Nattokinase: A 16-Year Study Shows a 25% Lower Risk of Heart-Related Death

If you are currently taking blood thinners or other cardiovascular medications, you should consult with your healthcare provider before using nattokinase, as potential contraindications or interactions may exist.

In 1992, researchers in Takayama City, Japan began following the health and dietary habits of tens of thousands of adults to understand how everyday food choices influence long-term disease risk [1]. Over the next 16 years, they tracked more than 29,000 people, carefully recording what they ate and linking those patterns to how often they died from cardiovascular causes such as heart disease and stroke. What makes this study stand out is not just its size or duration, but the specific food it highlighted. Among all the dietary variables they examined, one in particular showed a consistent and meaningful association with reduced cardiovascular mortality: natto, a traditional fermented soybean food that contains the enzyme nattokinase [1].

This article will review research on nattokinase, specifically what researchers observed in people who incorporated the compound into their diet, and then explain why Healthmasters' Nattokinase product can be a helpful tool for people to integrate this compound into their everyday diet.

The Role of Nattokinase in the Body

Nattokinase is not a general nutrient like protein or fiber. It is a specific enzyme that interacts directly with one of the most important systems in the body, the balance between clot formation and clot breakdown. Blood clotting is essential for survival, but the body must also continuously dissolve clots once they are no longer needed. This process is controlled in part by fibrin, a protein that forms the structural framework of a clot. 

When fibrin accumulates faster than it is cleared, blood becomes more prone to blockage, vessels experience greater stress, and the conditions that lead to stroke and heart disease begin to take shape. Nattokinase has been shown to break down fibrin and support the body’s natural ability to maintain this balance, reduce platelet aggregation, and improve the function of blood vessel lining, which is why its presence in natto drew attention in long-term population research [2]. This broad range of activity helps explain why its effects show up in different areas, including clotting, blood pressure, lipid metabolism, and atherosclerosis.

Study Design: How Researchers Isolated Natto

The Takayama Study was designed in a way that allowed researchers to look closely at this connection. At the start, participants completed a detailed food frequency questionnaire that included 169 different items. This level of detail made it possible to separate natto from other soy-based foods such as tofu, soy milk, and miso. That distinction turned out to be critical.

Over the course of the study, researchers identified 1,678 deaths from cardiovascular causes, including 677 from stroke. When they compared groups based on natto intake, they found that individuals who consumed the most natto had a significantly lower risk of dying from cardiovascular disease. The reduction was about 25 percent compared to those who consumed the least [1].

Key Findings: Cardiovascular and Stroke Risk Reduction

What makes this finding more compelling is where the effect was strongest. When the researchers looked specifically at stroke, the reduction in risk became even more pronounced.

Participants in the highest natto intake group had roughly a 32 percent lower risk of dying from stroke, and for ischemic stroke, which is caused by a clot blocking blood flow to the brain, the reduction was about 33 percent [1].

This aligns closely with what nattokinase is known to do inside the body. If an enzyme supports fibrin breakdown and helps prevent harmful clot formation, then the strongest effect should be observed in conditions where clotting plays a central role. That is exactly what the data shows.

Strength of the Evidence: Adjustments and Validation

The researchers tested whether these findings could be explained by other lifestyle factors. They adjusted for age, sex, body weight, smoking, alcohol use, physical activity, and multiple aspects of diet. They also performed additional analyses that excluded early deaths to reduce the chance that pre-existing illness influenced the results. Even after these adjustments, the association between natto intake and reduced stroke risk remained strong. While observational studies cannot prove cause and effect, the consistency of these findings over 16 years adds significant weight to the conclusion that regular intake of nattokinase-rich food is linked to better long-term cardiovascular outcomes [1].

Understanding the Findings in Simple Terms

Seen in simple terms, the study suggests that people who consistently supported their body’s ability to manage fibrin and circulation experienced fewer fatal cardiovascular events over time. A useful way to picture this is to think of the circulatory system as a network of roads. When everything is clear, traffic moves efficiently and the system functions as it should. Even if small blockages are not immediately noticeable, they create friction and slow movement. Over years, that friction can lead to serious breakdowns. Nattokinase appears to help keep those pathways clearer by supporting the body’s natural cleanup process.

2022 Study: Improvement in Cardiovascular Measurements After Nattokinase

While the Takayama Study shows what happens over decades, more recent clinical research helps explain what is happening inside the arteries during that time. A large study published in 2022 followed 1,062 participants for one year and examined the effects of direct nattokinase supplementation [3]. These participants had mild cardiovascular risk factors, including elevated cholesterol or early signs of atherosclerosis. They were given 10,800 fibrinolytic units of nattokinase per day, and researchers measured both blood markers and structural changes in the carotid arteries using ultrasound imaging [3].

