Nattokinase

What it is

Natto smells pungent and pulls threads like melted cheese. In 1987, the group around the Japanese researcher Hiroyuki Sumi described strong fibrinolytic activity in it and named the responsible enzyme nattokinase. It is a protease with a molecular weight of about 20,000 that digests fibrin, the building block of blood clots.

What may be sold in the EU as a dietary supplement is precisely defined: fermented soybean extract named NSK-SD, standardized to 20,000 to 28,000 fibrinolytic units, FU for short, per gram. During production, the vitamin K2 from the natto is removed. The EU Commission authorized the extract as a novel food in 2017.

How it is supposed to work

The narrative is that of a cleaning crew for the arteries: nattokinase is said to dissolve clots, make the blood more fluid and thus protect the heart and vessels. In the test tube the enzyme does break down fibrin, and in animals it had a thrombolytic effect when injected. The decisive question is what happens after swallowing. An enzyme is a protein, and proteins are normally broken down in the digestive tract.

A small study gives a hint: 12 healthy young men received a single dose of 2,000 FU or placebo in a double-blind design. Afterwards, the breakdown products of fibrin, the D-dimers, rose after 6 and 8 hours, coagulation factor VIII fell, and a clotting time was prolonged after 2 and 4 hours. All values remained within the normal range. So something does arrive; whether it is the active enzyme remains open.

Long COVID: what patients report

An important reason for the current popularity is long COVID. Researchers have described thrombotic changes and microclots there, and many patients therefore turn to nattokinase. A large online survey, published in PNAS in 2025, collected responses from 3,925 people with long COVID or chronic fatigue syndrome. Nattokinase and lumbrokinase, a similar enzyme from earthworms, were analyzed as one group. Of 475 ratings, 55.4 percent reported an improvement, 50 people even a marked one, and 6.9 percent a worsening.

The comparison benchmark is clever: since there was no placebo, the researchers used plain vitamin C, which nobody expects to treat these diseases. With it, 26.8 percent felt better. Serrapeptase, another enzyme, at 37.5 percent was not significantly above vitamin C. So the respondents distinguish fairly clearly. A qualitative analysis of social media posts, however, also shows a lot of disappointment and frustration with supplement use. All of this is anecdotal reports, not proof of efficacy, and there is no placebo-controlled study on long COVID.

What the studies show

Hodis et al., Clinical Hemorheology and Microcirculation 2021 — the long-term study

265 people without cardiovascular disease, median age 65.3 years, received 2,000 FU of nattokinase or placebo in a double-blind design. Every 6 months, the carotid artery was measured by ultrasound. After a median of 3 years, wall thickness and arterial stiffness did not differ; the primary endpoint was missed. Blood pressure, coagulation, fibrinolysis and inflammation values also remained unchanged.

Chen et al., Frontiers in Cardiovascular Medicine 2022 — the plaque study

The study with 1,062 participants features on many sales pages. Under 10,800 FU per day over 12 months, carotid wall thickness fell from 1.33 to 1.04 mm, and plaques became up to 36 percent smaller. However, it is a retrospective analysis of records without a control group; of 2,875 records screened, only people who had kept going for 12 months were included. 5 of the 10 authors worked for the manufacturer of the tablets, which is disclosed in the paper.

Li et al., Reviews in Cardiovascular Medicine 2023 — meta-analysis

6 randomized studies with 546 participants. Blood pressure reduction of 3.45 over 2.32 mmHg compared with placebo. For blood lipids, the result at a rather low dose was even unfavorable, with somewhat higher total and LDL cholesterol and lower HDL, plus a slight rise in blood glucose. No notable side effects were reported.

Where the data stop

The dissolution of blood clots is what is advertised; it has not been shown in humans. No study has investigated whether nattokinase prevents thromboses, heart attacks or strokes. EFSA noted that the available data do not allow a conclusion as to whether active nattokinase is absorbed. The only long placebo-controlled study found no effect on the vessel wall in healthy people and, unlike the shorter studies, none on blood pressure either.

The plaque data rest on an uncontrolled records analysis with manufacturer involvement and a considerably higher daily dose, 10,800 instead of 2,000 FU. One can argue that the long-term study was dosed too low, but then the high dose would have to be tested against placebo, and that has not happened so far. For long COVID there are only self-reports without placebo; in an Australian review, nattokinase was among the 14 candidates prioritized by clinicians and patients, but without a single placebo-controlled long COVID study.

Status, approval and legal

In the EU, fermented soybean extract containing nattokinase has been authorized as a novel food ingredient since Implementing Decision 2017/115, in dietary supplements for adults excluding pregnant and breastfeeding women, up to a maximum of 100 mg of extract per day. According to EFSA, this corresponds to a maximum of 2,800 FU. The EFSA assessment applied to healthy men and women over 35 years; pregnant and breastfeeding women were excluded. A statement is mandatory that intake should be medically supervised when medicines are taken at the same time. There are no authorized health claims; nattokinase is not a medicine.

Safety

EFSA’s safety assessment is based on rat experiments, because it considered the human studies insufficient due to low informative value and contradictory results. The critical group is people on anticoagulants. Two cases are documented: a patient who was taking aspirin after a stroke suffered a cerebellar hemorrhage after 7 days of additional nattokinase. Another, after a mechanical heart valve replacement, replaced his anticoagulant with nattokinase on his own initiative; after almost a year, a clot sat on the valve. Too much with the medication, too little instead of the medication. Anyone taking anticoagulants or aspirin, with a bleeding tendency or facing surgery should discuss nattokinase with a physician beforehand. With a soy allergy, the same allergy risk applies as with other soy products.

Sources

• Sumi et al., Experientia 1987
• EFSA NDA Panel, EFSA Journal 2016
• Commission Implementing Decision (EU) 2017/115
• Kurosawa et al., Scientific Reports 2015
• Li et al., Reviews in Cardiovascular Medicine 2023
• Hodis et al., Clinical Hemorheology and Microcirculation 2021
• Chen et al., Frontiers in Cardiovascular Medicine 2022
• Eckey et al., PNAS 2025
• Chang et al., Internal Medicine 2008
• Elahi et al., Baylor University Medical Center Proceedings 2015