Nattokinase dosage and evidence
Written by Aaron CuhaReviewed Sep 2026
The short answer
Nattokinase is a clot-busting enzyme made when bacteria ferment soybeans into natto, a Japanese food.
Evidence grade for Nattokinase: Strong. The rule: at least two finished studies in people, and at least 1,000 people who took it. The sum on this page: 9 completed trials, 1,795 people given it. A grade counts how much has been done to people, not whether it works.
- People given it
- 1,795
- Human studies
- 9
- Found nothing
- 3
Dose
No human dose established
Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose.
9 completed trials, 1,795 people given it
6 effects reported, 4 unwanted, 2 wanted, by people using it, not a trial
Goal pages: Ageing and longevity, Heart and circulation
In plain English
In plain English, from Aaron
This is how I would explain it to a friend. The evidence, with the numbers, is further down the page.
Nattokinase is an enzyme from natto, a fermented soybean food from Japan. It helps break down blood clots. It is sold as a supplement for blood pressure and heart health. It thins your blood a little, and that is also its main danger.
What people take it for
- Lower blood pressure.
- Clearing plaque from arteries.
- Heart and circulation health.
- Suspected microclots after COVID.
What studies in people showed
Blood pressure has the best support. A review that pooled 6 trials with 546 people found it lowered the top number by 3.45 points and the bottom by 2.32. That is modest. The plaque story is weaker. The best trial ran about 3 years in 265 healthy older adults against a dummy pill. It found no effect on artery walls, stiffness or blood pressure. The good plaque results came from studies with no dummy pill group, and the biggest had authors who worked for the maker. On its own, it did not lower cholesterol. No trial has checked heart attacks, strokes or deaths.
What people report
Reports, not study results
The good
- In a Long COVID survey, about 60% said they got some benefit, mostly within 2 weeks.
- People use it for general support of circulation and blood pressure, which is where the trial data is best.
The bad
- Bruising more easily.
- No noticeable effect is a common report.
- People take a blood thinner with no doctor and no blood tests. One older woman on it alone died of internal bleeding.
- With warfarin it is unpredictable. It can raise bleeding, and the vitamin K2 in some products can weaken warfarin.
Where these come from: The user patterns come from a pharmacist's survey of the Long COVID community and the other sources listed on this page. Those are self-reports. The trial numbers and case reports come from the studies on this page.
My bottom line
The blood pressure drop is real and small. The plaque claim does not hold up in the best trial. If you are on any blood thinner, do not touch this without your doctor. If your blood pressure is high, get it checked and treated properly first.
An opinion, not a finding. I am a coach, not a doctor.
What it has been measured to do
Measured in people
Goals Nattokinase has been tested for in people, biggest studies first. We count only what the studies on this page say, so the real numbers may be higher.
- Blood pressure608 people · 4 studies · 1 found nothing
- Cholesterol and blood fats225 people · 2 studies · 1 found nothing
- Kidney function45 people · 1 study · 1 found nothing
- Living longerno headcount stated · 1 study
What people using it report
Real people telling you what happened to them. Nobody checked it, and the people who post are not a fair sample, so it cannot prove anything works. It is still the best guide on this page to what people actually do with Nattokinase, what they expect, and what goes wrong. The full account, including the negative reports, is below.
29 of the 36 indexed goals have no study of any kind behind Nattokinase
No study in people, animals or cells on this page reports a result for these. That does not prove Nattokinase does nothing for them. It does mean anything you have heard about Nattokinase and one of these did not come from a study cited here.
Show full evidence
What is Nattokinase?
Nattokinase is a clot-busting enzyme made when bacteria ferment soybeans into natto, a Japanese food. For a supplement, it has a big human trial record. That includes blood pressure trials against a dummy pill and a 3 year trial with one. There is no trial of heart attacks or strokes. And its famous plaque result did not use a dummy pill for comparison.
Nattokinase is a 275 building block enzyme. It is made when the bacterium Bacillus subtilis natto ferments boiled soybeans into natto, a food eaten in Japan for centuries. Hiroyuki Sumi first found and named it in 1987, after seeing that natto extract strongly broke down blood clots. Unlike most things on this site, nattokinase has real human trial data. There are more than 15 published human studies, several against a dummy pill, including one that ran a median of 3 years. Blood pressure has the most consistent support. A 2023 review that pooled 6 trials with 546 people found it lowered the top blood pressure number by 3.45 points and the bottom number by 2.32, compared with a dummy pill. The biggest single trial found a similar effect in North Americans, not only in the Japanese, Chinese and Taiwanese groups most of the research comes from.
