Patient Education Blog


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 clot-dissolving abilities, similar to plasmin. Plasmin is an important enzyme that we all have in our blood as our natural defense mechanism to dissolve unwanted blood clots. The “clot busters” used in clinical medicine (tPA=tissue plasminogen activator, streptokinase, urokinase, etc) to dissolve blood clots all work through enhancing plasmin’s action.  They are sometimes used to dissolve clots causing heart attacks, strokes, pulmonary embolism or deep vein thrombosis. They have to be given intravenously, because they are not active when given orally.

Does it protect from clots?

This is not known. There are some research data that indicate that orally taken Nattokinase increases the clot dissolving activities (= fibrinolytic activity) of blood in animals and human volunteers and that it suppresses clot formation and enhances clot resolution in animals [ref 2-8]. 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 blood clots [ref 9]. 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 clot, all without symptoms, discovered by ultrasound; of the 94 individuals in the Nattokinase group none developed a clot. Main flaw of the study, limiting the usefulness of its conclusions, is, that the publication does not indicate whether this was a double-blinded study, or, at least, an investigator-blinded study. A non-blinded study has the potential for bias, limiting the validity of its findings and conclusions.

FDA’s assessment of Nattokinase

The FDA has warned that unsubstantiated and illegal claims are being published about the effectiveness of NSK-SD Nattokinase (ref 4) and that Nattokinase products are not “generally recognized as safe and effective” to prevent blood clots [ref 10,11]. Other health care professionals have also concluded that there is an absence of data at this time that Nattokinase has clinical effectiveness (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 you take Nattokinase – don’t count on it having any 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 by a 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 clot, it may be o.k. for him/her to take Nattokinase, arguing 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. 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.
  3. Sumi H et al.: Enhancement of the fibrinolytic activity in plasma by oral administration of Nattokinase. Acta Haematol 1990;84:139-143.
  4. 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.
  5. 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.
  6. 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.
  7. Suzuki Y et al.: Dietary supplementation of fermented soybeans suppresses intimal thickening. Nutrition 2003;19:261-264.
  8. 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.
  9. 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.
  10. FDA 2005 letter (website accessed on 9/17/2011).
  11. FDA 2011 letter (website accessed on 9/17/2011).
  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 Health Care Professionals:  The same blog entry, written for 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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2 Responses to “Nattokinase”

  1. Cassie Brown says:

    Would be nice if a huge thrombophilia center would do “appropriate human studies” on it to prove how effective it is. Personally, it helps me tremendously. I have FVL and MTHFR and have had multiple bouts of superficial clots. I can definitely tell when I forget to take my natto. I was taking it in my last pregnancy and decided to stop around 8w. Exactly one week later I got a repeat superficial blood clot where I’d had one before (and it was treated w/warfarin).