Nattokinase

We evaluated 29 human studies on Nattokinase, including 11 randomised controlled trials and one meta-analysis or systematic review; the controlled studies include 644 participants in total. As of 10 October 2026.

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1. What Is Nattokinase? Occurrence, Origin and Forms

Nattokinase is an enzyme of the serine protease group that forms when the bacterium Bacillus subtilis var. natto ferments soybeans. It occurs in natto, a fermented soybean dish traditionally eaten in Japan. As a supplement it is usually offered as an extract in capsules or tablets with a stated enzyme activity.

Nattokinase is found in natto and in other fermented soybean products made with this bacterium. In studies it is taken as a capsule or tablet, or consumed as natto through the diet.

It is obtained by fermenting cooked soybeans with Bacillus subtilis var. natto; the enzyme is separated from the fermented mass, purified and dried into a powder. Studies mainly examine oral capsules and tablets with a defined enzyme activity, as well as natto as a food.

Forms and Preparations Studied

• Natto (fermented soybeans)
• Capsules with nattokinase extract
• Tablets with nattokinase extract
• Powder for oral intake
• Combination products with further ingredients

Not covered on this page:

• Vitamin K2, which is present in natto but is a separate substance
• Other fibrinolytic enzymes such as lumbrokinase or serrapeptase
• Soy protein and soy isoflavones
• Anticoagulant drugs

2. What Does Nattokinase Do? Results by Area

How to read the table: counted are human studies whose results concern the area. “High” means at least one meta-analysis and two controlled studies showing improvement, or at least three controlled studies of which three quarters show improvement, with at least 300 participants in total. “Moderate” means at least two controlled studies showing improvement, as a majority, or one meta-analysis alongside controlled studies. “Low” means one controlled study showing improvement. Where an area has no controlled study, the strength of evidence is at most “low” (result “reviews only” or “observational data only”). Everything else is “unclear”. A study counts as showing improvement when at least half of its outcomes in this area improved. Reviews of combination products do not count as meta-analyses; results that only describe side effects or shares of users do not count as an effect. The same study is counted only once.

3. What the Studies Show in Detail

Nattokinase and Blood Pressure: Human Studies

In adults with elevated blood pressure, nattokinase showed improvements in systolic and diastolic blood pressure in several controlled studies and a meta-analysis 156. Mostly capsules with nattokinase extract were studied, in one study with stated enzyme activity 56. A randomized controlled trial tested a combination product of nattokinase extract and red yeast rice in patients with stable coronary artery disease and found an improvement in diastolic blood pressure; this finding cannot be attributed to nattokinase alone 2. The evidence is high, but the number of controlled studies is small and the follow-up duration is limited. It remains open whether the blood pressure lowering persists in the longer term and whether it differs between capsules, tablets and natto as a food.

Nattokinase and Blood Fluidity: Human Studies

In a randomized controlled trial with twelve healthy men, a single dose of nattokinase prolonged clotting time and lowered factor VIII activity, in each case within the normal range 8. In adults with elevated cholesterol, occlusion time and activated partial thromboplastin time were prolonged more than with placebo 12. These are laboratory values, not a proven clinical effect on blood flow or vascular events. In a randomized crossover trial with nine healthy men, the skin temperature of the hand recovered faster after cold water following a single dose than with placebo 9. Capsules with nattokinase extract were studied; controlled data are lacking for natto as a food, for tablets, powder and combination preparations, and for longer-term clinical endpoints. The strength of evidence is moderate; the studies are short, one of them very small.

Nattokinase and Fibrinolysis: Human Studies

A randomized controlled trial in twelve healthy young men found greater breakdown of fibrin, measured by D-dimer and fibrin degradation products, for capsules with nattokinase extract 8. These are laboratory findings on fibrinolysis, not a proven clinical effect. The strength of evidence is low: only a single dose was studied in a few healthy young men, and all values remained within the normal range. On natto as a food, on tablets, powder or combination preparations with other ingredients, no controlled comparisons are available in this area; it therefore remains open whether the laboratory changes can be transferred to other forms, dosages or to people with diseases.

Nattokinase and Blood Lipids: Human Studies

In adults with elevated blood lipids, combinations of nattokinase and red yeast rice showed improvements in total cholesterol, LDL cholesterol and triglycerides in several controlled studies 27. A randomized controlled trial with a combination preparation of nattokinase and Monascus also found more favorable total and LDL cholesterol levels as well as a better non-HDL cholesterol and LDL-C/HDL-C ratio 4. A meta-analysis, by contrast, found no improvement in blood lipids for nattokinase alone and in part even reported less favorable values 1; also in a study without a control group, blood lipids remained unchanged with nattokinase capsules 16. The favorable findings concern mixed preparations with red yeast rice or Monascus; for nattokinase alone, a reduction in blood lipids is not proven.