The claim you hear most, that it shrinks plaque in the neck arteries, stands on thinner ground. The most quoted good result is a 2017 Chinese trial of 82 patients. They got nattokinase or simvastatin, a statin. Plaque size and artery wall thickness fell more on nattokinase. But there was no dummy pill group, and everyone knew who got what. A bigger 2022 report of 1,062 patients found similar scan changes. It looked back at records with no comparison group, and five of its ten authors worked for the company that makes the product tested. Against both stands the best trial nattokinase has. It was run at USC in 265 healthy older adults, against a dummy pill, for a median of 3 years. It found no effect on artery wall thickness, artery stiffness, blood pressure or any lab marker measured. Pooled cholesterol data point the same careful way. The 2023 review found no cholesterol benefit from nattokinase alone, and total cholesterol ran slightly higher than on the dummy pill.
No trial of any size has tested whether nattokinase cuts heart attacks, strokes or deaths. Every good human result so far is a blood pressure number, a clotting marker or a neck artery scan, not a hard health result.
How does Nattokinase work?
Nattokinase works in several ways at once. It breaks down fibrin, the mesh that holds clots together, and fibrinogen, the protein fibrin is made from. It turns the body's own prourokinase into urokinase, an active clot dissolver. It breaks down PAI-1, the protein that normally holds back the body's own clot-dissolving system. And in a dish, heated natto bacteria and store-bought nattokinase both made human blood vessel cells and HeLa cells release more tPA, another clot dissolver, raising its activity several-fold. So it breaks clots directly, and it also boosts the body's own clot breakdown. In a trial of 12 healthy men, one dose changed clotting markers within hours. The clot breakdown markers D-dimer and fibrin fragments rose, clotting factor VIII fell, the natural blood thinner antithrombin rose, and blood took a little longer to clot. All of it stayed within the normal lab range. X-ray pictures show nattokinase is almost the same shape as a related enzyme, subtilisin E, differing at about one spot. In 11 healthy adults, the whole enzyme showed up in the blood, peaking about 13 hours after one swallowed dose. That was the first direct proof it survives digestion and reaches the blood in working form.
What have studies in people found about Nattokinase?
Nattokinase has more human data than almost anything else on this site. There are over 15 published human studies, several against a dummy pill, plus a 3-year trial with a dummy pill that is the biggest and longest ever run on it. Blood pressure has the best support. Clotting markers move the same way across several small trials, which fits how it works. Neck artery scans are where the record splits hardest. The most quoted good study had no dummy pill group, and the one careful long-term trial found nothing at all.
- Blood pressure, pooled review (Li and others, 2023): across 6 trials with 546 people, nattokinase lowered the top blood pressure number by 3.45 points and the bottom number by 2.32, compared with a dummy pill. Much of this comes from a Korean trial in 86 people with borderline or mild high blood pressure. It found 5.55 points off the top number and 2.84 off the bottom after 8 weeks at 2,000 FU a day. A separate North American trial in 79 adults with high blood pressure, paid for by the seller, found a similar drop in the bottom number, mostly in men.
- Neck arteries, the result that goes against it: the Nattokinase Atherothrombotic Prevention Study, run at USC in 265 healthy older adults against a dummy pill for a median of 3 years. It found no effect on artery wall thickness, artery stiffness, blood pressure or any lab marker tested. This is the best designed and longest nattokinase trial there is, and it found nothing.
- Neck arteries, the most quoted and most argued-over finding: an 82-patient Chinese trial compared nattokinase with simvastatin, with no dummy pill group and everyone knowing who got what. Plaque size and artery wall thickness fell more on nattokinase over 26 weeks. A bigger 1,062-patient look back at records from the same country found similar scan changes at a high dose, and none at a dose three times lower. It had no comparison group, and half its authors worked for the maker.
- Cholesterol, pooled review against single trials: the pooled data found no cholesterol benefit from nattokinase alone, and total cholesterol ran slightly higher than on the dummy pill. Single trials that report big cholesterol gains usually add red yeast rice, which lowers cholesterol on its own. That makes it hard to credit nattokinase. In one trial, nattokinase alone did nothing to cholesterol over 6 months, while the same product with red yeast rice worked from month 1.
- Clotting markers, several small trials: in 45 people with no comparison group, fibrinogen, factor VII and factor VIII all fell over 2 months at 4,000 FU a day. In 12 healthy men tested against a dummy pill, one 2,000 FU dose raised the clot breakdown markers D-dimer and fibrin fragments and made blood take a little longer to clot, within hours. Those changes stayed in the normal range. They fit how it works. They are not proof of a health benefit on their own.
- Two serious harms on record. A 92-year-old woman with an irregular heartbeat died of bleeding into her belly while taking store-bought nattokinase and no other blood-thinning drug. And a patient with a mechanical heart valve got a clot on the valve after swapping warfarin for nattokinase for about a year, and needed the valve replaced again.
- Running now: an independent trial with a dummy pill in 48 adults in Brazil with high blood pressure and high cholesterol (NCT06183307). No company is paying for it. Results are expected in 2026 or later.
