Nattokinase

What it is

Nattokinase is an enzyme (a protease) produced by the bacterium Bacillus subtilis var. natto during the fermentation of soybeans into the Japanese food natto. In the laboratory it breaks down fibrin, the protein mesh that holds a blood clot together. It is sold as a capsule, usually standardised in fibrinolytic units (FU) rather than milligrams. It is not a nutrient and the human body does not make it.

What the research says

The evidence is limited and mostly about surrogate markers, not about heart attacks or strokes. A 2023 systematic review and meta-analysis of six randomised trials (546 people) found small average reductions in systolic and diastolic blood pressure, and no lipid-lowering benefit; at lower total doses the lipid numbers actually moved the wrong way, and blood glucose rose slightly. A single-dose crossover study in 12 healthy men showed measurable shifts in clotting and fibrinolysis markers that all stayed inside the normal range. No trial has tested whether nattokinase prevents clots, strokes or heart attacks in people.

Evidence grade: Limited evidence.

What goes wrong

At relatively low total dosage, nattokinase moved total, HDL and LDL cholesterol in an unfavourable direction compared with placebo, and blood glucose rose slightly. (Source 1)

• Meta-analysis, Low certainty.
• Size: 546 participants across 6 randomised controlled trials.
• Who: adults in randomised trials of nattokinase supplementation.
• How long: trial durations varied; most 8 weeks.
• Result: Total cholesterol MD = 5.27 (95% CI 3.74 to 6.81, p < 0.00001); HDL-C MD = -2.76 (95% CI -3.88 to -1.64, p < 0.00001); LDL-C MD = 6.49 (95% CI 0.83 to 12.15, p = 0.02); blood glucose MD = 0.40 (95% CI 0.20 to 0.60, p < 0.0001)
• Funding: not stated in the abstract.

Limit of this finding: Two things in the source read oddly, and both are the published paper's own wording rather than a transcription error. First, it calls a mean difference of +5.27 for total cholesterol a 'negative effect': it means the effect was unwanted, because cholesterol went up on nattokinase relative to placebo, not that the number itself was negative. Second, the same abstract prints a systolic blood pressure interval that is not centred on its own point estimate. Read these cholesterol and glucose figures as showing movement in an unwanted direction in the lower-dose trials, not as precise estimates.

led a slight increase in blood glucose (MD = 0.40, 95% CI: 0.20 to 0.60, p < 0.0001) as compared to placebo

A patient already taking aspirin for stroke prevention developed an acute cerebellar haemorrhage after seven days of nattokinase 400 mg daily, with multiple cerebral microbleeds visible on MRI. (Source 2)

• Case report, Very low certainty.
• Size: 1 patient.
• Who: a patient using aspirin for secondary stroke prevention with cerebral microbleeds.
• How long: 7 consecutive days of nattokinase.
• Result: acute cerebellar haemorrhage; multiple microbleeds demonstrated on brain MR images.
• Funding: not stated.

We report a patient, having used aspirin for secondary stroke prevention, who had an acute cerebellar hemorrhage after taking nattokinase 400 mg daily for 7 consecutive days.

POSITION: the US Food and Drug Administration, in a warning letter dated 15 May 2026, told a seller that its nattokinase product's blood-pressure, blood-thinning and cholesterol claims made the product an unapproved new drug. (Source 3)

• Official position, Certainty not rated.
• Size: not applicable.
• Who: a US dietary supplement marketer (Meta Labs Pharmaceuticals, LLC)
• How long: letter dated 15 May 2026, following a facility inspection 8-18 December 2025.
• Result: FDA classified the products as new drugs under section 201(p) of the Federal Food, Drug, and Cosmetic Act and as misbranded.
• Funding: government agency.

Your products are not generally recognized as safe and effective for the above referenced uses and, therefore, the products are "new drugs" under section 201(p) of the Act

What the evidence supports

Pooling six randomised trials, nattokinase produced small average reductions in systolic and diastolic blood pressure versus placebo. (Source 1)

• Meta-analysis, Low certainty.
• Size: 546 participants across 6 randomised controlled trials.
• Who: adults enrolled in randomised trials of nattokinase supplementation, several with elevated blood pressure.
• How long: trial durations varied; most 8 weeks.
• Result: Systolic MD = -3.45 mmHg (95% CI -4.37 to -2.18, p < 0.00001); diastolic MD = -2.32 mmHg (95% CI -2.72 to -1.92, p < 0.00001)
• Funding: not stated in the abstract; registered on PROSPERO CRD42022315020.

Limit of this finding: The source's own numbers do not line up here. A mean difference of −3.45 mmHg should sit in the middle of its 95% confidence interval, but the interval the paper prints, −4.37 to −2.18, is centred on about −3.28. One of those three figures is misprinted in the published paper and the text does not say which. The direction of the result (a fall in blood pressure) and the significance the paper reports are as published; the exact size of the reduction should be read as approximate rather than precise.

