tuneTypical Dose
About 2,000 FU/day is the most common studied amount
Supplement
Nattokinase
Nattokinase
Evidence TierDWADA NOT PROHIBITED
watchEffect Window
Human studies generally ran 8 weeks.
check_circleCompliance
WADA NOT PROHIBITED
Overview
Clinical Summary
Nattokinase has limited but real human evidence for modest blood-pressure and hemostatic biomarker effects, but it is often marketed far beyond what the data support.
Nattokinase is best known for fibrinolytic marketing claims, yet the human evidence is much narrower than the sales language suggests. Small trials show modest blood-pressure lowering and changes in selected coagulation-related biomarkers over 8 weeks, but there is no strong evidence that nattokinase prevents cardiovascular events or safely substitutes for antithrombotic medication. The right framing is cautious and limited.
Nattokinase is a proteolytic enzyme derived from fermented soy that may influence fibrin turnover and selected hemostatic pathways, with limited human evidence for downstream blood-pressure and biomarker effects.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Modest blood-pressure reduction in small trials
- Reduced fibrinogen and selected coagulation-related biomarkers in a small uncontrolled study
Secondary Outcomes
- No reliable evidence for cardiovascular event prevention
- No reliable evidence that it safely substitutes for anticoagulant or antiplatelet therapy
Safety
Contraindications and Interactions
Contraindications
- Anticoagulant or antiplatelet medication use
- Upcoming surgery or invasive dental procedure
- Soy allergy
Side effects
- Easy bruising or bleeding concern
- Stomach upset
Interactions
- Anticoagulants or antiplatelet drugs
Avoid if
- You are using it instead of evidence-based blood-thinning or blood-pressure therapy
Evidence
Study-level References
nk-SRC-001Randomized controlled trial
Sourceopen_in_newKim JY, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K, Inoue K, Park S, Jang Y, Lee JH. Effects of nattokinase on blood pressure. A randomized, controlled trial. Hypertens Res. 2008;31(8):1583-1588. doi:10.1038/hr.2008.111. PMID:18971533.
Population: Adults aged 20 to 80 years with prehypertension or stage 1 untreated hypertension.
Dose protocol: 2,000 FU/day for 8 weeks in adults with prehypertension or stage 1 hypertension
Key findings: Net blood-pressure reduction versus placebo was about 5.6 mmHg systolic and 2.8 mmHg diastolic.
Notes: Best early randomized blood-pressure trial.
Paper content
Nattokinase lowered systolic and diastolic blood pressure over 8 weeks in adults with untreated elevated blood pressure, with a parallel reduction in plasma renin activity versus placebo.
nk-SRC-002Randomized controlled trial
Sourceopen_in_newJensen GS, Lenninger M, Ero MP, Benson KF. Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker. Integr Blood Press Control. 2016;9:95-104. doi:10.2147/IBPC.S99553. PMID:27785095.
Population: North American adults with elevated blood pressure.
Dose protocol: 100 mg/day for 8 weeks in adults with elevated blood pressure
Key findings: Diastolic blood pressure improved and selected hemostatic markers shifted in subgroup analyses.
Notes: Useful modern placebo-controlled confirmation, though several findings were subgroup-specific.
Paper content
In this placebo-controlled 8-week trial, nattokinase modestly lowered blood pressure and shifted selected hemostatic markers, though several effects appeared sex- or subgroup-specific.
nk-SRC-003Open-label intervention
Sourceopen_in_newHsia CH, Shen MC, Lin JS, Wen YK, Hwang KL, Cham TM, Yang NC. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009;29(3):190-196. doi:10.1016/j.nutres.2009.01.009. PMID:19358933.
Population: Healthy volunteers, patients with cardiovascular risk factors, and patients on dialysis.
Dose protocol: 2,000 FU/day for 2 months across healthy and high-risk adults
Key findings: Fibrinogen and clotting-factor biomarkers declined, while lipids did not materially change.
Notes: Interesting but uncontrolled biomarker study.
Paper content
In a small uncontrolled human study, nattokinase supplementation lowered several coagulation-related biomarkers over 2 months, but did not materially change blood lipids.
nk-pmid-33843667Double-blind, randomized, placebo-controlled trial.