What this does not tell you: No trial of any size has tested whether nattokinase changes the rate of heart attack, stroke or death. Every good finding is a blood marker or a scan, not a hard health result. The best designed trial ran 3 years against a dummy pill and found no effect on anything it measured. That includes the same scan measure the most quoted good studies rely on. Most of the good plaque and cholesterol results come from small studies at a handful of clinics in China. Many had no comparison group, and several had authors who worked for the company selling the product. That pattern should lower your trust in how big the effect is, even where a real signal exists. Fibrinolytic units (FU) are not an official standard. Makers use different lab tests to reach the FU number on the label, so the same number in one brand's capsule may not match another's.
What do people who took Nattokinase report?
This is what real people say happened to them, good and bad. Nobody measured it. A report cannot tell a real effect from the lift people get just from expecting it to work, from a diet or training change made at the same time, or from what was really in the vial. We still put it near the top. It is the next best thing to a study in people: what happens when real people use it, including what goes wrong.
- Store capsules almost all hold about 2,000 FU, roughly 100 mg of NSK-SD or a similar extract. That matches the dose in most of the published blood pressure trials. A survey of the Long COVID and ME/CFS community, published by pharmacist Martha Eckey, found people often took more, from 4,000 to 12,000 FU a day. 4,000 FU twice a day on an empty stomach was often called the sweet spot.
- Outside Long COVID, people take it for heart health in general: better circulation, artery health and blood pressure. A smaller, vocal group takes it for suspected microclots. In the Long COVID and ME/CFS survey, people took it for tiredness, brain fog and other after-virus symptoms, based on a microclot idea no controlled trial has proven. About 60% said they got some benefit, mostly within 2 weeks.
- Stacking it with serrapeptase or lumbrokinase is common, pitched online as boosting clot breakdown. Lumbrokinase is usually described as stronger and more likely to cause a strong early reaction. Serrapeptase is more often linked with nausea and headache, and in the same survey it gave less steady benefit than nattokinase itself.
- D-dimer is the blood test people mention most, on the idea that a rise means the enzyme is working. That loosely matches the trial finding that one dose raises D-dimer for a few hours. But checking D-dimer yourself months into daily use is a different measure, and nobody has shown it tells you whether nattokinase is working. Lp(a) and standard cholesterol panels also come up in heart-focused talk, with no trial evidence that nattokinase moves Lp(a).
- The problems named most often are no noticeable effect, bruising more easily, and one repeated worry: taking a clot-dissolving enzyme with no doctor involved and no blood test to check on it. That worry is sharpest for older adults and anyone who does not know their own bleeding or clotting risk. The medical reports back it up. The one published death fits exactly that pattern: an older patient on store-bought nattokinase, no other blood-thinning drug, and no monitoring.
- People on warfarin or other blood thinners get the most consistent warnings, from labels, pharmacists and forums. There are two reasons, and they pull in opposite directions. Nattokinase's own clot-breaking action can add to warfarin and raise bleeding risk. But the vitamin K2 left in whole natto and some less-purified extracts can work against warfarin and weaken it. Either way the mix is unpredictable, not just additive. Purified brands such as NSK-SD are sold as K2-free to remove that second problem, but you cannot check K2 content from a label.
- Reddit's r/Supplements and r/Biohackers could not be reached for this entry, because the research tools used here cannot open reddit.com. So nothing above comes from a specific Reddit post, and no quote is taken from any source.
Sources: A published pharmacist-run survey of the Long COVID and ME/CFS supplement-using community (Martha Eckey, PharmD, writing on Substack), which is the only named, citable source for dosing and outcome patterns used here; the Health Canada licensed natural health product label and the Canadian NHPID ingredient entry, which supply the specific warfarin and bleeding-disorder caution language quoted in the legal status section; Memorial Sloan Kettering's integrative medicine monograph on nattokinase, which was used to cross-check the case reports and mechanism claims against a clinical secondary source; and the case-report and clinical literature cited directly elsewhere on this page. Reddit's r/Supplements and r/Biohackers, and any other Reddit community, could not be retrieved for this entry.
The state of the research
Nattokinase is a clear example of something the trial system was never going to pay to test properly, and it is worth being exact about why. Fermenting soybeans with natto bacteria is a Japanese food process centuries old, written about in science since 1987. Nobody can patent the enzyme as a new invention. The trial that would settle it follows thousands of people for several years and costs hundreds of millions of dollars. No maker could earn that back if a dozen other companies could sell the same fermented soybean extract the day it was approved. That is not a knock on the compound. It is a plain money fact about who pays for large final-stage trials, and why something eaten for a thousand years still has no heart attack or stroke data.
