Education Blog for Healthcare Professionals


Your patient may inquire whether he/she can take Nattokinase instead of staying on warfarin to prevent future venous thromboembolism; or what you think about the effectiveness of Nattokianse in preventing a first or recurrent DVT or PE.

What is Nattokinase?

Nattokinase is a soybean food content, produced by the bacterium Bacillus subtilis (natto) during fermentation of soybeans. It is a 275 amino acid peptide. It is also called “Subtilisin NAT” [ref 1]. It is claimed to have fibrinolytic abilities, similar to plasmin, and is marketed aggressively with a number of unsubstantiated claims. The FDA has repeatedly warned some of the companies marketing the product about the inappropriate claims that Nattokinase protects from and prevents heart attacks, stroke, DVT and PE [ref 2,3].

Does it prevent thrombosis?

There are some research data that indicate that orally taken Nattokinase increases the fibrinolytic activity, decreases activity of coagulation factors of blood in animals and human volunteers, and that it suppresses thrombus formation and enhances clot resolution in animals [ref 5-11]. However, to my knowledge, only one clinical study has been performed to assess whether Nattokinase has any real benefit in humans in the prevention of thrombosis [ref 11]. In that study. Nattokinase or placebo was given to individuals prior to long distance (7-8 hours) flights. Of the 92 individuals in the placebo group, 7 developed a venous thromboembolism (VTE), all asymptomatic, ultrasound detected; of the 94 individuals in the Nattokinase group none developed a VTE. Main flaw of the study, limiting the usefulness of its conclusions, is, that the publication does not indicate whether the study was double-blinded or, at least, investigator-blinded or not, limiting the validity of the findings and conclusions.


NKCP® and NSK-SD™ are Nattokinase preparations from two different companies – NKCP® by Daiwa Pharmaceutical Co and NSK-SD™ from “Japan Bio Science Laboratories”. They are produced by different methods, and, thus, their composition is somewhat different, but they both contain Nattokinase, which is the compound said to have the fibrinolytic properties. Clinical studies investigating whether these preparations have any clinically relevant beneficial effect are lacking for both products.

FDA’s assessment of Nattokinase

As noted above, the FDA has warned that unsubstantiated and illegal claims are being published about the effectiveness of NSK-SD Nattokinase and that Nattokinase products are not “generally recognized as safe and effective” to prevent blood clots [ref 2,3]. Other health care professionals have also concluded that there is an absence of data at this time that Nattokinase has clinical efficacy [ref 12].

Personal comment

  • I think it is fair to conclude at present that Nattokinase MAY have some potential to protect from blood clots. However, it has not been appropriately studied in humans.
  • Nattokinase is not a substitute for warfarin! If a patient takes Nattokinase he/she should not count on it having any clinically useful effect.
  • Comments made that Nattokinase “is effective in preventing blood clots in humans” are, at present, speculation, and any claim that one should consider “using warfarin and Nattokinase together and titrate the warfarin downward” to “decrease the harmful effects of warfarin while maintaining a safer level of anticoagulation with the positive effects of nattokinase” [ref 13] are scientifically and clinically unsound, inappropriate and irresponsible.
  • If a patient would benefit from staying on warfarin (or Pradaxa), I think it is negligent /dangerous/inappropriate for the patient to (a) replace warfarin with Nattokinase or (b) take less warfarin, aiming at an INR below 2.0, but add Nattokinase instead.
  • However, if a patient is not on warfarin (or Pradaxa) any more due to a low risk of recurrent VTE, it may be o.k. for him/her to take Nattokinase, with the argument that it MAY have some protective effect.  However, Nattokinase has also not been studied regarding its safety profile, particularly when taken together with aspirin or warfarin.



  1. Urano T et al: The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis cleaves and inactivates plasminogen activator inhibitor type I. J Biol Chem 2001;27:24690-6.
  2. FDA letter 2005 (website accessed on 9/17/2011).
  3. FDA letter 2011 (website accessed on 9/17/2011).
  4. Sumi H et al.: A novel fibrinolytic enzyme (Nattokinase) in the vegetable cheese natto: A typical and popular soybean food in the Japanese diet. Experimentia 1987;1110-1111.
  5. Sumi H et al.: Enhancement of the fibrinolytic activity in plasma by oral administration of Nattokinase. Acta Haematol 1990;84:139-143.
  6. Fujita M et al.: Purification and characterization of a strong fibrinolytic enzyme (Nattokinase) in the vegetable cheese natto, a popular soybean fermented food in Japan. Biochem Biophys Res Commun 1993;30:1340-1347.
  7. Urano T et al: The profibrinolytic enzyme subtilisin NAT purified from Bacillus subtilis cleaves and inactivates plasminogen activator inhibitor type I. J Biol Chem 2001;27:24690-6.
  8. Suzuki Y et al.: Dietary supplementation of fermented soybean, natto, suppresses intimal thickening and modulates the lysis of mural thrombi after endothelial injury in rat femoral artery. Life Sci 2003;73:1289-1298.
  9. Suzuki Y et al.: Dietary supplementation of fermented soybeans suppresses intimal thickening. Nutrition 2003;19:261-264.
  10. Hsia CH et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res. 2009 Mar;29(3):190-6.
  11. Cesarone MR et al.: Prevention of venous thrombosis in long-haul flights with Flite Tabs: The LONG-FLITE randomized, controlled trial. Angiology 2003;54:T1-T9.
  12. Lee T et al. Harvard Heart Letter; Oct 2006,Vol.17, Issue 2,7-8.
  13. Ralph E. Holsworth, D.O.: The use of Nattokinase in combination with low-dose warfarin (Coumadin). Focus 2003 (May), page 3.

For patients:  The same blog entry, written for non-health care professionals, can be found here.

Disclosure: I have consulted for Ortho Mc Neil and Bayer, the companies developing Rivaroxaban.

Last updated: Sept 18th, 2011

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