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.