Nattokinase
Summary
Nattokinase lowered blood pressure modestly in short trials: a meta-analysis of 6 RCTs (546 people) found about 3.5/2.3 mmHg lower readings (grade C). But the longest, largest placebo-controlled trial, 265 adults over about 3 years, found no effect on carotid artery thickening, blood pressure or clotting markers. Bleeding-risk data with blood thinners are limited.
Key facts
- Blood pressure: modest drop in short trials (C); carotid atherosclerosis progression: no effect in a 3-year RCT (B); cognition: no effect on the primary outcome (C)[1][2][7]
- 2,000–10,800 fibrinolytic units (FU) per day; 100 mg/day of one standardized extract; 8 weeks to about 3 years[2][3][4][5]
- None set; nattokinase is an enzyme, not a nutrient[1]
- None established in trials; reviews flag possible added bleeding risk with anticoagulant or antiplatelet drugs[8]
- No notable adverse events reported across pooled RCTs[1]
- 6 graded human outcomes on this page
- October 10, 2026
How it works
ProposedNattokinase is a serine protease that breaks down fibrin in lab and animal studies, and in rabbit platelets it reduced aggregation and thromboxane formation. Whether enough intact enzyme is absorbed after swallowing to dissolve clots in people is not established; a 3-year human trial found no change in coagulation or fibrinolysis factors.[9][2]
What the human research says
Human trials only, one row per outcome. The form column shows what each trial actually tested. Grades follow our evidence-grading policy.
At a glance: strongest evidence per outcome
| Outcome | Grade | Effect | Strongest evidence | Rows |
|---|---|---|---|---|
| Atherosclerosis | Grade B | No effect | RCT · n = 265 · 2021 | 2 rows |
| Blood pressure | Grade C | Mixed | Meta-analysis of 6 trials · n = 546 · 2023 | 3 rows |
| Cognition | Grade C | No effect | RCT · n = 120 · 2026 | 1 row |
Every graded row
| Outcome | Effect | Grade | Best evidence | PMID |
|---|---|---|---|---|
| Carotid atherosclerosis progression, blood pressure and clotting markers | No effect | Grade B | RCT · n = 265 · 2021 Adults (median age 65) without cardiovascular disease (US) Form: nattokinase · Dose: 2,000 FU/day · Duration: Median 3 years Annual change in carotid intima-media thickness and arterial stiffness did not differ from placebo, and there was no effect on blood pressure or any laboratory measure, including coagulation and fibrinolysis factors. | 33843667 (opens PubMed)Source [2] |
| Blood pressure, lipids and glucose | Mixed | Grade C | Meta-analysis · n = 546 · 2023 Adults in 6 RCTs Form: nattokinase capsules · Dose: Varied across trials · Duration: Varied across trials Systolic BP fell 3.45 mmHg and diastolic 2.32 mmHg versus placebo, but total and LDL cholesterol rose slightly at lower doses and blood glucose rose 0.40 units; HDL fell at lower doses. No notable adverse events. | 39076715 (opens PubMed)Source [1] |
| Cognitive function in asymptomatic intracranial or carotid stenosis | No effect | Grade C | RCT · n = 120 · 2026 Adults (mean age 58) with asymptomatic intracranial or carotid artery stenosis (China) Form: nattokinase · Dose: 8,000 FU/day · Duration: 6 months MoCA score change did not differ from placebo (mean difference 0.04, p=0.95); an exploratory visuospatial score favored nattokinase. | 41325794 (opens PubMed)Source [7] |
| Blood pressure in prehypertension or stage 1 hypertension | Improved | Grade C | RCT · n = 86 · 2008 Adults 20–80 with untreated systolic BP 130–159 mmHg Form: nattokinase capsules · Dose: 2,000 FU/day · Duration: 8 weeks Net changes versus placebo were −5.55 mmHg systolic and −2.84 mmHg diastolic (both p<0.05); plasma renin activity also fell. | 18971533 (opens PubMed)Source [3] |
| Carotid plaque and lipids at high dose | Improved | Grade D | Open-label trial · n = 1,062 · 2022 Adults with atherosclerosis or hyperlipidemia (China) Form: nattokinase · Dose: 10,800 FU/day (3,600 FU/day also tested) · Duration: 12 months Carotid intima-media thickness, plaque size and lipids improved at 10,800 FU/day, but 3,600 FU/day was ineffective. No noticeable adverse effects were recorded. | 36072877 (opens PubMed)Source [5] |
| Blood pressure in a North American hypertensive population | Improved | Grade D | RCT · n = 79 · 2016 Adults with systolic BP ≥130 or diastolic ≥90 mmHg (North America) Form: NSK-SD nattokinase (vitamin K2 removed) · Dose: 100 mg/day · Duration: 8 weeks Diastolic BP fell from 87 to 84 mmHg versus no change on placebo (p<0.05), with larger drops in men; systolic reductions were reported for both sexes. | 27785095 (opens PubMed)Source [4] |
Forms
| Form | Elemental % | Absorption (human data) | GI tolerance | Studied for |
|---|---|---|---|---|
| Nattokinase capsules standardized by fibrinolytic units (FU) | Varies[1][5][9] | No human data in our sources on how much intact enzyme is absorbed.[9] | No notable adverse events in pooled RCTs; well tolerated at 10,800 FU/day for 12 months in an uncontrolled study.[1][5] | Blood-pressure trials (2,000 FU/day), atherosclerosis trials (2,000–10,800 FU/day) |
| NSK-SD (natto extract with vitamin K2 removed) | Varies[4] | No human absorption data in our sources.[4] | No adverse findings reported in an 8-week trial at 100 mg/day.[4] | North American blood-pressure trial (100 mg/day) |
| Natto (the fermented soybean food) | Varies[4] | Contains nattokinase along with vitamin K2, which some extracts remove.[4] | A traditional food; vitamin K2 content matters for people on warfarin.[4] | Not tested as a food in the trials cited here |
Studied doses
Doses studied in human trials ranged from 2,000 to 10,800 FU/day for 8 weeks to about 3 years; one North American trial used 100 mg/day of a standardized extract. The common 2,000 FU/day label dose showed no effect over 3 years in the largest placebo-controlled trial.[2][3][4][5]
Interactions
Published interactions only: each row cites a source. No row means none was found in our sources, not that a combination is safe.