The results showed improvements in several key areas. Cholesterol levels shifted in a favorable direction, with reductions in total cholesterol, LDL, and triglycerides, along with increases in HDL. More importantly, imaging revealed reductions in artery wall thickness and plaque size. These are not indirect markers. They are physical changes within the blood vessels that suggest improved vascular health. The study also found that lower doses did not produce the same effects, indicating that a certain level of enzymatic activity is required to meaningfully influence these processes [3].

2025 Study: Improvement in Blood-Brain Barrier Integrity

More recently, researchers have begun to explore how these same mechanisms might affect the brain [4]. A 2025 review examined nattokinase in the context of the blood-brain barrier, which is the system that controls what enters brain tissue. When this barrier becomes compromised, inflammatory substances and toxins can enter the brain and contribute to neurodegenerative conditions. The review found that nattokinase may help support the integrity of this barrier by improving blood flow, reducing inflammation, and limiting fibrin-related damage in experimental models [4]. While this area is still developing, it highlights how closely circulation is tied to both heart and brain health.

Safety Profile: What Research Shows

Safety is another important piece of the picture. A comprehensive toxicological assessment published in 2016 reviewed multiple laboratory tests, animal studies, and human trials conducted over several years. These studies examined whether nattokinase caused genetic damage, short-term toxicity, or long-term adverse effects. The findings showed no evidence of mutagenicity or toxicity, even at doses much higher than those used in human supplementation. Human trials also reported that nattokinase was well tolerated, with no significant adverse effects during regular use [5].

This safety profile is important because it suggests that nattokinase works with the body’s existing systems rather than disrupting them. Supporting clot breakdown is not the same as forcing anticoagulation. Instead, nattokinase appears to enhance processes that are already taking place, helping the body maintain a better balance.

Healthmasters’ Nattokinase

For those looking to apply this research in a practical way, supplementation becomes the most reliable option, especially since natto is not a common part of most dishes. Healthmasters’ Nattokinase is formulated to deliver a consistent level of fibrinolytic activity, at 1,000 fibrinolytic units per capsule, helping support the body’s natural ability to break down fibrin and maintain healthy circulation.

Conclusion

When all of this evidence is considered together, a clear theme emerges. The Takayama Study shows that long-term intake of nattokinase-rich food is associated with lower cardiovascular and stroke mortality. Clinical research shows that, within a year, nattokinase can influence cholesterol levels and the physical structure of arteries in a measurable way. Safety studies show that it is well tolerated. Mechanistic research explains how it works within the body.

None of this suggests that nattokinase replaces a healthy lifestyle. Diet, movement, and overall health habits still matter. But it does point to something deeper: supporting circulation, especially the body’s ability to regulate fibrin and maintain clear blood flow, may be one of the most important long-term strategies for protecting both the heart and the brain.

References:

[1] Nagata, C., Wada, K., Tamura, T., Konishi, K., Goto, Y., Koda, S., Kawachi, T., Tsuji, M., & Nakamura, K. (2017). Dietary soy and natto intake and cardiovascular disease mortality in Japanese adults: the Takayama study. The American journal of clinical nutrition, 105(2), 426–431. https://doi.org/10.3945/ajcn.116.137281

[2] Chen, H., McGowan, E. M., Ren, N., Lal, S., Nassif, N., Shad-Kaneez, F., Qu, X., & Lin, Y. (2018). Nattokinase: A Promising Alternative in Prevention and Treatment of Cardiovascular Diseases. Biomarker insights, 13, 1177271918785130. https://doi.org/10.1177/1177271918785130

[3] Chen, H., Chen, J., Zhang, F., Li, Y., Wang, R., Zheng, Q., Zhang, X., Zeng, J., Xu, F., & Lin, Y. (2022). Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants. Frontiers in cardiovascular medicine, 9, 964977. https://doi.org/10.3389/fcvm.2022.964977

[4] Mahakalakar, N., Mohariya, G., Taksande, B., Kotagale, N., Umekar, M., & Vinchurney, M. (2025). Nattokinase as a potential therapeutic agent for preventing blood-brain barrier dysfunction in neurodegenerative disorders. Brain research, 1849, 149352. https://doi.org/10.1016/j.brainres.2024.149352

[5] Lampe, B. J., & English, J. C. (2016). Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. Food and chemical toxicology, 88, 87–99. https://doi.org/10.1016/j.fct.2015.12.025

*The matters discussed in this article are for informational purposes only and not medical advice. Please consult your healthcare practitioner on the matters discussed herein.

*These statements have not been evaluated by the Food and Drug Administration. Healthmasters' products are not intended to diagnose, treat, cure, or prevent any disease.