You can see that in how it is regulated and sold. In the US it is a dietary supplement. A label may say something like supports healthy circulation, as long as it also says the FDA has not reviewed that claim. It may not claim to treat, prevent or lower the risk of any disease. The FDA has enforced that line on nattokinase. In August 2020 it sent a warning letter to a seller who said their nattokinase product cut plaque build-up and helped prevent heart attack and stroke. The FDA treated those as illegal drug claims, whatever evidence the company thought it had. That is the supplement law working as designed. Even a maker who truly believed the plaque studies could not say so on the label, because the law treats health-support claims and disease claims differently, and good data does not move that line.
The evidence splits right where the money picture predicts. The good plaque and cholesterol results mostly come from small clinics in China. Most had no comparison group, and everyone knew who got what. The biggest was written partly by staff of the company that makes the product tested. The one trial built to the standard a drug would need, against a dummy pill, over years, run by a university with no ties to any seller, found nothing. That does not mean the smaller good studies are wrong. A real effect can show up more easily in a small open study than in a strict multi-year trial. And a no-effect result in healthy older adults at low heart risk does not rule out a benefit in higher-risk people nobody has tested. But it does mean the confident story, that nattokinase shrinks artery plaque, rests on the weaker half of the evidence, not the stronger half.
The honest caveat cuts both ways. The money argument explains why no heart attack or stroke trial exists. It does not show nattokinase would pass one. A change in a marker or a scan is not the same as fewer strokes or heart attacks. Nobody knows whether the fairly solid blood pressure and clot-breaking effects would mean fewer heart events over years of use. Right now that question cannot be answered. That is not because it was tested and failed. It is because the trial has never been run, and probably never will be.
The evidence, in charts
Fig. 1a · how many people
1,806people, across 10 studies in people cited here
| Study | People | Share |
|---|---|---|
| Frontiers in Cardiovascular Medicine 2022 | 1,001 | 55% |
| Clinical Hemorheology and Microcirculation 2021 | 265 | 15% |
| Frontiers in Nutrition 2024 | 178 | 10% |
| Hypertension Research 2008 | 86 | 5% |
| Zhonghua Yi Xue Za Zhi (National Medical Journal of China) 2017 | 82 | 5% |
| Integrated Blood Pressure Control 2016 | 79 | 4% |
| and 4 more cited studies in people with a stated count | ||
One study holds 55% of these people, so the total rests more on one study than its size suggests. Counts are the number of people each study on this page says it signed up. That includes studies that only watched people and gave nobody the compound. 3 more studies in people give no headcount and are not counted here. Studies still signing people up are left out, and only studies cited on this page are counted.
Fig. 1b · evidence mix
13 of 22 sources here are studies in people. The rest are not.
- Study in people · done in people1359%
- Animal study · done in animals15%
- Lab (cells in a dish) · cells or tissue418%
- Review of studies · sums up other studies418%
Counted from the list of sources on this page. It counts only what we cite, so there may be more studies out there. A review counts once, however many studies it sums up.
Fig. 2 · evidence over time
The studies cover 15 different years, 1987 to 2026, counted from the list of sources on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four countries shown. This is what the law says, not a verdict on the science. See Legal status below for the full text and any notes.
Fig. 4 · how much does what
Nobody has tested different amounts in people
This chart would show how the effect changes as the amount goes up. For this compound, nobody has measured that in people. So we leave it empty. We will not borrow an animal chart and pretend it works the same in people.
Fig. 5 · what the molecule is
- Kind of compound
- Biologic
- Molecule weight
- 27.7 kDa (275 amino acids)
- Half-life
- About 13 hoursMedium, 6 to 24 hours
- Chain length
- None on file
Half-life as stated on file: Not established in humans; a pharmacokinetic pilot found intact enzyme peaks in serum around 13 hours after a single oral dose
No amino acid sequence is on file for Nattokinase, so none is drawn rather than guessed from a name.
The studies we cite
- Study in people2008Effects of nattokinase on blood pressure: a randomized, controlled trial
Nattokinase lowered blood pressure a little. 86 adults with borderline or mild high blood pressure took it or a dummy pill for eight weeks. The top number came down about 5 points more than on the dummy, and the bottom number by nearly 3. A hormone that helps set blood pressure fell at the same time, which fits. A few points is real, and it is modest.
Randomized, double-blind, placebo-controlled trial, 86 adults with pre-hypertension or stage 1 hypertension (73 completed), 2,000 FU/day for 8 weeks: net change versus placebo of -5.55 mmHg systolic (95% CI -10.5 to -0.57) and -2.84 mmHg diastolic (95% CI -5.33 to -0.33), with a matching fall in plasma renin activity.
