Enzyme

    Nattokinase

    Nattokinase

    TL;DR

    Nattokinase is a fibrinolytic enzyme from fermented soy that modestly lowers blood pressure and fibrinogen in small trials. Promising but under-powered, and it carries genuine bleeding risk with anticoagulants.

    Ideal For

    • Adults with mildly elevated blood pressure not on anticoagulants
    • People interested in circulation support who can stop two weeks before surgery

    Avoid If

    • You take warfarin, DOACs, aspirin or clopidogrel
    • You have a bleeding disorder or active peptic ulcer
    • You are within two weeks of scheduled surgery
    • You are pregnant or breastfeeding
    • You have a soy allergy

    Frequently Asked Questions

    Overview

    Nattokinase is a serine protease isolated from natto, a Japanese fermented soybean food. It degrades fibrin directly and also raises endogenous fibrinolytic activity by inactivating plasminogen activator inhibitor-1. Human evidence consists mostly of small Japanese, Korean and Chinese trials lasting 8 to 26 weeks. Meta-analyses of these report average reductions of roughly 3 to 6 mmHg systolic blood pressure, small declines in fibrinogen, factor VII and factor VIII, and in one longer trial a slowing of carotid plaque progression. Trial quality is the limiting factor: sample sizes are typically under 100, blinding is inconsistent, and most studies come from a narrow geographic and commercial base. No cardiovascular outcome trial exists. Dosing is expressed in fibrinolytic units (FU) rather than milligrams, and 2000 FU daily is the most commonly studied dose.

    How It Works

    • Directly cleaves fibrin, the protein scaffold of clots
    • Inactivates plasminogen activator inhibitor-1, increasing endogenous tPA activity
    • Lowers circulating fibrinogen, factor VII and factor VIII in small trials
    • May inhibit ACE weakly, contributing to modest blood pressure reduction

    Supporting Research
    7 studies

    Nattokinase atherothrombotic prevention study: a randomized controlled trial

    Score: 8/10
    2021
    rct
    n=265

    Hodis HN, Mack WJ, Meiselman HJ

    Nattokinase did not change carotid intima-media thickness progression or coagulation markers versus placebo over one year.

    View source

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

    Score: 5/10
    2015
    crossover
    n=12

    A single-dose of 2,000 FU nattokinase potentiated thrombolysis and anti-coagulation profiles in healthy male subjects.

    View source

    Nattokinase supplementation and cardiovascular risk factors: a systematic review and meta-analysis of randomized controlled trials

    Score: 7/10
    2024
    meta_analysis

    Li X, Long J, Gao Q +1 more

    Nattokinase reduced total cholesterol, LDL and systolic blood pressure modestly across randomised trials.

    View source

    Effects of nattokinase on blood pressure: a randomized, controlled trial

    Score: 6/10
    2008
    rct
    n=86

    Kim JY, Gum SN, Paik JK

    Nattokinase lowered systolic blood pressure by 5.6 mmHg versus placebo in pre-hypertensive adults.

    View source

    Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor: a randomized, double-blind, placebo-controlled, multicenter North American clinical trial

    Score: 6/10
    2016
    rct
    n=79

    Jensen GS, Lenninger M, Ero MP +1 more

    Nattokinase lowered blood pressure in men and reduced von Willebrand factor over eight weeks.

    View source

    Nattokinase: an updated critical review on challenges and perspectives

    Score: 5/10
    2018
    systematic_review

    Chen H, McGowan EM, Ren N

    Oral bioavailability and interaction with anticoagulants remain poorly characterised.

    View source

    Clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia

    Score: 4/10
    2017
    rct
    n=82

    Ren NN, Chen HJ, Li Y +1 more

    Nattokinase reduced carotid plaque size and improved lipids in a lower-quality Chinese trial.

    View source

    Safety Information

    Potential Side Effects

    Generally mild: GI upset, headache. The meaningful risk is bleeding, and case reports of cerebellar haemorrhage exist when combined with antiplatelet therapy.

    Contraindications

    Anticoagulant or antiplatelet therapy, bleeding disorders, imminent surgery, pregnancy.

    Drug Interactions

    • Warfarin and DOACs: additive bleeding risk
    • Aspirin, clopidogrel and NSAIDs: additive bleeding risk
    • Antihypertensives: possible additive blood pressure lowering

    Pregnancy & Breastfeeding

    Pregnancy: likely_unsafe

    Breastfeeding: insufficient_data

    Dosage Guidelines

    Dosage Used in Studies

    Consult healthcare provider

    Forms Compared

    Food & Timing

    On an empty stomach or before bed is conventional, though no trial has compared timing directly.

    Medical Disclaimer

    The information provided on this website is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any supplement regimen.

    Individual results may vary. The statements on this website have not been evaluated by the Food and Drug Administration. Products and information are not intended to diagnose, treat, cure, or prevent any disease.