Nattokinase supplementation significantly reduced systolic blood pressure (MD = –3.45, 95% CI: –4.37 to –2.18, p < 0.00001) and diastolic blood pressure (MD = –2.32, 95% CI: –2.72 to –1.92, p < 0.00001)

In a North American randomised trial of 100 mg/day nattokinase for 8 weeks, diastolic blood pressure fell significantly versus placebo, with the effect concentrated in men. (Source 4)

• Randomized trial, Low certainty.
• Size: 79 enrolled, 74 completed.
• Who: North American adults screened for elevated blood pressure (systolic >=130 or diastolic >=90 mmHg)
• How long: 8 weeks.
• Result: Diastolic fell 87 to 84 mmHg vs unchanged 87 mmHg on placebo (P<0.05); in males 86 to 81 mmHg (P<0.006)
• Funding: industry-funded (sponsored by JBSL-USA, the distributor of the nattokinase product tested)

The average reduction in diastolic BP in the nattokinase group from 87 mmHg to 84 mmHg was statistically significant when compared to that in the group consuming placebo, where the average diastolic BP remained constant at 87 mmHg (P<0.05)

What the evidence does not support

The same meta-analysis found no effect of nattokinase on triglycerides and concluded that lower-dose supplementation has no significant lipid-lowering effect. (Source 1)

• Meta-analysis, Low certainty.
• Size: 546 participants across 6 randomised controlled trials.
• Who: adults in randomised trials of nattokinase supplementation.
• How long: trial durations varied; most 8 weeks.
• Result: Triglycerides p = 0.71; at higher total dosage no significant differences in HDL-cholesterol or LDL-cholesterol.
• Funding: not stated in the abstract.

Limit of this finding: The triglyceride result quoted here is a straightforward null result. It comes, though, from a meta-analysis whose other reported figures are internally inconsistent: the same abstract prints a systolic blood pressure confidence interval that is not centred on its own point estimate, and describes a rise in total cholesterol as a 'negative effect'. Nothing in the paper explains either. Treat this review's numbers as indicative rather than exact.

No significant correlation was found between nattokinase supplementation and triglyceride (p = 0.71).

Where the evidence is mixed

A single 2,000 FU dose of nattokinase changed several coagulation and fibrinolysis markers in healthy young men, but every change stayed within the normal reference range. (Source 5)

• Randomized trial, Very low certainty.
• Size: 12 healthy young males.
• Who: healthy young Japanese men.
• How long: single dose, blood sampled at 2, 4, 6 and 8 hours.
• Result: D-dimer up at 6 and 8 h and FDP up at 4 h (p < 0.05); factor VIII activity down at 4 and 6 h (p < 0.05); antithrombin higher at 2 and 4 h (p < 0.05); aPTT prolonged at 2 and 4 h (p < 0.05 and p < 0.01)
• Funding: Grant-in-Aid for Scientific Research (KAKENHI) Japan; authors declare no competing financial interests; product supplied as NSK-SD by Japan Bio Science Laboratory.

As a result, D-dimer concentrations at 6 and 8 hours and blood fibrin/fibrinogen degradation products at 4 hours after NK administration elevated significantly (p < 0.05, respectively).

Where the research disagrees

Whether nattokinase improves blood lipids

• Li and colleagues, Reviews in Cardiovascular Medicine (2023), meta-analysis of 6 RCTs, 546 participants: relatively low-dose supplementation of nattokinase may have no significant lipid-lowering effect (Source 1)
• Meta Labs Pharmaceuticals marketing, as quoted by FDA (2026), product marketing claim, no trial cited: Nattokinase benefits: thins the blood (Source 3)

How much

• Reference intake: There is no recommended intake for nattokinase. It is not an essential nutrient and no body has set a reference intake; the clinical record is described by a 2023 narrative review as restricted to case series and volunteers rather than clinical studies. (Source 6)
• Upper limit: No human tolerable upper intake level has been set. The only quantitative safety ceiling in the literature is an animal one: a 90-day oral subchronic NOAEL of 1000 mg/kg-day in rats, the highest dose tested. (Source 7)
• Studied: 100 mg nattokinase per day for 8 weeks in a North American trial of adults with elevated blood pressure (Source 8)
• Studied: A single 2,000 FU dose (NSK-SD) in healthy young men, with blood sampled over 8 hours (Source 5)
• Studied: 400 mg daily for 7 consecutive days in the patient who developed a cerebellar haemorrhage (Source 2)

A common belief, and what the research shows

The belief: Nattokinase dissolves existing blood clots and arterial plaque, so it works like a natural blood thinner.

What the research shows: What has actually been measured in people is short-term movement of clotting and fibrinolysis markers, and those changes stayed inside the normal range: the single-dose study states "All the changes, however, were within the normal range." No randomised trial has shown that nattokinase prevents or dissolves clots, strokes or heart attacks. The one published case of serious injury runs the other way: "We suggest that nattokinase may increase risk of intracerebral hemorrhage in patients who have bleeding-prone cerebral microangiopathy and are receiving other antithrombotic agent at the same time."

