Japanese Nattokinase Might Help Clear Out Your Arteries

Nattokinase is an enzyme taken from natto, a traditional Japanese food made from fermented soybeans. It was first identified in 1987 and is known for its ability to break down fibrin, a protein involved in blood clots.

Because of that clot-busting effect, nattokinase has been sold around the world as a heart and circulation supplement. Early animal studies and small human studies suggested it might also lower cholesterol, reduce artery thickening and modestly lower blood pressure.

“Natto consumption has long been linked with lower cardiovascular mortality in Japan,” says study co-author Dr. Yiguang Lin. Researchers wanted to know whether a purified supplement version of nattokinase could offer similar benefits in people at risk for heart disease.

Most participants had mild or borderline-high cholesterol and early signs of atherosclerosis in the carotid arteries, which carry blood to the brain. Some had normal lab results but were focused on prevention and chose nattokinase as a supplement.

Everyone had blood tests and carotid ultrasound scans before starting nattokinase and again after 12 months. The ultrasound measured two key signs of artery health: the thickness of the carotid artery wall (CCA-IMT) and the size of any carotid plaque.

Participants usually took a tablet with 3,600 fibrinolytic units (FU) per pill, three times a day, for a total of 10,800 FU daily. A smaller comparison group took only 3,600 FU per day, which is closer to what many supplements on the market provide.

At the higher 10,800 FU dose, nattokinase was linked with clear improvements in cholesterol and triglycerides. Total cholesterol, LDL cholesterol, the "bad" kind, and triglycerides went down, while HDL cholesterol, the "good" kind, went up.

The authors reported improvement rates between about 66% and 95% across different lipid measures and artery outcomes. “We found that NK at a dose of 10,800 FU/day effectively managed the progression of atherosclerosis and hyperlipidemia,” says lead author Dr. Hongjie Chen.

Carotid artery ultrasound also showed changes in artery structure. The wall thickness went down, and existing plaque areas shrank over the 12 months in many participants, which suggests slower or even partly reversed atherosclerosis progression.

In contrast, the 3,600 FU per day group did not see meaningful lipid or artery improvements. “The lower dose of 3,600 FU per day is ineffective,” the authors conclude, directly challenging the commonly recommended 2,000 FU/day listed on many product labels.

Interestingly, nattokinase seemed to work better in some higher-risk groups. People who smoked, drank alcohol or had a higher body mass index (BMI) showed bigger improvements in their lipid profiles and artery measures.

Regular physical activity also seemed to boost nattokinase’s impact. Participants taking more than 5,000 steps per day, classified as the non-sedentary group, saw better changes than those who were more sedentary.

“Regular exercise further improved the effects of NK,” the authors note. That fits with what we see for many heart treatments: they tend to work best on top of, not instead of, a healthy lifestyle.

The study also looked at how nattokinase interacts with other common supplements and medicines. A group of participants took vitamin K2 at 180 micrograms per day along with nattokinase, and another group took low-dose aspirin at 100 milligrams daily.

Taking vitamin K2 and aspirin with nattokinase appeared to have a stronger effect, further improving lipids and slowing atherosclerosis progression compared with nattokinase alone. “Co-administration of vitamin K2 and aspirin with NK produced a synergetic effect,” the authors report.

Importantly, the researchers did not see serious safety problems over the 12-month period at 10,800 FU per day. Liver and kidney tests stayed within acceptable ranges, and no major bleeding events linked to nattokinase were reported in this group.

That said, this was not a randomized, placebo-controlled trial, and people on blood thinners or with bleeding risks were not the focus of the study. If you take anticoagulants, antiplatelet drugs or have a clotting disorder, do not start nattokinase without talking to your cardiologist.

It is easy to look at these findings and assume nattokinase is a proven alternative to statins or other heart medicines. That would be too much to conclude from this study alone.

This was a retrospective analysis, which means researchers looked back at existing records instead of randomly assigning people to nattokinase or placebo. There was no true control group, and most participants came from one country and one health system.

We also do not know exactly how nattokinase compares with standard treatments like statins, which have decades of strong data showing they reduce heart attacks and strokes. “Our findings provide clinical evidence on the effective dose of NK in the management of cardiovascular disease,” the authors write, but they also say more controlled trials are needed.

If you already have cardiovascular disease or very high cholesterol, nattokinase should be viewed, at best, as a possible add-on under medical supervision, not a replacement for treatments with proven benefits.

If you are curious about nattokinase after reading this study, start by thinking about your goal. Are you trying to lower mildly high cholesterol, support artery health or replace a medicine you were prescribed?

Then, have an honest conversation with your health care provider. Bring the study details, including the dose used (10,800 FU/day) and duration (12 months), and ask how that compares with your current plan and risk level.

• Check the dose.

• Review all medications.

• Monitor labs and imaging.

• Prioritize lifestyle.

The new 1,062-person study suggests that high-dose nattokinase, 10,800 FU per day for 12 months, may improve cholesterol and slow early artery plaque, especially when paired with healthy habits and, in some cases, vitamin K2 or low-dose aspirin.

However, the effective dose is much higher than what most supplements provide, the study design has important limits and nattokinase has not been proven to reduce heart attacks or strokes. If you are considering it, use it as a possible add-on, not a substitute, for evidence-based care, and only after a careful discussion with your health care team.