Can Nattokinase Help Your Heart? Inside a 1,062-Person Trial

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

Because of that clot-busting activity, nattokinase has been marketed worldwide as a heart and circulation supplement. Early animal and small human studies suggested it might also lower cholesterol, reduce artery thickening and even 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, supplemental form of nattokinase could deliver similar benefits in people at risk for heart disease.

Frontiers in Cardiovascular Medicine

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

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

Participants typically took a tablet providing 3,600 fibrinolytic units (FU) per pill, three times per 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 meaningful 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 structural changes. The thickness of the artery wall decreased, and existing plaque areas shrank over the 12 months in many participants, suggesting slower or even partially reversed atherosclerosis progression.

In contrast, the 3,600 FU per day group did not see significant 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 seen on many product labels.

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

Regular physical activity also appeared 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 pattern fits with what we see for many heart therapies: they tend to work best on top of, not instead of, a healthy lifestyle.

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

Co-administration of vitamin K2 and aspirin appeared to have a synergistic 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 observe serious safety signals over the 12-month period at 10,800 FU per day. Liver and kidney function tests remained within acceptable ranges, and no major bleeding events linked to nattokinase were reported in this cohort.

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, you should not start nattokinase without talking to your cardiologist.

It’s tempting to see these findings and assume nattokinase is a proven alternative to statins or other heart medications. That would be an overreach based on this study alone.

This was a retrospective analysis, meaning researchers looked back at existing records rather than randomly assigning people to nattokinase or placebo. There was no true control group, and most participants were from a single country and health system.

We also don’t know exactly how nattokinase stacks up against standard therapies like statins, which have decades of rigorous 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 acknowledge that more controlled trials are needed.

If you already have diagnosed 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 outcome benefits.

If you’re curious about nattokinase after reading this study, start by clarifying your goals. Are you trying to lower mildly elevated cholesterol, support artery health or replace a medication you’ve been prescribed?

Then, have a candid 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 profile.

• 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 combined 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 limitations and nattokinase has not been proven to reduce heart attacks or strokes. If you’re considering it, use it as a possible complement—not a substitute—to evidence-based care, and only after a thorough discussion with your health care team.