Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases

Nutrients. 2021 Jun 13;13(6):2031. doi: 10.3390/nu13062031.


Nattokinase (NK) is a serine protease enzyme with fibrinolytic activity. Even if it could be used for the treatment of several diseases, no data have been published supporting its use patients who underwent vascular surgery. In this study, we evaluated both the efficacy and the safety of nattokinase (100 mg/day per os) in patients admitted to vascular surgery. Patients were of both sexes, >18 years of age, with vascular diseases (i.e., deep vein thrombosis, superficial vein thrombosis, venous insufficiency), and naïve to specific pharmacological treatments (anticoagulants or anti-platelets). Patients were divided into three groups. Group 1: patients with deep vein thrombosis, treated with fondaparinux plus nattokinase. Group 2: patients with phlebitis, treated with enoxaparin plus nattokinase. Group 3: patients with venous insufficiency after classical surgery, treated with nattokinase one day later. During the study, we enrolled 153 patients (age 22-92 years), 92 females (60.1%) and 61 males (39.9%;), and documented that nattokinase was able to improve the clinical symptoms (p < 0.01) without the development of adverse drug reactions or drug interactions. Among the enrolled patients, during follow-up, we did not record new cases of vascular diseases. Attention to patients' clinical evolution, monitoring of the INR, and timely and frequent adjustment of dosages represent the cornerstones of the safety of care for patients administered fibrinolytic drugs as a single treatment or in pharmacological combination. Therefore, we can conclude that the use of nattokinase represents an efficient and safe treatment able to both prevent and treat patients with vascular diseases.

Keywords: Clinical Risk Management; clinical trial; low-molecular-weight heparin; nattokinase; safety of care in pharmacological treatments; vascular diseases.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Enoxaparin / therapeutic use
  • Female
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / therapeutic use*
  • Fondaparinux / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Subtilisins / adverse effects
  • Subtilisins / therapeutic use*
  • Vascular Surgical Procedures
  • Venous Insufficiency / drug therapy*
  • Venous Thrombosis / drug therapy*
  • Young Adult


  • Enoxaparin
  • Fibrinolytic Agents
  • Subtilisins
  • nattokinase
  • Fondaparinux