Nattokinase benefits and side effects: what the evidence shows

Nattokinase is an enzyme (a protein that speeds up a chemical reaction) taken from natto, a Japanese dish of soybeans fermented by the bacterium Bacillus subtilis, and it breaks down fibrin, the mesh that holds a blood clot together ¹³. In people whose blood pressure was already raised, 8-week trials found the top number fell by about 3 to 6 points ²⁴, but the only long trial, 3 years in 265 healthy older adults, found no effect on blood pressure, artery thickening or any blood test ¹. What it does reliably is nudge clotting tests toward slower clotting ⁶⁷, which is why the bleeding risk matters more than the benefits on this page.

What is nattokinase?

Nattokinase is an enzyme made by the bacterium that ferments soybeans into natto ¹³, and its target is fibrin ⁵. For the basics, what it is and what it does in your body has its own page, and this guide covers the evidence, how much studies use, when and how to take it, side effects and interactions.

How it might work in people is less settled than how it works in a test tube. Nattokinase is a large protein, and most proteins are broken down in the gut. A pilot study detected it in the blood of 11 healthy adults for up to 24 hours after one capsule ⁸, and a placebo-controlled study in 12 healthy young men found clot-breakdown markers rising and clotting times lengthening within hours ⁶. So something active reaches the bloodstream, even if the amount is not well measured.

You will see it sold as nattokinase, NSK-SD (a branded extract used in several trials ³⁶), natto extract, or as part of heart, circulation and enzyme blends, often next to serrapeptase. Because it comes from fermented soy, labels often carry a soy allergen statement.

What nattokinase is good for: the evidence, graded

We grade each use by the quality of the human evidence: Strong means several good randomised trials or a meta-analysis agree; Moderate means several randomised trials, mostly positive but small or short; Limited means few or small trials, or mixed results; Early means lab, animal or one pilot study only; Not supported means good trials found no benefit. Our guide to how to judge a supplement explains why these grades matter more than a product's claims.

One row is missing on purpose: no trial has measured whether nattokinase means fewer heart attacks, strokes or blood clots. The 3-year trial was designed to look at artery changes, not those events, and found none ¹.

Does nattokinase lower blood pressure?

The case rests on two 8-week trials. In South Korea, 86 adults aged 20 to 80 with untreated systolic blood pressure (the top number) of 130 to 159 took 2,000 FU of nattokinase or a placebo; 73 finished, and the nattokinase group's top number fell 5.55 points and bottom number 2.84 points more than placebo ². In a North American trial of 79 adults with raised readings, 100 mg a day of a branded extract lowered the bottom number from 87 to 84, while the placebo group stayed at 87; the drop was larger in men ³. A 2023 meta-analysis (a study that pools trials) of six trials and 546 people put the average effect at 3.45 points systolic and 2.32 diastolic ⁴.

Then the longest and largest trial cuts the other way. In the Nattokinase Atherothrombotic Prevention Study, 265 people with a median age of 65 and no heart disease took 2,000 FU or a placebo for a median of 3 years, and blood pressure did not differ between the groups ¹. One reading is that any effect is small and limited to people whose pressure starts high; another is that short, small trials overstate it. Either way, these are research findings, not a treatment: high blood pressure is diagnosed and managed by a clinician, nattokinase is not a treatment for it, and it is never a swap for a prescribed blood pressure medicine.

Arteries and plaque: does nattokinase clear arteries?

The marketing claim is that nattokinase dissolves plaque. The best test of it is the 3-year trial above, which used carotid ultrasound every 6 months to track artery wall thickness and stiffness and found no difference from placebo ¹. The positive result often quoted comes from a 26-week trial in China in which 76 people with carotid plaque took 6,000 FU a day of nattokinase or 20 mg of simvastatin; plaque area fell 36.6% in the nattokinase group versus 11.5% with the statin, but cholesterol fell more with the statin and there was no placebo group ¹¹. That design cannot show nattokinase works, and three times the usual amount also means three times the clotting effect. Plaque and cholesterol are covered in our guide to high cholesterol, which is diagnosed and treated by a clinician; nattokinase is not a treatment for it and never a swap for a statin.

Clotting markers: what changes, and how fast

This is where the human data are most consistent, and it is a safety finding as much as a benefit. After one 2,000 FU dose in 12 healthy young men, D-dimer (a fragment released when a clot breaks down) rose at 6 and 8 hours, fibrin and fibrinogen degradation products rose at 4 hours, factor VIII fell, and the aPTT (activated partial thromboplastin time, a clotting-time test) lengthened at 2 and 4 hours; every value stayed within the normal range ⁶. Over 8 weeks in 100 adults with borderline high cholesterol, nattokinase lengthened the aPTT and a platelet clotting test more than placebo, and the prothrombin time (PT) also rose ⁷. In an open study of 45 people over 2 months at 4,000 FU a day, fibrinogen fell 7 to 10%, factor VII 7 to 14% and factor VIII 17 to 19% ⁵. Our guide to clotting tests explains what each of these numbers measures.

Benefits for men and for women

Searches often ask about nattokinase benefits for men or for women. The only trial that split its results by sex found the blood pressure drop was larger in men, with the bottom number falling from 86 to 81, while women showed a trend toward lower von Willebrand factor, a protein that helps platelets stick ³. That was a secondary analysis of 74 people, so it is a clue for future trials, not a reason to expect different results.

How much nattokinase do studies use?

