Nattokinase: The Enzyme from Fermented Soybean for Vascular Health

In the northern regions of Japan, a traditional breakfast often includes a bowl of natto: soybeans fermented with the bacterium Bacillus subtilis, having a sticky texture and pungent smell that deters many on the first try. This food has been eaten in Japan for over a thousand years, but only in 1987 did Japanese researcher Hiroyuki Sumi discover that within this sticky mucilage hides an enzyme with an extraordinary ability: it can break down blood clots in a petri dish. He named this enzyme nattokinase.

Since then, nattokinase has become one of the most researched heart health supplements in East Asia, and more recently in the West. Its story is a fascinating example of how a traditional food becomes a potential medical tool. But it is also an example of how the very property that makes a supplement promising can make it dangerous in the wrong hands. Nattokinase thins the blood, and therefore it is not suitable for everyone.

What is Nattokinase?

Nattokinase is a proteolytic enzyme, meaning an enzyme that breaks down proteins. Here is what is important to know about it:

• Source: It is produced from the fermentation of soybeans by the bacterium Bacillus subtilis var. natto. It does not exist in regular soy, only after fermentation.
• Structure: A protein molecule of 275 amino acids, from the serine protease family of enzymes.
• Units of Measurement: Its activity is measured in FU (Fibrinolytic Units), not just in milligrams. The common studied dosage is 100 mg containing about 2000 FU.
• Stability: Unlike most enzymes, it survives passage through the digestive tract and is absorbed in an active form, allowing oral intake.
• Duration of Activity: Measurements have shown its effect on the coagulation system lasts between 8 to 12 hours after a single dose.

The Mechanism: How an Enzyme from Soy Breaks Down Clots

To understand why nattokinase is interesting, one must understand fibrin. When a blood clot forms, a protein called fibrin creates a network of threads that traps blood cells and builds the clot. In a healthy body, there is an opposing system that breaks down unnecessary clots, the fibrinolytic system, centered around an enzyme called plasmin.

Nattokinase acts on this system through several parallel pathways:

• Direct breakdown of fibrin: It can directly cut the fibrin threads that build the clot, similar to the action of natural plasmin.
• Increased production of plasmin: It encourages the body to produce more tPA, a protein that converts inactive plasminogen into active plasmin, which breaks down clots.
• Neutralization of coagulation inhibitor: It breaks down and neutralizes the protein PAI-1, the main inhibitor of the fibrinolytic system. The less PAI-1 there is, the more active the clot breakdown system.
• Reduction of fibrinogen: Studies indicate a decrease in the level of fibrinogen in the bloodstream, the raw material from which clots are built.

In a study published in the journal Scientific Reports in 2015, a single oral dose of nattokinase increased clot-dissolving activity and improved the anticoagulation profile in healthy volunteers, direct evidence that the enzyme is active in the human body and not just in the petri dish.

Current Evidence

Study 1: Blood Pressure, a Controlled Study from 2008

In a randomized, double-blind, placebo-controlled study published in the journal Hypertension Research, 86 participants aged 20 to 80 with an initial systolic blood pressure of 130 to 159 mmHg were recruited. They received nattokinase at a dose of 2000 FU or a placebo for 8 weeks. Compared to the control group, the net change in systolic blood pressure was a reduction of 5.55 mmHg (p less than 0.05), and in diastolic pressure a reduction of 2.84 mmHg. A moderate but consistent reduction.

Study 2: Atherosclerosis and Lipids, 1,062 Participants from 2022

This is the largest study to date, published in the journal Frontiers in Cardiovascular Medicine in August 2022. 1,062 participants took nattokinase for 12 months. At a high dose of 10,800 FU per day, significant improvement was observed in lipid profile, reduction in carotid artery intima-media thickness, and reduction in atherosclerotic plaque size. Improvement rates ranged from 66.5% to 95.4%. A critical point: at a low dose of 3,600 FU per day, the enzyme was not effective in lowering lipids. That is, the effect is dose-dependent.

