NutriDex

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Nattokinase

Natto-derived enzyme marketed for clots and blood pressure.

Mixed evidence 🫀Heart & Metabolic

✚ Updated · How we grade evidence

Evidence tier
Mixed
Research weight
Citations
8 verified / 8
Classification
Heart & Metabolic
❝
What the evidence says. Graded mixed: short RCTs and a meta-analysis show a small blood-pressure drop and enzymes that briefly raise fibrinolytic markers, but the only large 3-year placebo-controlled RCT found no effect on atherosclerosis or blood pressure, and the dramatic plaque-reversal data come from a non-randomized retrospective study. (Mixed evidence: Conflicting results across studies; benefit uncertain.)

What is Nattokinase?

Nattokinase is a heart and metabolic supplement used for modestly lower blood pressure. NutriDex grades the human evidence as Mixed. Nattokinase is a fibrin-degrading enzyme extracted from natto, a fermented-soybean food. In healthy volunteers a single oral dose transiently raises fibrinolytic markers (D-dimer up ~40%), and open-label use for 2 months lowered fibrinogen and clotting factors VII/VIII by roughly 7-19%. A meta-analysis of 6 RCTs (546 people) found a modest blood-pressure reduction (systolic about -3.5 mmHg, diastolic about -2.3 mmHg), and a retrospective study reported large drops in carotid plaque and LDL at high dose (10,800 FU/day). However, the best evidence undercuts the hype: a 3-year, 265-person double-blind RCT (NAPS) found no effect on carotid atherosclerosis progression or blood pressure. Trials are mostly short, small, or industry-linked, and the impressive plaque findings are not randomized. Net effect on real cardiovascular events is unproven.

Purported Benefits

✓Modestly lower blood pressure
✓Break down fibrin (fibrinolysis)
✓Lower fibrinogen / clotting factors
✓Marketed for circulation & plaque

Evidence by outcome

The same supplement can be well-proven for one use and unproven for another — here is the human evidence graded outcome by outcome.

OutcomeEvidenceEffectStudies
Lower blood pressureMeta-analysis of 6 RCTs shows ~-3.5/-2.3 mmHg, but the 3-yr NAPS RCT found no BP effect. Mixed ↔ mixed · small 3
Acute fibrinolysis (D-dimer/FDP)Single-dose crossover raised D-dimer ~44%, but all changes stayed within normal range. Preliminary ↑ benefit · small 1
Lower fibrinogen / clotting factorsOpen-label only (no placebo): fibrinogen and factors VII/VIII fell 7-19% over 2 months. Preliminary ↑ benefit · small 1
Slow carotid atherosclerosis progressionA large non-randomized study showed big plaque drops, but the 3-yr double-blind NAPS RCT found none. Mixed ↔ mixed 2

Dosing & Compounds

Typical Dose
Typically 2,000 fibrinolytic units (FU; ~100 mg) once daily; some plaque studies used 10,800 FU/day.
Active Compounds
Nattokinase (subtilisin NK, a serine protease)

Safety & Cautions

Generally well tolerated short-term; reported effects are mild GI upset. Because it promotes fibrinolysis, it raises bleeding risk and should be avoided with anticoagulants and antiplatelets (warfarin, aspirin, clopidogrel, apixaban, rivaroxaban, heparin) and stopped before surgery; a cerebellar hemorrhage was reported in a patient combining nattokinase with aspirin. Do not substitute it for prescribed anticoagulation (a mechanical-valve thrombosis occurred when one patient swapped warfarin for nattokinase). Use caution with bleeding disorders, recent stroke, or blood-pressure-lowering drugs; data in pregnancy and breastfeeding are lacking, so avoid. Educational only — always check with your doctor or pharmacist before combining Nattokinase with any medicine.

Nattokinase drug interactions

Known or theoretical interactions between Nattokinase and common medications — educational, not exhaustive. Always check with your doctor or pharmacist before combining Nattokinase with any medicine.

Caution
Blood thinners (warfarin, DOACs)
Nattokinase can add to blood thinners and raise bleeding risk; combined use has been linked to hemorrhage.
Nattokinase is a fibrinolytic enzyme that degrades fibrin and boosts plasmin activity, compounding anticoagulation. Nattokinase: oral antithrombotic agent (review, PMC) · Cerebellar hemorrhage with nattokinase + aspirin (PubMed)
Caution
Antiplatelet drugs (aspirin, clopidogrel)
Nattokinase plus aspirin or clopidogrel may significantly increase bleeding; a hemorrhage case is reported.
Fibrinolytic and antithrombotic actions add to platelet inhibition, amplifying bleeding tendency. Cerebellar hemorrhage with nattokinase + aspirin (PubMed)