- Study in people2016Consumption of nattokinase is associated with reduced blood pressure and von Willebrand factor, a cardiovascular risk marker: results from a randomized, double-blind, placebo-controlled, multicenter North American clinical trial
A second trial found a smaller blood pressure effect, and the distributor paid for it. 79 adults with high blood pressure took nattokinase or a dummy for eight weeks. The lower blood pressure number fell by about 3 points while the dummy group stayed flat. Men did better than women. A clotting marker fell in women only, and weakly. The company that sells the product in the United States funded the study, which is disclosed in the paper.
North American RCT, 79 hypertensive adults (74 completed), 100 mg/day (about 2,000 FU) of vitamin K2-depleted nattokinase (NSK-SD) for 8 weeks, sponsored by the product's US distributor: diastolic blood pressure fell from 87 to 84 mmHg versus a flat placebo group (p<0.05), with a larger drop in men (86 to 81 mmHg, p<0.006); a fall in von Willebrand factor was seen in women only at p<0.1.
- Study in people2009Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects
Three clotting proteins fell, and there was nothing to compare them against. 45 people, some healthy, some at risk of heart disease and some on dialysis, took a high daily dose for two months. Two of the proteins fell by up to about a tenth, and the third by nearly a fifth. Everyone got the supplement and knew it, so time, season or chance could explain some of that. Cholesterol did not move.
Open-label, self-controlled trial, 45 subjects across healthy, cardiovascular-risk and dialysis groups, 4,000 FU/day for 2 months: fibrinogen fell 7 to 10%, factor VII 7 to 14%, factor VIII 17 to 19% (all p<0.001 for the time effect) across groups; no placebo or control arm, and blood lipids did not change.
- Study in people2015A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles
One dose nudged the blood toward being slightly thinner, and never past normal. Twelve healthy men each took nattokinase and a dummy pill on separate days. Over the next eight hours, markers that rise when clots break down went up, a clotting factor fell, a natural blood thinner rose, and blood took a little longer to clot. Every reading stayed inside the normal range. The effect is real, and it is gentle.
Double-blind, placebo-controlled crossover RCT, 12 healthy men, single 2,000 FU dose: D-dimer and fibrin degradation products rose, factor VIII activity fell, antithrombin rose, and activated partial thromboplastin time prolonged over the following 8 hours; every change stayed inside the normal reference range.
- Study in people2013A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose
The enzyme really does reach the bloodstream when you swallow it. Eleven healthy adults took a single dose, and a blood test found intact nattokinase in their blood, peaking around 13 hours later. That is worth knowing, because most large proteins are broken into pieces by digestion before they get anywhere. This was a small pilot and it measured only that. It says nothing about what the enzyme then does.
Pharmacokinetic pilot, 11 healthy adults, single 2,000 FU dose: intact nattokinase was directly measurable in serum by immunoassay, peaking around 13 hours post-dose, the first direct evidence the enzyme reaches human blood in active form after oral dosing.
- Study in people2017A clinical study on the effect of nattokinase on carotid artery atherosclerosis and hyperlipidaemia
Plaque in the neck arteries shrank more on nattokinase than on a statin, but everyone knew who got what. 82 patients at one clinic in China took nattokinase or simvastatin for 26 weeks. Plaque size fell about a third on nattokinase and about a tenth on the statin. There was no dummy pill group, and cholesterol changes did not track the scan changes. This is the most quoted nattokinase result, from the weakest kind of study.
Randomized but open-label, active-controlled trial at one Sun Yat-sen University TCM outpatient clinic, 82 patients (76 completed), 6,000 FU/day nattokinase versus simvastatin 20 mg/day for 26 weeks: carotid plaque size fell 36.6% on nattokinase versus 11.5% on simvastatin (p<0.01) and carotid intima-media thickness fell in both groups. The most-cited source for nattokinase and carotid plaque, but not placebo-controlled or blinded; lipid change did not correlate with the imaging change (r=0.35, p=0.09).
- Study in people2022Effective management of atherosclerosis progress and hyperlipidemia with nattokinase: A clinical study with 1,062 participants
This is the thousand patient study people cite, and it was not a trial. Researchers went back through clinic records across China for patients on a high dose for a year. They reported neck artery wall thickness down about a fifth and plaque size down about a third. Nobody was assigned to anything. A lower dose in 61 patients showed no effect at all. Five of the ten authors worked for the maker, even though the paper said there was no commercial interest.
Retrospective, non-randomized, unblinded, uncontrolled record review across multiple China clinics (2016-2020), 10,800 FU/day for 12 months in 1,001 patients: carotid intima-media thickness fell 21.7% and plaque size fell 36%; a lower 3,600 FU/day dose in 61 patients showed no such effect. Five of ten authors were employed by Sungen Bioscience, the nattokinase manufacturer, despite the paper's stated absence of commercial interest; a later corrigendum corrected a baseline-characteristics table without changing the results.