Trials report amounts in fibrinolytic units. These are the amounts studied, a record of research, not a dose for anyone reading. There is no official upper limit for nattokinase from the NIH or any US agency.

One LifeFrom capsule holds 200 mg of nattokinase with an activity of 2,000 FU, the same activity used in the blood pressure trial in South Korea, the 3-year trial and the single-dose clotting study ²¹⁶. It is half of what the fibrinogen study used and a third of the plaque study's amount.

When and how to take nattokinase

No trial has tested nattokinase with food against without, or morning against evening, so there is no evidence-based best time. In the pilot study, blood levels peaked about 13 hours after a capsule and were still detectable at 24 hours ⁸, so with daily use some is always on board. That matters for anyone also on an anticoagulant: taking the two at different times of day does not stop their effects overlapping.

How long nattokinase takes to work depends on what you measure. Clotting tests moved within 2 to 4 hours of one dose ⁶, fibrinogen fell steadily over 2 months ⁵, and the blood pressure trials reported results at 8 weeks ²³. None of these changes can be felt, so the only honest way to know whether it does anything for a given person is a blood pressure log kept over weeks, read with a clinician. Cycling (taking breaks) has not been studied.

Nattokinase side effects

Across the randomised trials, nattokinase was well tolerated: the 2023 meta-analysis reported no notable adverse events in any of its six trials ⁴, and the 2-month clotting study saw none, including in people on dialysis ⁵. Those trials were small and mostly short, and they excluded people on blood thinners, which is where the real risk sits.

The liver question comes up often in searches. The 3-year trial checked laboratory measures at least every 6 months and found nattokinase did not change any of them ¹, and none of the shorter trials reported a liver problem. That is reassuring for healthy adults but not proof for people with liver disease, where clotting is often already affected. Signs of liver injury from any supplement (dark urine, yellow eyes or skin, pain under the right ribs, unusual tiredness) mean stopping the supplement and getting same-day care.

Who should avoid nattokinase or ask first

• Anyone on an anticoagulant or antiplatelet medicine, or with a bleeding or clotting disorder. Memorial Sloan Kettering's integrative medicine service lists these as reasons not to take it ¹².
• Anyone with a past deep vein thrombosis: Memorial Sloan Kettering advises avoiding nattokinase, noting that in theory it could cause an existing clot to dislodge ¹².
• Anyone with a past stroke or brain bleed, or known small bleeds in the brain (microbleeds), as in the reported cerebellar hemorrhage ⁹.
• Surgery, dental work or procedures: tell the team about nattokinase well before the date, because it lengthens clotting times ⁷. No study has set how many days before surgery to stop it; that is the surgical team's call.
• Low blood pressure, or blood pressure medicines: it may add a few points of lowering ⁴.
• Pregnancy and breastfeeding: no human safety data exist, and bleeding risk around delivery is a particular concern, so this is a conversation with an obstetric clinician first.
• Children: not studied.
• Soy allergy: nattokinase is made from fermented soybeans.
• Liver or kidney disease: both can affect clotting, and the trials included few such patients ⁵.

Nattokinase interactions

Most of nattokinase's interactions come from one mechanism: it lengthens clotting times ⁷, so it stacks with anything else that does. Memorial Sloan Kettering lists anticoagulant, antiplatelet and clot-busting drugs as theoretical bleeding risks, and aspirin as a documented one ¹².

Supplements to pair with nattokinase or keep apart

The biggest stacking risk is two or more supplements that each nudge bleeding risk. Everything in a pouch, or a pill organizer, is swallowed at once, and with nattokinase detectable for up to 24 hours ⁸, spacing by hours does not separate the effects.

Blood tests worth knowing about

Nattokinase is one of the few supplements whose effect shows up on standard clotting tests ⁶⁷¹². None of these tests is a way to dose it, and a changed result belongs with a clinician. If you already have results, ask your clinician whether any of them need rechecking, and tell them about nattokinase so a shifted number is read correctly.

Our guide to clotting tests walks through PT, INR, aPTT, fibrinogen and D-dimer, and the blood clotting topic collects every related marker. A single reading matters less than a trend, especially for INR.

Where nattokinase comes up: blood pressure, cholesterol and clots

Nattokinase is mostly discussed around heart health. Raised blood pressure, high cholesterol and clotting problems are all diagnosed and treated by a clinician, and nattokinase is not a treatment for any of them. If a lipid panel is the reason you are reading, our guide to reading a lipid panel and the LDL calculator explain the numbers; the pooled trials found nattokinase did not lower cholesterol ⁴. The heart topic gathers the related markers. If you take a statin, our statins guide covers what the LDL response should look like; nattokinase is never a swap for one.

Nattokinase in the LifeFrom pouch

The 2,000 FU in one capsule matches the amount in the blood pressure trial from South Korea and the 3-year trial, and is lower than the clotting-factor and plaque studies used ²¹⁵¹¹. Everything in a pouch is swallowed together, so a pouch that also holds fish oil, turmeric or ginger combines several bleeding nudges at once; anyone building a pouch with those alongside nattokinase, or taking any blood thinner, is best checking with a pharmacist first. See the shop and its packs.

This guide is general education, not medical advice. Under US law the FDA does not approve dietary supplements for safety or effectiveness before they are sold ¹⁴, and a product's strength can differ from its label. Because nattokinase acts on clotting, the clinician who knows your history and medicines is the right person to decide whether it fits, especially if you take anything that affects bleeding. Read our medical disclaimer for more.

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