattokinase is an enzyme isolated from nattō, the traditional Japanese fermented soybean. Its mechanism of action is unusual: it operates on the cardiovascular system through three distinct, well-characterized pathways.

01

Direct fibrin cleavage

Nattokinase is a serine protease that hydrolyzes fibrin — the structural protein that makes up blood clots — directly, without requiring activation by other enzymes.

02

Activates the body's own clot-clearing system

It potentiates endogenous fibrinolysis by raising plasmin activity and inactivating plasminogen activator inhibitor-1 (PAI-1), the brake on the body's natural clot-resolution pathway.

03

Reduces vascular pressure

Across randomized trials, supplementation has produced consistent, modest reductions in both systolic and diastolic blood pressure, with effects appearing within 8 weeks in most studies.

The studies, on the record.

We've selected four publications that represent the strongest available human evidence for nattokinase — the trials most often cited, peer-reviewed, and independently replicated.

Key findings from the study

“A significant reduction in the thickness of the carotid artery intima-media and the size of the carotid plaque was observed. The improvement rates ranged from 66.5 to 95.4%.“

Retrospective clinical study · 1,062 participants · 12 months · 10,800 FU/day

Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants

The largest published clinical study of nattokinase to date. At a daily dose of 10,800 FU over 12 months, the authors observed a significant reduction in carotid plaque size and intima-media thickness. The study also found that a lower dose of 3,600 FU produced no measurable effect — a finding the authors describe as a direct challenge to the commonly recommended dose of 2,000 FU.

Chen H, Chen J, Zhang F, et al. Front Cardiovasc Med. 2022;9:964977. doi:10.3389/fcvm.2022.964977
Read the full study on PubMed Central →
Key findings from the study

“Nattokinase supplementation significantly reduced systolic blood pressure (MD = −3.45, 95% CI: −4.37 to −2.18, p < 0.00001) and diastolic blood pressure (MD = −2.32, 95% CI: −2.72 to −1.92, p < 0.00001).“

Systematic review & meta-analysis · 6 RCTs · 546 participants

Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

A 2023 meta-analysis pooling six randomized controlled trials of nattokinase supplementation. Across 546 participants, the authors found statistically significant reductions in both systolic and diastolic blood pressure compared to placebo, with the conclusion that nattokinase can be used as an effective adjunctive therapy for hypertension. No notable adverse events were reported in any of the included studies.

Li X, Long J, Gao Q, et al. Rev Cardiovasc Med. 2023;24(8):234. doi:10.31083/j.rcm2408234
Read the full study on PubMed Central →
Key findings from the study

“A single-dose of NK administration appears enhancing fibrinolysis and anti-coagulation via several different pathways simultaneously.“

Double-blind, placebo-controlled crossover · 12 healthy males · 2,000 FU single dose

A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles

A randomized, double-blind, placebo-controlled crossover trial measuring the acute fibrinolytic response to a single oral dose. The authors reported significant elevations in D-dimer and fibrin/fibrinogen degradation products, alongside reductions in Factor VIII activity and prolongation of aPTT — all within normal physiological ranges. Evidence that even a single dose engages multiple coagulation pathways.

Kurosawa Y, Nirengi S, Homma T, et al. Sci Rep. 2015;5:11601. doi:10.1038/srep11601
Read the full study on PubMed Central →
Key findings from the study

“Oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.“

Open-label clinical trial · 45 subjects · 8 weeks

Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects

An open-label trial across three groups: healthy volunteers, patients with cardiovascular risk factors, and dialysis patients. After two months of nattokinase supplementation, fibrinogen, factor VII, and factor VIII — three established markers of cardiovascular risk — declined significantly across every group. No notable adverse events were observed in any subject.

Hsia CH, Shen MC, Lin JS, et al. Nutr Res. 2009;29(3):190–196. doi:10.1016/j.nutres.2009.01.009
Read the abstract on PubMed →

What the long record shows.

Tolerability

Across the six randomized trials in the 2023 meta-analysis (Li et al.), no notable adverse events were attributed to nattokinase supplementation. A 2021 post-market surveillance study in Nutrients (Gallelli et al.) supported the same conclusion in patients with vascular disease

Who should talk to a doctor first

Anyone taking prescription anticoagulant or antiplatelet medication (warfarin, apixaban, clopidogrel, aspirin), anyone with a bleeding disorder, pregnant or nursing women, and anyone scheduled for surgery within two weeks. Nattokinase is a supplement — it does not replace prescribed therapy.

Parting Thoughts

A high-quality nattokinase supplement should do three things well: deliver a clinically meaningful dose, pair the enzyme with the cofactors your cardiovascular system actually needs, and protect that enzyme through digestion so it reaches your bloodstream intact. NatoCore was built around all three.

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