- Study in people2021Nattokinase atherothrombotic prevention study: A randomized controlled trial
The one long, careful, independent trial found nothing. 265 adults without heart disease took nattokinase or a dummy pill for a median of three years, with neck artery scans every six months. The artery wall thickened at the same rate in both groups. Stiffness, blood pressure, and every clotting, inflammation and metabolic marker measured came out the same. A trial this long would have found a real effect on plaque if there was one to find.
The Nattokinase Atherothrombotic Prevention Study (NAPS, NCT02080520), the only large, long, placebo-controlled Western academic RCT of nattokinase: 265 adults without cardiovascular disease, median age 65.3, 2,000 FU/day for a median of 3 years, with carotid ultrasound every 6 months. No significant difference from placebo in the rate of change of carotid intima-media thickness, carotid arterial stiffness, blood pressure, or any coagulation, fibrinolysis, inflammatory or metabolic marker measured.
- Study in people2009Combined nattokinase with red yeast rice but not nattokinase alone has potent effects on blood lipids in human subjects with hyperlipidemia
On its own, nattokinase did nothing to cholesterol. 47 patients with high cholesterol took nattokinase alone, nattokinase with red yeast rice, or a dummy, for six months. The nattokinase-only group came out no different from the dummy. The combination improved every blood fat from the first month onwards. That positive result cannot be pulled apart, because the red yeast rice was in it too.
RCT, 47 patients with hyperlipidemia, nattokinase alone versus nattokinase plus red yeast rice versus placebo for 6 months: the nattokinase-only arm showed no significant lipid change against placebo, while the combination arm improved triglycerides, total cholesterol, LDL-C and HDL-C from month 1. Nattokinase's own lipid contribution cannot be separated from red yeast rice's in the positive result.
- Study in people2024Lipid-lowering, antihypertensive, and antithrombotic effects of nattokinase combined with red yeast rice in patients with stable coronary artery disease: a randomized, double-blinded, placebo-controlled trial
In a better built trial, nattokinase alone moved one blood fat and nothing else. 178 patients with stable heart disease, already on their usual medicines, took nattokinase, red yeast rice, both, or a dummy pill for 90 days. Nattokinase alone lowered LDL, the harmful cholesterol, compared with the dummy. Total cholesterol, triglycerides and good cholesterol did not budge. The combination improved every blood fat, and blood pressure as well.
Double-blind, placebo-controlled RCT, 178 patients with stable coronary artery disease already taking statins, aspirin or beta-blockers, randomized to nattokinase (3,615 FU/day), red yeast rice, the combination, or placebo for 90 days: nattokinase alone significantly lowered LDL-C versus placebo but not total cholesterol, triglycerides or HDL-C. The combination arm improved every lipid and blood pressure measure and raised antithrombin III more than placebo.
- Study in people2015Consequence of patient substitution of nattokinase for warfarin after aortic valve replacement with a mechanical prosthesis
A man stopped his warfarin and took nattokinase instead after getting a mechanical heart valve. About a year later a clot formed on the valve and he needed another operation to replace it. The doctors who reported it call this the first documented case of that swap, and they strongly warn against it. A supplement that nudges clotting markers is not a substitute for a prescribed blood thinner.
Case report: a patient self-substituted nattokinase for warfarin after mechanical aortic valve replacement. After roughly a year without warfarin, a thrombus formed on the valve and the patient needed repeat valve replacement surgery. The authors call it the first documented case of nattokinase substituted for warfarin after valve replacement and strongly discourage that use.
- Study in people2021Nattokinase-Associated Hemoperitoneum in an Elderly Woman
A 92-year-old woman taking over-the-counter nattokinase bled into her abdomen and died. She had an irregular heartbeat and was on no prescribed blood thinner and no antiplatelet drug. The doctors reporting the case warn against supplements of this kind, and nattokinase in particular, in patients like her. This is one case. It is also why the bleeding risk is not theoretical.
Case report: a 92-year-old woman with atrial fibrillation, taking over-the-counter nattokinase and no prescribed anticoagulant or antiplatelet drug, developed spontaneous bleeding into the abdominal cavity and died. The authors warn against consumption of herbal supplements, especially nattokinase, in this kind of patient.
- Study in people2026Effects of Nattokinase on Inflammation and Cardiovascular Risk Markers in Patients With Dyslipidemia (NCT06183307)
An independent trial is running now, which this field badly needs. 48 adults in Brazil with high blood pressure and high cholesterol are taking nattokinase or a dummy pill. No company is paying for it. It is due to finish at the end of 2026. It is one of only two nattokinase trials recruiting anywhere in the world.
An independent, non-industry, double-blind, placebo-controlled RCT of nattokinase in 48 hypertensive, dyslipidemic adults in Brazil, recruiting since 2024 with primary completion estimated December 2026, one of only two nattokinase trials currently recruiting worldwide.
