Original Articles
16 May 2023
Vol. 17 No. 1 (2023)
https://doi.org/10.4081/itjm.2023.1583

Nattokinase historical sketch on experimental and clinical evidence

Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
nattokinase, fibrinolysis, thrombolysis, subtilisin, serin proteases
2380
Views
623
Downloads
653
HTML

Authors

Pierpaolo Di Micco
pdimicco@libero.it
AFO Medicina, ASL Napoli 2 nord, Pozzuoli, Naples, Italy.
Francesca Futura Bernardi
Department of Experimental Medicine, Università degli studi della Campania “Luigi Vanvitelli”, Naples, Italy.
Giuseppe Camporese
Department of Internal Medicine, General Medicine Unit, Thrombotic and Haemorrhagic Disorders Unit, University Hospital of Padua, Padua, Italy.
Mario Biglietto
Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Alessandro Perrella
Department of Infectious Disease, PO Cotugno, AO dei Colli, Naples, Italy.
Tiziana Ciarambino
Department of Internal Medicine, Hospital of Marcianise, Caserta, Italy.
Vincenzo Russo
University Vanvitelly, Department of Translational Science, Caserta, Italy.
Egidio Imbalzano
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.

Nattokinase (NK) is a protease derived from food used mainly in the Japanese diet that has several properties. The main activity is related to improving fibrinolytic activities. Other activities have been demonstrated in the regulation of blood pressure by the action toward angiotensin proteases and in the antiplatelet activities. NK can be given orally and reaches its maximal concentration after 12 hours. In addition, an antithrombotic activity based on various NK activities has been proposed. First, increased fibrinolytic activity increases thrombus dissolution and/or the formation of atherosclerotic plaques; second, its enhanced antiplatelet action adds to clot dissolution. All activities have been studied in animals and humans in vitro and in vivo. Relevant adverse effects of NK therapy have not been described, however clinical experience is restricted to case series and volunteers and is not based on clinical studies, thus clinical trials are required to confirm.

