Nattokinase is an enzyme produced during the fermentation of soybeans into natto, a traditional Japanese food with a sticky, stringy texture. It was first identified by researcher Hiroyuki Sumi in 1987 and has since become one of the most studied natural enzymes for cardiovascular health. Nattokinase works primarily by breaking down fibrin, a protein that forms the structural framework of blood clots, and this clot-dissolving ability is at the center of its growing popularity as a supplement.
How Nattokinase Is Made
Nattokinase is produced by a specific strain of bacteria called Bacillus subtilis natto. When these bacteria ferment soybeans, they secrete the enzyme as a byproduct. The enzyme itself is a relatively small protein made up of 275 amino acids. In supplement manufacturing, the bacteria are grown under controlled conditions, typically at around 30°C with a carefully maintained pH of 7.0. Peak enzyme production occurs after roughly 26 hours of fermentation.
The supplement form is not the same as eating natto. Manufacturers extract and concentrate the enzyme, and many remove vitamin K2 during processing. This matters because natto is one of the richest dietary sources of vitamin K2, which interferes with the blood-thinning drug warfarin. The Japan NattoKinase Association certifies products that have had vitamin K2 removed, so people taking warfarin can look for that distinction on the label.
What It Does in Your Body
Nattokinase’s primary action is fibrinolysis: it breaks down fibrin, the mesh-like protein that holds blood clots together. Your body naturally produces its own clot-dissolving enzymes, but nattokinase appears to enhance that process. After you take it orally, the enzyme is absorbed through the small intestine. Blood levels peak around 2 to 4 hours after ingestion, and it stays active in the bloodstream for roughly 8 hours before being cleared.
Beyond direct fibrin breakdown, nattokinase may also thin the blood through other pathways, which is why researchers have explored its effects on blood pressure, cholesterol, and overall cardiovascular risk.
Effects on Blood Pressure
Clinical trials have shown modest but consistent blood pressure reductions with nattokinase supplementation. In a randomized, double-blinded trial of patients with stable coronary artery disease, those taking nattokinase alone saw their systolic blood pressure (the top number) drop by about 6.3 mmHg over 90 days. The placebo group dropped only 3.8 mmHg over the same period. When nattokinase was combined with red yeast rice, the reduction was even larger at 9.5 mmHg for systolic and 7.4 mmHg for diastolic pressure.
These are not dramatic numbers compared to prescription blood pressure medications, but they’re meaningful for people with mildly elevated readings who are exploring lifestyle and supplement-based strategies.
Effects on Cholesterol
A four-month randomized trial tested a nattokinase-based supplement (containing 2,500 fibrinolytic units of nattokinase plus a small amount of naturally occurring lovastatin from red yeast rice) against a placebo in 113 people with abnormal lipid levels. After 120 days, the supplement group had significantly lower total cholesterol, LDL cholesterol (the “bad” kind), and non-HDL cholesterol compared to placebo. LDL dropped by about 0.43 mmol/L more than placebo, which translates to roughly a 17 mg/dL difference.
HDL cholesterol (the “good” kind) and triglycerides did not change significantly. It’s worth noting that these trials combined nattokinase with red yeast rice, which contains a natural statin compound, so the cholesterol-lowering effect likely comes from both ingredients working together rather than nattokinase alone.
Typical Dosage
Nattokinase supplements are measured in fibrinolytic units (FU), which reflect the enzyme’s clot-dissolving activity rather than just its weight. The standard dose used in most clinical research is 2,000 FU per day, equivalent to about 100 mg. Some trials have used 4,000 FU daily (split into two doses). Study durations typically run 8 to 12 weeks.
Supplement labels vary in how they present this information. Some list milligrams, some list FU, and some list both. Looking for the FU number gives you the most reliable comparison between products, since the enzyme’s potency per milligram can differ depending on how it’s manufactured.
Risks and Side Effects
Nattokinase’s clot-dissolving properties are exactly what make it risky for certain people. Because it actively breaks down fibrin, it can increase bleeding risk, especially if you’re already taking blood-thinning medications like warfarin, aspirin, or direct oral anticoagulants. People with clotting disorders or a history of deep vein thrombosis should avoid it entirely.
There is also a theoretical risk that nattokinase could dislodge an existing blood clot, potentially sending it to the lungs or brain. Case reports from Memorial Sloan Kettering Cancer Center illustrate the real-world consequences of misuse. One elderly woman with atrial fibrillation died from internal bleeding after taking over-the-counter nattokinase on her own, without any other blood thinners. In another case, a patient who replaced their prescribed warfarin with nattokinase after a mechanical heart valve replacement developed a clot on the valve and needed a second surgery.
Allergic reactions are another concern. Nattokinase is derived from fermented soybeans, and people with soy or fermented soybean allergies have experienced severe reactions, including anaphylaxis. In clinical trials using standard doses, common side effects like mouth ulcers, stomach pain, or digestive issues were not reported at higher rates than placebo.
Who Should Be Cautious
The people most at risk are those who treat nattokinase as a substitute for prescribed medications. It is not equivalent to pharmaceutical blood thinners, and swapping one for the other without medical guidance has led to serious harm. If you’re taking any anticoagulant, antiplatelet, or fibrinolytic medication, adding nattokinase on top creates compounding bleeding risk that’s difficult to predict or monitor.
People scheduled for surgery should also stop nattokinase well in advance, given its 8-hour half-life and cumulative effects on clotting. And because the supplement industry is not as tightly regulated as pharmaceuticals, product quality varies. Choosing a product certified by the Japan NattoKinase Association or verified by a third-party testing organization helps ensure you’re getting what the label claims, with vitamin K2 removed if that matters for your situation.