Nattokinase

Last Updated: September 28 2022

Nattokinase is one of many enzymes derived from the food product Nattō (boiled soybeans fermented by the bacteria Bacillus subtilis) and appears to have some direct fibrinolytic activity (fibrin degrading). It is thought to reduce the risk of cardiovascular events, but is fairly underresearched.

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Nattokinase is most often used for

Summary

Nattokinase is one of many enzymes isolated from the fermented food product known as Nattō (boiled soybeans fermented specifically with the bacteria Bacillus subtilis) and was initially though to be a kinase, hence its name. It is a serine protease of the subtilisin class for its technical designation, and is used as a health supplement due to its 'fibrinolytic' properties (being able to enzymatically degrade fibrin, which is thought to reduce cardiovascular incidents by preventing thrombus formation and subsequent blood clotting).

The enzyme appears to be active following ingestion, although it is not known whether it is directly active. In vitro experiments (experiments performed outside a living body) suggest that nattokinase directly digests fibrin, and a few interventions do note that oral ingestion of nattokinase results in decreased thrombus formation. Nattokinase can be metabolized into bioactive peptides that also induce a factor (tissue plasminogen activator) which can subsequently also have fibrinolytic effects, so although the overall effect (fibrinolysis causing less clotting potential) appears to exist the underlying mechanisms are not fully elucidated.

The breakdown products of nattokinase, following heat or acid destruction, are bioactive peptides that may also reduce blood pressure via reducing renin activity and angiotension II. With respect to effect on triglycerides and cholesterol, nattokinase and its bioactive peptides all appear to be wholly inactive.

When looking at human intervention research, there appears to be a minor blood pressure reducing effect associated with nattokinase supplementation. Although there is limited evidence to support the fibrinolytic effects in humans following oral consumption, the trials using nattokinase in isolation are either limited in statistical power or they used nattokinase with other agents (the most convincing study currently used pycnogenol alongside nattokinase).

Overall, although the enzymatic activity and pharmacodynamics of nattokinase are novel, there is not enough evidence to support the usage of nattokinase over other supplemental or pharmacological options. Especially in regard to using an agent as prophylactic, aspirin is much more well researched and no comparative evidence exists right now comparing nattokinase to said reference drug.

The heart health benefits attributed to Nattō are confounded both with the inclusion of other enzymes from bacteria, as well as a high Vitamin K content inherent to Nattō.

What else is Nattokinase known as?
Note that Nattokinase is also known as:
  • Natto extract
  • subtilisin NAT
  • Orokinase
  • NSK-SD
Nattokinase should not be confused with:
  • Nattō (food product)
Dosage information

There is not enough evidence to suggest the optimal dose of oral nattokinase, but studies in humans tend to use around 500mg or 5,000 FU (Fibrinolysis Units) daily, usually divided into two separate doses taken with meals.

Nattō itself can be used, and some anti-clotting effects have been noted with 12g of nattō daily over 2 weeks.