Sourceopen_in_newHodis HN, Mack WJ, Meiselman HJ, Kalra V, Liebman H, Hwang-Levine J, et al. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clin Hemorheol Microcirc. 2021;78(4):339-353. doi:10.3233/CH-211147. PMID:33843667.
Population: Healthy adults without clinical cardiovascular disease.
Dose protocol: 2,000 FU/day for median 3 years in 265 healthy adults
Key findings: No significant effect on carotid intima-media thickness, arterial stiffness, blood pressure, or coagulation markers versus placebo over 3 years.
Notes: Longest and most rigorous nattokinase RCT. Important null evidence against cardiovascular prevention claims in low-risk populations.
Paper content
The Nattokinase Atherothrombotic Prevention Study (NAPS) was a double-blind RCT that randomized 265 healthy adults (median age 65.3 years) to nattokinase 2,000 FU daily or placebo for a median of 3 years. The primary outcomes were rate of change in carotid intima-media thickness and carotid arterial stiffness. Nattokinase showed no significant effect on either primary endpoint, blood pressure, or any laboratory measure of coagulation, fibrinolysis, or inflammation. This is the longest and most rigorous nattokinase RCT to date and provides important null evidence against cardiovascular prevention claims in low-risk adults.
nk-pmid-38812930Randomized, double-blind, placebo-controlled trial with 4 arms.
Sourceopen_in_newLiu M, Xu Z, Wang Z, Wang D, Yang M, Li H, Zhang W, He R, Cheng H, Guo P, Li Z, Liang H. Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease. Front Nutr. 2024;11:1380727. doi:10.3389/fnut.2024.1380727. PMID:38812930.
Population: Patients with stable coronary artery disease.
Dose protocol: Nattokinase alone or combined with red yeast rice for 90 days in 178 stable CAD patients
Key findings: The combination group showed significant improvements in triglycerides, total cholesterol, diastolic blood pressure (-7.39 mmHg), and HDL cholesterol (all P<0.01). The four-arm design allows partial isolation of nattokinase effects.
Notes: Relevant for nattokinase in a higher-risk cardiovascular population, though the combination was more effective than nattokinase alone.
Paper content
This four-arm double-blind RCT enrolled 178 patients with stable coronary artery disease and compared nattokinase plus red yeast rice (NK+RYR), nattokinase alone, red yeast rice alone, and placebo over 90 days. The combination group showed significant improvements in triglycerides (-0.39 mmol/L), total cholesterol (-0.66 mmol/L), diastolic blood pressure (-7.39 mmHg), and HDL cholesterol (+0.195 mmol/L), all P<0.01. Antithrombotic markers also improved. The combination was more effective than either supplement alone. This trial is relevant for nattokinase because the four-arm design allows partial isolation of nattokinase-specific effects, though the combination results are the strongest.
nk-pmid-37836525Randomized double-blind placebo-controlled clinical trial
Sourceopen_in_newLiu X, Zeng X, Mahe J, Guo K, He P, Yang Q, Zhang Z, Li Z, Wang D, Zhang Z, Wang L, Jing L. The Effect of Nattokinase-Monascus Supplements on Dyslipidemia: A Four-Month Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients. 2023;15(19):4239. doi:10.3390/nu15194239. PMID:37836525.
Population: Adults with dyslipidemia.
Dose protocol: Nattokinase-monascus supplement for 120 days in adults with dyslipidemia
Key findings: Improved total cholesterol, LDL-C, non-HDL-C, and LDL-to-HDL ratio without changing triglycerides, HDL-C, or carotid intima-media thickness.
Notes: Combination-product evidence only. Useful for scope control, not for proving nattokinase monotherapy.
Paper content
This 120-day randomized clinical trial tested a nattokinase-monascus supplement in 113 adults with dyslipidemia. The combination improved total cholesterol, LDL cholesterol, non-HDL cholesterol, and the LDL-to-HDL ratio without changing triglycerides, HDL cholesterol, or carotid intima-media thickness. Safety labs and coagulation outcomes were not meaningfully different. Because the product combined nattokinase with Monascus, the study broadens the cardiovascular literature around nattokinase-containing products but does not prove nattokinase alone lowers lipids.