Key Studies

Meta-analysis Li 2023 ✓ PubMed
Meta-analysis of 6 RCTs (546 people): nattokinase cut systolic BP -3.45 mmHg and diastolic -2.32 mmHg; low-dose raised total cholesterol and lowered HDL.
RCT Hodis 2021 (NAPS) ✓ PubMed
3-year double-blind RCT, 265 adults, 2,000 FU/day: NO difference vs placebo in carotid intima-media thickness, arterial stiffness, blood pressure, or labs.
RCT Kurosawa 2015 ✓ PubMed
Crossover RCT, 12 healthy men, single 2,000 FU dose: D-dimer rose +44.5% at 6 h and fibrin-degradation products increased; all changes stayed within normal range.
RCT Kim 2008 ✓ PubMed
RCT, 86 pre-hypertensives, 2,000 FU/day x8 wk: net systolic -5.55 mmHg and diastolic -2.84 mmHg vs placebo (both p<0.05).
RCT Hsia 2009 ✓ PubMed
Open-label, 2 months, 4,000 FU/day: fibrinogen fell 7-10%, factor VII 7-14% and factor VIII 17-19% across healthy, cardiovascular and dialysis groups; lipids unchanged.
Cohort Chen 2022 ✓ PubMed
Retrospective, 1,062 people, 12 mo: 10,800 FU/day linked to -21.7% carotid IMT, -36% plaque area and -18% LDL; 3,600 FU/day was ineffective. Not randomized.
Review Chen 2018 ✓ PubMed
Review of nattokinase as a cardiovascular nutraceutical: summarizes antithrombotic, antihypertensive and anti-atherosclerotic effects and urges larger outcome trials.
Review Weng 2017 ✓ PubMed
Review of nattokinase as an oral antithrombotic agent: details the fibrinolytic mechanism and the gap between mechanistic promise and limited hard clinical-outcome data.
8 sources cited · 8 verified Search all studies on PubMed ↗

Common questions about Nattokinase

What is Nattokinase used for?

Nattokinase is most often taken for Modestly lower blood pressure, Break down fibrin (fibrinolysis), Lower fibrinogen / clotting factors, Marketed for circulation & plaque. Natto-derived enzyme marketed for clots and blood pressure.

Does Nattokinase work — what does the evidence say?

Mixed evidence. Conflicting results across studies; benefit uncertain. Nattokinase is a fibrin-degrading enzyme extracted from natto, a fermented-soybean food. In healthy volunteers a single oral dose transiently raises fibrinolytic markers (D-dimer up ~40%), and open-label use for 2 months lowered fibrinogen and clotting factors VII/VIII by roughly 7-19%. A meta-analysis of 6 RCTs (546 people) found a modest blood-pressure reduction (systolic about -3.5 mmHg, diastolic about -2.3 mmHg), and a retrospective study reported large drops in carotid plaque and LDL at high dose (10,800 FU/day). However, the best evidence undercuts the hype: a 3-year, 265-person double-blind RCT (NAPS) found no effect on carotid atherosclerosis progression or blood pressure. Trials are mostly short, small, or industry-linked, and the impressive plaque findings are not randomized. Net effect on real cardiovascular events is unproven.

What is the typical dose of Nattokinase?

Typically 2,000 fibrinolytic units (FU; ~100 mg) once daily; some plaque studies used 10,800 FU/day.

Is Nattokinase safe? Any cautions or side effects?

Generally well tolerated short-term; reported effects are mild GI upset. Because it promotes fibrinolysis, it raises bleeding risk and should be avoided with anticoagulants and antiplatelets (warfarin, aspirin, clopidogrel, apixaban, rivaroxaban, heparin) and stopped before surgery; a cerebellar hemorrhage was reported in a patient combining nattokinase with aspirin. Do not substitute it for prescribed anticoagulation (a mechanical-valve thrombosis occurred when one patient swapped warfarin for nattokinase). Use caution with bleeding disorders, recent stroke, or blood-pressure-lowering drugs; data in pregnancy and breastfeeding are lacking, so avoid.

How many studies support Nattokinase?

NutriDex cites 8 sources for Nattokinase, graded "Mixed".

Does Nattokinase interact with any medications?

Yes — known or theoretical interactions include: Blood thinners (warfarin, DOACs) (caution), Antiplatelet drugs (aspirin, clopidogrel) (caution). This is educational and not exhaustive; always check with your doctor or pharmacist before combining Nattokinase with any medicine.

Cite this page
APA

Peh, D. (2026). Nattokinase: Benefits, Dosage, Side Effects & Evidence. NutriDex — The Supplement Research Compendium. Retrieved 26 Jun 2026, from https://nutridex.info/s/nattokinase

BibTeX
@misc{nutridex_nattokinase,
  author       = {Peh, Daryl},
  title        = {Nattokinase: Benefits, Dosage, Side Effects \& Evidence},
  year         = {2026},
  howpublished = {NutriDex --- The Supplement Research Compendium},
  url          = {https://nutridex.info/s/nattokinase},
  note         = {Reviewed by Dr Daryl Peh, MBBS Singapore, MMed FM. Accessed 2026-06-26}
}

For medical claims, citing the underlying primary studies linked above is preferred. NutriDex is an educational reference, not medical advice.

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