- Review of studies2017Nattokinase: An Oral Antithrombotic Agent for the Prevention of Cardiovascular Disease
A review of how nattokinase may work, how it is made, and its safety data. It noted that a US trial on preventing clot-related heart disease was under way at the time.
Review of proposed mechanisms (direct fibrin/fibrinogen hydrolysis, prourokinase-to-urokinase conversion, PAI-1 degradation, tPA stimulation), production methods, and safety data; notes a US Phase 2 atherothrombotic-prevention trial was underway at the time of writing.
- Review of studies2023Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
A 2023 review that pooled 6 trials with 546 people. Nattokinase lowered the top blood pressure number by 3.45 points and the bottom by 2.32, compared with a dummy pill. Cholesterol went the other way. Total cholesterol ran higher than on the dummy pill, and blood sugar a little higher.
Meta-analysis of 6 RCTs, 546 participants: nattokinase significantly lowered systolic (-3.45 mmHg) and diastolic (-2.32 mmHg) blood pressure versus placebo. Pooled lipid results ran the other way: total cholesterol was higher than placebo at both low and high total dose, HDL lower and LDL higher at low dose, and glucose slightly higher, with no significant effect on triglycerides.
- Review of studies2025Navigating the Effects of Anti-Atherosclerotic Supplements and Acknowledging Associated Bleeding Risks
A 2025 review of supplements for artery health, including nattokinase, omega-3s, berberine and garlic. Results depend on the form and dose. All of them carry bleeding and drug interaction risks.
Review grouping nattokinase with omega-3s, berberine and garlic: favorable metabolic and vascular effects are reported across the class, but clinical efficacy depends on formulation and dose, and bleeding risk and drug-interaction potential apply to all of them, nattokinase included.
- Review of studies2020Dr. Sam Robbins, Inc. dba HFL Solutions, LLC - Warning Letter
An FDA warning letter from 2020. A seller claimed its nattokinase product cut artery plaque and helped prevent heart attacks and strokes. The FDA said those claims made it an illegal unapproved drug.
FDA objected to marketing a nattokinase-containing product as able to decrease arterial plaque buildup and help prevent a heart attack or stroke, concluding these disease claims made the dietary supplement an unapproved new drug regardless of the underlying data.
- Animal study2016Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto
In rats and in lab tests, plus a small human group. It did not damage genes, and rats showed no harm at up to 1,000 mg per kg a day for 90 days. Separately, people handled 10 mg per kg a day well over 4 weeks.
GLP-compliant toxicology package for NSK-SD nattokinase: non-mutagenic and non-clastogenic in vitro, no adverse effect in 28-day and 90-day rat studies up to 1,000 mg/kg/day (the highest dose tested, set as the NOAEL); a small human arm found 10 mg/kg/day well tolerated over 4 weeks.
- Lab (cells in a dish)1987A novel fibrinolytic enzyme (nattokinase) in the vegetable cheese Natto; a typical and popular soybean food in the Japanese diet
In a lab. The discovery paper. Sumi and colleagues pulled a strong clot-dissolving enzyme out of natto and named it nattokinase.
The discovery paper. Sumi and colleagues extracted a strong fibrinolytic enzyme from natto, named it nattokinase, and estimated its molecular weight at about 20 kDa, the first published characterisation of the enzyme now studied in human trials.
- Lab (cells in a dish)2013X-ray structure determination and deuteration of nattokinase
In a lab. X-ray pictures of the enzyme show it is almost the same shape as a related bacterial enzyme, subtilisin E, differing at about one spot.
Crystal structure at 1.74 angstrom resolution confirms nattokinase as a subtilisin-family serine protease whose three-dimensional structure is nearly identical to subtilisin E from Bacillus subtilis, differing at essentially one residue.
- Lab (cells in a dish)2006Effects of nattokinase, a pro-fibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity
In a dish, with human blood. Nattokinase made red blood cells clump less and made the blood thinner, more so at higher amounts.
Confirms nattokinase is a 275-residue, 27.7 kDa subtilisin-family protease. Incubating human blood samples with nattokinase produced a dose-dependent fall in red-cell aggregation and low-shear blood viscosity, at concentrations similar to those used in prior animal trials.
- Lab (cells in a dish)2008Nattokinase-promoted tissue plasminogen activator release from human cells
In a dish. Natto bacteria and store-bought nattokinase made human cells release more tPA, the body's own clot dissolver, with activity up to about 24 times higher. That suggests a second way it breaks down clots.
Heat-inactivated Bacillus subtilis natto culture and marketed nattokinase both stimulated tissue plasminogen activator (tPA) release from human vascular endothelial cells and HeLa cells, raising tPA activity up to roughly 24-fold over control, evidence for an indirect fibrinolytic mechanism beyond direct fibrin cleavage.
Common questions
Has Nattokinase been tested in people?
