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Printed from https://bottledhope.co/supplements/nattokinase/. Last reviewed 2026-10-01. Check the site for the latest version.

Nattokinase

An enzyme first isolated from natto, a Japanese fermented soybean food. People take it hoping to lower blood pressure or cholesterol, or break down clots.

Explained simply · Last reviewed

What it is

Nattokinase is an enzyme. EFSA, the EU's food safety agency, says it was first isolated from natto, a traditional Japanese food made by fermenting soybeans with the bacterium Bacillus subtilis var. natto, and describes it as a serine protease, a type of enzyme that breaks down proteins. It says nattokinase's ability to break down fibrin, a protein in blood clots, was first found in the laboratory in 1987.

More about Nattokinase

EFSA, the EU's food safety agency, says it was first isolated from natto, a traditional Japanese food made by fermenting soybeans with the bacterium Bacillus subtilis var. natto, and describes it as a serine protease, a type of enzyme that breaks down proteins. It says nattokinase's ability to break down fibrin, a protein in blood clots, was first found in the laboratory in 1987.

A 2023 review of the clinical trials says that use of nattokinase is growing among both healthy people and people with cardiovascular disease, especially in Asian countries. It says research has widened from its effects on blood clotting to cholesterol and blood pressure. A 2015 case report describes it as gaining popularity in non-medical health publications and websites as an over-the-counter clot dissolver.

Nattokinase supplements are not the same as natto, the food. The 2023 review left out trials of natto because the food contains many other nutrients. NIH's Office of Dietary Supplements states that natto has high amounts of vitamin K2. EFSA states that vitamin K2 is removed during the manufacture of the one nattokinase extract it assessed; its statement covers only that extract.

EFSA reviewed that extract, NSK-SD, in 2016, after the company Japan Bio Science Laboratory applied to sell it in the EU as a novel food. It is meant for food supplements sold as capsules, tablets and powder, with its strength stated in fibrin degradation units. EFSA says its opinion covers safety only and is not an assessment of whether the extract works.

The trials in the 2023 review were small. Seven placebo-controlled trials met its criteria, in the United States, South Korea, Taiwan and Vietnam, lasting from 60 days to three years.

Also known as: NK, subtilisin NAT, fermented soybean extract

At a glance

Safety: known risks, 2 groups who should avoid it or take extra care and 2 documented interactions. See Safety ↓

Claims made about Nattokinase, and how strong the evidence is for each:

Each rating follows our published rules and the sources cited for it. We don’t add our own medical judgment. How we rate

Safety

Read this before the ratings below.

Risks

  • EFSA, the EU’s food safety agency, assessed one nattokinase extract, with the trade name NSK-SD, in 2016. It concluded that the extract is safe under the conditions of use the applicant proposed: food supplements for healthy men and women over 35, excluding pregnant and breastfeeding women. EFSA based that conclusion on the safety margin from a 90-day study in rats. It judged the human studies it was given, some in people taking blood thinners, too low in statistical power and too inconsistent to conclude on the extract’s safety.
  • EFSA notes that some EU member states were concerned the extract might affect blood clotting. In the human studies it reviewed, some measures of clotting changed after nattokinase in some studies and not in others. EFSA says these studies were too small, too short or without a comparison group to draw conclusions about safety.
  • A 2023 review of seven placebo-controlled trials, six of which recorded adverse events, reports no notable adverse events due to nattokinase or placebo in any group. The trials were small, which the reviewers list as a main limitation. They also note case studies with contradictory findings on “allergic and bleeding risks”.
  • In the same 2023 review, two trials pooled together showed slightly higher blood sugar with nattokinase than with placebo. The reviewers describe this as very little influence on blood sugar.
  • A 2015 case report describes a 53-year-old man with a mechanical aortic heart valve who stopped his prescribed warfarin, a blood thinner, and took nattokinase instead. After nearly a year, clot had formed on the valve, and it was replaced in a second operation. The authors write that they strongly discourage using nattokinase as a substitute for warfarin after valve replacement.

Who should avoid it or take extra care

  • Soy allergy: EFSA states that the nattokinase extract it assessed contains materials from soybeans. It considers the risk of allergic reactions to the extract not dissimilar to that of other soy-derived products.
  • Pregnancy and breastfeeding: the use EFSA assessed excluded pregnant and breastfeeding women, and EFSA’s safety conclusion covers only the intended conditions of use.

