Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease

Int J Mol Sci. 2017 Feb 28;18(3):523. doi: 10.3390/ijms18030523.


Natto, a fermented soybean product, has been consumed as a traditional food in Japan for thousands of years. Nattokinase (NK), a potent blood-clot dissolving protein used for the treatment of cardiovascular diseases, is produced by the bacterium Bacillus subtilis during the fermentation of soybeans to produce Natto. NK has been extensively studied in Japan, Korea, and China. Recently, the fibrinolytic (anti-clotting) capacity of NK has been recognized by Western medicine. The National Science Foundation in the United States has investigated and evaluated the safety of NK. NK is currently undergoing a clinical trial study (Phase II) in the USA for atherothrombotic prevention. Multiple NK genes have been cloned, characterized, and produced in various expression system studies. Recombinant technology represents a promising approach for the production of NK with high purity for its use in antithrombotic applications. This review covers the history, benefit, safety, and production of NK. Opportunities for utilizing plant systems for the large-scale production of NK, or for the production of edible plants that can be used to provide oral delivery of NK without extraction and purification are also discussed.

Keywords: antithrombotic agent; cardiovascular disease; gene expression; nattokinase; oral; plant molecular farming.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Products / administration & dosage*
  • Biological Products / adverse effects
  • Biological Products / metabolism
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / prevention & control*
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Fibrinolytic Agents / metabolism
  • Genetic Engineering
  • Humans
  • Hydrolysis
  • Premedication
  • Proteolysis
  • Recombinant Proteins
  • Subtilisins / administration & dosage*
  • Subtilisins / adverse effects
  • Subtilisins / isolation & purification
  • Subtilisins / metabolism


  • Biological Products
  • Fibrinolytic Agents
  • Recombinant Proteins
  • Subtilisins
  • nattokinase