Study 3: Meta-Analysis of Cardiovascular Risk Factors

A systematic review and meta-analysis that pooled six randomized controlled trials with 546 participants found that nattokinase supplementation significantly lowered systolic blood pressure by about 3.45 mmHg and diastolic by about 2.32 mmHg. No significant side effects were reported in the reviewed studies, supporting the use of the enzyme as an adjunctive treatment for hypertension, not as a replacement for medications.

What About Preventing Events, Stroke, and Heart Attacks?

The truly interesting question is not whether nattokinase lowers blood pressure by a few units, but whether it prevents real cardiovascular events: stroke, heart attack, venous thrombosis. Here the evidence is still thin. Most studies measured biomarkers, blood pressure, lipid levels, arterial wall thickness, and not hard clinical outcomes like mortality or hospitalization.

The biological logic is appealing: an enzyme that breaks down fibrin, lowers fibrinogen, and improves blood flow should theoretically reduce the risk of clots. But biological logic is not a substitute for long-term research on hard endpoints. Until large studies tracking thousands of people over years are conducted, nattokinase remains in the category of a promising supplement with moderate evidence, not a proven drug for stroke prevention.

Critical Warning: Nattokinase Thins the Blood

This is the most important part of this article, and it should be read before any other consideration. Nattokinase affects the blood coagulation system. Precisely the property that makes it interesting is also its main risk.

• Do not combine with anticoagulants and blood-thinning medications. Combining with warfarin (Coumadin), apixaban (Eliquis), rivaroxaban, clopidogrel (Plavix), or even regular-dose aspirin may dangerously increase the risk of bleeding. Do not start nattokinase if you are taking any of these medications without explicit approval from your doctor.
• Discontinue before surgery: Nattokinase intake should be stopped at least two weeks before any surgery or invasive dental treatment, due to the risk of increased bleeding.
• Bleeding disorders: People with bleeding disorders, active stomach ulcers, or a history of hemorrhagic stroke should avoid it entirely.
• Pregnancy and breastfeeding: There is insufficient safety data, so it is recommended to avoid it.
• Soy allergy: Since the enzyme is derived from soy, those with allergies should check that the product has been sufficiently purified or avoid it.

The bottom line: Nattokinase received a 🟡 Yellow rating in our evaluation system, not due to a lack of evidence, but because of its safety profile that requires caution and supervision. It is not a supplement to be taken without thought.

What to Take Away from the Research?

1. If you are healthy and not taking blood thinners: The studied dosage is 100 mg (2000 FU) per day. This is a reasonable starting point, preferably after consulting a doctor.
2. If you are taking heart medications or blood thinners: Do not start on your own. Talk to your cardiologist or primary care physician first. This is not a polite cautionary recommendation; it is a real safety warning.
3. Prefer the natural source if possible: Eating natto itself provides the enzyme along with vitamin K2, protein, and fiber. This is a gentler and safer way for most people, if they can get used to the taste.
4. Do not expect miracles: A reduction of 5 mmHg in blood pressure is statistically significant but moderate. Nattokinase is a complementary supplement, not a replacement for blood pressure medications, diet, or physical activity.
5. Choose a product with a stated FU standard: Quality products explicitly state the number of FU. Avoid products that only list mg without enzymatic activity.

If you would like to check which supplements are suitable for your heart and vascular goals personally, try our personal supplement selector. For those who have already decided, you can purchase nattokinase on iHerb in various FU levels.

The Broader Perspective

Nattokinase is a nice reminder that much of modern medicine begins with traditional food. A thousand-year-old Japanese dish gave rise to an enzyme studied today in hundreds of studies. But it is also a reminder that a powerful biological property is a double-edged sword: the same enzyme that may improve blood flow can cause dangerous bleeding in the wrong combination.

Healthy longevity of the cardiovascular system does not rest on a single supplement. It is built from balanced blood pressure, physical activity, a diet rich in omega-3 and fiber, and avoiding smoking. Nattokinase, at best, is one small brick in that wall, not the wall itself. And in the case of a supplement that changes the way your blood clots, caution is not an option: it is a necessity.

References:
Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants, Frontiers in Cardiovascular Medicine, 2022
Effects of Nattokinase on Blood Pressure: A Randomized, Controlled Trial, Hypertension Research, 2008
A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles, Scientific Reports, 2015