Documented interactions

  • Warfarin (Coumadin) and similar anticoagulants: EFSA reviewed a 6-month placebo-controlled study of nattokinase in adults with cardiovascular disease who were taking warfarin. It found the differences between groups inconsistent and not related to dose. It states that the study was not designed or powered to show harmful effects on the blood, and that it is insufficient to conclude on safety in these patients. Separately, a 2015 case report describes a mechanical heart valve that clotted after a man replaced his warfarin with nattokinase. Source [1]Source [2]
  • Aspirin: EFSA describes a published case of a 52-year-old woman taking low-dose aspirin and blood pressure medicines to prevent another stroke. She had bleeding in the brain (a cerebellar hemorrhage) after taking nattokinase for seven days. EFSA considers that no conclusion about whether nattokinase caused it can be drawn from this report. Source [1]

Safety sources: Source [1]Source [2]Source [3]

What the evidence says

Each claim is rated on its own evidence. Ratings follow the scale on our methodology page.

  • Lowers blood pressure Evidence rating: Limited

    People with high blood pressure take it hoping it will bring their readings down.

    A 2023 review pooled a few small eight-week trials and found lower blood pressure than with placebo, but its authors call the finding preliminary.

    A 2023 meta-analysis pooled placebo-controlled trials of nattokinase capsules. Its blood pressure results come from small eight-week trials in people with high blood pressure or high cholesterol. It reports systolic blood pressure (the top number) 3.45 mmHg lower and diastolic (the bottom number) 2.32 mmHg lower than with placebo.

    The review’s text and its figure disagree on how many trials that rests on. The text says three trials in 223 people for both numbers. The review’s forest plot shows three trials for diastolic pressure but only two for systolic pressure, with high variation between those two. This page reports both and does not choose between them.

    The reviewers did not grade how sure they could be (certainty). They write that the number of studies was small and the findings should be interpreted cautiously. They conclude that nattokinase “could be considered as a promising adjunctive tool” (an add-on) for high blood pressure, but that the findings are preliminary. They say a definitive conclusion could not be drawn.

    EFSA, the EU’s food safety agency, describes a separate 4-week safety trial in 31 healthy volunteers, in which blood pressure did not change. It was a safety trial, not designed to test blood pressure, and a small trial that finds no change is too little evidence to rule out an effect. This page rates the claim limited: a few small, short trials.

    Sources: Source [1]Source [2]

  • Lowers blood cholesterol and triglycerides Evidence rating: Insufficient

    People take it hoping it will lower their cholesterol.

    A 2023 review of four trials found no cholesterol lowering, and total cholesterol was higher with nattokinase; the authors say more work is needed on higher, longer use.

    This claim is about blood fat levels, which are markers, not heart attacks or strokes. A 2023 meta-analysis pooled four placebo-controlled trials that measured cholesterol, in 399 people. It split them by the total amount taken: two eight-week trials (lower total) and two longer trials of six months and three years (higher total).

    Neither group showed lower cholesterol. In both, total cholesterol was higher with nattokinase than with placebo. In the two short trials, LDL (“bad”) cholesterol was also higher and HDL (“good”) cholesterol lower. In the two longer trials, LDL and HDL did not differ significantly from placebo. Triglycerides, pooled from three trials, did not differ significantly either. The reviewers conclude that short-term, low-dose nattokinase “might have no significant lipid-lowering effects”.

    The reviewers did not grade their certainty, and the results varied a lot between trials. They suggest that the effect on blood fats might depend on dose, and call for longer trials at higher doses. They cite a 2022 study of 1,062 people that reported lower cholesterol and triglycerides after a year of nattokinase.

    That 2022 study was a retrospective look back at the records of people with high blood fats, with no comparison group. Its authors say it was not a randomized controlled trial. Five of its authors were employed by the company that made the tablets.

    Under this site’s rules, an insufficient rating means the cited evidence is too limited to show whether there is an effect.

    Sources: Source [1]Source [2]

  • Slows the thickening of artery walls (atherosclerosis) in the neck arteries Evidence rating: Insufficient

    People take it hoping it will keep their arteries clear and slow hardening of the arteries.

    The one placebo-controlled trial a 2023 review describes found no significant difference in neck-artery wall thickening over three years in healthy older adults.

    This claim is about the thickness of the carotid (neck) artery wall, a marker measured by ultrasound, not heart attacks or strokes. A 2023 review describes one placebo-controlled trial that measured it. That trial followed healthy older adults for three years. The yearly thickening of the artery wall did not differ significantly between the nattokinase and placebo groups. Nor did artery stiffness. The review did not pool this outcome.

    A single trial that finds no difference is too little evidence to rule out an effect. The review’s authors also mention a 2017 Chinese study reporting that high-dose nattokinase over 26 weeks inhibited the progression of artery plaques.

    A 2022 study looked back at the records of 683 people with signs of atherosclerosis who took nattokinase tablets for a year. It reported thinner carotid artery walls and smaller plaques afterwards than before. It had no comparison group, and its authors say it was not a randomized controlled trial. Five of its authors were employed by the company that made the tablets.

