Is nattokinase safe to take?

Safety of Nattokinase Supplementation

Nattokinase should not be recommended for routine use due to significant bleeding risks, particularly when combined with other antithrombotic medications, and the lack of standardized clinical guidelines for its use 1.

Safety Concerns

Nattokinase is a serine protease enzyme derived from natto (fermented soybeans) that has fibrinolytic (clot-dissolving) properties. However, several important safety concerns exist:

• Bleeding risk: Nattokinase may significantly increase bleeding risk, particularly when combined with:

  • Anticoagulants (warfarin, heparin, LMWHs)
  • Antiplatelet agents (aspirin, clopidogrel)
  • NSAIDs 1

• Documented adverse events: There is a case report of cerebellar hemorrhage in a patient taking both nattokinase and aspirin who had cerebral microbleeds 2

• Lack of standardization: Unlike FDA-approved fibrinolytic agents, nattokinase lacks:

  • Standardized dosing regimens
  • Established monitoring parameters
  • Clear contraindications 1

Potential Contraindications

Based on established contraindications for fibrinolytic agents, nattokinase should be avoided in patients with:

• History of intracranial hemorrhage
• Known cerebral vascular lesions
• Recent ischemic stroke
• Active bleeding or bleeding diathesis
• Recent major surgery or trauma 1
• Severe hepatic disease 3
• Pregnancy and lactation 3

Evidence for Potential Benefits

Despite safety concerns, some research suggests potential benefits:

• A small clinical trial showed nattokinase decreased plasma levels of fibrinogen, factor VII, and factor VIII in healthy subjects and patients with cardiovascular risk factors 4

• A study of 153 patients with various vascular diseases reported that nattokinase (100 mg/day) improved clinical symptoms without adverse drug reactions when used in combination with standard treatments 5

• Preclinical safety studies found no evidence of mutagenicity or genotoxicity, and high acute oral tolerability in animal models 6

Risk Assessment Before Use

If considering nattokinase (which is generally not recommended), a thorough risk assessment should include:

1. Complete medication review: Identify potential interactions with anticoagulants, antiplatelets, or other medications affecting hemostasis 3

2. Medical history screening: Assess for:

   • History of bleeding disorders
   • Cerebrovascular disease
   • Recent surgery
   • Hypertension
   • Renal or hepatic impairment 3

3. Laboratory evaluation: Consider baseline coagulation studies if the patient has risk factors for bleeding

Conclusion

While some research suggests potential cardiovascular benefits of nattokinase, the lack of standardization, potential bleeding risks, and absence of clinical guidelines make it difficult to recommend for routine use. For patients seeking cardiovascular disease prevention, evidence-based approaches (proper diet, exercise, smoking cessation, and guideline-directed medical therapies) should be prioritized over supplements with limited evidence like nattokinase 1.

If a patient insists on using nattokinase, they should be strongly advised to:

• Discontinue use before any surgical procedures
• Avoid concurrent use with anticoagulants or antiplatelet medications
• Report any unusual bleeding or bruising immediately
• Inform all healthcare providers about their nattokinase use