Medicines
- Anticoagulants and antiplatelet drugsReviewReviews flag a possible added bleeding risk because nattokinase has fibrinolytic and antiplatelet activity, while noting that long-term human bleeding data are limited. Do not combine without your prescriber.[8]
- Warfarin (vitamin K2 in natto-derived products)RCTNatto contains vitamin K2, which some nattokinase extracts remove; check the label if you take warfarin.[4]
Who should be careful
- Blood thinners or bleeding disorders
- Nattokinase may add to the effect of anticoagulant or antiplatelet drugs, and long-term bleeding data are limited.[8]
- Before surgery
- Because of its fibrinolytic activity, tell your surgical team if you take it; human data on stopping times do not exist.[8][9]
- Soy allergy
- Nattokinase comes from fermented soybeans; check labels for soy-derived ingredients.[1]
- Relying on it for heart disease
- A 3-year placebo-controlled trial found no slowing of carotid artery disease at 2,000 FU/day.[2]
Talk to your pharmacist or clinician before starting a supplement, especially if you take prescription medicines.
Safety
Short trials report no notable side effects, but bleeding risk with blood thinners is the open question.
- Adverse events
- No notable adverse events were reported across 6 pooled RCTs.[1]
- Bleeding
- A 2025 review notes clinical data on long-term bleeding tendency and liver effects are limited.[8]
- Clotting markers
- Over about 3 years at 2,000 FU/day, coagulation and fibrinolysis factors did not change versus placebo.[2]
How to read the label
- Label dose vs clinical doseMost labels give 2,000 FU per capsule, the dose used in the 8-week blood-pressure trial and the 3-year null trial. An uncontrolled Chinese study argued 10,800 FU/day is needed for plaque effects.[2][3][5]
- FU, not milligramsPotency is measured in fibrinolytic units; milligram amounts alone do not tell you the dose.[3][4]
- Vitamin K2-free extractsSome extracts, such as the one in the North American trial, remove natto's vitamin K2.[4]
Cost per studied dose, without the sales pitch
Compare any product you already have by the amount it delivers, not by capsule count or front-of-pack weight.
Cost per studied dose
Enter the price, servings and the amount per serving from your label.
Frequently asked questions
Does nattokinase lower blood pressure?
Modestly in short trials: pooled RCTs found about 3.5 mmHg lower systolic pressure. A 3-year trial at 2,000 FU/day found no effect.[1][2]
Does nattokinase dissolve plaque or clots?
Not shown in placebo-controlled trials. The 3-year NAPS trial found no change in carotid artery thickening or clotting markers; plaque claims rest on an uncontrolled, industry-authored study and a small trial with no placebo arm (compared against a statin).[2][5][6]
How much nattokinase is used in studies?
2,000 to 10,800 FU/day; 2,000 FU/day is the typical label dose.[2][3][5]
Can I take nattokinase with blood thinners?
Not without your prescriber. Reviews flag possible added bleeding risk, and long-term data are limited.[8]
Is nattokinase safe?
Trials up to about 3 years reported no notable side effects, but bleeding risk with blood thinners has not been well studied.[1][2][8]
Does nattokinase contain vitamin K2?
Natto does; some nattokinase extracts remove it, which matters if you take warfarin.[4]
Sources
- [1]Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Rev Cardiovasc Med, 2023. meta-analysis
- [2]Nattokinase atherothrombotic prevention study: A randomized controlled trial.. Clin Hemorheol Microcirc, 2021. RCT
- [3]Effects of nattokinase on blood pressure: a randomized, controlled trial.. Hypertens Res, 2008. RCT
- [4]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.. Integr Blood Press Control, 2016. RCT
- [5]Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants.. Front Cardiovasc Med, 2022. open-label
- [6][A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia].. Zhonghua Yi Xue Za Zhi, 2017. RCT
- [7]Nattokinase supplementation for cognitive enhancement in asymptomatic intracranial/carotid stenosis: A randomized controlled trial.. J Stroke Cerebrovasc Dis, 2026. RCT
- [8]Navigating the Effects of Anti-Atherosclerotic Supplements and Acknowledging Associated Bleeding Risks.. Int J Mol Sci, 2025. review
- [9]Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease.. Int J Mol Sci, 2017. review
What changed
- First draft. Every PMID checked against NCBI E-utilities esummary (title and year taken from the record) and abstracts read for the cited rows.
- Adversarial review pass: every evidence row re-read against its PubMed abstract; JBSL-USA sponsorship taken from PMC5066864, Sungen Bioscience employment from the PubMed conflict statement; the vs-statin trial (PMID 28763875) is cited only in the FAQ, not as an evidence row, because it had no placebo arm. Retraction, expression-of-concern and erratum check run on all 9 PMIDs via PubMed records and an independent reviewer pass on the PubMed pages: no retractions or expressions of concern; one erratum (PMID 36072877, corrigendum 36545015, Table 1 values only) disclosed on its row. Page set indexable.