Table of Contents
Key Takeaways:
Nattokinase has been studied since its discovery in 1980, with research spanning fibrinolytic activity, lipid markers, blood pressure, and cardiovascular biomarkers.
The largest human study to date followed 1,062 participants over 12 months using 10,800 FU/day, and found that dose dependency matters. Lower doses in the same study did not show statistically significant effects.
The science is promising but still emerging. Nattokinase is a dietary supplement, not a clinically proven treatment, and should always be used under a physician's guidance.
Most research on nattokinase is scattered across medical journals, where casual consumers are unlikely to see it. This makes it confusing for people to make an informed decision about using nattokinase, or even if it's safe for them to do so.
It's a lot easier to find marketing claims than it is to find properly interpreted, credible research. Remove marketing claims from the equation. Let's interpret the major nattokinase studies, what researchers actually found, and what to know about Toku Flow.
Nattokinase Discovery and Early Research (1980-2000)
Nattokinase was discovered around 1980 by Dr. Hiroyuki Sumi, but it wasn’t on purpose. It was actually by accident. While researching natural compounds with fibrinolytic activity, Sumi dropped natto onto an artificial blood clot in a petri dish and watched it dissolve. That observation led to the identification of the enzyme responsible, which was first described in the scientific literature in Sumi et al., 1987. The enzyme is produced during the fermentation of soybeans using Bacillus subtilis natto, the bacteria used to make the traditional Japanese food natto.
Early research focused primarily on mechanisms of action. Researchers observed that nattokinase appeared to interact with fibrin, the structural protein involved in blood clot formation. This led to growing interest in its fibrinolytic properties, suggesting its potential role in supporting the body’s natural ability to break down fibrin and clear clots.
One foundational study by Fujita and colleagues in 1995 explored whether orally consumed nattokinase could survive digestion and remain biologically active after absorption (Kurosawa et al., 2015: https://doi.org/10.1038/srep11601). Many enzymes are broken down during digestion before reaching circulation, but the findings showed that nattokinase retained biological activity after passing through the digestive process.
Nattokinase Fibrinolytic and Antithrombotic Studies
A 2017 review paper published through PMC summarized decades of research surrounding nattokinase’s fibrinolytic and antithrombotic properties, including evidence suggesting nattokinase may:
Directly cleave fibrin
Influence plasmin activity
Enhance tissue plasminogen activator (t-PA) pathways
Affect coagulation-related biomarkers
The review also emphasized an important limitation. Most available studies remained relatively small, short-term, or focused on biomarkers rather than hard cardiovascular outcomes.
In 2021, Gallelli and colleagues published a real-world safety evaluation examining nattokinase for cardiovascular wellness. Findings suggested a generally favorable safety profile in monitored populations, but researchers also reinforced the need for caution in people taking anticoagulants or antiplatelet medications.
Nattokinase Lipid and Atherosclerosis Research
The most valuable nattokinase study to date is Chen et al. (2022), published in Frontiers in Cardiovascular Medicine. This is the largest nattokinase study to date, following 1,062 participants over 12 months.
Researchers evaluated nattokinase supplementation at 10,800 FU/day co-administered with 180 mcg of Vitamin K2 (MK-7) and examined effects on lipid profiles, carotid artery measurements, and markers of atherosclerosis progression. The study reported improvements in several cardiovascular-related biomarkers and imaging measurements over the study period.
One of the most discussed findings involved dose dependency:
10,800 FU/day produced measurable effects
Lower-dose arms did not demonstrate statistically significant changes
That result became highly influential because many commercial nattokinase products still contain only 2,000 FU per serving. The study was retrospective and not placebo-controlled. It's important to note that improvements in biomarkers don’t automatically translate into reduced cardiovascular events.
Nattokinase Meta-Analysis Findings
In 2023, researchers published a systematic review and meta-analysis through IMR Press examining six randomized controlled trials involving 546 participants. Meta-analyses are useful because they combine multiple studies to identify broader trends.
The review evaluated outcomes like:
Cholesterol markers
HDL levels
Blood rheology
Blood pressure
Researchers concluded that lower-dose nattokinase showed limited lipid-related effects overall, while blood pressure-related findings appeared more consistent across studies. Importantly, the authors rated the overall study quality as relatively high, while acknowledging that many trials remained small and heterogeneous.
Researchers are also exploring inflammation-related biomarkers more directly. An active randomized controlled trial is currently evaluating nattokinase’s effects on inflammatory and cardiovascular risk markers in dyslipidemic patients.
Toku Flow Spotlight
Toku Flow was formulated at 10,800 FU, consistent with the dose studied in the 1,062-participant Chen et al. (2022) clinical trial published in Frontiers in Cardiovascular Medicine. Toku Flow also uses chickpea-based fermentation rather than traditional soy fermentation and undergoes third-party testing for quality and transparency.
Toku Flow is a dietary supplement, not a medication. Always speak with your healthcare provider before starting nattokinase, especially if you take blood thinners, anticoagulants, or cardiovascular medications.
The Bottom Line on Nattokinase Research
The nattokinase research landscape in 2026 is much more substantial than many people realize, but it is also more nuanced than simple marketing claims suggest. Blood pressure support and fibrinolytic activity are among the most consistently replicated findings, while lipid and atherosclerosis-related effects appear increasingly tied to higher studied doses, such as 10,800 FU.
At the same time, there's a lot of research still to be done. Research must continue, particularly on long-term cardiovascular outcomes and large-scale randomized trials. For now, nattokinase remains an actively researched supplement with a growing body of evidence.
FAQs
Is there strong scientific evidence for nattokinase?
The research is promising but still emerging. Multiple peer-reviewed studies have explored its fibrinolytic properties and effects on lipid markers. However, large-scale RCTs measuring hard cardiovascular outcomes are still limited. Nattokinase remains classified as a dietary supplement, not a clinically proven treatment.
What doses have been studied in clinical research?
Clinical studies have used doses ranging from 2,000 to 10,800 FU per day. The largest human study to date (Chen et al., 2022, n=1,062) used 10,800 FU/day over 12 months.
Has nattokinase been compared to statins in research?
Nattokinase has not been directly compared to statins in large-scale RCTs. A 2024 Biomolecules paper compared mechanisms of NOACs vs. nattokinase, but this is mechanistic research, not a clinical efficacy head-to-head trial. Nattokinase is not considered equivalent or comparable to statin therapy.
These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure or prevent any disease. Keep out of reach of children. Consult with your physician before use if you are pregnant, nursing, have a medical condition, or taking anticoagulants. Discontinue use and consult with your health care professional if you experience any adverse reaction to this product.
Sources:
Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease | PMC
Research Progress of Nattokinase in Reducing Blood Lipid | PMC