Altmetrics

Downloads

Download data is not yet available.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
Sumi H, Hamada H, Tsushima H, et al. A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese
Natto; a typical and popular soybean food in the Japanese diet. Experientia 1987;43:1110‐1. DOI: https://doi.org/10.1007/BF01956052
Fujita M, Nomura K, Hong K, 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;197(3):1340‐7. DOI: https://doi.org/10.1006/bbrc.1993.2624
Sumi H, Hamada H, Nakanishi K, Hiratani H. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84:139‐43.
Weng Y, Yao J, Sparks S, Wang KY. Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease. Int J Mol Sci 2017;18:523. DOI: https://doi.org/10.3390/ijms18030523
Li D, Hou L, Hu M, et al. Recent Advances in Nattokinase‐Enriched Fermented Soybean Foods: A Review. Foods 2022;11:1867. DOI: https://doi.org/10.3390/foods11131867
Dubey R, Kumar J, Agrawala D, et al. Isolation, production, purification, assay and characterization of fibrinolytic enzymes (nattokinase, streptokinase and urokinase) from bacterial sources. Afr J Biotechnol 2011;10:1408-20.
Wang C, Du M, Zheng D, et al. Purification and characterization of nattokinase from Bacillus subtilis natto B‐12. J Agric Food Chem 2009;57:9722‐9. DOI: https://doi.org/10.1021/jf901861v
Fujita M, Ito Y, Hong K, Nishimuro S. Characterization of nattokinase-degradaded products from human fibrinogen or cross-linked fibrin. Fibrinolysis 1995;9:157-64. DOI: https://doi.org/10.1016/S0268-9499(95)80005-0
Zhang X, Tong Y, Wang J, et al. Screening of a Bacillus subtilis strain producing both nattokinase and milk‐clotting enzyme and its application in fermented milk with thrombolytic activity. J Dairy Sci 2021;104:9437‐49. DOI: https://doi.org/10.3168/jds.2020-19756
Murakami K, Yamanaka N, Ohnishi K, et al. Inhibition of angiotensin I converting enzyme by subtilisin NAT (nattokinase) in natto, a Japanese traditional fermented food. Food Funct 2012;3:674‐8. DOI: https://doi.org/10.1039/c2fo10245e
Zhang F, Zhang J, Linhardt RJ. Interactions between nattokinase and heparin/GAGs. Glycoconj J 2015;32:695‐702. DOI: https://doi.org/10.1007/s10719-015-9620-8
Hsia CH, Shen MC, Lin JS, et al. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. Nutr Res 2009;29:190‐6. DOI: https://doi.org/10.1016/j.nutres.2009.01.009
Jang JY, Kim TS, Cai J, et al. Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation. Lab Anim Res 2013;29:221‐5. DOI: https://doi.org/10.5625/lar.2013.29.4.221
Chen H, Chen J, Zhang F, et al. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants. Front Cardiovasc Med 2022;9:964977. DOI: https://doi.org/10.3389/fcvm.2022.1076420
Hsu RL, Lee KT, Wang JH, et al. Amyloid‐degrading ability of nattokinase from Bacillus subtilis natto. J Agric Food Chem 2009;57:503‐8. DOI: https://doi.org/10.1021/jf803072r
Fujita M, Hong K, Ito Y, et al. Thrombolytic effect of nattokinase on a chemically induced thrombosis model in rat. Biol Pharm Bull 1995;18:1387-91. DOI: https://doi.org/10.1248/bpb.18.1387
Xu J, Du M, Yang X, et al. Thrombolytic effects in vivo of nattokinase in a carrageenan‐induced rat model of thrombosis. Acta Haematol 2014;132:247‐53. DOI: https://doi.org/10.1159/000360360
Kamiya S, Hagimori M, Ogasawara M, Arakawa M. In vivo evaluation method of the effect of nattokinase on carrageenan‐induced tail thrombosis in a rat model. Acta Haematol 2010;124:218‐24. DOI: https://doi.org/10.1159/000321518
Sumi H, Hamada H, Nakanishi K, Hiratani H. Enhancement of the fibrinolytic activity in plasma by oral administration of nattokinase. Acta Haematol 1990;84:139-43. DOI: https://doi.org/10.1159/000205051
Kurosawa Y, Nirengi S, Homma T, et al. A single‐dose of oral nattokinase potentiates thrombolysis and anti‐coagulation profiles. Sci Rep 2015;5:11601. DOI: https://doi.org/10.1038/srep11601
Gallelli G, Di Mizio G, Palleria C, et al. Data Recorded in Real Life Support the Safety of Nattokinase in Patients with Vascular Diseases. Nutrients 2021;13:2031. DOI: https://doi.org/10.3390/nu13062031
Cesarone MR, Belcaro G, Nicolaides AN, et al. Prevention of venous thrombosis in long‐haul flights with Flite Tabs: the LONFLIT‐FLITE randomized, controlled trial. Angiology 2003;54:531-9. DOI: https://doi.org/10.1177/000331970305400502
Hodis HN, Mack WJ, Meiselman HJ, et al. Nattokinase atherothrombotic prevention study: A randomized controlled trial. Clin Hemorheol Microcirc 2021;78:339‐53. DOI: https://doi.org/10.3233/CH-211147
Ramachandran L, Aqeel A, Jafri A, et al. Nattokinase‐Associated Hemoperitoneum in an Elderly Woman. Cureus 2021;13:e20074. DOI: https://doi.org/10.7759/cureus.20074
Chang YY, Liu JS, Lai SL, et al. Cerebellar hemorrhage provoked by combined use of nattokinase and aspirin in a patient with cerebral microbleeds. Intern Med 2008;47:467-9. DOI: https://doi.org/10.2169/internalmedicine.47.0620

How to Cite



Nattokinase historical sketch on experimental and clinical evidence. (2023). Italian Journal of Medicine, 17(1). https://doi.org/10.4081/itjm.2023.1583
Copyright (c) 2023 the Author(s) Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

PAGEPress has chosen to apply the Creative Commons Attribution NonCommercial 4.0 International License (CC BY-NC 4.0) to all manuscripts to be published.