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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.

Our evidence-based analysis on nattokinase features 39 unique references to scientific papers.

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Summary of Nattokinase

Primary information, health benefits, side effects, usage, and other important details

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.

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How to Take

Medical Disclaimer

Recommended dosage, active amounts, other details

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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Human Effect Matrix

Unlocked for Examine members

The Human Effect Matrix summarizes human studies to tell you what effects Nattokinase has on your body, how much evidence there is, and how strong these effects are.

Full details are available to Examine members.
Grade Level of Evidence
Robust research conducted with repeated double-blind clinical trials
Multiple studies where at least two are double-blind and placebo controlled
Single double-blind study or multiple cohort studies
Uncontrolled or observational studies only
Level of Evidence
? The amount of high quality evidence. The more evidence, the more we can trust the results.
Outcome Magnitude of effect
? The direction and size of the supplement's impact on each outcome. Some supplements can have an increasing effect, others have a decreasing effect, and others have no effect.
Consistency of research results
? Scientific research does not always agree. HIGH or VERY HIGH means that most of the scientific research agrees.
grade-c Minor - See study
A possible blood pressure reducing effect seen with nattokinase, notable but with high variability
grade-c Minor - See study
In hypertensive persons, there is a decrease in renin activity seen with nattokinase ingestion
grade-c - - See study
No significant influence on HDL-C levels
grade-c - - See study
No significant influence on LDL cholesterol
grade-c - - See study
No significant influence on liver enzymes noted
grade-c - - See study
No significant influence on total cholesterol seen with supplementation
grade-c - - See study
No significant influence on triglycerides
grade-d Minor - See study
Factor VII (involved in blood clotting) has been noted to be reduced with nattokinase ingestion
grade-d Minor - See study
Factor VIII (involved in blood clotting) appears to be reduced following nattokinase ingestion
grade-d Minor - See study
A decrease in fibrinogen appears to exist following nattokinase ingestion
grade-d Minor - See study
The rate of degradation of fibrin appears to be enhanced slightly following nattokinase ingestion

Studies Excluded from Consideration

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Things to Note

Primary Function:

Also Known As

Natto extract, subtilisin NAT, Orokinase, NSK-SD

Do Not Confuse With

Nattō (food product)

Caution Notice

As nattokinase may thin the blood, it should not be paired with other blood thinning agents such as Aspirin or Warfarin

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Click here to see all 39 references.