Nattokinase: A Comprehensive Review of its Biochemical Properties and Therapeutic Potential in Cardiovascular Health
- Randy Justus
- Apr 27
- 3 min read
Updated: 2 days ago
Disclaimer: This paper is for informational and educational purposes only, based on research available as of early 2026. It does not provide medical advice or endorse the use of unapproved compounds.
This information is for informational purposes only and does not replace professional medical advice. Always consult a licensed healthcare provider for concerns about your health.
Abstract Nattokinase (NK), a potent fibrinolytic serine protease derived from the traditional Japanese fermented soybean food natto, has emerged as a significant subject of research due to its multifaceted cardiovascular benefits. Produced by Bacillus subtilis var. natto, this enzyme exhibits strong antithrombotic, antihypertensive, and anti-atherosclerotic activities. Unlike traditional thrombolytic agents, nattokinase can be administered orally and possesses a superior safety profile with a prolonged half-life in human blood. This paper synthesizes current findings on its biochemical mechanisms, clinical efficacy, and emerging therapeutic applications beyond cardiovascular medicine.
1. Introduction and Origins
Nattokinase was first identified in 1980 by Dr. Hiroyuki Sumi, who discovered that an enzyme from natto could dissolve fibrin in vitro. Natto is produced through the fermentation of soybeans by Bacillus subtilis (natto). While traditionally consumed as an everyday food in Japan, NK is now widely available globally as a dietary supplement due to its potential to reduce cardiovascular disease (CVD) mortality.
2. Biochemical Properties and Mechanisms
Nattokinase is a subtilisin-like serine protease consisting of 275 amino acid residues with a molecular weight of approximately 27,728 Da. Its primary physiological action is fibrinolysis, which it achieves through several pathways:
Direct Fibrin Degradation: It directly cleaves cross-linked fibrin to dissolve blood clots.
Plasminogen Activation: It increases the production of tissue-type plasminogen activator (t-PA) and converts prourokinase to urokinase, both of which enhance the body's natural clot-dissolving ability.
PAI-1 Inhibition: It degrades plasminogen activator inhibitor-1 (PAI-1), a primary inhibitor of fibrinolysis.
NK is relatively stable between 40°C and 65°C and maintains over 95% activity after multiple freeze-thaw cycles, though it loses activity in acidic environments (pH below 5.0).
3. Therapeutic Efficacy: Clinical Evidence
3.1. Atherosclerosis and Lipid Management
Recent large-scale studies have indicated that high-dose NK (approx. 10,800 FU/day) can significantly reduce carotid artery plaque size and intima-media thickness (IMT). One 12-month study involving over 1,000 participants reported a 36% reduction in carotid plaque size and improved lipid profiles, including lower LDL-C and total cholesterol. However, some randomized controlled trials using lower doses (2,000 FU) found no significant changes in vessel blockage over three years, suggesting that NK's benefits may be dose dependent.
3.2. Hypertension and Thrombosis
Clinical trials have demonstrated that NK supplementation can mildly lower both systolic and diastolic blood pressure, particularly in hypertensive patients. It also shows efficacy in preventing deep vein thrombosis (DVT) during long-haul flights and reducing blood viscosity.
4. Safety and Contraindications
Nattokinase is generally considered safe with few reported adverse effects. However, its potent antithrombotic activity necessitates caution:
Bleeding Risk: NK may increase the risk of bleeding if taken with anticoagulant or antiplatelet drugs like aspirin or warfarin.
Gastrointestinal Stability: While stable at neutral pH, its degradation in stomach acid often requires enteric-coated capsules for optimal oral delivery.
5. Emerging Research and Future Directions
Beyond cardiovascular health, NK is being investigated for:
Respiratory Health: Potential to shrink nasal polyps and thin mucus in conditions like COPD.
Neuroprotection: Preclinical studies suggest NK may alleviate blood-brain barrier (BBB) dysfunction and reduce brain inflammation.
Oncology: Recent studies explore NK's ability to degrade the extracellular matrix (ECM) in solid tumors to improve CAR-T cell infiltration.
Antiviral Activity: In vitro data suggests NK can degrade the S protein of SARS-CoV-2, potentially inhibiting host cell entry.
6. Conclusion
Nattokinase represents a promising natural alternative for managing cardiovascular risk factors due to its potent fibrinolytic and anti-atherosclerotic properties. While high-dose clinical evidence is compelling, further large-scale, placebo-controlled trials are required to standardize therapeutic dosages and fully elucidate its long-term impact on global heart health.
References
1. Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases
2. Research Progress of Nattokinase in Reducing Blood Lipid
3. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants
4. Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
5. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease
6. Research Progress of Nattokinase in reducing blood lipid
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