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References
4.^Rufo GA Jr, Sullivan BJ, Sloma A, Pero JIsolation and characterization of a novel extracellular metalloprotease from Bacillus subtilisJ Bacteriol.(1990 Feb)
5.^Omura K, Hitosugi M, Zhu X, Ikeda M, Maeda H, Tokudome SA newly derived protein from Bacillus subtilis natto with both antithrombotic and fibrinolytic effectsJ Pharmacol Sci.(2005 Nov)
8.^Sugimoto S, Fujii T, Morimiya T, Johdo O, Nakamura TThe fibrinolytic activity of a novel protease derived from a tempeh producing fungus, Fusarium sp. BLBBiosci Biotechnol Biochem.(2007 Sep)
10.^Cho YH, Song JY, Kim KM, Kim MK, Lee IY, Kim SB, Kim HS, Han NS, Lee BH, Kim BSProduction of nattokinase by batch and fed-batch culture of Bacillus subtilisN Biotechnol.(2010 Sep 30)
11.^Kwon EY, Kim KM, Kim MK, Lee IY, Kim BSProduction of nattokinase by high cell density fed-batch culture of Bacillus subtilisBioprocess Biosyst Eng.(2011 Sep)
15.^Yin LJ, Lin HH, Jiang STBioproperties of potent nattokinase from Bacillus subtilis YJ1J Agric Food Chem.(2010 May 12)
16.^Wang C, Du M, Zheng D, Kong F, Zu G, Feng YPurification and characterization of nattokinase from Bacillus subtilis natto B-12J Agric Food Chem.(2009 Oct 28)
18.^Yatagai C, Maruyama M, Kawahara T, Sumi HNattokinase-promoted tissue plasminogen activator release from human cellsPathophysiol Haemost Thromb.(2008)
20.^Wei X, Luo M, Xie Y, Yang L, Li H, Xu L, Liu HStrain screening, fermentation, separation, and encapsulation for production of nattokinase functional foodAppl Biochem Biotechnol.(2012 Dec)
21.^Fujita M, Hong K, Ito Y, Misawa S, Takeuchi N, Kariya K, Nishimuro STransport of nattokinase across the rat intestinal tractBiol Pharm Bull.(1995 Sep)
22.^Hsu RL, Lee KT, Wang JH, Lee LY, Chen RPAmyloid-degrading ability of nattokinase from Bacillus subtilis nattoJ Agric Food Chem.(2009 Jan 28)
24.^Hsia CH, Shen MC, Lin JS, Wen YK, Hwang KL, Cham TM, Yang NCNattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjectsNutr Res.(2009 Mar)
25.^Fujita M, Hong K, Ito Y, Fujii R, Kariya K, Nishimuro SThrombolytic effect of nattokinase on a chemically induced thrombosis model in ratBiol Pharm Bull.(1995 Oct)
26.^Chang CT, Fan MH, Kuo FC, Sung HYPotent fibrinolytic enzyme from a mutant of Bacillus subtilis IMR-NK1J Agric Food Chem.(2000 Aug)
28.^Tai MW, Sweet BVNattokinase for prevention of thrombosisAm J Health Syst Pharm.(2006 Jun 15)
29.^Sumi H, Hamada H, Nakanishi K, Hiratani HEnhancement of the fibrinolytic activity in plasma by oral administration of nattokinaseActa Haematol.(1990)
30.^Fujita M, Ohnishi K, Takaoka S, Ogasawara K, Fukuyama R, Nakamuta HAntihypertensive effects of continuous oral administration of nattokinase and its fragments in spontaneously hypertensive ratsBiol Pharm Bull.(2011)
31.^Cesarone MR, Belcaro G, Nicolaides AN, Ricci A, Geroulakos G, Ippolito E, Brandolini R, Vinciguerra G, Dugall M, Griffin M, Ruffini I, Acerbi G, Corsi M, Riordan NH, Stuard S, Bavera P, Di Renzo A, Kenyon J, Errichi BMPrevention of venous thrombosis in long-haul flights with Flite Tabs: the LONFLIT-FLITE randomized, controlled trialAngiology.(2003 Sep-Oct)
35.^Sultana A, Nabi AH, Nasir UM, Maruyama H, Suzuki KM, Mishima S, Suzuki FA dipeptide YY derived from royal jelly proteins inhibits renin activityInt J Mol Med.(2008 Jun)
36.^Kim JY, Gum SN, Paik JK, Lim HH, Kim KC, Ogasawara K, Inoue K, Park S, Jang Y, Lee JHEffects of nattokinase on blood pressure: a randomized, controlled trialHypertens Res.(2008 Aug)
37.^Suzuki Y, Kondo K, Ichise H, Tsukamoto Y, Urano T, Umemura KDietary supplementation with fermented soybeans suppresses intimal thickeningNutrition.(2003 Mar)
38.^Uesugi Y, Usuki H, Iwabuchi M, Hatanaka THighly potent fibrinolytic serine protease from StreptomycesEnzyme Microb Technol.(2011 Jan 5)