Questions and answers

What is it?

Nattokinase is an enzyme - specifically a protease - that comes from food rather than being made by the body. It is produced by Bacillus subtilis var. natto during the fermentation of soybeans into natto, a traditional Japanese food. Supplements are extracts of that fermentation, usually standardised in fibrinolytic units. (Source 6)

What does it do in the body?

Its best-described laboratory action is breaking down fibrin, the protein mesh in a clot. In a single-dose crossover study in 12 healthy men, markers of clot breakdown such as D-dimer and fibrin degradation products rose measurably within hours. Those shifts were real but small, and the authors note every change stayed inside the normal reference range. (Source 5)

Is it good or bad for you?

It depends heavily on context. Pooled across six randomised trials it lowered blood pressure by about 3/2 mmHg on average, which the reviewers called an effective adjunctive therapy for hypertension, but the same pooling found no lipid benefit and a slight rise in blood glucose. Against that, a published case links it to a brain haemorrhage in a person already on aspirin. Nothing has tested whether it prevents heart attacks or strokes. (Source 1)

How do you get more of it?

The only dietary source is natto, the fermented soybean food in which the enzyme is produced. Otherwise it comes from capsules of the fermentation extract. Trials have used defined amounts: the North American blood-pressure trial gave 100 mg per day for eight weeks. (Source 8)

If it is harmful, what reduces it?

Nattokinase is not stored in the body and there is no described way of removing it other than stopping intake. The published safety concern is about combining it with drugs that already affect clotting: the single reported serious injury occurred in someone taking aspirin at the same time. No antidote or reversal agent has been described in the literature. (Source 2)

Why might someone be low in it or missing it?

There is no deficiency state, because nattokinase is not a nutrient and the body does not make it. Someone has none in their diet simply because they do not eat natto or take a supplement; it is described in the literature as a fibrinolytic enzyme from fermented soybean. (Source 1)

Which whole foods contain it or feed it?

Natto - soybeans fermented by Bacillus subtilis var. natto - is the food that contains it, and the toxicology literature describes the enzyme as central to that fermentation. No other common food is described as a source. Plain soybeans, soy milk and tofu are not fermented by this organism and are not described as sources. (Source 7)

What happens if you do not have it?

Nothing is known to go wrong from not consuming nattokinase: no deficiency syndrome has been described, and it is not an essential nutrient. A 2023 review of the field is explicit that the human evidence base is thin and rests on case series and volunteer studies rather than clinical trials, so no consequence of absence has been studied. (Source 6)

We searched: Searched for nattokinase deficiency, requirement and essentiality in PubMed-indexed reviews, the 2023 Reviews in Cardiovascular Medicine meta-analysis and the 2016 Food and Chemical Toxicology safety assessment; none describes a deficiency state.

How can you test for it?

There is no validated clinical test for nattokinase status in the literature we searched. Research studies do not measure the enzyme itself; they measure downstream clotting markers such as D-dimer, fibrin degradation products, factor VIII and activated partial thromboplastin time, and those are general coagulation tests, not tests for nattokinase. (Source 5)

We searched: Searched for a nattokinase assay, blood level or status test across the 2023 meta-analysis, the 2015 single-dose pharmacokinetic/pharmacodynamic study, the 2016 toxicology assessment and the 2023 Italian Journal of Medicine review; only downstream coagulation markers are measured.

References

1. Reviews in Cardiovascular Medicine. Nattokinase Supplementation and Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. 2023. DOI 10.31083/j.rcm2408234. Read the source
2. Internal Medicine. Cerebellar Hemorrhage Provoked by Combined Use of Nattokinase and Aspirin in a Patient with Cerebral Microbleeds. 2008. DOI 10.2169/internalmedicine.47.0620. Read the source
3. US Food and Drug Administration. Warning Letter: Meta Labs Pharmaceuticals, LLC - 725130 - 05/15/2026. 2026. Read the source
4. Integrated Blood Pressure Control. Consumption 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 (results section of the abstract). 2016. DOI 10.2147/IBPC.S99553. Read the source
5. Scientific Reports. A single-dose of oral nattokinase potentiates thrombolysis and anti-coagulation profiles. 2015. DOI 10.1038/srep11601. Read the source
6. Italian Journal of Medicine. Nattokinase historical sketch on experimental and clinical evidence. 2023. DOI 10.4081/itjm.2023.1583. Read the source
7. Food and Chemical Toxicology. Toxicological assessment of nattokinase derived from Bacillus subtilis var. natto. 2016. DOI 10.1016/j.fct.2015.12.025. Read the source
8. Integrated Blood Pressure Control. Consumption 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 (materials and methods section of the abstract). 2016. DOI 10.2147/IBPC.S99553. Read the source