Key Takeaways:
Nattokinase research examines blood pressure, fibrinolysis, clotting factors, lipid markers, and vascular health
Blood pressure support is one of the more consistently replicated findings in human nattokinase trials
Larger effects on lipids and atherosclerosis appear dose-dependent in current nattokinase research
Nattokinase has accumulated a significant body of research over the last 30-plus years, but most of it lives inside academic journals that are dense, technical, and not exactly bedside reading.
You've probably seen bold claims about nattokinase, but you might have seen less of a straight account of what the actual studies found. So, here’s a walkthrough of the key clinical research and where the gaps still are. Plus, we’ll discuss Toku Flow and how it can complement your wellness routine.
How To Read This Summary
Nattokinase studies range from small pilot trials with a few dozen participants to larger randomized controlled trials. Some focus on mechanistic biomarkers, while others examine broader cardiovascular outcomes.
This summary calls it like it is. Where evidence is strong, it says so. Where it's limited or preliminary, it says that too.
Hsia et al. (2009): Fibrinogen and Clotting Factors
Published in Nutrition Research , this study involved 45 participants taking 4,000 FU of nattokinase daily for 8 weeks. Researchers found reductions in fibrinogen, factor VII, and factor VIII ranging from approximately 7% to 19%. These markers are involved in clotting and fibrinolytic balance.
This study provided some of the earliest human evidence suggesting nattokinase may influence coagulation-related biomarkers, but it is important to note that the study was very small and that biomarkers don't always reflect clinical outcomes of trial participants.
Kim et al. (2008): Blood Pressure
This randomized controlled trial, published in Hypertension Research , included 86 participants over 8 weeks.
Researchers found nattokinase supplementation was associated with an average systolic blood pressure reduction of 5.55 mmHg compared with placebo. Among all nattokinase findings, blood pressure support is one of the more consistently replicated across studies.
The repeated appearance of modest blood pressure effects across multiple trials is one reason researchers continue studying the enzyme, but it's still too early to draw strong conclusions. Nattokinase shouldn't replace your doctor's plan for blood pressure management or prescribed medications.
Kurosawa et al. (2015): Bioavailability and Mechanism
If a supplement can’t survive digestion or act within the body, it’s not suitable for oral use.
Researchers in the Kurosawa et al. study found that a single oral dose of nattokinase significantly increased fibrinolysis and anticoagulation-related markers within hours of ingestion. This study established that orally administered nattokinase can enter the circulation in a functionally meaningful way.
Jensen et al. (2016): Replication in a Western Population
This 8-week double-blind randomized controlled trial included 79 participants in North America and was published in Integrated Blood Pressure Control .
Researchers reported associations between nattokinase supplementation and reduced blood pressure. In addition, they noted an approximately 15% reduction in von Willebrand factor, a clotting-related cardiovascular risk marker.
This study was important because it replicated earlier findings in a Western population rather than an exclusively East Asian cohort. Replication is one of the most important things to establish in clinical trials. If something happens once, it should happen again. This trial proved that the findings were repeatable in a different test group.
NAPS: Nattokinase Atherothrombotic Prevention Study
The NAPS study , conducted through the University of Southern California, is arguably the most rigorous nattokinase study to date.
This quadruple-blind randomized controlled trial followed 240 participants over 3 years and evaluated:
Carotid arterial wall thickness
Arterial stiffness
Cognitive decline
Fibrinolytic markers
The study is registered under ClinicalTrials.gov identifier NCT02080520.
Chen et al. (2022): The Largest Human Trial
The Chen et al. study published in Frontiers in Cardiovascular Medicine is currently the largest nattokinase human study available. The study followed 1,062 participants over 12 months and examined effects on atherosclerosis progression and lipid-related biomarkers.
The most important finding was dose-related:
10,800 FU/day produced measurable changes in atherosclerosis progression markers and lipid profiles
3,600 FU/day produced no statistically significant effect
This dose-response finding changed the nattokinase conversation considerably because many commercial products remain formulated around 2,000 FU. The findings of this study established that results are significantly dose-dependent, and most people would need to consume a much larger amount of nattokinase to experience the potential benefits.
It's important to note that this study was retrospective rather than a gold-standard prospective RCT, and it wasn’t placebo-controlled. While the findings are promising, they don't necessarily indicate positive clinical outcomes for the participants.
Li et al. (2023): Systematic Review and Meta-Analysis
Meta-analyses combine multiple studies together. This review, published in Reviews in Cardiovascular Medicine , analyzed 6 randomized controlled trials involving 546 participants.
The findings reinforced what the Chen et al. study suggested: that low-dose nattokinase showed no significant lipid-lowering effect, while blood pressure effects remained relatively consistent across studies regardless of dose.
The takeaway is fairly straightforward: if lipid-related outcomes are the goal, the nattokinase dose appears to matter significantly. If blood pressure support is the focus, the evidence is more reproducible even at lower doses.
The Bottom Line on Nattokinase Research
The nattokinase evidence base is substantive, and a bit more nuanced than the skeptics give it credit for. Fibrinolytic activity and blood pressure effects appear relatively consistent across studies. Lipid-related outcomes and atherosclerosis findings are more dose-dependent and require stronger trial designs to confirm.
At Toku , we lean on the research. Toku Flow is formulated at 10,800 FU per serving, matching the dose where the strongest clinical evidence currently exists.
That said, our formula is a dietary supplement, not a medication, and should never replace a physician's care. Always speak with your healthcare provider before adding nattokinase to your routine, especially if you take blood thinners, anticoagulants, or cardiovascular medications.
FAQs
Does nattokinase actually work?
Research suggests nattokinase may support fibrinolytic activity and normal blood pressure. Evidence quality varies by outcome, dose, and study design.
What is the strongest nattokinase study?
The Chen et al. (2022) study is currently the largest human nattokinase study published.
Why does FU matter?
FU measures fibrinolytic enzyme activity. Current research suggests nattokinase effects may be dose-dependent.
*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:
Wei et al. Research Progress of Nattokinase in Reducing Blood Lipid. Nutrients | MDPI
Nattokinase Atherothrombotic Prevention Study (NAPS) | ClinicalTrials.gov
Effects of Nattokinase on Inflammation and Cardiovascular Risk Markers | ClinicalTrials.gov
