Nattokinase
Protease commonly found in natto
From Wikipedia, the free encyclopedia
Nattokinase (pronounced nuh-TOH-kin-ayss) is an enzyme originally extracted from a Japanese food called nattō. Nattō is produced by fermentation by adding the bacterium Bacillus subtilis var. natto, which also produces the enzyme, to boiled soybeans. In spite of its name, nattokinase is not a kinase enzyme (and should not be pronounced as such, i.e. nuh-toh-KYN-ayss), but an extracellular serine protease of the subtilisin family (99.5% identical with subtilsin E). Rather, it is named for the fact that it is an enzyme produced by nattōkin (Japanese: 納豆 菌).
This enzyme is known as subtilisin NAT (S08.044) in the MEROPS database. Synonyms include nattokinase, subtilisin QK, subtilisin QK02. The gene encodes a prepropeptide with a signal peptide and an inhibitor propeptide before the main enzyme chain (residues 107–381, theoretic molecular mass 27726.74).[2][3] It has the designation Bac s 1 under the WHO/IUIS allergen nomenclature.[4]
Catalytic activity
In vitro
When in contact with human blood or blood clots, it exhibits a strong fibrinolytic activity. It can both cleave fibrin and inactivate plasminogen activator inhibitor-1 (PAI-1).[5][6][7][8]
Fibrinolytic unit
The fibrinolytic unit (FU) is a measure of fibrinolytic activity used in the labeling of nattokinase supplements. It specifically measures the rate of tyrosine liberation in a solution of fibrin.[9]
In vivo
Intravenous route
Nattokinase is able to dissolve blood clots when injected intravenously into rats.[10]
Oral route
Although it should be expected to be digested and inactivated in the human gut like other proteins, one group reported that nattokinase has some effect even when taken orally and consumed.[11]
There are a total of two studies that examine the fate of nattokinase in the gut:
- A 1995 article reported that after rats have received nattokinase injected into the duodenum, specific bands show up when the blood serum is analyzed using Western blot and an anti-NK antibody. One of the band occurs at the same location as control nattokinase (28 kDa).[12]
- A 2013 article reported that after ingestion of nattokinase by human volunteers, it can be detected in blood using enzyme-linked immunosorbent assay (ELISA).[13] However, this is not sufficient proof that nattokinase is absorbed in a functional form as ELISA frequently cross-reacts with digested versions of an antigen.[14]
A 2018 review states that there remains "current convincing data available to demonstrate the bioavailability and metabolism of NK administered as an oral dose."[15]
A double-blind randomized controlled trial published in 2021 reports that in "healthy individuals at low risk for CVD", nattokinase has no effect on carotid artery intima-media thickness and carotid arterial stiffness, two measures of subclinical atherosclerosis progression.[16]
Production
Nattokinase used to be extracted from nattō. The same molecule can now be produced more efficiently by recombinant means[17][18] and in batch culture.[19][20]
There are many legume products fermented using Bacillus subtilis (or a close relative) worldwide. Many of them contain an identical or near-identical protease also with the ability to dissolve fibrin in vitro. These enzymes are also referred to as nattokinase in some academic sources.[21]
Society and culture
The Japan Nattokinase Administration, an industry interest group, runs a certification program for nattokinase products that are strictly only derived from natural Bacillus subtilis var. natto. It considers all other sources "counterfeit".[22]