Nattokinase, Heart and Circulation: Human Studies

A randomized controlled trial of a combination preparation of nattokinase and Monascus showed no difference in carotid intima-media thickness in patients with dyslipidemia; the result cannot be attributed to nattokinase alone 4. In a randomized crossover trial with nine healthy men, a single dose of nattokinase did not change heart rate, cardiac output or sympathetic activity compared with placebo 9. The strength of evidence is low; endpoints such as heart attack or stroke were not examined.

Nattokinase and Thrombosis: Human Studies

A randomized controlled trial in 178 patients with stable coronary artery disease found more favorable values for thromboxane B2 and antithrombin III than with placebo only under the mixture of nattokinase and red yeast rice 2. These are laboratory values, not a proven effect against thromboses. A case series reports an improvement in clinical symptoms in patients with vascular diseases, although nattokinase was there given partly together with fondaparinux or enoxaparin and no comparison took place 15. A case report, by contrast, describes a thrombus on a mechanical aortic valve prosthesis after a patient had replaced warfarin himself with an over-the-counter nattokinase preparation 22. The strength of evidence is low: controlled trials with thromboses as an endpoint are lacking, and the controlled laboratory finding comes from a mixture with red yeast rice.

Nattokinase and Inflammation: Human Studies

A randomized controlled trial in adults with prediabetes tested a mixture of aronia, red ginseng, shiitake mushroom and only a small proportion of nattokinase 10. High-sensitivity C-reactive protein did not differ significantly from placebo; moreover, any effect could not be attributed to nattokinase alone 10. It remains open whether nattokinase in capsules, tablets or as natto alone has an influence on inflammation markers.

Nattokinase: Further Outcomes in Studies

In this area, nattokinase preparations were studied in several controlled trials with different questions, predominantly as capsules with nattokinase extract. With slightly elevated blood pressure, renin activity fell more with nattokinase than with placebo; this is a laboratory finding 5. In a randomized controlled trial in asymptomatic narrowing of the cerebral or carotid arteries, nattokinase did not improve general cognition; only an exploratory analysis found better visuospatial performance 3. In a double-blind crossover study, a nattokinase extract served only as an active placebo and did not change shoulder stiffness, back pain and cold sensation; these were improved by a different natto preparation with the enzyme bacillopeptidase F 13. The findings come in each case from individual studies and predominantly from laboratory values; the long-term clinical effect is open.

Further studies in this area: 19 21 23 25 27

4. How Is Nattokinase Dosed? Preparation, Dose and Duration in Studies

Mostly capsules with nattokinase extract were studied, some with stated enzyme activity, as well as tablets and combination products with other ingredients 256. Natto as a food and powders for oral intake have hardly been tested in controlled studies. The stated enzyme activity and dose differ between products, which limits comparability.

5. Is Nattokinase Safe? Side Effects in Studies

A meta-analysis of controlled studies found no notable adverse events from nattokinase 1. No intervention-related adverse events were reported with mixtures with red yeast rice or Monascus either 24. A case report describes a thrombus on a mechanical aortic valve prosthesis after a patient had replaced warfarin himself with an over-the-counter nattokinase product 22. The authors explicitly advise against taking nattokinase as a substitute for anticoagulants 22. Because nattokinase prolonged coagulation times in studies 812, an additional effect with anticoagulant drugs is conceivable; a review mentions a possible bleeding risk and interactions 27.

6. What Remains Open: Limits of the Evidence

• Most controlled studies are small and short; longer-term clinical endpoints such as heart attack or stroke have not been examined.
• Capsules, tablets, powders and natto as a food are hardly comparable due to different enzyme activity and dose.
• Favorable findings on blood lipids come from combination products and cannot be attributed to nattokinase alone.
• Many results are laboratory values, not proven clinical effects.
• There are only few data on interactions with anticoagulant drugs and on people with pre-existing conditions.

7. Bottom Line: What Is Established About Nattokinase

Nattokinase is a serine protease enzyme from the fermentation of soybeans by Bacillus subtilis var. natto and is offered as a capsule, tablet or powder product with stated enzyme activity. Blood pressure is the best studied: several controlled studies and a meta-analysis showed improvements in systolic and diastolic values in adults with elevated blood pressure 156. For blood flow properties and fibrinolysis, two randomized controlled trials found longer coagulation times and increased fibrinolysis; these are laboratory findings without proven clinical effect 812.

Favorable results on blood lipids are tied to mixtures with red yeast rice or Monascus and cannot be attributed to nattokinase alone 247. A meta-analysis found no lowering of blood lipids for nattokinase alone, but in part higher cholesterol values and slightly elevated blood glucose 1. Overall, the evidence for clinical endpoints is low; the comparability of forms and the long-term effect remain open.