Does taking nattokinase increase the risk of intracranial bleeds?

Risk of Intracranial Bleeding with Nattokinase

Taking nattokinase may increase the risk of intracranial bleeding, particularly in patients who are already on antiplatelet medications or have cerebral microbleeds. 1

Mechanism of Risk

Nattokinase is a serine protease enzyme with fibrinolytic (clot-dissolving) properties that has been shown to:

• Decrease plasma levels of fibrinogen, factor VII, and factor VIII by 7-19% after 2 months of administration 2
• Potentially enhance the effects of other anticoagulant or antiplatelet medications
• Affect hemostasis in a manner similar to other fibrinolytic agents

Evidence of Risk

The most direct evidence comes from a case report of a patient who developed cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days while also using aspirin for secondary stroke prevention 1. This patient was found to have multiple cerebral microbleeds on MRI, suggesting that nattokinase may increase bleeding risk in those with underlying cerebral microangiopathy.

Risk Factors That May Increase Bleeding Risk with Nattokinase

Several factors may increase the risk of intracranial bleeding when taking nattokinase:

1. Concomitant use of anticoagulants or antiplatelets

   • Combined use with aspirin, other antiplatelet agents, or anticoagulants significantly increases bleeding risk 1
   • This is similar to the increased risk seen with traditional anticoagulants 3

2. Uncontrolled hypertension

   • Hypertension is a major risk factor for intracranial bleeding with anticoagulants (OR 2.69) 4
   • The European Heart Journal guidelines emphasize that controlling blood pressure is crucial to minimize bleeding risk in patients on anticoagulants 3

3. Pre-existing cerebral microbleeds

   • Patients with cerebral microangiopathy or previous microbleeds appear to be at higher risk 1

4. Advanced age

   • Older patients generally have higher bleeding risk with anticoagulant therapies 3

5. Recent initiation of therapy

   • The first 12 months of anticoagulant therapy carries a higher risk of intracranial bleeding (OR 3.74) 4

Safety Considerations

While one study reported no adverse drug reactions with nattokinase (100 mg/day) in 153 patients with vascular diseases 5, this study was not specifically designed to detect intracranial bleeding events. Additionally, toxicological assessments in rodents and healthy human volunteers showed that nattokinase was well-tolerated at doses up to 10 mg/kg-day for 4 weeks 6.

Recommendations for Clinical Practice

1. Avoid combining nattokinase with antiplatelet or anticoagulant medications due to the potential for increased bleeding risk 1

2. Exercise caution in patients with:

   • History of cerebrovascular disease or intracranial hemorrhage
   • Uncontrolled hypertension
   • Known cerebral microbleeds or amyloid angiopathy
   • Advanced age

3. Monitor for warning signs of intracranial bleeding:

   • Severe headache of sudden onset
   • Neurological deficits
   • Altered mental status

4. Discontinue nattokinase before surgical procedures that may carry bleeding risk, similar to management of traditional anticoagulants

5. Control modifiable risk factors, particularly hypertension, in patients choosing to take nattokinase 3

While nattokinase has shown potential benefits for cardiovascular health, the risk of intracranial bleeding should be carefully considered, particularly in high-risk populations or those taking other medications affecting hemostasis.