Yes. 1,795 people given it across 9 completed trials cited here, 3 of which found nothing. Nattokinase is a clot-busting enzyme made when bacteria ferment soybeans into natto, a Japanese food.
What is the Nattokinase dosage?
No human dose established. Amounts that were given in studies sit in Human evidence on this page. None of them is a personal dose. 9 completed trials, 1,795 people given it
Is Nattokinase FDA-approved?
Sold as a dietary supplement under the US supplement law. It is not an approved drug, and the FDA has never checked it for safety or whether it works. A label may say how it supports the body, such as supporting healthy blood flow, if it carries the required disclaimer that the FDA has not checked the statement. It may not claim to treat, prevent, or lower the risk of a disease. In August 2020, the FDA sent a warning letter to a supplement seller. The seller had marketed a product with nattokinase in it as able to cut plaque build-up in the arteries and help prevent a heart attack or stroke. The FDA said those were illegal disease claims, no matter what the research showed.
Does nattokinase actually lower blood pressure?
This is its best supported claim. A 2023 review that pooled 6 trials against a dummy pill, with 546 people, found average drops of 3.45 points on the top number and 2.32 on the bottom. The single trials behind it agree. An 8-week Korean trial in 86 people with borderline or mild high blood pressure found drops of 5.55 and 2.84 at 2,000 FU a day. A North American trial found a similar drop in the bottom number, bigger in men. These are modest drops, about the size one lifestyle change might give. They are not a stand-in for prescribed blood pressure medicine.
Does nattokinase reduce arterial plaque?
The evidence is real but weaker than its reputation. The most quoted study gave 82 people nattokinase or simvastatin, and neck artery plaque shrank more on nattokinase over 26 weeks. But it had no dummy pill group, and everyone knew who got what. A bigger study of 1,062 patients found similar scan changes. It looked back at records with no comparison group, and half its authors worked for the maker of the product tested. Against both, the one careful multi-year trial with a dummy pill, in 265 healthy older adults at USC, found no effect on artery wall thickness or stiffness at all. No study has tested whether any scan change means fewer strokes or heart attacks.
Can nattokinase be taken with warfarin, aspirin, or other blood thinners?
Not without a doctor involved. Nattokinase thins the blood a little on its own. Trials show one dose raises D-dimer, lowers factor VIII and makes blood take longer to clot. So combining it with warfarin, aspirin, clopidogrel or other blood thinners is a real bleeding risk, not just a theory. A published case describes an older woman with an irregular heartbeat who died of internal bleeding while taking store-bought nattokinase alone, with no other blood thinner. That shows nattokinase carries real bleeding risk even on its own. In another case, a heart valve patient swapped prescribed warfarin for nattokinase, got a clot on the valve, and needed surgery again. That is the opposite danger: dropping a proven blood thinner without supervision. Licensed Canadian labels warn against use by anyone on blood-clotting products, and say to stop 7 days before any planned surgery.
Does the vitamin K2 in natto interfere with warfarin?
It can, and it pushes the opposite way from nattokinase's clot-breaking effect. That is what makes the mix truly unpredictable, not just additive. Whole natto and some less-purified extracts still hold vitamin K2. K2 helps the body make clotting factors and can work against warfarin, weakening it and raising clot risk. Meanwhile nattokinase itself can raise bleeding risk. Purified brands such as NSK-SD are sold as K2-free for exactly this reason. But you usually cannot check K2 content from a label. Anyone on warfarin should treat any nattokinase product as something that needs a doctor and probably a blood test, not something to manage alone.
Why is there so much human data on nattokinase compared to other supplements on this site, and why no outcome trial?
Nattokinase is cheap, safe enough to dose, and easy to test in short studies, which is why so many small trials exist. What it lacks is the trial that would settle whether it prevents heart attacks or strokes. That means several thousand people followed for years. It costs hundreds of millions of dollars, and it is normally paid for by whoever holds the sole right to sell the product. Nattokinase comes from a centuries-old fermentation process nobody can patent, so no company has a money reason to fund that trial. And US law bars a supplement seller from advertising a disease-prevention claim anyway, which cuts the payoff further. That explains the funding gap. It does not prove nattokinase would pass such a trial if one were run.
What do people in health and longevity communities actually report?
A survey of the Long COVID and ME/CFS community, run by a pharmacist, found people often taking 4,000 to 12,000 FU a day, well above the roughly 2,000 FU in most trials. Many paired it with serrapeptase or lumbrokinase. About 60% said they got some benefit, mostly within 2 weeks, for tiredness and brain fog blamed on suspected microclots. No controlled trial has tested that idea. Outside that community, people frame it as general heart support. The problems that come up most are no effect, bruising more easily, and unease about taking a clot-dissolving enzyme with no doctor or blood test involved. The published case reports back that worry up. Reddit's r/Supplements and r/Biohackers could not be reached for this entry, so no claim here comes from a specific Reddit post.