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Crystal structure of nattokinase from Bacillus subtilis natto. PDB 4dww[1]

Nattokinase (pronounced nat-oh-KY-nase) is an enzyme (EC extracted and purified from a Japanese food called nattō. Nattō is made from fermented soybeans and has been eaten in Japan for about a thousand years. Nattō is produced by fermentation by adding the bacterium Bacillus natto to boiled soybeans. Nattokinase is produced by the bacterium acting on the soybeans. While other soy foods contain enzymes, it is only the nattō preparation that contains the specific nattokinase enzyme.

In spite of its name, nattokinase is not a kinase enzyme, but a serine protease of the subtilisin family. It exhibits a strong fibrinolytic activity.[2][3] Nattokinase can now be produced by recombinant means[4][5] and in batch culture,[6][7] rather than relying on extraction from Nattō.

Nattokinase was first isolated and marketed under the name of NSK-SD in 1998 by Japan Bio Science Laboratory, which had removed vitamin K2.[8]

Use as an alternative medicine[edit]

Heart disease[edit]

Nattokinase may be potentially useful as a clot-buster and blood thinner, and is considered by some in the alternative medicine community as a possible adjunctive therapy in cardiovascular disease. There is some evidence for its effectiveness.[9][10][11][12][13][14][15][16][17] Possible side effects have been reported. In one case, a patient concurrently taking aspirin and 400 mg of nattokinase daily for seven consecutive days to prevent stroke suffered an acute cerebellar hemorrhage.[18]

Alzheimer's Disease[edit]

A 2009 study showed that nattokinase may be effective in catabolism of toxic amyloid fibrils associated with Alzheimer's Disease, as well as the insulin fibrils associated with diabetes and the prion peptide fibrils associated with prion diseases.[19] The study reported that its effects were similar to those seen when proteinase K was applied in the same manner. The study's authors noted that "[t]his amyloid-degrading ability of nattokinase suggests that it may be useful in the treatment of amyloid-related diseases," particularly as "[p]revious results in rats, dogs and humans have suggested that nattokinase can enter the circulation when taken orally." However, they cautioned that their results were preliminary, and made the following suggestion:"[S]ince natto has been ingested by humans for a long time, it would be worthwhile to carry out an epidemiological study on the rate of occurrence of various amyloid-related diseases in a population regularly consuming natto." Indeed, 2011 WHO data shows nearly a tenfold increased incidence of death by Alzheimer's and dementia in the United States versus Japan, where natto is regularly consumed by a significant portion of the populace.[20] Since Bacillus subtilis depends heavily on amyloid proteins for its cellular structure, nattokinase may be most effective in the presence of live B. subtilis, which sequesters such proteins in its cell membrane. This compounds the difficulty of conducting in vivo efficacy studies on nattokinase isolate, as it is unclear what portion of nattokinase's effect stems from activity in the gastrointestinal tract versus once it enters circulation.


Digestive enzymes appear to cleave nattokinase into constituent amino acids, from which the components are absorbed into the bloodstream, therefore nattokinase should not have any direct fibrinolytic effects beyond the lumen.

See also[edit]


  1. ^ Yanagisawa, Y.; Chatake, T.; Chiba-Kamoshida, K.; Naito, S.; Ohsugi, T.; Sumi, H.; Yasuda, I.; Morimoto, Y. (2010). "Purification, crystallization and preliminary X-ray diffraction experiment of nattokinase fromBacillus subtilis natto". Acta Crystallographica Section F. 66 (12): 1670–1673. doi:10.1107/S1744309110043137. PMC 2998380Freely accessible. PMID 21139221. 
  2. ^ Fujita, M.; Nomura, K.; Hong, K.; Ito, Y.; Asada, A.; Nishimuro, S. (1993). "Purification and Characterization of a Strong Fibrinolytic Enzyme (Nattokinase) in the Vegetable Cheese Natto, a Popular Soybean Fermented Food in Japan". Biochemical and Biophysical Research Communications. 197 (3): 1340–1347. doi:10.1006/bbrc.1993.2624. PMID 8280151. 
  3. ^ Sumi, H.; Hamada, H.; Tsushima, H.; Mihara, H.; Muraki, H. (1987). "A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet". Experientia. 43 (10): 1110–1111. doi:10.1007/bf01956052. PMID 3478223. 
  4. ^ Liang, X.; Jia, S.; Sun, Y.; Chen, M.; Chen, X.; Zhong, J.; Huan, L. (2007). "Secretory Expression of Nattokinase from Bacillus subtilis YF38 in Escherichia coli". Molecular Biotechnology. 37 (3): 187–194. doi:10.1007/s12033-007-0060-y. PMID 17952663. 
  5. ^ Li, X.; Wang, X.; Xiong, S.; Zhang, J.; Cai, L.; Yang, Y. (2007). "Expression and purification of recombinant nattokinase in Spodoptera frugiperda cells". Biotechnology Letters. 29 (10): 1459–1464. doi:10.1007/s10529-007-9426-2. PMID 17581705. 
  6. ^ Cho, Y. H.; Song, J. Y.; Kim, K. M.; Kim, M. K.; Lee, I. Y.; Kim, S. B.; Kim, H. S.; Han, N. S.; Lee, B. H.; Kim, B. S. (2010). "Production of nattokinase by batch and fed-batch culture of Bacillus subtilis". New Biotechnology. 27 (4): 341–346. doi:10.1016/j.nbt.2010.06.003. PMID 20541632. 
  7. ^ Kwon, E. Y.; Kim, K. M.; Kim, M. K.; Lee, I. Y.; Kim, B. S. (2011). "Production of nattokinase by high cell density fed-batch culture of Bacillus subtilis". Bioprocess and Biosystems Engineering. 34 (7): 789–793. doi:10.1007/s00449-011-0527-x. PMID 21336955. 
  8. ^ Raw Nattokinase
  9. ^ Prevent Heart Attack and Stroke with Potent Enzyme that Dissolves Deadly Blood Clots in Hours. Health Sciences Institute, March 2002.
  10. ^ Maruyama M, Sumi H. Effect of Natto Diet on Blood Pressure. JTTAS, 1995.
  11. ^ Sumi H, Hamada H, Nakanishi K, Hiratani H. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84(3):139-43.
  12. ^ Sumi H, Hamada H, Mihara H. A novel strong fibrinolytic enzyme (nattokinase) in the vegetable cheese "natto." International Journal of Fibronolysis and Thrombolysis.
  13. ^ Abstracts of the ninth international congress on fibrinolysis, Amsterdam, 1988, Vol.2, Sup.1:67. 5.
  14. ^ Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet. Experientia 1987, Oct 15;43(10):1110-1.
  15. ^ Sumi H. Healthy Microbe "Bacillus natto". Japan Bio Science Laboratory Co. Ltd.
  16. ^ Sumi H. Interview With Doctor of Medicine Hiroyuki Sumi. Japan Bio Science Laboratory Co. Ltd. 8.
  17. ^ Sumi H. Structure and Fibronolytic Properties of Nattokinase.
  18. ^ Chang YY, Liu JS, Lai SL, Wu HS, Lan MY (2008). "Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds". Intern. Med. 47 (5): 467–9. doi:10.2169/internalmedicine.47.0620. PMID 18310985. 
  19. ^ Ruei-Lin Hsu et al. J. Agric. Food Chem. 2009, 57(2), pp.503-508
  20. ^

External links[edit]