Good stuff here on Nattokinase
Oral Fibrinolytic agents:
• Nattokinase: Nattokinase (NK) is a serine protease purified and extracted from natto, a traditional Japanese (cheese like) food produced from the fermentation of soybeans with the bacterium, Bacillus subtilis. [74-76] Recent studies demonstrated that a high natto intake was associated with decreased risk of total cardiovascular disease mortality and, in particular, a decreased risk of mortality from ischemic heart diseases. [77] Nattokinase has potent fibrinolytic, antithrombotic, and antiplatelet activity. [74;75;78-81] NK degrades fibrin directly and also increases the release of tPA with a subsequent increase in the formation of plasmin. [82] Furthermore, NK enhances fibrinolysis through cleavage and inactivation of PAI-1. [76;81] In a study comparing the antiplatelet effects of NK and aspirin, NK was shown to display excellent antiplatelet aggregation and antithrombotic activities in vitro and in vivo, inhibiting thromboxane B2 formation from collagen-activated platelets. [83] In addition, in both animal and human studies, NK also has antihypertensive, anti-atherosclerotic, lipid-lowering, and neuroprotective actions. [75;81;84] Of particular relevance to patients with spike-related clotting, nattokinase causes the proteolytic cleavage of both spike protein and amyloid proteins. [85] In a randomized study, NK proved to be more effect than statins (simvastatin) in reducing carotid artery atherosclerosis. [86] Chen et al demonstrated that high dose NK (10 800 Fibrolytic Units [FU]/day; ~ 500 mg/day) reduced the thickness of the carotid artery intima-media and the size of the carotid plaque. [87] The authors reported a synergistic effect between NK and ASA. Studies indicate that an oral administration of NK can be absorbed by the intestinal tract. [84;88] NK, unlike most proteins, is more resistant to the highly acidic gastric fluids in the stomach and can be absorbed in the later sections of the digestive tract. The optimal dose of nattokinase is unclear, however, a dose of 100-200 mg (4000- 8000 FU/day) twice daily has been suggested. While NK appears to have an excellent safety profile, [87;89] bleeding has rarely been reported in patients with risk factors for bleeding (advanced age, renal failure, hypertension, concomitant ASA, etc). [90;91] High concentrations of vitamin K2 in natto can reduce the INR when coadministered with warfarin; this may also occur with nattokinase supplements if vitamin K2 is not removed during the production process. Information regarding safety and efficacy in pregnancy and lactation is lacking.
74. Sumi H, Hamada H, Tsushima H, Mihara H, Muraki H.
A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular food in Japanese diet. Experientia 1987; 43:1110-1111.
75. Weng Y, Yao J, Sparks S, Wang KY.
Nattokinase: An oral antitrombotic agent for the prevention of cardiovascular disease. Int J Mol Sci 2017; 18:523.
76. Dabbagh F, Negahdaripour M, Berenjian A, Behfar A, Mohammadi F, Zamani M.
Nattokinase: production and application. Applied Microbiology and Biotechnology 2014; 98:9199-9206.
77. Nagata C, Wada K, Tamura T, Konishi K, Goto Y, Koda S et al.
Dietary soy and natto intake and cardiovascular disease mortality in Japanese adults: the Takayama study. Am J Clin Nutr 2017; 105:426-631.
78. Sumi H, Hamada H, Nakanishi K, Hiratani H.
Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990; 84:139-143.
79. Hsia CH, Shen MC, Lin JS, Wen YK, Hwang KL, Cham TM.
Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutrition Research 2009; 29:190-196.
80. Kurosawa Y, Nirengi S, Homma T, Esaki K, Ohta M.
A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. Scientific Reports 2015; 5:11601.
81. Chen H, McGowan EM, Ren N, Lal S, Nassif N, Qu X et al. Biomarker Insights 2018; 13:1-8.
Nattokinase: A promising alternative in prevention and treatment of cardiovascular diseases.
82. Yatagai C, Maruyama M, Kawahara T, Sumi H.
Nattokinase-promoted tissue plasminogen activator release form human cells. Pathoyphysiol Haemost Thromb 2009; 36:227-232.
83. Jang JY, Kim TS, Cai J, Kim J, Kim Y, Shin K.
Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation. Lab Anim Res 2013; 29:221-225.
84. Fujita M, Ohnishi K, Takaoka S, Ogaswara K, Fukuyama R
, Nakamuta H. Antihypertensive effects of continuous oral administraion of nattokinase and its fragment in spontaneously hypertensive rats. Biol Pharm Bull 2011; 34:1696-1701.
85. Tanikawa T, Kiba Y, Yu J, Hsu K, Chen S, Ishii A et al.
Degradative effect of Nattokinase on spike protein of SARS-CoV-2. Molecules 2022; 27:5405.
86. Ren NN, Chen HJ, Li Y, Megowan GW, Lin YG.
A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidemia [Chinese, Abstract in English]. Zhonghua Yi Vue Za Zhi 2017; 97:2038-2042.
87. Chen H, Chen J, Zhang F, Li Y, Wang R, Zheng Q.
Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,1062 participants. Front Cardiovasc Med 2022; 9:964977.
88. Fujita M, Hong K, Ito Y, Misawa S, Takeuchi N, Kariya K et al.
Transport of nattokinase across the rat intestinal tract. Biol Pharm Bull 1995; 18:1194-1196.
89. Gallelli G, Di Mizio G, Palleria C, Siniscalchi A, Rubino P.
Data recorded in real life support the safety of Nattokinase in patients with vascular diseases. Nutrients 2021; 13:2031.
90. Ramachandran L, Aqeel A, Jafri A, Sidhu Y, Djirdeh TM.
Nattokinase-associated hemoperitoneum in an elderly woman. Cureus 2022; 13:-e20074.
91. Chnag YY, Liu JS, Lai SL, Wu HS, Lan MY.
Cerebellar hemorrhage provoked by combinaed use of nattokinase and aspirin in a patient with cerebral microbleeds. Inter Med 2008; 47:467-469.
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