    The randomized trial and the uncontrolled study point in different directions, so this page takes the lower rating. Under this site’s rules, an insufficient rating means the cited evidence is too limited to show whether there is an effect.

    Sources: Source [1]Source [2]

  • Helps the body break down blood clots (measured as clotting and clot-breakdown markers in the blood) Evidence rating: Insufficient

    People take it hoping it will thin their blood or dissolve clots and keep their circulation healthy.

    Trials report mixed changes in clotting markers; EFSA, assessing safety only, found the human studies underpowered and inconsistent and could not say if active enzyme is absorbed.

    This claim is about laboratory markers of blood clotting and clot breakdown, not about strokes, heart attacks or clots in the legs. No cited source reports whether nattokinase prevents those events. A 2023 review found too few trials measuring clotting to pool them. It describes three. In the largest, healthy adults took nattokinase or placebo for three years. The review reports no detectable effects on clotting and clot-breakdown measures at 1 week and 1, 3 and 6 months.

    In an eight-week trial, two laboratory clotting-time measures (collagen–epinephrine closure time and activated partial thromboplastin time) rose more with nattokinase than with placebo. A third trial, in people with high blood pressure, reported a 15% fall in von Willebrand factor, a clotting protein. The review reports it with a p value of less than 0.09, while it treats values below 0.05 as statistically significant. In their discussion, the reviewers write that even a single dose has been shown to enhance clot breakdown and anticoagulation in humans, citing two single-dose studies.

    EFSA, the EU’s food safety agency, describes both. In one, 12 healthy young men had changes in several clotting markers that stayed within normal ranges. The other gave one dose to 11 healthy people; EFSA notes it had no control group, used a non-validated test and did not assess the enzyme’s activity in blood. It describes an uncontrolled 2-month study in which three clotting factors fell, and says no conclusions on safety can be drawn from it.

    EFSA notes that nattokinase breaks down fibrin in the laboratory, and clots in animals when given by a route other than the mouth (parenterally). It says the data do not allow conclusions on whether active nattokinase is absorbed when swallowed. It judges the human studies too low in power and too inconsistent to conclude on safety.

    This page rates the claim on those sources. An insufficient rating means the evidence is too limited to show whether there is an effect.

    Sources: Source [1]Source [2]

Which form the evidence used

Supplements are sold in several forms. This is what the sources on this page say about them — which form the research used, and any comparison those sources themselves made. Where they made none, this page does not rank the forms.

  • Nattokinase capsules, What the sources supportDetails

    The 2023 review states that in the trials it pooled, nattokinase and placebo were given in the same capsule form, and that all the trials used purified nattokinase products. The daily amounts varied widely between trials. They were measured in fibrin units (FU), which the review describes as a measure of the enzyme’s ability to break down fibrin, a protein in blood clots, in the laboratory. No cited source compared capsules with tablets, powders or other forms, so this page cannot say that one works better than another. Source [1]

  • Natto (the fermented soybean food), Details

    Natto is not the same as a nattokinase supplement. The 2023 review left out trials of natto, because the food contains many other nutrients besides nattokinase. NIH’s Office of Dietary Supplements (ODS) states that natto has high amounts of vitamin K in the form of menaquinones (vitamin K2). EFSA, the EU’s food safety agency, states that vitamin K2 is removed during the manufacture of the one nattokinase extract it assessed. EFSA’s statement covers only that extract. Source [1]Source [2]Source [3]

Also documented elsewhere on this site

Other supplements we cover that document an interaction with the same thing. This is a pointer to what those pages say, not a statement about taking them together — we have no source reviewing these in combination.

Sources

  1. Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
    Reviews in Cardiovascular Medicine, 2023 · Meta-analysis · Primary source
  2. Safety of fermented soybean extract NSK-SD® as a novel food pursuant to Regulation (EC) No 258/97
    EFSA Panel on Dietetic Products, Nutrition and Allergies (EFSA Journal), 2016 · Health authority summary · Primary source
  3. Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants
    Frontiers in Cardiovascular Medicine, 2022 · Observational study · Supporting source
    Some of its authors disclose ties to industry.
  4. Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis
    Proceedings (Baylor University Medical Center), 2015 · Observational study · Supporting source
  5. Vitamin K: Fact Sheet for Health Professionals
    NIH Office of Dietary Supplements, 2021 · Health authority summary · Primary source

Page history

Show all 2 changes to this page
  • — First drafted. Blood pressure rated limited on a 2023 meta-analysis of a few small eight-week trials. Cholesterol, artery-wall thickening and clot-breakdown markers rated insufficient: the trials found no cholesterol lowering, no significant slowing of artery-wall thickening, and mixed changes in clotting markers.
  • — Published.