Nattokinase

Nattokinase: Fibrinolytic Enzyme Research

Exploring the cardiovascular and preliminary cancer research of this Japanese fermented soybean enzyme

What is Nattokinase?

Nattokinase is an enzyme extracted from natto, a traditional Japanese fermented soybean food. This fibrinolytic enzyme is primarily recognized for its ability to dissolve blood clots and support cardiovascular health. The enzyme is produced during the fermentation process by the bacterium Bacillus subtilis and has been consumed safely in Japan for centuries as part of the traditional diet.

Primary Mechanism of Action

Nattokinase functions as a serine protease with potent fibrinolytic (clot-dissolving) activity. It breaks down fibrin, a protein involved in blood clot formation, and has been studied extensively for cardiovascular benefits including blood pressure reduction and thrombosis prevention. Recent preclinical research suggests additional anti-tumor mechanisms.

Preclinical Cancer Research

Laboratory and animal studies have revealed several potential anti-cancer mechanisms, though these findings have not been validated in human clinical trials.

Fibrin Degradation

Dissolves fibrin coatings in tumor microenvironment, potentially increasing oxygen levels and drug accumulation

Anti-Angiogenesis

Inhibits blood vessel formation that supports tumor growth and metastasis

Apoptosis Induction

Triggers programmed cell death in cancer cells through various cellular pathways

Therapy Enhancement

May improve efficacy of chemotherapy, radiotherapy, and immunotherapy

Notable Preclinical Studies

Hepatocellular Carcinoma (Mouse Model)

Results: Oral nattokinase crude extract (NCE) improved survival rates to 58-63% compared to 25-31% in controls

Mechanisms: Reduced tumor growth and suppressed expression of cancer-related markers including FOXM1, CD31, CD44, and vimentin

Breast Cancer Research

• Tumor Physical Microenvironment: Increased oxygen levels and drug accumulation in mouse-human breast tumor model
• Molecular Targets: Suppressed FOXM1 and MMP2 expression linked to cancer stem cell proliferation and metastasis
• Prevention: Inhibited tumor occurrence in breast cancer cell lines

Chemotherapy Synergy (Colorectal Cancer)

Enhanced sensitivity of cancer cells to oxaliplatin by increasing reactive oxygen species (ROS), leading to mitochondrial dysfunction and reduced DNA synthesis. Demonstrates potential for combination therapy approaches.

Multi-Cancer Cell Line Research

Cancer Types Studied: Breast, colorectal, lung, prostate, ovarian, and pancreatic cancers

Observed Effects: Inhibited proliferation, prevented metastasis, and synergized with treatments like 5-fluorouracil and photodynamic therapy

Pathways Modulated: NF-κB, MAPK, and PI3K/AKT signaling cascades

Human Clinical Evidence

Current Clinical Trial Status

Completed Trials for Cancer: None. No completed human clinical trials have demonstrated nattokinase's effectiveness for tumor reduction or cancer treatment.

Ongoing Research: Some sources indicate trials exploring nattokinase as adjuvant therapy for breast, colorectal, and lung cancers, focusing on safety, dosing, and synergy with standard treatments, but results remain pending.

Established Human Applications

Existing human clinical trials have focused primarily on cardiovascular health benefits, including reducing carotid plaque, lowering blood pressure, and decreasing inflammation. These cardiovascular effects are well-documented and form the basis for nattokinase's established therapeutic applications.

Safety Considerations & Limitations

⚠️ Bleeding Risk Warning

High Risk Combinations: Nattokinase significantly increases bleeding risk when combined with blood thinners, anticoagulants, or aspirin

Potential Consequences: Excessive bleeding, clot dislodgement causing strokes or emboli, and complications requiring immediate medical intervention

Documented Adverse Events

• Severe allergic reactions
• Internal bleeding (including one fatal case)
• Complications in heart condition patients
• Laboratory test alterations

Research Limitations

• Poor bioavailability challenges
• Unclear optimal dosing protocols
• Unknown long-term side effects
• Lack of human cancer efficacy data

Contraindications & Precautions

• Bleeding Disorders: Absolute contraindication for individuals with bleeding disorders
• Anticoagulant Use: Avoid with warfarin, heparin, aspirin, or other blood-thinning medications
• Laboratory Interference: May alter prothrombin time and fibrinogen levels
• Surgical Considerations: Discontinue before surgical procedures to prevent excessive bleeding

Theoretical Mechanisms & Future Research

Tumor Microenvironment Theory

Theoretical mechanisms include dissolving fibrin coatings on tumors to increase oxygen levels and inhibit growth. This could potentially enhance the effectiveness of conventional cancer treatments by improving drug delivery and reducing tumor hypoxia. However, these mechanisms remain unproven in human clinical settings.

Future Research Priorities

• Phase I Safety Trials: Establish safe dosing ranges for cancer patients
• Bioavailability Studies: Develop formulations with improved absorption
• Combination Therapy Trials: Evaluate synergy with standard cancer treatments
• Biomarker Development: Identify patients most likely to benefit

Current Evidence-Based Applications

Established Uses:

• Cardiovascular Health: Blood pressure reduction and clot prevention
• Fibrinolytic Activity: Well-documented clot-dissolving properties
• Traditional Consumption: Safe consumption as part of natto food in Japanese diet

Unproven Applications:

• Cancer Treatment: No human clinical evidence for anti-tumor effects
• Tumor Reduction: Preclinical findings not validated in human studies
• Cancer Prevention: No epidemiological evidence supporting preventive effects

Clinical Recommendation: Nattokinase should be considered primarily for cardiovascular applications under medical supervision. Cancer-related uses remain experimental and should not be pursued outside of clinical trial settings.

References & Research Sources

Cardiovascular Research: Multiple clinical trials demonstrate nattokinase's fibrinolytic activity and blood pressure lowering effects in human subjects

Hepatocellular Carcinoma Study: Mouse model research showing improved survival rates with nattokinase crude extract treatment

Breast Cancer Models: Preclinical research demonstrating tumor microenvironment modulation and enhanced drug delivery

Multi-Cancer Cell Lines: In vitro studies across various cancer types showing pathway modulation and treatment synergy

Safety Case Reports: Documentation of adverse events including bleeding complications and allergic reactions

Clinical Trial Databases: Ongoing research status for cancer applications remains preliminary with no completed efficacy trials

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Nattokinase has significant bleeding risks and drug interactions. Cancer-related applications remain experimental without human clinical validation. Always consult healthcare providers before using nattokinase, especially if taking blood-thinning medications or considering cancer applications. Never use as an alternative to proven cancer treatments.

Last updated: September 2025